Objective: To explore the application effect of Atropine injection combined with nursing intervention on the interventional treatment of PATENTS with ST-segment elevation myocardial infarction. Methods: A total of 60 patients with ST-segment elevation myocardial infarction treated in our hospital from January 2022 to January 2023 were selected as the research objects. According to different nursing methods, they were divided into conventional group (n = 30) and systematic group (n = 30), both groups were treated with percutaneous coronary intervention (PCI). The conventional group received routine nursing before and after operation. On the basis of routine nursing, systematic nursing cooperation was given in the system group. The time of opening infarct vessels, the incidence of total adverse reactions during interventional treatment, mortality, success rate of treatment, improvement of cardiac function and length of hospital stay were compared between the two groups. Results: The time of opening infarct vessel in system group was significantly better than that in routine group (P < 0.05). The total adverse reaction rate in system group was significantly lower than that in routine group (P < 0.05); The mortality of routine group was significantly higher than that of system group (P < 0.05). The success rate of system group was significantly higher than that of routine group (P < 0.05); The number of patients with improved cardiac function and length of hospital stay in system group were significantly better than those in routine group (P < 0.05). Conclusion: Good intraoperative cooperation and nursing is an important guarantee for patients with ST-segment elevation myocardial infarction, which can effectively reduce the occurrence of adverse reactions during interventional treatment, improve the success rate of treatment, and reduce the death of patients during interventional treatment.

Background: Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare disease entity characterized by the emergence of an extramedullary tumour which may be antecedent, coexisting or manifest secondarily to an ongoing malignancy of lymphoid origin. Owing to its low prevalence, scientific reports addressing this matter comprise mainly retrospective studies with a limited number of participants, rather low-quality research and only few case reports. Despite MS’s rarity, the need for enhancing diagnostic tools and refinement of therapeutic regimens is broadly recognised among physicians. Case summary: In this case series, we present the clinical histories of two patients diagnosed with MS. The former (Case 1) exhibited MS of the sternum alongside chronic myeloid leukemia (CML), while in case of the latter (Case 2) MS was the initial manifestation of a current acute myeloid leukemia (AML). Regardless of treatment institution comprising chemotherapy (CHTH) and radiotherapy (RT), the patient afflicted by CML did eventually pass due to cardiorespiratory insufficiency secondary to an infection, whereas the second one is in clinical remission up to this date, that is 16 months since MS had been diagnosed. Furthermore, a comprehensive analysis of previously reported cases was conducted which involves MS in patients with AML and CML. Conclusion: The objective of this report is to emphasize the heterogeneity among the clinical manifestations of MS, to underline the relevance of histopathological and molecular diagnostic tools in opting for the appropriate therapy and that, in spite of it occurring rather uncommonly, physicians should think of MS in presence of pathological masses in patients under risk of hematological malignancies.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. AML with mutated Nucleophosmin1 (NPM1-mut) is the largest of the genetically defined groups, involving about 30% of adult AMLs and is currently recognized as a distinct entity in the actual AML classifications. NPM1-mut AML usually occurs in de novo AML and is associated predominantly with a normal karyotype and relatively favorable prognosis. However, NPM1-mut AMLs are genetically, transcriptionally, and phenotypically heterogeneous. Furthermore, NPM1-mut is a clinically heterogenous group. Recent studies have in part clarified the consistent heterogeneities of these AMLs and have strongly supported the need for an additional stratification aiming to improve the therapeutic response of the different subgroups of NPM1-mut AML patients.

Background: The incidence of traumatic acute subdural hematomas (ASDH) in elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays a no clear role as predictor. We investigated if the timing of surgery has a major role in influencing outcome in these patients.Methods: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 years period in 5 Italian Hospitals. Patients were divided in 3 surgical timing groups from hospital arrival: ultra-early (within 6h); early (6-24h); delayed (after 24h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed.Results: We included 136 patients. About 33% died for consequences of ASDH and among the survivors only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting GCS, which was on average lower in ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared associated neither with survival nor with functional outcome also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. Conclusions: An earlier surgery was offered to patients with worse clinical-radiological findings. Also after stratification for GCS it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.

Acute myeloid leukemia (AML) is a hematological malignancy that is the culmination of genetic and epigenetic alterations in the hematopoietic progenitor cells, leading to uncontrolled proliferation at the expense of normal hematopoiesis and bone marrow exhaustion. Although the outcomes for pediatric AML have improved in recent decades, at least one third of children still have relapses. Recent studies have notably highlighted the important role of dysregulated epi-genetic mechanisms in myeloid leukemogenesis. Epigenetic modifications are frequently reversible compared to genetic alterations, thus providing opportunities for targeted epigenetic therapy. In this review, we summarize the landscape of epigenetic alterations and the progress to date in epigenetic targeted therapy, and focus on the future role of epigenetic abnormalities in predicting relapse and the precision therapy in pediatric AML.

Acute Oak Decline (AOD) is complex syndrome affecting Britain’s keystone native oak species, (Quercus robur L. and Q. petraea L. (Matt.) Liebl.), in some cases causing mortality within five years of symptom development. The most distinguishable symptom is weeping stem lesions, from which four species of bacteria have been isolated: Brenneria goodwinii, Gibbsiella quercinecans, Lonsdalea britannica and Rahnella victoriana. We do not yet know where else these bacteria exist, and little is known about the relationship of the wider oak leaf microbiome (phyllosphere) to acute oak decline. Here we investigate whether incidental evidence from a large oak genome re-sequencing dataset could be used to detect these bacteria in oak foliage, and whether bacterial incidence co-varied with AOD status or location. Oak leaves and buds were sampled from 421 trees at five sites in England. Whole genomic DNA from these samples was shot-gun sequenced with short reads. Non-oak reads were extracted from these data and queried to microbial databases. Reads uniquely matching AOD-associated bacterial genomes were found to be present on trees from all five sites and included trees with active lesions, trees with historic lesions and trees without AOD symptoms. The abundance of the AOD-associated bacteria did not differ between tree health categories but did differ among sites. We conclude that the AOD-associated bacteria may be members of the normal oak microbiome, whose presence on a tree is not sufficient to cause AOD symptoms.

The cork oak (Quercus suber L.), endemic essence of the Mediterranean Basin, is commonly used in traditional pharmacopoeia. The main objective of this work is to enhance the valorization of this plant species through the study of the anticandidosic activity of cork oak bark methalonic extracts in order to develop an efficient natural formulation for Candidiasis treatment.The anticandidosic activity of methanolic extracts of Q. suber bark stemming from decoction, maceration and Soxhlet methods of extraction in was tested on five different Candida albicans strains. Our results showed that all the tested extracts displayed an inhibitive activity, which varies according to the obtained extract and the tested strain. The best anticandidosic potential was observed with extracts obtained with Soxhlet method. The study of the acute toxicity showed that the lethal dose is 1150 mg/kg in mice, which remained moderately toxic according to Hodge and Sterner classification scale. Thus, this extract can be used in phytotherapy without danger in doses that are below 300 mg/kg of corporal weight. Based on these results, we can conclude that Cork oak bark extracts can be used to treat Candida albicans infections.

Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute cor-onary syndrome (NSTE-ACS) requiring revascularization remain undefined. Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included and 300 matched patients with normal renal function were selected as a control cohort. Results: Diagnostic performance for patients with severe CKD was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p=0.68) and the ROC-derived cutoff value at presentation was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3-hour changes, sensitivity increased to 98%, PPV and NPV improved up to 93% and 86%, re-spectively. (4) Conclusions: In patients with severe CKD and suspected ACS the diagnostic accu-racy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay specific cutoff levels combined with early absolute changes.

