Background Research in the subject of the influence of SARS-CoV-2 mechanisms on human’s homeostasis remains actual problem. Particular interest is the study of pathomorphological changes in the appendix in children with COVID-19. Objectives Aim of the study: morphological and molecular biological evaluation of the appendix in children of different age groups with COVID-19. Methods Groups were formed on the basis of anamnestic, clinical and morphological data: I (n = 42; aged 2 to 18 years, average - 10.8 years) – with an established clinical diagnosis: coronavirus infection (COVID-19; PCR+); II (n = 55; aged 2 to 18 years, average - 9.7 years) – with a confirmed clinical diagnosis of acute appendicitis; collected before the onset of the COVID-19 pandemic in 2017-2019; III (n = 38; aged 2 to 18 years, average - 10.3 years) - control group. Histological and immunohistochemical studies were conducted using primary antibodies to CD3, CD4, CD68, CD163, CD20, CD138 and to pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Results In most samples of appendix in children with COVID-19 were discovered signs of destructive phlegmonous-ulcerative and gangrenous appendicitis. An increase in CD3+, CD4+, CD68+, CD163+, CD20+ CD138+ immunocompetent cells was found in the appendix of children with COVID-19. As well, there is an increase in pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Conclusions The aforementioned pathological and immunohistochemical changes were more pronounced in the group of children aged 6-12 years (childhood).

Background: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved, and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. Methods: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to see if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. Results: Escherichia coli, Pseudomonas aeruginosa and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria, polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen, were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented four times higher risk of complicated appendicitis. Conclusion: Polymicrobial presentation and gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

Background: Acute appendicitis (AA) is the most common cause of emergency surgery. Perforation is more common than adults. Early diagnosis and new markers are needed. The aim of this study was to investigate the effects of plasma Fetuin-A (FA) levels in patients with the acute abdomen (AB). Material and Method: This prospective study included 107 patients younger than 16 years of age who were admitted to the emergency department for abdominal pain between January 2018 and December 2018. The patients who presented to abdominal pain were divided into two groups as AA and other causes (OC) of AB. T Patients with acute appendicitis; intraperitoneal, retrocolic / retrocecal and appendicitis were divided into three groups. Also, the AA group was divided into two groups as perforated appendicitis and non-perforated appendicitis. Serum FA levels of the patients were evaluated in the emergency department. Results: In the AA group, C-reactive protein (CRP) and white blood cell (WBC) levels were higher, and FA levels were significantly lower than in the AB group. Intraperitoneal localization was 95.2% and perforation was frequent. When significant values in the univariate regression analysis for acute abdomen and perforation were compared in the multivariate regression analysis, CRP, WBC, and FA levels were found to be prognostic. Also, decreased FA levels were associated with AA while too much decreased FA levels were associated with the risk of perforation. Conclusion: While trying to diagnose AA in children, the FA level, CRP and WBC may be predictive values to identify risk factors.

Background: To investigate the preoperative clinical and radiological factors that predict the development of a postoperative intraabdominal abscess (IAA) in patients with acute appendicitis who were treated by laparoscopic appendectomy (LA). Methods: Two hundred sixteen patients with pathologically proven acute appendicitis underwent LA between January 2013 and March 2018 in our department. Of these, 147 patients were diagnosed with complicated appendicitis (CA) (CA group), while the other 69 patients were diagnosed with simple appendicitis (SA) (SA group). We compared the perioperative clinical and radiographic factors between the two groups and investigated the predictive factors of postoperative IAA. Results: Sixteen patients developed postoperative IAA in the CA group, while no patients did in the SA group. The univariate analysis revealed that time from onset to surgery more than 3 days (p = 0.011), the preoperative CT finding of periappendiceal fluid (p = 0.003), abscess (p < 0.001), and free air (p <0.001), operation time more than 120 minutes (p = 0.023) and placement of a drainage tube (p <0.001) were significantly associated with the development of IAA. Multivariate analysis revealed that the preoperative CT finding of free air was independently associated with the development of IAA (p = 0.007, odds ratio = 5.427). Conclusions: IAA was developed predominantly in the patients with CA. Preoperative CT findings of free air was found to be an independent predictor for the development of IAA. Surgeons should be meticulous in managing the postoperative course of patients with this finding.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To contain the virus, numerous preventive measures have been taken including isolation of patients, careful infection control, social distancing, and taking vaccine. So far, new confirmed and death cases are still increasing. SARS-CoV-2 invades cells by using the angiotensin converting enzyme 2 (ACE2). ACE2 is an essential enzyme of the renin-angiotensin system (RAS) which converts angiotensin II (Ang II) to angiotensin (1-7). ACE2 is expressed in different organs, including lung, heart, and kidney. A high number of COVID-19 patients developed kidney injury has been reported. Renal impairment and acute injury are associated with mortality of COVID-19, which is 14-16 times higher than other general patients. Acute Kidney Injury has been occured in 2.9 up to 43% of intensive care unit patients. The increasing evidence show that the components of RAS can activate the complement cascade, and cytokines production. Kidney injury caused by SARS-CoV-2 is related mainly to systemic and local inflammation. Moreover, the uncontrolled immune responses mediated by SARS-CoV-2 including hypercytokinaemia, secondary hemophagocytic lymphohistiocytosis, antibody dependent enhancement, complement system, and phagocytic cells activation can contribute in the virus pathogenesis leading to associated renal dysfunction. However, the role and crosstalk between of RAS components and immune response in mediating kidney injury remain undefined. In this review, we focus on the recent studies to provide the pathogenesis of SARS-CoV-2 interacting with RAS and immune responses to mediate kidney injury.

The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (alcohol-oxygen vapor therapy and fluid management) may be great helpful for reducing occurrence of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown to the deep of the small airways, oxygen therapy should be given at the early stages. The optimal time and SpO₂ threshold for oxygen therapy are also discussed.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind in the form of the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of April 22, 2020, COVID-19 has claimed 169, 006 human lives and had spread to over 200 countries with more than 2,471,136 confirmed cases. The perpetually increasing figures associated with COVID-19 are disrupting the social and economic systems globally. The losses are unmatched and significantly higher compared to those from previously encountered pathogenic infections. Previously, two CoVs (SARS-CoV and Middle East respiratory syndrome-CoV) affected the human population in 2002 and 2012 in China and Saudi Arabia, respectively. Based on genomic similarities, animal-origin CoVs, primarily those infecting bats, civet cats, and pangolins, were presumed to be the source of emerging human CoVs, including the SARS-CoV-2. The cohesive approach amongst virologists, bioinformaticians, big data analysts, epidemiologists, and public health researchers across the globe has delivered high-end viral diagnostics. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. The rapidly evolving and popular technology of artificial intelligence played a major role in confirming and countering the COVID-19 pandemic using digital technologies and mathematical algorithms. In this review, we discuss the noteworthy advancements in the mitigation of the COVID-19 pandemic, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology, animal reservoirs, laboratory animal models, disease transmission, diagnosis using artificial intelligence interventions, therapeutics and vaccines, and disease mitigation measures to combat disease dissemination.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Since association between myocardial infarction (MI) and respiratory infections has been described for influenza-viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. First data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss: pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; what emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

The coronavirus disease caused by SARS-CoV-2 (known as COVID 19) is highly contagious and has spread rapidly over 200 countries over last three months. WHO suggested urgent escalation in testing, isolation and contact tracing, as the "backbone" of managing the pandemic. Globally, the detection of SARS-CoV-2 in patients are done by RT-PCR and blood antibody-based testing. In addition to the existing processes, flow-cytometry could be used as a high-throughput and efficient diagnostic method for detection of COVID 19. The suspected COVID 19 samples can be analyzed using ‘Indirect flow cytometry’, with the specific primary antibody and fluorescent tagged secondary antibodies. The fluorescence signal can distinguish the infected v/s non-infected samples. In the present article, we have summarized the applications of Flow virometry to study various viruses and have proposed possible application in the detection of COVID 19.

