Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

Human serum albumin (HSA) is the ultimate, homeostatic determinant of fluid volume (FV) in all compartments of the body. The ability to change the pressure and flow of nutrient medium to cellular structures selectively has clinical significance in almost all areas of clinical medicine. We have shown that present fluid therapy (FT) using either colloid or saline dilutes nutrients. HSA binds and delivers nutrients, a lack of HSA binding causes Albumin Binding Disease (ABD) changing both colloidal pressure and nutrients leading to symptoms of sepsis. A reduction in HSA binding can be through lack of HSA or external ligands taking up binding sites on HSA. Many diseases cause ABD when immunoglobulins, infectious particles and by products bind to HSA including COVID-19 and other bacterial diseases like streptococcus as well as metabolic and cardiac disease due to incorrect pressure and nutrients. To raise HSA binding potential and remove vulnerabilities to these diseases we propose raising HSA. We show how present methods of fluid therapy (FT) are inefficient in that control of both pressure and nutrients forms initial equilibrium in the liver. HSA production and binding to nutrients is maintained at a level by the pressure in hepatocytes with the pancreatic and adrenal hormones moderating. Glucose and Ke-tone production are critical in the management of HSA binding and control of blood, colloidal pressure, and health of cells. Ketones provide a distinct mechanism of liver to lungs-heart metabolism during hypoglycaemia and activity. This known chain of nutrition becomes critical during disease like acute respiratory distress syndrome (ARDS) when ketones may be overproduced. HSA must therefore be infused into the liver to raise HSA levels safely. We investigated the control of HSA as a product of the actions of pressure in hepatocytes and changes in pancreatic and adrenal hormones. We found that in addition to pressure during glucose abundancy HSA is re-leased with ketones on administration of insulin and consider that this mechanism retains HSA moderation. HSA can therefore be increased by increasing insulin in the presence of glucose in the correct amounts. We suggest a protocol to increase FV, blood, lymph volume by infusion of HSA, insulin, and glucose direct to the liver so that the level of HSA stabilises. We suggest this will raise all other nutrients in the new FV, blood, lymph culminating in the creation of new blood cells. We propose that in a clinical situation maintaining this protocol will alleviate the symptoms of ABD and decrease the likelihood of serious illness and death.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

The following narrative review embarks on a comprehensive exploration of the pivotal role played by the gut microbiome within the Diet-Microbiota-Immunity (DMI) tripartite, aiming to enhance anti-cancer immunotherapy efficacy. While revolutionizing cancer treatment, resistance to immunotherapy and immune-related adverse events (irAEs) remain challenges. The tumor microenvironment (TME), shaped by cancer cells, influences immunotherapy resistance. The gut microbiome, influenced by genetics, environment, diet, and interventions, emerges as a critical player in TME reshaping, thereby modulating immune responses and treatment outcomes. Dietary patterns like the Mediterranean diet, caloric restriction modifications, and specific nutritional components show promise in influencing the tumor microenvironment and gut microbiome for better treatment outcomes. Antibiotics, disrupting gut microbiota diversity, may compromise immunotherapy efficacy. This review emphasizes the need for tailored nutritional strategies to manipulate microbial communities, enhance immune regulation, and improve immunotherapy accessibility while minimizing side effects. Ongoing studies investigate the impact of dietary interventions on cancer immunotherapy, pointing towards promising developments in personalized cancer care. This narrative review synthesizes existing knowledge and charts a course for future investigations, presenting a holistic perspective on the dynamic interplay between dietary interventions, the gut microbiome, and cancer immunotherapy within the DMI tripartite.

Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard-of-care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.