Introduction: Otitis media with effusion (OME) is common in pediatric primary care consultations. Its etiology is multifactorial, although it has been proven that inflammation factors mediate and that immunity is in a phase of relative immaturity. The objective of this study was to assess the effects of the Traditional Mediterranean Diet (TMD) modulating inflammation and immunity in patients diagnosed with OME.

In recent years, many studies have highlighted the consistent finding of amoxicillin in waters destined for wastewater treatment plants, in addition to superficial waters of rivers and lakes in both Europe and North America. In this paper, the amoxicillin degradation pathway was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants at three different pH values. The structures of 16 isolated degradation byproducts (DPs), one of which was isolated for the first time, were separated on a C-18 column via a gradient HPLC method. Then, combining mass spectrometry (MALDI-MS/TOF) and nuclear magnetic resonance, we compared commercial standards and justified a proposed formation mechanism beginning from the parent drug. Microbial growth inhibition bioassays with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were performed to determine the potential loss of antibacterial activity in isolated degradation byproducts. An increase of antibacterial activity in the DPs was observed compared to the parent compound.

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.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

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.

Aflatoxins continue to raise health concerns as unavoidable and widespread natural contaminants of foods and feeds with serious impact on health, agricultural and livestock productivity, and food safety. They are secondary metabolites produced by Aspergillus species distributed on three main sections of the genus (section Flavi, section Ochraceorosei, and section Nidulantes). Aflatoxin-producing species, mainly A. flavus and A. parasiticus thrive under hot and humid conditions in the field or during storage, which are met in tropical and sub-tropical regions. Poor economic status of a country exacerbates the risk and the extent of crop contamination due to faulty storage conditions that are usually suitable for mold growth and mycotoxin production; temperature of 22 to 29°C and water activity of 0.90 to 0.99. This situation paralleled the prevalence of high liver cancer and the occasional acute aflatoxicosis episodes that have been associated with these regions. Few of the presently known aflatoxins (>18) have been sufficiently 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. A review of publications on the incidence and concentrations of aflatoxins in selected foods and feeds from countries whose crops are classically known for their highest contamination with aflatoxins, reveals that despite the intensive efforts made to reduce such an incidence, there has been no clear tendency, with the possible exception of South Africa, towards sustained improvements. The levels and incidence are essentially influenced by the rainfall and temperature during the cultivation year or two successive years with alternating dry and wet seasons. This review aimed to update the main aspects of aflatoxin production, occurrence and incidence in selected countries, and associated adverse health effects. In addition to AFB1 which was the main focus of the review, other aflatoxins were addressed whenever relevant data were available.

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.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

The role of inflammation in the pathophysiology of acute myocardial infarction (AMI) is well established. Recognizing inflammation's pivotal role in AMI, this manuscript systematically traces historical studies, spanning from early attempts to the present landscape. Several anti-inflammatory trials targeting inflammation in post-AMI have been performed. The review includes key trials, examining their designs, patient demographics, and primary outcomes. Efficacy and challenges are analyzed, shedding light on the translational implications of trial outcomes. The article also discusses emerging trends, ongoing research, and potential future directions in the field. Practical applications and implications for clinical practice are considered, providing a holistic view of the evolving landscape of anti-inflammatory interventions in the context of AMI.

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.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 x 109/l. A count equal or above 0.5 x 109/l is considered eosinophilia, while a count equal or above 1.5 x 109/l is defined as hypereosinophilia. In bone marrow, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non- hematologic, whether non-neoplastic (allergic diseases, drugs, infections or immunological diseases) or neoplastic (solid tumors). Eosinophilia associated with a haematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphoid variant of hypereosinophilic syndrome and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia associated with a haematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with origin in stem cell (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with Core Binding Factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive o clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of haematological malignancies with eosinophilia.

Background Acute kidney injury (AKI) is a common comorbidity in the intensive care unit (ICU), with higher mortality rate among those who receive continuous renal replacement therapy (CRRT). This study aimed to investigate the association of white blood cell (WBC) levels with all-cause mortality in AKI patients undergoing CRRT. Method We conducted a post hoc analysis of ICU patient data from multiple centers in Korea. First, the levels of WBCs were classified into four groups based on quartiles. Second, the relationship between different WBC levels and mortality was investigated with the Kaplan-Meier (K-M) survival curves, Cox proportional hazards model, and generalized additivity model (GAM). Finally, we used multiple imputation to avoid bias caused by non-randomized missing data. The endpoints were short-term (28 days) and long-term (90 days) mortality. Result In our analysis, a total of 1,100 ICU patients were included. Among them, 670 (60.90%) and 781 (71.00%) died within 28 and 90 days, respectively. K-M survival curves showed that patients with the lowest WBC levels had the highest risk of mortality for both outcomes. Adjusted multivariate Cox regression analysis confirmed that compared with the reference level (quartile 2), low WBC levels increased the risk of both 28-day mortality (quartile 1, HR = 1.43, 95% CI: 1.13–1.83, P = 0.004) and 90-day mortality (quartile 1: HR = 1.32; 95% CI: 1.05-1.66, P = 0.016). GAM analysis showed a non-linear, U-shaped relationship between pre-CRRT WBC levels and all-cause mortality (non-linear P < 0.05). Conclusion The baseline WBC level is an independent predictor of prognosis for ICU patients receiving CRRT. Patients in the lowest WBC quartile had the highest risk of all-cause mortality. These results provide further evidence that early observation and intervention may have a prognostic value for these high-risk patients.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardiac-skeletal muscle coupling during exercise was then elucidated. The exercise capacity via cardiopulmonary exercise testing (CPX), cardio-ankle vascular index (CAVI), and body composition of 101 patients with AMI were measured at discharge. Patients were categorized based on their CAVI into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and peak VO2 (VO2 Peak) during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak in patients with AMI. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply defines systemic exercise limits in patients with AMI. This suggested that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

This study aimed to investigate the potential correlations and differences between patients with Acute Coronary Syndrome (ACS) and controls. Emphasis was placed on examining the relationship between arterial blood gas PH value and arterial blood gas lactate value as well as assessing the utility of the Peripheral Perfusion Index (PI) in ACS management. Materials and Methods: A prospective observational study was conducted between January 1, 2023, and July 1, 2023, involving 60 ACS patients and 30 control subjects in an emergency department. The diagnosis of ACS was confirmed by experienced emergency physicians, and various parameters, such as peripheral perfusion index, blood gas values, and cardiac biomarker values, were collected. The statistical analyses included Pearson’s chi-square test, Mann-Whitney U test, Student’s t-test, and others, using SPSS version 18.0. There were significant differences in the mean age, perfusion index, and lactate levels between the patient and control groups. A robust negative correlation was found between age and PI, and a moderate negative correlation was observed between pH and lactate levels (r = -0.301, p=0.004). The perfusion index in the patient group was significantly lower, indicating its potential diagnostic utility. The findings demonstrate the importance of arterial blood gas pH and lactate values in understanding ACS patient profiles, emphasizing the potential of PI as a noninvasive diagnostic method. The negative correlation between pH and lactate levels may offer valuable insights into risk stratification and treatment strategies for patients with ACS.