Background: The information on the difference in clinical characteristics between severe and non-severe cases is limited in some countries including Iran. The objective of this case series is to compare the clinical characteristics, radiologic features, and laboratory findings between COVID-19 severe cases who received the intensive care unit (ICU) care with non-severe cases who did not receive ICU care. Methods: In this retrospective cohort study, 186 laboratory-confirmed patients with COVID-19 diagnosed from 1 March 2020 to 30 March 2020 were investigated. Results: This study population included 186 hospitalized patients with confirmed COVID-19. The median age was 47 years, and 88 (47.31%) were female. Of these patients, 48 were admitted and transferred to ICU. Of 186 patients, 44.62% had medical comorbidities including hypertension and diabetes. The most common clinical manifestation were shortness of breath 86.56%, myalgia 74.19%, and headache. Higher neutrophil counts, CRP, and LDH as well as the lower levels of lymphocytes were the most important laboratory finding among COVID-19 patients. As of April 15, 2020, 33 were still hospitalized. A total of 116 patients (62.70 %) had been discharged, and 36 patients (19.94 %) had died. Of the 48 patients admitted to the ICU, 33.33% have died. Conclusion: In the present study, shortness of breath was the most common clinical symptom, and the mortality rate in patients admitted to the ICU was about 33%, indicating that about one-third of patients with severe illness who admitted to the ICU section died.

Human bocavirus (HBoV) is an emerging virus that has been detected worldwide that could be associated with cases of acute gastroenteritis (AGE). However, its contribution to AGE has not been elucidated. This study aimed to describe the frequency, clinical features, and HBoV genotypes circulation in children up to 5 years with or without AGE symptoms in Acre, Northern Brazil. A total of 480 stool samples were collected between January and December 2012. Fecal samples were used for extraction, nested PCR amplification, and sequencing for genotyping. Statistical analysis was applied to verify the association between epidemiological and clinical characteristics. Overall HBoV-positivity was 10% (48/480), being HBoV-positivity rates of 8.4% (19/226) and 11.4% (29/254) recorded among diarrheic and non-diarrheic children, respectively. The most affected age group was between 7 and 24 months (50%). HBoV infection was more frequent in children living in urban areas (85.4%), using water from the public network (56.2%), and living with adequate sewage facilities (50%). Co-infection with other enteric viruses was 16.7% (8/48) and the most prevalent coinfection was RVA+ HBoV (50%, 4/8). HBoV‐1 was the most frequent species detected, responsible for 43.8% (21/48) of cases, followed by HBoV-3 (29.2%, 14/48) and HBoV-2 (25%, 12/48). In the present study, HBoV infections are not associated with AGE, as most HBoV cases belonged to the non-diarrheal group without AGE symptoms. Future studies are warranted to determine the role of HBoV in causing acute diarrhea disease.

Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)¹. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response^2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

Introduction: Post-COVID-19 syndrome (PCS) is a multisystemic disorder marked by impaired physical performance as one lead symptom. Since it has been suggested that endurance training as part of medical rehabilitation may be effective to improve physical performance capacity in PCS, this study aimed to compare different modes of aerobic endurance training. Methods: Hundred-ten PCS patients (49.3±11.8 years, 38% women, time after infection=260.2±127.5 days) underwent detailed clinical screening including symptom-limited cardiopulmonary exercise testing at admission and after 4-6 weeks of inpatient medical rehabilitation. Questionnaires were used to assess disease perception. Patients performed controlled isocaloric cycle ergometer training (3-5 sessions/week, 18 min) as either continuous training (CT) at 50% of maximal workload or as interval training (IT, load=60%, relief=30%). Outcomes of PCS patients were compared to coronary artery disease patients (CAD, n=96) to evaluate overall training effectiveness. Results: Training participation was comparable between both groups with no indication of training-specific exercise-induced fatigue. Overall, PCS patients improved significantly by a mean of 6.8±12.1% for W at VT1, 3.1±10.0% for VO2 at VT1, 5.5±14.7% for O2-pulse at VT1, 7.5±15.0% for W at VO2peak, 2.7±11.0% for VO2peak and 4.6±12.4% for O2-pulse at VO2peak (all p<0.05) with no significant differences between groups (p>0.05). Both groups showed reduced levels of fatigue, anxiety and depression as well as improved quality of life and wellbeing (all p<0.05). Compared to guideline-based cardiac rehabilitation, PCS patients showed a similar improvement in workload and oxygen uptake compared to CAD patients. Conclusion: PCS patients benefit from aerobic endurance training, performed as moderate continuous or interval training as part of a medical rehabilitation program in terms of improved physical exercise capacity and disease perception. Results for PCS patients are comparable to guideline-based rehabilitation of CAD patients. Clinical Trial: NCT06016192

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

United Nations Scientific Committee on the Effects of 2006 report was the first document released by an abandoned the classical paradigm that ionizing suppressive, considering the idea that at low doses enhances the appearance of antiinflammatory biomarkers [UNSCEAR 2006]. It considers energetic an immune modulation agent due to the multitude the innate immune system, depending on various age, health status, co-morbidities, genetic background, co-stressors [Lumniczky et al.]. Natural background radiation is the most hazardous public health, followed by medical imaging as a close Naturally occurring radionuclides attach to particulate ionizing radiation after inhalation and deposition in the in this article that exposure to particle radioactivity of inflammation. With that purpose, we have done an on common anti-inflammatory biomarkers between cases on COVID-19 elderly patients, and those found low-intensity natural ionizing radiation in locations with hypothesize that radioactivity increases biomarkers of strategy involved the use of databases from PubMed, (e.g., dose response, hormesis, J-shaped, NLRP3 LNT model, etc.). Extrapolating these effects to artificial ionizing radiation drawn conclusions on the over use of X-ray computed images in elderly ICU admitted patients with pulmonary oxygen species (ROS) generation by this action seems inflammation of leucine-rich protein 3 (NLRP3) inflammasome, waking up an over cytokine production.

The emergence of acute, severe non hepA–E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs, and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendations very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA–E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are mainly nephrotoxicity, mucositis and myelosuppression especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5′-regulatory regions of genes. Recent studies have demonstrated a significant role of miRNAs in the transport and metabolism of drugs, and in the regulation of target genes. The last few years, the number of annotated miRNAs is continually rising, as well as the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Lung ultrasound (LUS) allows the detection of a series of manifestations of COVID-19 such as B lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the impact of performing the test in the longitudinal or transverse orientation. 33 physicians with advanced experience in LUS, independently evaluated ultrasound videos previously acquired with the ULTRACOV system of 20 patients with confirmed COVID-19. In each patient, 24 videos of 3 seconds were acquired (using 12 positions with the probe in longitudinal and transverse orientations). Physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), only a fair IRR for the presence of individual B lines (κ = 0.36) and for confluent B lines occupying &lt;50% (κ = 0.26), and a moderate IRR in consolidations and B-lines &gt;50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR in LUS of COVID-19 patients may benefit from more standardization of the clinical protocols.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.