Objectives: The study aimed to develop a deep learning-based edge AI model deployed on electrocardiograph (ECG) devices for real-time detection of atrial fibrillation (AF)-risk during sinus rhythm (SR) using standard 10-second 12-lead electrocardiograms (ECGs). Methods: A novel approach was used to convert standard 12-lead ECGs into binary images for model input, and a lightweight convolutional neural network (CNN)-based model was trained using data collected by the Japan Agency for Medical and Research Development (AMED) between 2019 and 2022. Patients over 40 years old with digital, SR ECGs were retrospectively enrolled and divided into AF and non-AF groups. Data labeling was supervised by cardiologists. The dataset was randomly allocated into training, validation, and internal testing datasets. External testing was conducted on data collected from other hospitals.　Results: The best-trained model achieved an AUC of 0.82 and 0.80, sensitivity of 79.5% and 72.3%, specificity of 77.8% and 77.7%, precision of 78.2% and 76.4%, and overall accuracy of 78.6% and 75.0% in the internal and external testing datasets, respectively. The deployed model and app package utilized 2.5MB and 40MB of the available ROM and RAM capacity on the edge ECG device, correspondingly. Processing time for AF-risk detection was approximately 2 seconds.　Conclusion: The model maintains comparable performance and improves its suitability for deployment on resource-constrained ECG devices, thereby expanding its potential impact to a wide range of healthcare settings. Its successful deployment enables real-time AF-risk detection during SR, allowing for timely intervention to prevent AF-related serious consequences like stroke and premature death.

The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. By our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD) is a pervasive public health concern, intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and metabolic dysfunction-associated fatty liver disease (MAFLD) is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among metabolic dysfunction-associated fatty liver disease (MAFLD) patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.

Treatment options for sarcopenia are currently limited, primarily relying on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. Our objective is to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719 70-year-olds born in 1944 (54,1 % females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength) and appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple tests, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients for maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.

This study aimed to establish a predictive model for neoadjuvant chemoradiotherapy (nCRT) response in patients with locally advanced rectal carcinoma (LARC) using clinicopathological (CP) features along with radiomics from pretreatment Magnetic Resonance Imaging (MRI) 3D T2W contrast sequence scans. The study also assessed the impact of radiomic dimensionality on predictive performance. Seventy-five patients were prospectively enrolled with clinicopathologically confirmed LARC who underwent nCRT before surgery. Tumor properties were assessed by calculating 2142 shape, first-order, and second-order radiomics features. Least absolute shrinkage and selection operator (LASSO) and multivariate regression were used for feature selection. Two predictive models were constructed, one using 72 CP and 107 radiomics features, and the other using 72 CP and 1862 radiomics features. The models revealed moderately advantageous impact of increased dimensionality, while their predictive performance was in the range generally considered excellent, with respective AUCs of 0.86 and 0.90. A CP-only model (AUC=0.80) served as the benchmark for predictive performance without radiomics. The predictive models developed in this study using pretreatment MRI data, radiomics features, and clinicopathological parameters could potentially be used to routinely predict chemoradiotherapy responders, enabling clinicians to personalize treatment strategies for rectal carcinoma.

Total hip arthroplasty (THA) is one of the most successful orthopedic procedures and is highly effective in improving function and quality of life. However, after discharge patients commonly experience edema, which can lead to health consequences and lower quality of life. For these rea-sons, the aim of this study is to evaluate the effectiveness of a specific intermittent leg pneumatic compression on lower limb edema and physical outcomes in patients after total hip arthroplasty, compared to standard conservative treatment. A total of 47 patients were enrolled and randomly allocated into two groups: the pneumatic compression group (PG=24) and the control group (CG=23). We evaluated thigh and calf circumferences, knee and ankle range of motion, pain and walking autonomy. Our results showed a greater reduction in thigh and calf circumference for PG (p<0.001), while other outcomes were similar for the two groups (p>0.05). The combination of standard therapy with pneumatic leg compression was more effective in reducing lower limb edema, thigh, and calf circumferences compared to the use of standard treatment. Our results suggest that pressotherapy treatment is a valuable and efficient option for managing lower limb edema and preventing VTE after THA.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer. Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME). Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed. Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that affects the axial skeleton, causing intense pain, progressive joint destruction, and a gradual reduction in physical function. It has been recognized not only as affecting the axial skeleton but as a systemic disease. Since it also causes an increase in the rates of inflammatory bowel disease, psoriasis, acute anterior uveitis, and mental disorders affecting the quality of life. Furthermore, an association with neurological and cardiovascular events is documented. With the advent of biologics, treating AS dramatically changed due to its high efficacy and tolerable safety. AS can be treated with various biological treatments. Nevertheless, there are differences in traits, including rapidity of onset, long-term efficacy, safety profile, and influence on comorbidities. A better understanding of such traits enables clinicians to make the best decision for each patient, increasing persistence, extending medication survival, enhancing patient satisfaction, and reducing the disease effect of ankylosing spondylitis. In this article, we emphasize biologics' efficacy and safety profile in patients with ankylosing spondylitis. In addition, we discuss the impact of biologics on comorbidities and health-related quality of life.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Recent in-vitro studies have investigated the effects of CytoSorb hemoadsorption on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but to this day there is a lack of clinical studies showing whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We analyzed the data on administered fluid volumes and catecholamines to determine the potential benefit of CytoSorb hemoadsorption therapy on endothelial function in a clinical scenario. We performed a retrospective analysis of 124 septic shock patients who had undergone adjunctive treatment with CytoSorb hemadsorption therapy. We collected volume requirements, and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. We also calculated catecholamine requirements. With regard to the entire study cohort our findings revealed a significant reduction in fluid balance at 72 hours (T72) compared to both baseline (T0) and the 24-hour mark (T24). Fluid balances from T72 – T0 were significantly lower in hospital survivors compared to non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings showed that use of hemoadsorption therapy results in a reduced positive fluid balance paralleled by reductions in vasopressor needs suggesting a positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights that may greatly improve our understanding of the multiple effects of hemoadsorption treatment in septic shock patients.