Leukemia cutis (LC) is defined as leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and in T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis and treatment of leukemic skin involvement in different types of leukemia

In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has ac-cumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 848 reconstructed patients, 9 trials were analyzed. The survival data from these trials were pooled into three types of treatments: i) treatments based on ty-rosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs as-sociated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

Background: Sensor usage in the classical scientific process has allowed new experimentation in medicine. We report on the design process of a MEMS sensor being used for muscle trauma evaluation in diagnosing acute compartment syndrome (ACS), a medical ailment costing society billions of dollars per year. Objectives: Modeling the disease with scientific process allows a more complete under-standing of the disease. The goal was to formulate a hypothesis that could be tested to aid in making the diagnosis of ACS accurately. Methods: Scientific process was observed throughout the disease modelling process. Background information was improved and clarified, new pre-clinical models were de-signed and verified, a hypothesis built on pressure measurement with MEMS sensors was carried out, and the testing of the model as verified against previous clinical data was accomplished. Results: Scientific process resulted in hypothesis generation around the relationship of intracompartmental pressure measurement and the disease process and therapy. This resulted in new understanding of ACS, accurate modelling, and sensor design resulting in a MEMS device that has an extremely high sensitivity and specificity (over 99%) in treating and diagnosing the disease. Conclusion: MEMS sensor technology defines the new gold standard of implanting a sensor in a muscle compartment that allows accurate diagnosis of ACS with continuous trends in pressure.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

Although automated Acute Lymphoblastic Leukemia (ALL) detection is essential, it is challenging due to the morphological correlation between malignant and normal cells. The traditional ALL classification strategy is arduous, time-consuming, often suffers inter-observer variations, and necessitates experienced pathologists. This article has automated the ALL detection task, employing deep Convolutional Neural Networks (CNNs). We explore the weighted ensemble of deep CNNs to recommend a better ALL cell classifier. The weights are estimated from ensemble candidates' corresponding metrics, such as accuracy, F1-score, AUC, and kappa values. Various data augmentations and pre-processing are incorporated for achieving a better generalization of the network. We train and evaluate the proposed model utilizing the publicly available C-NMC-2019 ALL dataset. Our proposed weighted ensemble model has outputted a weighted F1-score of 88.6%, a balanced accuracy of 86.2%, and an AUC of 0.941 in the preliminary test set. The qualitative results displaying the gradient class activation maps confirm that the introduced model has a concentrated learned region. In contrast, the ensemble candidate models, such as Xception, VGG-16, DenseNet-121, MobileNet, and InceptionResNet-V2, separately produce coarse and scatter learned areas for most example cases. Since the proposed ensemble yields a better result for the aimed task, it can experiment in other domains of medical diagnostic applications.

Many neonates undergoing whole body hypothermia (WBH) following moderate to severe perinatal asphyxia suffer from renal impairment. While recent data suggest a WBH-related reno-protection, the differences in serum creatinine (Scr) patterns to reference patterns were not yet reported. We therefore aimed to document Scr trends and patterns in asphyxiated neonates undergoing WBH, and compared these to centiles reference Scr dataset of non-asphyia neonates. Using a systematic review strategy, reports on Scr trends (mean ± SD, or median and range) were collected (day 1-7) in WBH cohorts, and compared to centiles of an earlier reported reference cohort of non-asphyxia cases. Based on 13 papers on asphyxia+WBH cases, a pattern on postnatal Scr trends in asphyxia+WBH cases was constructed. Compared to the reference cohort, mean or median Scr values at birth (>90th centile) and the first two days of WBH (>75th centile) remained clinical relevantly higher in asphyxia+WBH cases, with a subsequent decline to reach at best high or high normal creatinine values (all >50th centile, but mainly >75th centile) from day 4 onwards. Such patterns are valuable to anticipate average changes in renal clearance capacity relevant for pharmacotherapy, but do not yet cover the relevant inter-patient variability observed in WBH cases.

Background: Acute injuries of the hamstring muscle complex (HMC) Type 3b (interfascicle / bundle-tear) are frequently observed in various sports disciplines both in elite and recreational sport. The treatment of choice of acute HMC injuries Type 3b is a progressive physiotherapeutic exercise program. Besides this, there is currently only insufficient scientific evidence to support other treatment methods, including local infiltrations and injections of platelet-rich-plasma. Very recently it was demonstrated that extracorporeal shock wave therapy (ESWT) may accelerate regeneration after acute skeletal muscle injury. The aim of the present study is to test the hypothesis that the combination of radial ESWT (rESWT) and a specific rehabilitation program (RP) is effective and safe in treatment of acute HMC injury Type 3b in athletes, and is statistically significantly more effective than the combination of sham-rESWT and RP. Methods/Design: We will perform a double blind, randomized, sham-controlled clinical trial at the clinic KinEf Kinesiología Deportiva, Ciudad Autónoma de Buenos Aires, Argentina. Fourty patients with acute HMC injury Type 3b will be randomly allocated to receive either rESWT (nine rESWT sessions; three sessions per week; 2500 radial extracorporeal shock waves (rESWs) per session; energy density depending on what the patient tolerates) or sham-rESWT. In addition, all patients will receive a specific rehabilitation program that will last for eight weeks. The primary outcome measure will be the individual time (days) necessary to return to play. Secondary outcomes will include the presence or absence of reinjury during a time period of six months after inclusion into the study. Discussion: Because of the lack of adequate treatment options for acute HMC injury Type 3b in athletes and particularly the high reinjury rate, we hypothesize that the results of this trial will be of importance and have impact on clinical practice. Trial registration: ClinicalTrials.gov ID NCT03473899. Registered March 22, 2018.

Multiple lines of evidence indicate that CD8$^+$ T cells are important in the control of HIV-1 (HIV) replication. However, CD8$^+$ T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8$^+$ T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8$^+$ T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8$^+$ T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8$^+$ T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8$^+$ T cells in the chronic infection. The breadth of HIV-specific CD8$^+$ T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8$^+$ T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8$^+$ T-cell responses and the presence of intra- and interclonal competition between multiple CD8$^+$ T-cell responses; such competition may limit the magnitude of CD8$^+$ T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8$^+$ T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

We report the case of a 44-year-old woman who suffered gastric perforation after receiving bag-valve-mask (BVM) ventilation in the setting of alcohol intoxication. She had a markedly distended abdomen and cold, dusky lower extremities upon arrival to the emergency department. Imaging revealed a large volume intraabdominal accumulation of air with compression of the aorta. Needle decompression relieved symptoms of lower extremity arterial insufficiency. However, the patient quickly decompensated and subsequent exploratory laparotomy confirmed gastric rupture. A subtotal gastrectomy was performed but the patient ultimately passed on post-operative day two due to multi-organ dysfunction. Although BVM ventilation is commonplace in both the hospital and field, there is a lack of awareness of the serious complications of abdominal air accumulation due to their rareness in the adult population. Checking for abdominal distention during resuscitation ought to be routine in all patients. Signs of arterial insufficiency accompanying abdominal distention, once confirmed by diagnostic imaging that shows extensive pneumoperitoneum, are indicators of having reached a life-threatening level of air accumulation, calling for immediate needle decompression and exploratory laparotomy.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

Background: As a relatively high number of ST-segment elevation myocardial infarction (STEMI) patients develop major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI), our aim was to determine the significance, and possible predictive value of QRS complex width and ST-segment elevation. Methods: Our patient sample included 200 PCI-treated STEMI patients, which were divided into two groups, based on the duration of symptoms: (I) less than 6 hours, and (II) 6-12 hours. For every patient, ECG was performed at 6 different time points. Long-term follow-up lasted 6 years from the STEMI onset. Statistical analysis was performed. Results: The mean age was 60.6±11.39 years, and 142 were male. Wider QRS complex, more pronounced ST-segment elevation, and more frequently absent ST-segment resolution were more common in the second group. Presentation of MACE was more frequent in this group. An increase of pre-PCI QRS complex width by 1 msec increases the risk of 6-year MACE by 3%, and an increase in pre-PCI ST-segment elevation by 1mm increases the risk of 6-year MACE by 3.26 times. Conclusion: To the best of our understanding, this study represents a pioneer research that utilized these ECG elements in the context of predicting a 6-year MACE. A wider QRS complex and a more pronounced ST-segment elevation were associated with longer total ischemic time. More research is needed to confirm these findings.