People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19 than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A2, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A2 from endothelial cells and macrophages stimulates platelets to release microvesicles which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases and lastly, examine the therapeutic targets and potential treatments for the two diseases.

Introduction: The 2019 novel coronavirus (COVID-19) is very contagious, and can be transmitted to other people by droplet, aerosol, sneezing, infected surface, and cough. There is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020, from Embase, Scopus, PubMed, Web of Science, and the Cochrane library to collect the studies that reported clinical and laboratory characteristics of COVID-19 infected patients. The study quality was assessed with the Critical Appraisal Checklist. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Result: Twenty studies were included in the meta-analysis, including a total of 52,251 patients with confirmed COVID-19 infection. 69.5% (95% CI 54.5-81, p < 0.001) of patients had a history of recent travel to Wuhan, contact with people from Wuhan, or lived in Wuhan. The most common symptoms among COVID-19 infected patients were fever 85.6 % (95% CI 73 -93, p < 0.001), and cough 63 % (95% CI 55.5-70, p < 0.001), respectively. The laboratory analysis showed that thrombocytosis was present in 91% (95% CI 81-98, p < 0.001) CRP was elevated in 81% (95% CI 65-91, p < 0.001), and lymphopenia in 62.5% of cases (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 76.8% (95% CI 62.5-87, p < 0.001) and consolidation in 75.5% (95% CI 50.5-91, p < 0.001) of patients. Most patients (85.4%) were hospitalized, 20.6% of patients were admitted to the ICU in critical condition, and the mortality rate was 5.6%. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. The most common radiographic sign was bilateral involvement in and consolidation. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

Long Covid or post-acute sequelae of SARS-CoV-2 infection (PASC) can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint for recovering severe COVID-19 patients in three consecutive time points and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase, and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3-4 months post hospitalization.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

In New Orleans, Louisiana the population’s poor baseline health led to its establishment as an early epicenter for severe acute COVID-19. Antici-pating future outbreaks of COVID-19 and other respiratory viruses, we need to identify correlates of outcome, from real clinical experience. 89 patients were recruited into the ClinSeqSer acute COVID-19 longitudinal observational study, from the beginning of the outbreak in March to July 2020. Patients admitted for acute COVID-19 were enrolled in person. The cohort is unique as it is 68% Black, 53% female, of average age of early 60s, and prevalence of obesity and hypertension respectively of 55% and 83%. The outcomes are: 53% severe (20% fatal, 33% non-fatal) and 47% non-severe, with severe defined as death or requiring mechanical ventila-tion or high flow oxygen. Obesity and admit systolic blood pressure (SBP) >140mmHg are each associated with severe outcome and, despite respective sensitivity of 71% and 76%, specificity ~66% for both, and ac-curacy of 60% and 70% by ROC analysis, would likely provide useful predictors of outcome in critically stressed health care systems. We discuss pathophysiologic hypotheses to explain why high admit SBP is observed only in half of patients with pre-COVID hypertension and is associated with severe outcome.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

Background and Objectives: The current study aimed to determine the impact of fasciotomy on mortality and morbidity in children and adults with crush-related AKI following the 2023 Kahramanmaraş earthquakes. Materials and Methods: The study included individuals who had suffered crush injuries after the 2023 Kahramanmaraş earthquakes and were identified as having acute kidney injury (AKI). Patients with AKI were divided into two groups based on age: those under 18 years and those over 18 years. A comparative analysis was conducted between the mortality and morbidity rates of patients who underwent fasciotomy and those who did not. Disseminated intravascular coagulopathy (DIC), sepsis, and adult respiratory distress syndrome (ARDS) have all been identified as contributors to morbidity. Results: The study was conducted with a total of 40 patients (21 males and 19 females) aged between four and 83 years. A total of 21 patients underwent fasciotomy and the patients underwent varying numbers of fasciotomy, ranging from zero to 11. The mortality rate was 12.5%, corresponding to five adult patients. No instances of mortality were reported in the paediatric cohort. The application of fasciotomy in instances of crush-induced AKI did not result in elevated levels of mortality in either the paediatric or adult demographic. Within the adult population, a substantial difference in the duration of dialysis was observed between individuals who underwent fasciotomy and those who did not. A statistically significant increase in the number of fasciotomy incisions was observed in patients diagnosed with sepsis compared with those without sepsis. The study found a significant positive correlation between the number of fasciotomy incisions and dialysis days. Conclusions: Neither adult nor paediatric patients with crush-induced AKI showed an increased risk of death after fasciotomy. The number of fasciotomy incisions significantly correlated with the development of sepsis. Despite experiencing delays in hospital admission for paediatric patients, the incidence of both crush syndrome and mortality rates among children remained relatively low.

Isolated fallopian tube torsions presenting to the emergency department are a very rare cause of childhood acute abdominal pain. Since the diagnosis to be made in the early period is of importance in terms of affecting tubal damage and fertility, it was aimed to evaluate the cases in the light of literature. Materials and Methods: This study included 10 patients under 18 years of age presented to the emergency department with abdominal pain between January 2003 and December 2018. The mean age was 14.5±1.43 years (range: 12-17years). The demographic characteristics, surgical findings, and methods, concomitant pathology results of these patients were retrospectively evaluated. Results: The reason for admitting to the emergency department of 10 patients included in the study was abdominal pain. The mean duration of hospital admission with pain was 4.97 days. The onset of pain was less than 24 hours in 7 patients (70%) and was more than 24 hours in three patients (30%). Of the patients, 9 (90%) had tenderness in the lower abdominal quadrant, 5 (5%) had the defense, and 3 (30%) had a rebound. Nausea, vomiting, and leucocytosis were present in 50% of the cases. Right and left tubal involvement of the cases was equal. Seven (70%) of the isolated tubal torsions were accompanied by paraovarian cysts. Of the patients, 8 (80%) underwent open surgery and 2 (20%) underwent laparoscopic intervention. Detorsion was performed in 5 (50%) and salpingectomy was performed in 5 (50%) cases. Conclusion: Isolated tubal torsion should be considered in children presenting with acute abdominal pain in early adolescence. Early diagnosis is important for the maintenance of fertility.

Alterations in the composition and diversity, metabolism, and products of the microbiome, and of the gut microbiome (GM), have been shown to be closely associated with the onset and progression of many human diseases, including cancer (i.e. hematological neoplasms). Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Affected cases present typical alterations of GM, followed by inflammation, which contribute to its progression, response to therapy, as well as possible relapses. Recent evidence also reports that GM influences the development and functions of the newborn's hematopoietic system through the process of developmental programming during fetal life, as well as its susceptibility to the onset of onco-hematological pathologies, namely ALL. Furthermore, in children with ALL, GM has been found to vary in composition, variety, and functions during the clinical stages of ALL, and such variation may influence and predict the complications and prognosis of ALL after chemotherapy treatment or stem cell hematopoietic transplant. Here, we suggest some therapeutic strategies, which can be applied at two levels of intervention to recover the microbiome, and consequently prevent/delay ALL or arrest its progression.