AIM Non-alcoholic　fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of the pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. METHODS One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. RESULTS Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not change significantly, but M2-BPGi, an index of fibrosis, decreased significantly. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

The aim of this study is to improve the therapeutic effectiveness of the sorafenib loaded polymeric nanoparticles, surface modified by the pluronic F-127 for the treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly Lactic co-glycolic acid (PLGA) was used to encapsulate sorafenib by simple modified solvent evaporation technique. The nanoparticles were prepared with different concentration of sorafenib and pluronic F-127 keeping PLGA concentration constant. There were no incompatibilities among the sorafenib, PLGA and pluronic F-127 showing that the integrity of polymer, stabilizer and drug remain the same under different conditions. The size of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 200 ± 10.1 nm, respectively. The in-vitro release studies demonstrated that the PLGA controlled the release of sorafenib, avoiding the initial burst release. The effect of coated and plain nanoformulations was found out in squamous cell carcinoma cells. The results showed that surface modified nanoparticles treated hepatocellular and renal carcinoma in a better way as compared to plain PLGA nanoparticles and free dug by keeping the dose constant (20 mg/kg body weight).The targeted delivery of polymeric PLGA nanoparticles into squamous cell carcinoma was improved. The pharmacokinetic parameters have been improved significantly as compared to the reported nanoformulations.

The first half of the 20th century was noteworthy for the introduction of a unique group of drugs – antibiotics. It drastically changed concepts of infectious diseases treatment, which for centuries remained a scourge of the human population. With improvement of the antibiotic treatment efficacy, humanity has faced the problem of a dramatic increase in antibiotic resistance in bacteria. The COVID-19 pandemic has only exacerbated the problem and posed a new challenge to the medical community in finding solutions, both clinical and organizational and methodological, to fight antibiotic resistance widespread all over the globe. This publication covers some aspects of evolutionary processes in either pathogens or diseases, including ethical perspective.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

Systemic lupus erythematosus (SLE) is a chronic idiopathic autoimmune disease affecting various organs. Patients with SLE also present numerous neuropsychiatric manifestations. These neuro-psychiatric manifestations are referred to as neuropsychiatric systemic lupus erythematosus (NPSLE). Neuropsychiatric involvement in patients with SLE was first mentioned by Kaposi more than 100 years ago and is a generic term that refers to neurological and psychiatric symp-toms resulting directly from or as a complication of SLE. NPSLE affects both the CNS and PNS and can manifest as various symptoms, such as cognitive dysfunction, organic brain syndromes, delirium, seizures, headache, and psychosis. NPSLE was previously referred to as ‘lupus cerebri-tis’ or lupus sclerosis. However, these terms are no longer recommended because there is no de-finitive pathological cause for the neuropsychiatric manifestations of SLE.[2]