Active vitamin D derivatives (VDDs) – 1α,25-dihydroxyvitamin D3/D2 and their synthetic analogs – are well-known inducers of cell maturation with the potential for differentiation therapy of acute myeloid leukemia (AML). However, their dose-limiting calcemic activity is a significant obstacle to using VDDs as an anticancer treatment. We have shown that different activators of the NF-E2-related factor-2/Antioxidant Response Element (Nrf2/ARE) signaling pathway, such as the phenolic antioxidant carnosic acid (CA) or the multiple sclerosis drug monomethyl fumarate (MMF), synergistically enhance the antileukemic effects of various VDDs applied at low concentrations in vitro and in vivo. This study aimed to investigate whether glutathione, the major cellular antioxidant and the product of the Nrf2/ARE pathway, can mediate the Nrf2-dependent differentiation-enhancing activity of CA and MMF in HL60 human AML cells. We report that glutathione depletion using L-buthionine sulfoximine attenuated the enhancing effects of both Nrf2 activators concomitant with downregulating vitamin D receptor (VDR) target genes and the activator protein-1 (AP-1) family protein c-Jun levels and phosphorylation. On the other hand, adding reduced glutathione ethyl ester to dominant negative Nrf2-expressing cells re-stored both the suppressed differentiation responses and the downregulated expression of VDR protein, VDR target genes, as well as c-Jun and P-c-Jun levels. Finally, using the transcription factor decoy strategy, we demonstrated that AP-1 is necessary for the enhancement by CA and MMF of 1α,25-dihydroxyvitamin D3-induced VDR and RXRα protein expression, transactivation of the vitamin D response element, and cell differentiation. Collectively, our findings suggest that glutathione mediates, at least in part, the potentiating effect of Nrf2 activators on VDDs-induced differentiation of AML cells, likely through the positive regulation of AP-1.

(1) Background: The chemotherapeutic drug cisplatin exerts toxic side effects causing acute kidney injury. Mesenchymal stromal cells can ameliorate cisplatin-induced kidney injury. We hypothe-size that the MSC secretome orchestrates the vicious cycle of injury and inflammation by acting on proximal tubule epithelial cells (PTECs) and macrophages individually, but further by coun-teracting their cellular crosstalk. (2) Methods: Conditioned medium (CM) from adipose stromal cells was used, first assessing its effect on cisplatin injury in PTECs. Second, effects of cisplatin and CM on macrophages were measured. Lastly, in an indirect co-culture system the interplay between the two cell types was assessed. (3) Results: First, CM rescued PTECs from cisplatin-induced apoptosis by reducing oxidative stress and expression of nephrotoxicity genes. Second, while cisplatin exerted only minor effects on macrophages, CM skewed macrophage phenotypes to the anti-inflammatory M2-like phenotype and increased phagocytosis. Finally, in the co-culture system, CM suppressed PTEC death by inhibiting apoptosis and nuclei fragmentation. CM lowered TNF-α release. While cisplatin inhibited macrophage phagocytosis, PTECs, and CM to a greater extent, enhanced it. CM strongly dampened the inflammatory macrophage cytokine secretion triggered by PTECs. (4) Conclusion: ASC-CM surpasses the PTEC-macrophage cross-talk in cisplatin injury. The positive effects on reducing cisplatin cytotoxicity, on polarizing mac-rophages and on fine-tuning cytokine secretion underscores MSCs CM benefit to prevent kidney injury progression.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylamino)(phenyl) phosphonium iodides (bromides) 1 containing one, two, or three diethylamino groups were obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions and high yields. The structure of compounds 1 was established by NMR and XRD. In vitro a high cytotoxicity against the lines M-Hela, HuTu 80, PC3, DU-145, PANC-1 and MCF-7 was found. Selectivity index are in the range of 0.06-4.0 M (SI 17-277) for the most active compounds. ROS production, mitochondrial localization and the process of cellular apoptosis were investigated. Decorated by 1 of lipid systems (liposomes and solid lipid nanoparticles) improve the cytotoxicity and a decrease in toxicity against normal cell lines. Compounds 1 induce apoptosis proceeding along the mitochondrial pathway. Aminophosphonium salts 1 also exhibit a high selective activity against the Gram-positive bacteria strains S. aureus 209P, B. segeus 8035, including methicillin-resistant strains of S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead compounds.

The short-term intake (ESTI) of Hungarian consumers to pesticide residues was assessed based on 2331 test results obtained during 2017-2021 monitoring program in the frequently analyzed apples, sour cherries, table grapes, peaches, nectarines, peppers and strawberries (23.5% of all samples taken from 119 crops). The age-specific consumption data were obtained from two representative national food consumption surveys (2009 and 2018-2020). The exposure was characterized with Hazard Quotient and Hazard Index considering the acute reference doses of pesticide residues detected in the samples. When ESTI was calculated with all detected “single“ residues and variability factor of 3.6, recommended for evaluation of monitoring results, the HI only exceeded 1 for children &lt;3 years old eating grape (1.50-1.81). HI was &lt;1 when any of the 6 foods were eaten together within one day. Between forty and fifty percent of samples contained 2-23 residues. Though, the individual residue concentrations were below the corresponding MRLs, multiple residues being present in one sample resulted in maximum HI values in apples (1.14); grapes (6.57); peaches and nectarines (2.57); strawberries (2.74); peppers (10.44). Residues with low ARfD values contributed most. Applying HI is simple, but provides only point estimates; therefore, it should only be used in first-tier risk assessment.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

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.

: In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyse all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyse Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 562 reconstructed patients, 8 trials were analyzed. The survival data from these trials were pooled into three types of treatment: i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs associated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. In conclusion, the multi-treatment Kaplan-Meier graph generated in this study has effectively summarized the current evidence on these treatments in comparative terms.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

Background: Acute pancreatitis is a common emergency. Morbidity control requires early detection of disease severity. METHODS: A total of 131 AP patients were analyzed retrospectively. Patients were divided into two groups mild AP (MAP: Ranson score <3) and severe AP (SAP: Ranson score ≥3), according to Ranson’s criteria. Demographic data, hospitalization duration, PNI, CRP, and RDW levels were compared. Any p-value below 0.05 (p<0.05) was accepted as statistically significant. RESULTS: Study included 67 (51.15%) males and 64 (48.85%) females. The age average was 59.74 (19-90) years. 95 (72.52%) patients had MAP, and 36 (27.48%) patients had SAP. Mean hospitalization time, PNI, and CRP differed significantly between the two groups (p=0.010, p<0.05, p<0.05, respectively). The RDW (p=0.380) level difference was insignificant. For SAP prediction; the sensitivity, specificity and cut-off value according to Ranson code cut-off point for PNI were determined as 80.0% (95% CI:54.8-85.8), %72.2 (95% CI:70.5-87.5) and ≤45.6 (gr/L) + (mm3), respectively, and 94.7% (95% CI:57.8-87.9), %75.0 (95% CI:88.1-98.3) and >105,1 mg/L, respectively for CRP. CONCLUSION: PNI and CRP values (but not RDW values) were compatible with the disease severity determined by the Ranson criteria.

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.

Transplant of human cancer cells into zebrafish larvae has emerged as a useful methodology in cancer research. Zebrafish have very low husbandry costs, are amenable to large-scale drug screening, and are unmatched for optical clarity in live animal imaging. However, there is currently no consensus on the ideal methods for xenograft of human cancer cells into zebrafish. Here, we have examined the effects of transplant site and housing temperature on both zebrafish larvae and human cancer cells using survival analyses, metabolomic approaches, and in vivo imaging. Our data show that while zebrafish larvae can adapt to the ideal conditions for mammalian cells, human cancer cells are highly sensitive to both temperature change and transplant site. Human cells housed in slightly cooler than physiologic temperatures had a significantly altered metabolism that resulted in changes in growth, survival, and response to chemotherapy. Cancer cells xenografted into the yolk of the larvae also had reduced proliferation and drug response compared to those xenografted into the soma, in part due to the differences in metabolites available at these sites. In total, temperature and transplant site can have profound effects on xenografted cells. Standardization of zebrafish xenograft methods will enhance data reproducibility between individual laboratories.