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Nebulized thrombolysis offers locally targeted therapy with potentially lower bleeding risk than systemic administration for coronavirus disease 2019 (COVID-19) respiratory failure. In a proof-of-concept safety study, adult patients with COVID-19-induced respiratory failure and a <300mmHg PaO2/FiO2 (P/F) ratio, requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care during the first two UK COVID-19 waves. Matched historical controls (MHC; n=18) were used in C1. Safety co-primary endpoints were treatment-related bleeds and fibrinogen reduction to <1.0–1.5 g/L. A dose escalation strategy for improved efficacy with the least safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA per day for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeding events (one severe and three mild) in three patients were considered treatment-related. No significant fibrinogen reductions were reported. Greater improvement in mean P/F ratio from baseline to end of study was observed in C1 compared with MHC [C1; 154 to 299 vs MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in P/F ratio was observed in NIRS patients [NIRS; 126 to 240 vs IMV; 120 to 188) and they required fewer treatment days (NIRS; 7.86 vs IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, showing a trend of improved oxygenation and faster recovery in patients with acute COVID-19-induced respiratory failure requiring respiratory support; this effect was more pronounced in the NIRS group. Further investigation is required to study the potential of this novel treatment approach.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Background: The aim of this study was to analyze the relationship between breastfeeding duration and adenoid size, snoring and acute otitis media (AOM). Methods: We analyzed the medical history, reported symptoms, ear, nose and throat (ENT) examination, and flexible nasopharyngoscopy examination of 145 children aged 3-5 years. Results: Breastfeeding duration of 3 and 6 months or more had a significant effect on the reduction of snoring (p = 0.021; p = 0.039). However, it had no effect on the adenoid size, mucus coverage and sleeping with an open mouth. Snoring was correlated with open mouth sleeping (p &lt; 0.001), adenoid size with a 75% A/C ratio or more (p &lt; 0.001), and adenoid mucus coverage in the Mucus of Adenoid Scale by Nasopharyngoscopy Assessment - MASNA scale (p = 0.009). Children who were breastfed for less than 3 months had more than a 4-fold greater risk of snoring. There was a statistically significant correlation between AOM and gender (p = 0.033), breastfeeding duration in groups fed 1, 3 or 6 months or more (p = 0.018; p = 0.004; p = 0.004) and those fed with mother’s breast milk 3 or 6 months or more (p = 0.009; p = 0.010). Moreover, a correlation was found between adenoid size and mucus coverage, tympanogram, and open-mouth sleeping (p &lt; 0.001). Independent factors of snoring in 3- to 5-year-old children were breastfeeding duration of less than 3 months (p = 0.032), adenoid size with an A/C ratio of 75% or more (p = 0.023) and open mouth sleeping (p = 0.001). Conclusion: Children breastfed for 3 and 6 months or more exhibited reduced rates of snoring. There was no effect of breastfeeding duration on adenoid size in children aged 3 to 5 years, suggesting that the link between breastfeeding duration and snoring is primarily associated with craniofacial development and muscle tone stimulation. A breastfeeding duration of 1 month or more plays a key role in reducing the rate of AOM. The mother’s milk plays a protective role against AOM. The presence of mucus might be responsible for snoring in preschool children. A medical history of breastfeeding should be taken into consideration when snoring children are suspected of adenoid hypertrophy.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Background: Treatment at stabilization center is an important intervention to avert the huge burden of mortality for children with complicated severe acute malnutrition (SAM). Recent reviews indicated a wide range in recovery rate (34-88%) due to several context-specific factors. This study aimed to estimate time to recovery and to determine predictors of time to recovery among children aged 6-59 month with severe acute malnutrition. Method: Retrospective cohort study was used among 375 children aged 6-59 months admitted in Jimma university medical center, from September 2015 to September 2017. Kaplan Meir estimate and survival curve was used to compare the time to recovery using log-rank test among different characteristics. Cox Proportional Hazard Model was used to identify significant predictors of time to recovery. Results: Median time of recovery for cohort of SAM children’s was 19 days (95%CI: 17.95-20.05). Independent predictors of time to recovery were: Play stimulation, vaccination status, Tuberculosis, malaria, use of amoxicillin, deworming and shock. Conclusion: The findings of this study showed that the average length of stay on treatment and median time for recovery are within the sphere standard. Psychosocial stimulation, appropriate provision of routine medication and management of medical co-morbidity are needed to promote fast recovery.

Objectives To develop and validate a prediction model for 28-day in-hospital mortality among adult patients critically ill with COVID-19 in the UK. Design Observational cohort study. Setting 287 adult critical care units in England, Wales and Northern Ireland, of which 260 admitted at least one eligible patient. Participants 10,933 patients with confirmed COVID-19 of whom 10,401 were eligible (excluding 532 patients with a duration of critical care less than 24 hours and 1 patient with unknown 28-day outcome): 8,666 development (March-April 2020) and 1,735 temporal validation (May-August 2020). Main outcome measures 28-day in-hospital mortality from start of critical care. Results Two models were developed using 14 patient level predictors selected from 30 candidate predictors, with and without adjustment for calendar time. In the temporal validation data, the model discrimination was maintained (c index 0.78) but calibration was poor, particularly for the model not adjusted for calendar time (ratio of observed to predicted mortality 0.74 versus 0.88 for the model adjusted for calendar time). Conclusions We developed and validated a prediction model for 28-day in-hospital mortality for patients critically ill with COVID-19. Although absolute predictions were inaccurate due to changing outcomes, the models will support risk-adjustment in analyses and monitoring changes in risk-adjusted outcome over time.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

Introduction: On March 11, 2020, the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) as a pandemic. The spread of the Delta variant of coronavirus started in June 2021 and accounted for the fifth peak of COVID-19 in Iran in July 2021. According to reports from other countries, vaccination protects against severe diseases caused by COVID-19, including the Delta variant. Studies have also shown that vaccination provides strong protection against SARS-CoV-2 infection, COVID-19-related hospitalization, and mortality. This retrospective cohort study was designed based on the medical care monitoring center (MCMC) database of Sayyad Shirazi Hospital.Methods: The following patient data were extracted for this study: demographic characteristics, signs and symptoms, ICU admission, need for aggressive oxygen therapy, including intubation, mortality, and vaccination status. Results: Being vaccinated was associated with a 4.14-fold increase in survival (adjusted OR=4.14; 95% CI: 2.22 to 7.69; P<0.01), and individuals in a younger age group demonstrated a 5.58-fold higher likelihood of surviving (adjusted OR=5.58; 95% CI: 4.25 to 8.14; P<0.01). The risk of severe COVID-19 was significantly lower in vaccinated individuals, showing a 3.12-fold decrease in risk (adjusted OR=3.12; 95% CI: 2.06 to 4.72; P<0.01), and in younger age groups, the risk exhibited a 3.28-fold decrease (adjusted OR=3.28; 95% CI: 2.66 to 4.04; P<0.01).Conclusion: The present results suggest that receiving at least one dose of COVID-19 vaccine had a significant relationship with decreased COVID-19 severity and mortality in vaccinated patients compared to unvaccinated patients.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines’ storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, rather than thrombolysis performed, to avoid potential adverse events of the latter in the setting of SCAD.