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.

Chikungunya virus is a re-emerging mosquito-borne alphavirus. Outbreaks are unpredictable and explosive in nature. Fever, arthralgia, and rash are common symptoms during the acute phase. Diagnostic tests are required to differentiate chikungunya virus from other co-circulating arboviruses, as symptoms can overlap, causing a dilemma for clinicians. Arthritis is observed during the sub-acute and chronic phases, which can flare up, resulting in increased morbidity that adversely affects activities of daily living. During the 2019 chikungunya epidemic in Thailand, cases surged in Bangkok in the last quarter of the year. Here, we demonstrate the chronic sequelae of post-chikungunya arthritis in one of our patients 1 year after the initial infection. An inflammatory process involving edema, erythema, and tenderness to palpation of her fingers' flexor surfaces was observed, with positive chikungunya IgG and negative IgM tests and antigen. The condition produced stiffness in the patient’s fingers and limited their range of motion, adversely affecting daily living activities. Resolution of symptoms was observed with a short course of an anti-inflammatory agent. More research is required to determine whether sanctuaries enable chikungunya virus to evade the host immune response and remain latent, flaring up months later and triggering an inflammatory response that causes post-chikungunya arthritis.

Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following FDA guidance. At Day 1 (diagnosis) the mean(SD) sum score of the six ACSS typical symptoms reached 10.60(2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favoured ACSS criteria (sum score of typical symptoms 0.98(1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. Conclusion The American-English ACSS showed high predictive ability and responsiveness, and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice or for self-diagnosis of women with symptoms of UC.

Artificial intelligence methods may help in unveliling information hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data but have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell acute lymphoblastic leukemia. In this paper we analysed flow cytometry data obtained on diagnosis from 54 paediatric B-cell acute lymphoblastic leukemia patients from two local institutions. We constructed classifiers based on the Fisher’s Ratio to quantify differences in expression levels of immunophenotypical markers between patients with relapsing and non-relapsing disease. The distribution of the marker CD38 was found and validated to have a strong discriminating power between both patient cohorts, thus providing a classifier.

Background and Aims: The impact of antibody response after direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association of changes in anti-HCV antibody titers after pre-LT DAA therapy with allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (DAA-naïve group). Higher incidence of post-LT BCs was observed in the DAA group (P = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (P = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (P < 0.005). Conclusion: In conclusion, we speculated that anti-HCV antibody titer upregulation, which might have been induced by restoration of HCV-specific immune responses with pre-LT DAA therapy, were associated with post-LT allograft injury.

Estrogens play a protective role during early life stages. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression in low-grade inflammatory conditions like established atherosclerosis. Our single-center cohort study assessed sex-specific associations of gonadal hormones with oxidative stress, inflammation, and myocardial injury markers in 111 patients (37% women) diagnosed with acute myocardial infarction (MI) between July 2011 and December 2013. Blood samples were collected within 48 hours of symptom onset, and we measured sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitive C-reactive protein (CRP), white blood cell counts (WBC), and cardiac enzymes (creatine kinase [CK], the CK Muscle-Brain fraction [CK-MB], and high-sensitive troponin T [hsTnT]). The SYNTAX score gauged coronary disease severity from coronary angiography results. In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels (OR 1.011, p=0.047 - CK; OR 1.018, p=0.013 - CK- MB; OR 1.019, p=0.005 - TnT), peak WBC count (OR 1.487, p=0.015 - CK ; OR 1,709, p=0,005 - CK- MB; OR 1.391, p=0.012 - TnT), and peak CRP plasma levels (OR 1.040, p=0.033 - CK; OR 1.024, p=0.029 - CK-MB; OR 1.063, p=0.006 - TnT). T levels and E2/T ratio were associated with post-PCI CRP in these men (OR 0.980, p = 0.024 - T, OR 1.010, p = 0.076 - CRP). For women, peak WBC was a marker of highest testosterone (OR 1.348, p = 0.062), and only WBC was a significant indicator of myocardial injury extent (OR 1.426, p=0.039 - CK; OR 1.384, p=0.036 - CK-MB; OR 1.299, p=0.048 - TnT). During acute MI, elevated endogenous estradiol levels correlate with myocardial necrosis severity in men, while in women, increased leukocyte levels indicate acute myocardial damage. Elevated plasma T is associated with increased WBC in women. In men, post-PCI plasma CRP specifically indicates endogenous T levels and E2/T ratio during the acute phase.

Background: This study investigated the incidence, characteristics and functional outcomes associated with unplanned Acute Care Unit Readmissions (ACUR) during inpatient traumatic brain injury (TBI) rehabilitation in an Asian cohort. Methods: Retrospective review of electronic medical records from single rehabilitation unit was conducted from 1 Jan 2012 to 31 Dec 2014. Inclusion criteria were first TBI, aged &gt;18 years, admitted &lt; 6 months of TBI. ACUR were characterized into either of neurological, medical or neurosurgical subtypes. The main outcome measure was discharge Functional Independence Measure (FIM). Secondary outcomes included rehabilitation length of stay (RLOS). Results: Of 121 eligible TBI records, the incidence of ACUR was 14% (n=17), comprising neurologic (76.5%) and medical (23.5%) subtypes, occurring at median of 13 days (IQR 6, 28.5) after rehabilitation admission. Patients without ACUR had significantly higher admission mean (SD) FIM score compared to those with ACUR (FIM ACUR-negative 63.4 (21.1) vs FIM ACUR-positive 50.53(25.4), P =0.026). Significantly lower discharge FIM was noted in those with ACUR compared to those without. (FIM ACUR-positive 65.8(31.4) vs FIM ACUR-negative 85.4 (21.1), P = 0.023) Furthermore, a significant near-doubling of RLOS was noted in ACUR patients compared to non-ACUR counterparts [ACUR-positive median 55 days (IQR 34.50, 87.50) vs ACUR-negative median 28 days (IQR 16.25, 40.00), P = 0.002]. Conclusion: This study highlights the significant negative functional impact and lengthening of rehabilitation duration of ACUR on inpatient rehabilitation outcome for TBI.

(1) Background: Acute myocardial infarction in pregnancy (pAMI) is a rare event, often caused by non-classical factors rather than atherosclerosis. The management of pAMI poses unique chal-lenges as it requires considering both maternal and fetal well-being.; (2) Methods: We present the case of a 36-week pregnant woman who presented with antero-lateral ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock. To ensure comprehensive decision-making, an emergency Pregnancy Heart Team meeting was convened, comprising interventional cardi-ologists, gynecologists, and anesthesiologists. The team prioritized interventional treatment for pAMI and opted for primary percutaneous coronary intervention (PCI) due to the unstable ma-ternal condition.; (3) Results: The patient underwent primary PCI as the chosen intervention for pAMI. A rapid response gynecology team closely monitored the procedure and was prepared to intervene in case of irreversible hemodynamic compromise leading to cardiac arrest. A caesarean section was deemed necessary if cardiac activity was not restored within 4 minutes.; (4) Conclusions: Managing pAMI requires a multidisciplinary approach that balances the maternal and fetal well-being. In this particular case, the Pregnancy Heart Team decided to prioritize interventional treatment with primary PCI due to the unstable maternal condition. The presence of a closely monitored gynecology team ensured prompt action in case of complications.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study we investigate the clinical use in these directions of a “damage” type biomarker - Neutrophil Gelatinase-Associated Lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasmsa NGAL was determined at baseline, at 4 and 24 hours after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (132.33±72.83 ng/ml versus 111.48±65.06 ng/ml, p=0.006) and at the 24th hour (212 .93±276.61 ng/ml, p=0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (128.18±99 ng/ml, p=0.002) and reached levels close to those in patients with CI-AKI. Unlike new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good - AUC 0.847 (95% CI: 0.677-1.000; p=0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539 – 0.924; p=0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

Background and Objectives: Acute Heart Failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying the pulmonary hypertension (PH) in patients admitted due to AHF, predict the evolution of the disease during hospitalization and identify areas of improvement in the care of patients with AHF. Materials and Methods: Patients were evaluated with a standard exam of lung ultrasound, echocardiography, inferior vena cava (IVC) and femoral, renal, hepatic, portal venous Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation – SD 13,4). Seven patients (23.3%) had a renal function worsening. Regarding ultrasound findings, venous excess ultrasonography score (VExUS) score was calculated at admission and at discharge, surprisingly remaining unchanged or even worsened in most of them (21 patients, 70.0%). The area under the curve for the Lung Score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (p &lt;0.001), hepatic vein Doppler (p &lt;0.001), portal vein Doppler (p = 0.030), intra-renal vein Doppler (p = 0.025) and VExUS score (p = 0.023), remaining similar the femoral vein Doppler (p = 0.177) and IVC (p = 0.132). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VExUS score, should be further studied in different populations before expanding its use in AHF patients.

Scrub typhus is a neglected tropical disease predominantly occurring in Asia. The causative agent is a bacterium transmitted by the larval stage of mites found in rural vegetation in endemic regions. Cases of scrub typhus frequently present as acute undifferentiated febrile illness, and without early diagnosis and treatment, the disease can develop fatal complications. We retrospectively reviewed de-identified data from a 23-year-old woman who presented to an emergency department with complaints of worsening abdominal pain. On presentation, she appeared jaundiced and toxic-looking. Other positive findings on abdominal examination were a positive Murphey’s sign, abdominal guarding and hepatosplenomegaly. Magnetic resonance cholangiopancreatography demonstrated acalculous cholecystitis. Additional findings included eschar on the medial aspect of the left thigh with inguinal regional lymphadenopathy. Further, positive results were obtained for immunoglobulins M and G, confirming scrub typhus. Workups for other infectious causes of acute acalculous cholecystitis detected human herpesvirus 4 (Epstein-Barr virus). Whether that represented acute infection or re-activation of the Epstein-Barr virus could not be determined. As other reports have described acute acalculous cholecystitis in adult scrub typhus patients, we recommend doxycycline to treat acute acalculous cholecystitis in endemic regions while awaiting serological confirmation.

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.

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.

In this study, we wanted to discuss the acute coronary syndromes in the pregnant womens which are very important for life ofthe fetus. Spontaneous coronary artery dissection and management, which is the most common cause of acute coronary syndrome in pregnant women is also discussed. About 300 articles were examined and 35 articles which published in high quality journals with high level of evidence were chosen and this review was prepared.

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.

This review paper presents a flashback on the evolution of the disease throughout the centuries, describes in summary pathophysiologic mechanisms, discusses briefly the mechanism of action of the diuretics, presents their role in decongesting heart failure patients and unfolds the data behind ultrafiltration in the management of acutely or chronically decompensated heart failure (ADHF), focusing on all the available data and advancements in this field. Acutely decompensated heart failure (ADHF) presents a critical clinical condition characterized by worsening symptoms and signs of heart failure, necessitating prompt intervention to alleviate congestion and improve cardiac function. Diuretics have traditionally been the mainstay for managing fluid overload in ADHF. Mounting evidence suggests that due to numerous causes, such as coexisting renal failure or chronic use of the loop diuretics, an increasing rate of diuretic resistance is noticed and needs to be addressed. There has been a series of trials that combined diuretics of different categories, without the expected results. Emerging evidence suggests that ultrafiltration may offer an alternative or adjunctive approach.

(1) Background: Usually, the majority of patients suffering from vertigo and dizziness can be identified in four major categories: acute spontaneous vertigo, episodic (recurrent) vertigo, recurrent positional vertigo, chronic imbalance. Our purpose is to retrospectively evaluate the main causes of episodic vertigo and to find indications for a reliable clinical suspicion useful for a definitive diagnosis, comparing patients affected by different presenting symptomatology (acute vertigo, recurrent episodic vertigo, and imbalance) (2) Methods: we retrospectively evaluated the clinical records in a population of 249 consecutive patients observed for vertigo in our tertiary referral center in the period 1 January 2019 – 31 January 2020. On the basis of the reported clinical history, patients were divided into three groups: patients with first ever attack of vertigo, patients with recurrent vertigo and dizziness; patients with chronic imbalance. (3) Results: On the basis of the results of the instrumental examination, we arbitrary divided (for each type of symptoms) the patients in a group with a normal vestibular instrumental examination and a group of patients in which the clinical-instrumental evaluation showed some pathological results; a highly significant difference (p: 0.157) was found between recurrent and acute vertigo and between recurrent vertigo and imbalance. (4) Conclusions: patients with recurrent vertigo more frequently exhibit a negative otoneurological examination since they are often examined in the intercritical phase. A precise and in-depth research of the patient's clinical history is the key to suspect or make a diagnosis together with the search for some instrumental or clinical hallmark, especially in cases where the clinical picture does not fully meet the international diagnostic criteria.

The 30-day postoperative outcome after elective endovascular aneurysm repair (EVAR) was evaluated and the possible predictors were identified. Demographics, medical history, laboratory values, length of hospitalization (LOH), intensive care unit (ICU) admission and 30-day complications, classified as major [major adverse cardiovascular events (MACE), acute kidney injury (AKI) and death of any cause] and minor [post-implantation syndrome (PIS), postoperative delirium (POD), urinary tract infection (UTI) and technical graft failure] were documented, respectively. We included 322 patients (median LOH 4 days). One-hundred and twenty one (37.5%) complications, mostly minor (n=103, 31.9%), were recorded. Eleven patients (3.4%) evolved MACE, 5 (1.6%) AKI and 2 patients (0.6%) died in ICU. Seventy-seven patients (23.9%) suffered from PIS, eleven from POD, 11 from UTI and 4 from technical graft failure. Multivariate logistic regression analysis revealed that aneurysm diameter (p=0.01) and past smoking (p=0.003) were predictors for postoperative complications. PAD was an independent predictor of MACE (p=0.003), preoperative neutrophil to lymphocyte ratio (NLR) value of AKI (p=0.003) and past smoking of PIS (p=0.008), respectively. Our study showed that 30-day morbidity after EVAR exceeded 35%. However, the majority of complications were classified as minor and the associated mortality was low. Aneurysm diameter and past smoking were independent predictors for postoperative outcome.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity &amp; mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p&lt;0.001) and other cardiac reasons (3.0% vs. 0.4%, p&lt;0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

Type A acute aortic dissection are associated with significant morbidity and mortality with prompt referral imaging and management to tertiary referral centres needed urgently. Surgery is usually needed emergently but the choice of surgery often varies depending on the patient and presentation. Staff and center expertise also play a major role in determining the surgical strategy employed The aim of this study is to compare early and medium term outcomes of patient across 3 European referral centers. We also identified risk factors for poorer outcomes irrespective of surgical strategy employed. A retrospective study was conducted across 3 sites between January 2008 and December 2021. 601 patients were included within the study of which 30% were female and the median age was 64.4 years. The most common operation was ascending aorta replacement (n= 246, 40.9%). The aortic repair was extended proximally (i.e., root n= 105; 17,5%) and distally (i.e., arch n = 250; 41,6%). A more extensive approach, extending from the root to the arch, was employed in 24 patients (4.0%). Operative mortality occurred in 146 patients (24.3%), and the most common morbidity was stroke (75, 12.6%). An increased length of ICU admission was noted in the extensive surgery group who were younger and more frequently male No significant differences were noted in surgical mortality from patients managed with extensive surgery vs those managed conservatively. However, age, arterial lactate levels, “intubated/sedated” status on arrival, and “emergency or salvage” status at presentation were independent predictors of mortality both within the index hospitalization and also during follow-up. Overall survival was similar between the groups.