Background: Low-income families often depend on fuels such as wood, coal, and animal dung for cooking. Such solid fuels are highly polluting and are a primary source of indoor air pollutants (IAP). We examined the association between solid fuel use (SFU) and acute respiratory infection (ARI) among under-five children in Afghanistan and the extent to which this association varies by socioeconomic status (SES) and gender. Materials and Methods: This is a cross-sectional study based on de-identified data from Afghanistan’s first standard Demographic and Health Survey conducted in 2015. The sample consists of ever-married mothers with under-five children in the household (n=27,565). We used mixed-effect Poisson regression models with robust error variance accounting for clustering to examine the associations between SFU and ARI among under-five children after adjusting for potential confounders. We also investigated potential effect modification by SES and sex. Additional analyses were conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking/kitchen (High Exposure, Moderate, and No Exposure). Results: Around 70% of households reported SFU, whereas the prevalence of ARI was 17.6%. The prevalence of ARI was higher in children living in households with SFU compared to children living in households with no SFU (adjusted prevalence ratio [aPR]= 1.10; 95%CI: 0.98, 1.23). We did not observe any effect modification by SES or child sex. When using the augmented measure of exposure incorporating the kitchen’s location, children highly exposed to IAP had a higher prevalence of ARI compared to unexposed children (aPR 1.17; 95% CI: 1.03, 1.32). SES modified this association with the strongest associations observed among children from the middle wealth quintile. Conclusion: The findings have significant policy implications and suggest that ARI risk in children may be reduced by ensuring clean cookstove as well as clean fuels and acting on the socio-environmental pathways.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on immune system. There was a high incidence of COVID-19 induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity, long-term disability, and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show a significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF.

Coronavirus infection disease -2019 (COVID-19) was a global pandemic with high mortality and morbidity, that lead to an increased health burned all over the world. Although the virus affects mostly pulmonary tract, cardiovascular implications were often among COVID-19 positive patients, and are predictive for poor outcomes. Increased values of myocardial biomarkers such as Troponin I or NT-proBNP were proven to be risk factors for respiratory failure (26). Although the risk of acute coronary syndromes (ACS) was greater in acute-phase of COVID-19, there were lower rates of hospitalization for ACS, due to patient’s hesitation for presenting at the hospital (22). Hospitalized ACS patients with COVID-19 infection, had a prolonged symptom-to-first medical contact time, and longer door-to-balloon time. The mechanisms of myocardial injurie in COVID -19 patients are not still not clear, most often is incriminated: the down-regulation of ACE2 inhibitors, endothelial disfunction, pro-coagulant status, increased levels of pro-inflammatory cytokines. The aim of this paper is to evaluate the long-term outcomes of COVID-19 survivors that presented an acute myocardial infarction by reviewing existing data.

Children with severe acute malnutrition (SAM) are at high risk of impaired development. Contributing causes include inadequate intake of specific nutrients such as polyunsaturated fatty acids (PUFA) and lack of adequate stimulation. We conducted a pilot study assessing developmental and nutritional changes in children with SAM provided with a modified ready-to-use therapeutic food and a context-specific psychosocial intervention in Mwanza, Tanzania. We recruited 82 children with SAM (6-36 months) and 88 sex- and age-matched non-malnourished children. We measured child development, using the Malawi Development Assessment Tool (MDAT), measures of family and maternal care for children, and whole blood PUFA levels. At baseline, the mean total MDAT z-score of children with SAM was lower than non-malnourished children; -2.37 (95% confidence interval: -2.92; -1.82) as was their total n-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels. After 8 weeks’ intervention, MDAT z-scores improved in all domains, especially fine motor, among children with SAM. Total n-3, and EPA levels increased, total n-6 fatty acids decreased, and DHA remained unchanged. Family and maternal care also improved. The suggested benefits of the combined interventions on developmental and nutritional status of children with SAM will be tested in a future trial.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

This article provides a thorough overview of biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI), acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical application. The pathophysiological mechanisms underlying AKI, AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses, with the impact on renal injury. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and cellular senescence of renal cell. Key signaling pathways, such as Wnt/β-Catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The Renin-Angiotensin-Aldosterone System (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating oxidative stress and cellular changes that promote fibrosis. Clinical evidence suggests RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

Long coronavirus disease 2019 (COVID-19) may occur after experiencing acute COVID-19 infec-tion with many effects on patients´ kidneys. This study aimed to evaluate the clinical and labora-tory aspects of kidney function in individuals with long COVID in the Amazon region of Brazil. This cross-sectional study selected participants from a ‘long COVID’ clinical care program. Clini-cal data and baseline demographics were obtained, and blood samples were collected to quantify kidney-related markers. Patients were evaluated after COVID-19 infection at several time points as follows: 0–3 months, 3–6 months, 6–12 months, and 12 months. Altogether, 246 patients were selected for this study, and only 79 were hospitalised (9 in the intensive care unit because of COVID-19. Of the patients, 38 were diagnosed with hypertension after COVID-19, 52 cases had to have their medications adjusted, and 83 patients presented with kidney function decline. The older age group and individuals with glycaemic alterations presented with a higher risk of devel-oping kidney dysfunction. Therefore, health professionals should monitor long-term kidney mark-ers in long COVID.

Background: This systematic review aims to investigate whether percutaneous transhepatic gallbladder drainage (PTGDB), as definitive treatment, is superior to emergency cholecystectomy (EC) in high-risk patients with acute cholecystitis (AC). Material and methods: A systematic literature search was performed until December 2022 using Scopus, Medline/PubMed and Web of Science databases in order to compare PTGDB as definitive treatment vs EC in AC. Results: Seventeen studies (1 Randomized Control Trials and 16 observational studies) have been included with a total of 783,672 patients (32,634 treated with PTGDB vs 4,663 who underwent laparoscopic cholecystectomy, 343 who underwent open cholecystectomy and 746,032 who underwent cholecystectomy, but without laparoscopic or open approach being specified). The quality assessment (ROBINS-I) of the not randomized studies showed a serious risk, differently the evaluation of the randomized study (RoB 2) showed a low risk of bias. Analysis of the results shows that PTGDB, despite being minimally invasive, do not have different incidence of complications than EC (RR 0.77 95% CI [0.44 to 1.34]; I2 = 99%; P=0.36). A lower postoperative mortality was reported in patients who underwent EC (2.37%) than in PTGDB group (13.78 %) (RR 4.21; 95% CI [2.69 to 6.58]; P < 0.00001), furthermore the risk of hospital readmission for biliary complications (RR 2.19 95% CI [1.72 to 2.79]; I2 = 48 %; P<0.00001) and hospital stay (MD 4.29 95% CI [2.40 to 6.19]; P<0.00001) were lower in EC group. Conclusions: No advantage in using PTGDB as a definitive treatment over EC in the management of critically ill patients with AC has been demonstrated; the results of our systematic review and meta-analysis suggest using EC as the treatment of first choice, even for very high-surgical-risk patient in which PTGDB should be reserved. The major limitation of this systematic review and meta-analysis is associated to a low quality of evidence for the serious bias in the not randomized studies. For this reason, new high powered and well-designed clinical trials are needed to recommend PTGDB as definitive treatment in patients unfit for surgery or those who refuse to undergo surgery.