Cardiopulmonary complications remain the major cause of mortality despite newer therapies and improvements in lifespan of patients with sickle cell disease (SCD). Inflammation has been identified as a major risk modifier in the pathogenesis of SCD associated cardiopulmonary complications in recent mechanistic and observational studies. In this review, we discuss recent cellular and molecular mechanisms of cardiopulmonary complications in SCD and summarize the most recent evidence from clinical and laboratory studies. We emphasize the role of inflammation in the onset and progression of these complications to better understand the underlying pathobiological processes. We also discuss future basic and translational research in addressing questions about the complex role of inflammation in the development of SCD cardiopulmonary complications, which may lead to promising therapies and reduce morbidity and mortality in this vulnerable population.

Abstract: Our goal is to create point-of-care (POC) strategies that accelerate decision making, increase efficiency, improve outcomes, and enhance standards of care in island communities faced with global warming, rising oceans, population migration, and intensifying weather disasters. We assessed needs in the Bantayan Archipelago and mainland Cebu Province, Visayas Islands, Philippines, to map POC diagnostics, rescue times, and spatial care paths. Significant deficiencies were lack of cardiac troponin testing for rapid diagnosis of acute myocardial infarction, absence of blood gas and pH testing for support of critically ill patients, and geographic gaps prolonging patient transfers and delaying treatment. Strengths comprised primary care that can be facilitated by POC testing, logical inter-island transfers for which decision making and triage could be accelerated with onboard diagnostic testing, and healthcare small-world networks amenable to POC advances, such as pre-hospital testing, that avoid overloading emergency rooms. Healthcare resources must be distributed to archipelago islands, not concentrated in large metropolitan areas inaccessible for emergency interventions. We conclude that a point-of-need focus will help improve public health, decrease disparities in mortality among rural islanders versus urban dwellers, and pave the way for heightened resilience in anticipation of the adverse impact of global warming on vulnerable coastal areas.

Acute low back pain (LBP) stands as a leading cause of activity limitation and work absenteeism, and its associated healthcare expenditures are expected to become substantial when acute LBP develops into a chronic and even refractory condition. Therefore, early intervention is crucial to prevent progression to chronic pain whose management is particularly challenging and for which the most effective pharmacological therapy is still controversial. Current guideline treatment recommendations vary and are mostly driven by expertise with opinion differing across different interventions. Thus, it is difficult to formulate evidence-based guidance when relatively few randomized clinical trials did explore the diagnosis and management of LBP while employing different selection criteria, statistical analyses, and outcome measurements. This narrative review aims to provide a critical appraisal of current acute LBP management by discussing the unmet needs and areas of improvement from bench-to-bedside and proposes multimodal analgesia as the way forward to attain an effective and prolonged pain relief and functional recovery in patients with acute LBP.

Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.

The digital transformation of healthcare is advancing, leading to an increasing availability of clinical data for research. Perioperative big data initiatives were established to monitor treatment quality and benchmark outcomes. However, big data analyzes have long exceeded the status of pure quality surveillance instruments. Large retrospective studies nowadays often represent the first approach to new questions in clinical research and pave the way for more expensive and resource intensive prospective trials. As a consequence, utilization of big data in acute pain and regional anesthesia research considerably increased over the last decade. Multicentric clinical registries and administrative databases (e.g., healthcare claims databases) have collected millions of cases until today, on which basis several important research questions were approached. In acute pain research, big data was used to assess postoperative pain outcomes, opioid utilization, and the efficiency of multimodal pain management strategies. In regional anesthesia, adverse events and potential benefits of regional anesthesia on postoperative morbidity and mortality were evaluated. This article provides a narrative review on the growing importance of big data for research in acute postoperative pain and regional anesthesia.

Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients

Since its 2013 emergence in the Americas, chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a Ct cutoff of 22. As the Ct value increased from 22, ELISA sensitivity decreased. We then developed and validated two lateral flow tests using independent antibody pairs. The sensitivity and specificity reached 100% for both lateral flow tests using 39 samples from Colombia and Honduras at Ct cutoffs of 20 and 27, respectively. For both lateral flow tests, sensitivity decreased as the Ct increased after 27. Because CHIKV E1/E2 are exposed in the virion surfaces in serum during the acute infection phase, these sensitive and specific assays demonstrate opportunities for early detection of this emerging human pathogen.

Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

A short review of the important studies was conducted to evaluate the potential of aerosol transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The minimum size of droplets potentially carrying the SARS-CoV-2 was newly estimated and discussed in this review.

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.

Lp16-PSP from Lentinula edodes strain C91-3 has been reported previously in our laboratory to have selective cytotoxic activity against a panel of human cell lines. Herein, we have used several parameters in order to characterize the Lp16-PSP-induced cell death using HL-60 as model cancer. The results of phase contrast microscopy, nuclear examination, DNA fragmentation detection and flow cytometry revealed that high doses of Lp16-PSP resulted in the induction of apoptosis in HL-60 cells. The colorimetric assay showed the activation of caspase-8, -9 and -3 cascade highlighting the involvement of Fas/FasL-related pathway. Whereas, western blot revealed the cleavage of caspase-3, increased expression of Bax, the release of cytochrome c and decreased expression of Bcl-2 in a dose-dependent manner, suggesting the intrinsic pathway might be involved in Lp16-PSP-induced apoptosis either. Low doses of Lp16-PSP resulted in the anchorage-independent growth inhibition, induction of G1 phase arrest accompanied by the increased expression of p21WAF1/CIP1 along with the decreased expression of cyclin D, E, and cdk6. Our findings suggest that induction of apoptosis and p21WAF1/CIP1 mediated G1 arrest might be one of the mechanisms of the action of Lp16-PSP, however, further investigations on multiple leukemia cell lines and in vivo models are of ultimate need.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

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.”

Background: Delayed graft function (DGF) is common after kidney transplantation from de-ceased donor and may significantly affect post-transplant outcomes. This study aimed to evaluating whether an innovative approach, based on the administration of intravenous prostaglandin-analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomised (1:1), place-bo-controlled study enrolled all consecutive patients who received a kidney transplantation from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin-analogue iloprost at 0.27 μg/min through elastomeric pump (treatment group) or placebo (control group). Results: A total of 476 patients were included : DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that donor’s age > 70 years (OR 2.50, 95% Confidence Interval (CI) 1.40-3.05, p < .001), cold ischemia time > 24 h (OR 2.60, 95 CI 1.50-4.51, p < .001), donor’s AKI (OR 2.71, 95% CI 1.61-4.52, p = .021) and, above all, recipient’s arterial hypotension (OR 5.06, 95% CI 2.52-10.1, p < .0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p< .001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.58.3 v s13.46.7, days, p= .016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased donor kidneys, allowing a better graft functionality as well as a better graft survival.