The hematopoietic transcription factor Ikaros (IKZF1) regulates normal B cell development and functions as a tumor suppressor in precursor B cell acute lymphoblastic leukemia (B-ALL). MicroRNAs (miRNAs) are small regulatory RNAs that through post-transcriptional gene regulation play critical roles in intracellular processes including cell growth in cancer. However, the role of Ikaros in the regulation of miRNA expression in developing B cells is unknown. In this study, we examined the Ikaros-regulated miRNA targets using patient-derived IKZF1-mutated B-ALL xenograft-derived cell lines. Inducible expression of wild-type Ikaros (the Ik1 isoform) caused B-ALL growth arrest and exit from the cell cycle. Global miRNA expression analysis revealed a total of 31 miRNAs regulated by IK1, and ChIP-seq analysis showed that Ikaros bound to several Ik1-responsive miRNA genes. Examination of the prognostic significance of miRNA expression in B-ALL indicate that the IK1-regulated miRNAs hsa-miR-26b, hsa-miR-130b and hsa-miR-4649 are significantly associated with outcome in B-ALL. Our findings establish a potential regulatory circuit between the tumor-suppressor Ikaros and the oncogenic miRNA networks in IKZF1-mutated B-ALL. These results indicate that Ikaros regulates the expression of a subset of miRNAs, of which several may contribute to B-ALL growth.

The simplified, combined protocol admits children with a mid-upper-arm circumference (MUAC) of <125 mm or edema to malnutrition treatment with ready-to-use therapeutic food (RUTF) prescribing 2 daily RUTF sachets to children with MUAC <115 mm or edema and 1 daily sachet to those with MUAC ≥115 mm but <125 mm. This treatment has previously been shown to result in non-inferior programmatic outcomes compared to standard treatment. We aimed at observing its effectiveness in a routine setting at scale, including via delivery by community health workers (CHW). A total of 27 601 children were admitted to the simplified, combined treatment. Treatment resulted in 96% overall recovery with a mean LOS of 40 days and a mean RUTF consumption of 63 sachets per child treated. Among children admitted with MUAC <115 mm or edema 94% recovered with a mean LOS of 55 days and consuming an average of 97 RUTF sachets. Recovery in all sub-groups studied exceeded 90%.Treatment by CHWs resulted in similar (96%) recovery as treatment by formal health care workers (96%). The simplified, combined protocol results in high recovery and low RUTF consumption per child treated, and can safely be adopted by CHWs to provide treatment in the community-level.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Acute pancreatitis (AP) is a leading gastrointestinal disease that cause hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer’s solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. Routine use of prophylactic antibiotics is generally limited, and the procalcitonin based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and prevent recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP.

This case report describes a 71-year-old female with multiple comorbidities who presented with symptoms suggestive of stroke and was subsequently found to have severe acute kidney injury (AKI) due to acute interstitial nephritis (AIN). The patient has normal kidney function at baseline. She has been on hydrochlorothiazide and metoprolol succinate for hypertension for several years. Due to severe acute kidney injury, a kidney biopsy was performed, revealing severe Acute Interstitial Nephritis secondary and multiple intratubular oxalate crystals. The patient's renal function improved after withdrawing HCTZ, volume repletion and initiating prolonged prednisone taper. We attempt to provide some insights through our paper into the mechanism of acute renal failure from crystal nephropathy and its management.

Aortic dissection is a clinicopathological entity caused by rupture of the intima leading to a high mortality if not treated. Over time, diagnostic and investigative methods, antihypertensive therapy, and early referrals have resulted in improving outcomes according to registry data. Some data has also emerged from recent studies suggesting a link between Human Cytomegalovirus (HCMV) infection and aortic dissection. Furthermore, the use of microRNAs have also become increasingly widespread in the literature. These have been noted to play a role in aortic dissections with elevated levels noted in studies as early as 2017. This review aims to provide a broad and holistic overview of the role of miRNAs, while studying the role of HCMV infection in the context of aortic dissections. The role of long non-coding RNAs, circular RNAs and microRNAs are explored to identify changes in expression during aortic dissections. The use of such biomarkers may one day be translated into clinical practice to allow early detection and prognostication of outcomes and drive preventative and therapeutic options in the future.

Background： Sepsis-induced acute lung injury (ALI) is characterized by disruption of the epithelial barrier and activation of alveolar macrophages (AMs), which leads to uncontrolled pulmonary inflammation. However, effective treatments for ALI are unavailable. This study aimed to discover potential diagnostic molecular biomarkers based on bioinformatics, which will benefit the diagnosis and treatment of sepsis-induced ALI. Methods: GSE10474 was analyzed for differentially expressed genes (DEGs) in sepsis patients with ALI (sepsis + ALI) compared with sepsis patients without ALI. Functional enrichment analysis and protein-protein interaction (PPI) network were performed. on the DEGs via R package “clusterProfiler”, and visualized via Cytoscape. Prediction analysis of microarrays (PAM) was performed to identify diagnostic biomarkers and the diagnostic ability of diagnostic biomarkers was accessed via receiver operating characteristic (ROC) curves. Moreover, interactions among diagnostic biomarkers were analyzed via GeneMANIA. We also analyzed the function of diagnostic biomarkers and predicted their corresponding drugs via Cytoscape plugin BiNGO and web tool DGIdb. At last, we analyzed the transcriptional regulation of the diagnostic biomarkers via the web tool miRNet. Results: 71 genes were found to be differentially expressed in the sepsis + ALI group, mainly involved in immune-related biological processes and pathways. STRING database indicated 31 DEGs have protein-protein interactions. In addition, the PAM identified 6 diagnostic biomarkers, including HIST1H4H, CDKN1A, HMOX1, NQO2, RHOB, and TREM1, from these 31 DEGs. Conclusion: In conclusion, through bioinformatics analyses, we identified 6 potential diagnostic biomarkers and targets for sepsis-induced ALI.

Background: This study aimed to present the development process and characteristics of the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centers (KRAMI-RCC). Methods: We developed KRAMI-RCC, a web-based registry for patients with AMI. Patients from 14 RCCs were registered for more than 3 years from July 2016. It includes an automatic error-checking system, and user training and on-site monitoring are performed to manage data quality. Results: A total of 11,700 AMI patients were registered in KRAMI-RCC over 3 years (73.9% men). The proportions of patients with ST-elevation and non-ST-elevation myocardial infarction at discharge were 43.4% and 56.6%, respectively. Of the total 3-year patients, 5.6% died in the hospital and 4.4% died 12 months after discharge. The case fatality within 12 months was 9.7%. Prehospital care data showed delayed arrival time after onset of symptoms (median 153 min) and low transportation rate by public ambulance (25.2%). Post-hospital care data showed lower participation rate in the second rehabilitation program (16.8%). Conclusions: The recently developed KRAMI-RCC registry has been more focused on pre-hospital and post-hospital data, which will be helpful in understanding the current state of AMI disease management and in making policy decisions to reduce case fatality in Korea.

Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.

Background: The assessment of the incidence and characteristic of acute and chronic post-operative endophthalmitis (POE) after cataract surgery in Poland during 2010 - 2015. Patients and methods: All hospitalizations of patients, in the National Database of Hospitalizations, who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015, with a billing code of endophthalmitis, were selected. Acute endophthalmitis was identified if symptoms occurred within 1 - 42 days from the cataract surgery and chronic endophthalmitis if symptoms occurred ≥ 43 days after cataract surgery, respectively. Results: In total, 1331 cases of POE after 1,218,777 cataract extractions were identified. The overall incidence of POE decreased from 0.125% in 2010 to 0.066% in 2015. In multiple logistic regression analyses, increasing age was significantly associated with acute POE, while type II diabetes mellitus, extracapsular cataract extraction and one-day surgery were significantly associated with chronic POE. The combined cataract surgery and male sex were significant risk factors for both acute and chronic POE. A total of 62.51% of all eyes affected by POE received antibiotic treatment and 37.49% had vitrectomy treatment. Conclusions: During the study period, the total incidence of post-operative endophthalmitis after cataract surgery decreased significantly.

INTRODUCTION Recently there has been a significant increase in age in the United States. It is necessary to better understand the physiological and surgical needs of these patients in order to optimize outcomes. The vast majority of procedures performed in adult patients are low-risk operations, such as laparoscopic cholecystectomy. Our aim is to investigate the outcomes, including length of stay, morbidity, mortality, re-admission and discharge disposition of the elderly population (>80) undergoing low-risk operations in our tertiary community hospital. METHODS A retrospective chart review was done at a tertiary community hospital. The time frame utilized was 2011-2015. Patients were excluded only on the basis of their age (< 80) at the time of operation. RESULTS There were a total of 30 patients who underwent laparoscopic cholecystectomy from 2011 to 2015. 21 patients (70%) were female and 9 (30%) were male. No patients were converted to an open procedure. The average age was 86.4 years and average ASA classification prior to surgery was 2.88. Higher ASA class, specifically those that were class III/IV were more likely to have an increased length of stay that was statistically significant. Overall age greater than 80 was an independent risk factor for transfer to a higher level of care upon discharge (SNF, LTAC, etc.), a surrogate marker for physical decompensation following surgery. CONCLUSIONS Routine surgery, such as the laparoscopic cholecystectomy, effects the elderly population in a more substantial way, and early recognition coupled with increased education for physicians regarding geriatric patients can help to reduce length of stay, morbidity, and overall physical and mental deconditioning.

Background: The morbidity of myocardial infarction is keeping raise in this decade. Because of high safety and operability , percutaneous coronary intervention(PCI) has been used to conquer this disease for more than 20 years.An important complication of PCI is contrast induced nephropathy(CIN), which raises our attention. Previously, we started a study to explore the correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention. Our study showed that the rate of CI-AKI in patients with post-procedural myocardial injury and undergoing elective PCI was higher than that in patients free of injury. Methods: In this study,forty male rats were randomly divided into four groups: control group (n=8), CM group (n=12), AMI group (n=8) and AMI+CM group (n=12), then velocity of renal artery blood flow (VRABF), computer tomography (CT), serum creatinine(Scr), reactive oxidative species (ROS), periodic acid-Schiff (PAS) and TUNEL were used to estimate the injury of kidney. We analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. Serum levels of creatinine (SCr) and the eGFR before coronary angiography, and 24–72 h after contrast administration were recorded to assess the renal function. Results: The data showed that VRABF was lower in AMI+CM group than CM group from 0 minute to 24h and CT number in cortex was higher in AMI+CM group than CM group at 4-hour. As well as the level of Scr in AMI+CM group displayed a significantly increase at 24-hour compared with CM group. The histopathologic scores and percentage of tubular cell apoptosis were higher in AMI+CM group at 24-hour. In 327 patients, we found that CI-AKI occurred more often in subjects with post-procedural myonecrosis (PMN) than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Conclusion: Compared to the elective patient, the injury of CIN exhibited a higher severity in AMI patient.

Acute myeloid leukemia (AML) remains a challenging hematologic malignancy. The presence of TP53 mutations in AML poses a therapeutic challenge, considering that standard treatments face significant setbacks in achieving meaningful responses. There is a pressing need for the development of innovative treatment modalities to overcome resistance to conventional treatments attributable to the unique biology of TP53-mutated (TP53mut) AML. This review underscores the role of TP53 mutations in AML, examines the current landscape of treatment options, and highlights novel therapeutic approaches, including targeted therapies, combination regimens, and emerging immunotherapies as well as agents being explored in preclinical studies, for their potential to address the unique hurdles posed by TP53mut AML.

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: 1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; 2) to create a national database with information on health care in ACS patients treated in Kosovo; 3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, length of hospital stay, and quality of clinical care; and 4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (Unstable angina, NSTEMI or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the Registry.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

In this work, we tried to emphasize whole transcriptome expression changes in the Wistar rats brainstem two hours after acute stress. Most of the genes were upregulated. We detected massive shift of neuropeptides Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptors Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as Glutamate Grin3b, Grm2 and GABA Gpr156, Acetylcholine Chrm4,Chrne, Adreno- Adra2b receptors expression uprising. Intensive increase in expression of intermediate filaments Krt83/Krt86/Krt80/Krt84/Krt87/Krt4/Krt76 and motor proteins Myo7a, Klc3 was detected. Remarkably, at this time we also observed signs of microglia activation. Both expression of anti-inflammatory cytokines Il13, Ccl24 and proinflammatory cytokin’s receptors Il9r, Il12rb1, Tnfrsf14, Tnfrsf13c, Tnfrsf25, Tnfrsf1b were increased. In the Wnt signaling pathway, we have seen increased expression of ligands-receptors Wnt1, Wnt11, Ror2, and also negative regulators Notum, Sfrp5, Sost. Also we conducted cDNA libraries normalization with duplex specific nuclease and compared results. On the basis of our RNAseq data, we chose reference genes for RT-qPCR best suitable for experiments with acute stress.

Abstract: Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully un-derstood and causal treatment options are not available. Recently we demonstrated that Hepa-ranase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that As-pirin has inhibitory effect on Hpa. Another compound, which possesses a mild pan-creato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesize that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhib-itors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in ex-perimental model of AP induced by Cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the se-rum levels of Lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in heparanase transgenic (Hpa-Tg) mice vs wild-type (WT) mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

The definition of Early Cholecystectomy (EC) is still debatable. This paper aims to find whether the timing of EC affects outcomes. This is a multicentric prospective observational study including patients with acute calculous cholecystitis (ACC) who had cholecystectomy within ten days from the onset of symptoms. Kruskall-Wallis test, Fisher’s Exact test and Spearman rank correlation were used for statistical analysis. The patients were divided into three groups depending on the timing of the operation: 0-3 days, 4-7 days, or 8-10 days from the onset of symptoms. 1117 patients were studied over a year. The time from the onset of symptoms to EC did not affect the postoperative complications and mortality, the conversion and the reintervention rate. It was a significant risk factor for intraoperative complications (0-3 days, 2.8%; 4-7 days, 5.6%; 8-10 days, 7.9%; p=0.01) and subtotal cholecystectomies (0-3 days, 2.7%; 4-7 days, 5.6%; 8-10 days, 10.9%; p&lt;0.001). ACC is an evolutive inflammatory process and, as the days go by, the local and systemic inflammation increases which makes surgery more complex and difficult with higher risk of intraoperative complications. We recommend performing EC for ACC as soon as possible within the first ten days of the onset of symptoms.