The study aimed to assess the prevalence of the frailty syndrome in older patients hospitalized in the geriatric ward depending on the diagnostic criteria used, the feasibility of particular diagnostic scales in hospitalized patients, and their compatibility. Material and methods: Patients admitted to the Department of Geriatrics of Hospital of the Ministry of the Interior and Administration in Bialystok within eight months were included in the study. Four diagnostic scales were used to identify the frailty syndrome: Fried criteria, 7-point Clinical Frailty Scale (CFS), 40-item Frailty Index (FI), and FRAIL Scale. The compatibility of the scales was determined using Cohen's Kappa statistics. Results: 416 patients (mean age 81.2 ± 6.91 years, 77.4% women) were included in the study. Depending on the scale, the prevalence of frailty syndrome varied from 26.8% ( FRAIL Scale), 52.3% (Clinical Frailty Scale), and 58.1% (Fried criteria) up to 62.9% (Frailty Index). We observed the highest feasibility for CFS (100%), intermediate for Frailty Index (95.2%), FRAIL Scale (89.7%), and the lowest for Fried scale (79.8%). The highest level of agreement was found between the CFS and Fried scale, with 70.2% consistent ratings (Cohen Kappa 0.49). Conclusions: Patients in the geriatric ward are characterized by a high prevalence of frailty, although it differs depending on the criteria. The Frailty Index found the highest prevalence and the lowest in the case of the FRAIL scale. The feasibility of scales and their comparability differed; the most difficult to use in daily practice was the Fried scale, while the Clinical Frailty Scale was determined feasible in all patients. The highest agreement was observed between the Fried criteria and the Clinical Frailty Scale and the lowest between the FRAIL scale and the remaining ones.

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now known also as a modulator of gene expression. What is important for cancer, is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts the enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NFκB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which have a significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. In general, the capacity of cancer cells to adapt to oxidative stress depends on molecular systems such as the interface of OGG1 with NFκB, which bestows a cancer cell with the molecular mechanism of transformation of its microenvironment to enable adaptation and survival of malignant clones.

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is the secreted and membrane-associated proteins, which regulate diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence revealed that excess SEMA3A expression and subsequent signaling pathway aggravates kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports demonstrated that inhibition of SEMA3A ameliorated kidney injury via reduction of cell apoptosis, fibrosis and inflammation, thus SE-MA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized current knowledges regarding the role of SEMA3A signaling in kidney pathophysiology and their potential use in kidney diseases.

In the Emergency Department (ED), pain is one of the symptoms that is most frequently reported, making it one of the most significant issues for the emergency physician, but is frequently under treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondary, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a systematic review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library and Controlled Trials Register finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. IN is simple to administer, non-invasive, rapid onset and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Analgesia needs to be tailored to each patient's features and type of pain: IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.

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.

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.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

Introduction: Despite the introduction of increasingly multifaceted diagnostic techniques and the general progress of emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross-polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). Methods and Participants: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), where the ischemic segments of the intestine were examined. Nine others were operated for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. Results: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT image of non-ischemic (control group), viable ischemic and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations and the type and density of the vasculature. Conclusion: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

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.

Background: Pre-treatment with lipopolysaccharide (LPS) protected the kidney against a later lethal ischemia. To reveal the mechanisms of renal cross-tolerance and septic acute kidney injury we investigated the effects of LPS on miRNA expression in the kidney. Methods: Male NMRI mice were injected with 40 and 10 mg/kg LPS ip. and sacrificed at 1.5 and 6 hours (early preconditioning, EP) and at 24 and 48 hours (late preconditioning, LP). The miRNA profile was established using miRCURY LNA™ microarray and confirmed with qPCR. Results: Plasma urea concentration peaked at 24 hours after LPS and decreased thereafter. Renal TNF-α and IL-6 mRNA were extremely elevated at all time-points. miRNome changes were mild at 1.5 hours, most miRNAs were altered at 6 and 24 hours and declined by 48 hours. Not all miRNAs could be assayed or validated by qPCR. In EP miR-762 was newly identified and validated and was the most elevated miRNA with both methods. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p and miR-146a-5p. MiR-21a-3p increased significantly in both EP and LP. Conclusion: miR-762 might attenuate the LPS-induced immune response during EP and the miR-144/451 cluster is involved in LPS-induced renal preconditioning.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6-8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving. Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-, IL-6, and neopterin). VGE exhibits a progressive reduction followed by an increase (p<0.0001) which parallels in-flammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min−1 (p<0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg-1 creatinine (p<0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.ml-1 (p<0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol−1 creatinine (p=0.005), respectively. The variation after each dive was held constant around 158.3 ± 6.9% (p = 0.021); 151.4 ± 5.7% (p <0.0001); 176.3 ± 11.9% (p<0.0001); and 160.1 ± 5.6% (p<0.001), respectively. When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of “first generation” pre-existing micronuclei.

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

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment modality, frequently applied in patients suffering from haematological malignancies. In the last two decades, there have been multiple randomised controlled trials (RCTs), review articles, and meta-analyses addressing the efficacy of rabbit anti-thymocyte globulin (r-ATG) as a graft-versus-host disease (GvHD) prophylaxis. Nevertheless, only a few aimed to compare the effectiveness of different r-ATG formulations. We performed a systematic literature review of articles published since 2017 to this day utilising PubMed, Scopus, Cochrane, and MEDLINE, with the main endpoints being prophylaxis of acute GvHD (aGvHD) and chronic GvHD (cGvHD). We subjected to scrutiny a total of 5 studies, of which 4 compared the differences between Thymoglobulin (ATG-T) and Grafalon (ATG-G), and 1 discussed the impact of ATG-T dose. Overall cGvHD, aGvHD grades II-IV, TRM, OS, NRM, LFS, relapse, overall infections, and EBV reactivation do not seem to be affected by the type of utilised rATG. However, data on aGvHD grades III-IV, GRFS, moderate-severe cGvHD, and CMV reactivation is conflicting. Through our research, we sought to summarise the most recent findings concerning r-ATGs in allo-HCT, and provide insight into the differences between the targets and origin of various ATG formulations.

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is characterized by biphasic seizures following febrile viral infections and delayed reduced diffusion of the cerebral white matter on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) (bright tree appearance, BTA). However, hypoxic encephalopathy with biphasic seizures and AESD-mimicking imaging findings has not been reported. Herein, we report an case of hypoxic encephalopathy due to suffocation with concomitant biphasic seizures and BTA, mimicking AESD. On day 1, a 5-month-old female was found face down with breathing cessation and deteriorating consciousness level. The electroencephalography (EEG) revealed periodic epileptic discharges, suggesting possible nonconvulsive status epilepticus. Despite the improvements in consciousness level and EEG abnormalities on day 2, her consciousness level deteriorated again with generalized tonic-clonic seizures on day 3, and head MRI-DWI revealed restricted diffusion predominantly in the subcortical areas, suggesting BTA. Treatment for acute encephalopathy resolved clinical sei-zures and EEG abnormalities. The persistence of abnormal EEG, reflecting abnormal excitation and accumulation of neurotoxic substances caused by hypoxia, may have contributed to the devel-opment of AESD-like findings. As hypoxic encephalopathy causes AESD-like biphasic seizures, monitoring the consciousness level, seizure occurrence, and EEG abnormalities even after acute symptoms have temporarily improved following hypoxia is essential.

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.

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.

The COVID-19 pandemic first observed in December 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has influenced every individual on the planet. The virus has influenced our lifestyle, education, economy and the environment. Though the vaccines against COVID-19 have provided protection against the disease; new strains of the virus have lowered the efficiency of the vaccines. There is still no effective therapy for the treatment of the disease. Understanding the protein structure of the virus may lead to the development of effective therapies for the disease. We recently mapped the structural proteins and non-structural proteins of SARS-CoV-2. The accessory proteins (Open reading frames, Orfs) of SARS-CoV-2 modulate the host environment to favor virus replication. This paper reports mapping the accessory proteins (Orfs) of SARS-CoV-2.