In this study, a case of acute cattle death was investigated. The pathogen was identified, and its molecular characteristics and vector were analysed. This study provides a reference for the prevention and control of babesiosis and the healthy breeding of cattle. In this study, unengorged and engorged Rhipicephalus microplus ticks were collected from the Chongqing area. The unengorged ticks were cultured on cattle under laboratory conditions, and the engorged ticks were cultured to lay eggs. In the process, the cattle suddenly died at 12 days from the bite of an unengorged R. microplus tick. In addition, the larvae hatched from R. microplus eggs, which were cultured on the other cattle, and the experimental cattle died in approximately 14 days. Blood was collected from a second dying and stored at 4 ℃ for one week. Two millilitres of anticoagulated blood was injected subcutaneously into the third cow without piriformis infection. On the fourth day, the body temperature rose to 41 ℃ with slight lymphadenopathy. On the fifth day, the cow suddenly fell and died approximately 4 hours later. DNA was extracted from the blood of all dead cattle and amplified by PCR with piriformis universal primers. The results showed that the cattle were infected with Babesia bovis. The phylogenetic tree based on 18S rRNA showed that the Chongqing strain of B. bovis, which caused the death of cattle, was closely related to the Yunnan strain in China and had the same taxonomic status as the Spanish strain. This case report will draw people's attention to B. bovis once again, and positive control measures should be taken to reduce the losses of farmers to achieve the goal of healthy breeding.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications and chromatin remodelling. However, recently, RNA modification (m6A-methylation) also termed ‘epitranscriptomics’ has emerged as a new layer of epigenetic regulation due to its diverse role in various biological processes. In this review, we have summarized the therapeutic potential of m6A-modifiers in controlling haematological disorders especially acute myeloid leukemia (AML). It is a type of blood cancer affecting specific subsets of blood-forming hematopoietic stem/progenitor cells (HSPCs) which proliferate rapidly and acquire self-renewable capacities with impaired terminal cell-differentiation and apoptosis leading to abnormal accumulation of white blood cells, and thus an alternative therapeutic approach is required urgently. Here, we have described how RNA m6A-modification machineries EEE (Editor/writer: Mettl3, Mettl14; Eraser/remover: FTO, ALKBH5 and Effector/reader: YTHDF-1/2) could be reformed into potential druggable candidate or as RNA modifying drug (RMD) to treat leukemia. Moreover, we have shed-light on the role of microRNA and suppressor of cytokine signalling (SOCS/CISH) in increasing anti-tumor immunity towards leukemia. We anticipate, our investigation will provide a fundamental knowledge in nurturing the potential of RNA modifiers in discovering novel therapeutics or immunotherapeutic procedures.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

The study evaluates the toxic effects of acute and sub-acute oral administration of methanol extracts of Geophila obvallata in rats. During acute study, a dose of 1600, 2900 and 5000 mg/kg bw of extract was orally administered to rats. Rats were observed for signs of toxicity for two weeks. During sub-acute study (28 days), the extract, at doses of 100, 500 and 1000 mg/kg bw were administered orally to rats while control rats were given only tap water. At the end of the study, samples were collected for analyses. In acute toxicity studies, the extract did not induce death after single dose administration. Hence, the LD50 was estimated above 5000mg/kg. The results of sub-acute toxicity study show that no significant changes were observed in the body weights, organ weights, kidney function and organ histology. There were significant changes in hematology and biochemical indices investigated at elevated doses of 500 and 1000 mg/kg bw compared to the control. GOE may be considered non-toxic at a dose of 100 mg/kg with promising applications in drug therapy.

There are presently more than 18 known aflatoxins (>18) most of which have been insufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has by far been the most studied; and yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity, which are the best known still suffer from many limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the algal hepatotoxic microcystins, the mechanisms of this synergy remain unclear. This study reviews the most recent advances in the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.

Background: Evaluation of nutrition programs is essential to guarantee the effectiveness of community-based management of acute malnutrition (CMAM). Methods: The Rainbow Project Supplementary Feeding Programs (SFPs) in Zambia were evaluated between years 2015-17, following implementation of new recommendations based on previous evaluations (years 2012-14). Outcomes of the program were compared with International Standards and with those of 2012-14. Cox proportional risk regression analysis was performed to identify predictors of mortality and defaulting. Results: Data for 900 under age 5 years malnourished children (48.8% male; mean age 19.7months ±9.9) were analyzed. Rainbow 2015-17 program outcomes met International Standards, for general malnutrition or stratified moderate acute malnutrition (MAM) and severe acute malnutrition (SAM). When comparing with 2012-14 outcomes, better performance was noted: mortality rates were reduced by half (5.6% vs 3.1%, p = 0.01; for SAM: 12.4% vs 6.7%, p = 0.006), with significant improvement in average weight gain and mean length of stay (p<0.001), and increased awareness of HIV status (+30%; p < 0.001). HIV infection (5.5; 1.9–15.9), WAZ < −3 at baseline (4.6; 1.3–16.1) and kwashiorkor (3.5; 1.2–9.5) remained the major predictors of mortality. Conclusion: The effectiveness of the Rainbow SFPs for child malnutrition treatment and prevention in Zambia has significantly improved after evaluation and implementation activities, with impressive outcomes which resulted in a 50% reduction in mortality.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS through additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events and aberrant expression of CRLF2, JAK2 mutations, and RAS pathway activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

OBJECTIVES: To assess the predictive value of serum trypsin and Trypsinogen Activation Peptide (TAP) for the severity of AP by means of a single center cohort study as well as a systematic review of the current literature. METHODS: The literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2, but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP: 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p=0.053 and for TAP 0.74 (95% CI: 0.54-1.01), p=0.055 respectively. CONCLUSION: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

Background: Limited data exist on postoperative acute kidney injury (AKI) in patients underwent esophageal cancer surgery. The purpose of the study was to evaluate the incidence, risk factors and consequences of postoperative acute kidney after esophagectomy. Methods: This was a retrospective cohort study. The study was conducted in a tertiary specialized cancer center in Italy. All patients undergoing elective esophageal cancer surgery between 2016 and 2021 were included in the study. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria (both serum creatinine and urine output), within 48 hours after surgery. Preoperative and intraoperative data were registered. We also collected data concerning progression of AKI, need for kidney replacement therapy, mortality, medical (pulmonary, cardiovascular, septic) and surgical complications within 30 days from surgery, as well as length of hospital stay. Results: Incidence of postoperative AKI was 32%. The independent risk factors were body mass index and the invasive surgical approach. Persistent AKI accounted for 15% of the cases and it was associated with increased risk of major cardiovascular events (odds ratio 4.14, 95% CI 1.05-15.8, p-value 0.036), pulmonary complications (OR 3.67, 95% CI 1.04-14.9, p-value 0.050) and increased length of hospital stay (AME 7.2, 0.5-13.9, p-value 0.035). Conclusions: Postoperative AKI is common after esophageal cancer surgery. BMI and totally invasive surgical approach are independent risk factors. Persistent AKI lasting more than 48 hours increased the risk for cardiovascular and pulmonary complications, with prolonged length of hospital stay.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating acquisition of a rapid supply of ATP for proliferation in AML. Therefore, targeting of mesothelin presents a potentially promising approach for mitigating the progression of AML through inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolyte and acid base, and is associated with poor prognosis and prolonged hospitalization. Therefore, early diagnosis and treatment to avoid the severe AKI stage is important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.