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically-based lipid disorder with the underestimated actual prevalence. In the recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. However, there is not enough data on their use in real-world clinical implementation. We studied the applicability of the most accessible biochemical algorithms to diagnose FD in clinical practice. We also investi-gated the prevalence of FD in one of the European regions of Russia based on a population sample. In this study there was detected a high prevalence of FD: 1 in 151. We demonstrated that the diagnostic algorithms of FD including a diagnostic apoB levels require correction, taking into account the characteristics of the distribution of apoB levels in the population. At the same time a triglycerides cutoff ≥1.5 mmol/L may be a useful tool in identifying subjects with FD. We also analyzed the presence and pathogenicity of APOE variants associated with the autosomal dominant FD in a large research sample.

Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis and ANCA serves to distinguish PAN from other type of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.

Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

This paper first introduces the main classification of brain diseases and the main causes of these diseases. It is followed by wavelet analysis, which is a mathematical function or wave-like pattern used to transform data, which can decompose the signal into different wavelet functions, each of which is related to a specific scale or frequency. Wavelet analysis has been applied in many fields such as image processing, data analysis and engineering. In addition, wavelet is also used in the analysis of biological signals. Wavelet analysis breaks down brain signals, such as EEG or fMRI data, into various frequency components at different scales. Wavelet analysis provides time-frequency localization. Pattern recognition can be enhanced by isolating salient features in the data. Wavelet denoising can effectively separate noise from underlying brain signals. Wavelet denoising usually adopts threshold method. Wavelet analysis can enhance pattern recognition by isolating salient features in the data. Researchers can train machine learning models based on these wavelet-derived features to recognize specific patterns associated with different neurological disorders. Wavelet analysis can track these changes by continuously evaluating the frequency content of the neuroimage data over time. Through continuous efforts, wavelet theory and technology have become valuable tools in the field of neuroscience and brain disease research.

The incidence of liver diseases is on the leading rise worldwide, but there is a lack of exact research models mimic liver diseases. Using the normothermic machine perfusion (NMP) platform to study diseased livers recovered from the liver transplantation (LT) recipients seems promising. Therefore, the aim of this study was to establish the first machine perfusion system called Life-XDL to cultivate diseased liver. Four diseased livers recovered from LT recipients within different diagnoses were collected. The diseased livers were connected to the Life-XDL machine perfusion system that circulated Life-XDL perfusate providing oxygen and nutrients. The pressure and flow of the device was recorded and blood gas analysis and laboratory test of perfusate and bile was examined to analyze the function of the diseased livers. Liver tissues after perfusion were collected for histological analysis. Experiments showed that Life-XDL kept the diseased livers at the physiological state with providing stable hemodynamics and suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory test results demonstrated restoration and maintenance of metabolism and less damage. Moreover, the bile production of case 1, 3 and 4 diseased livers represented its vivid functionality. The pathological characteristics were kept stable before and after NMP. Overall, we successfully establish the Life-XDL machine perfusion system which specially for diseased human whole liver and develop a new diseased human whole organ model in vitro through normothermic machine perfusion that recapitulate the main features of the human liver disease, which showing great promise as disease modeling platforms.

Post-extubation dysphagia (PED) can lead to serious health problems in critically ill patients. Contrasting its high incidence rate of 12.4% reported in a recent observational study, many ICUs lack routine bedside screening, likely due to limited awareness. This study aimed to establish baseline data on the current approaches and the status of perceived best practices in PED screening and treatment, as well as to assess awareness of PED. A nationwide cross-sectional, online survey was conducted in all fourteen adult ICUs in the Republic of Cyprus in June 2018, with a 100% response rate. Over 85% of ICUs lacked a standard screening protocol for PED. The most commonly reported assessment methods were cough reflex testing and the water swallow test. Treatment approaches included muscle strengthening exercises without swallowing and swallowing exercises. Only 28.6% of ICUs acknowledged PED as a common issue. The study identified significant gaps in awareness and knowledge regarding PED screening and treatment in Greek-Cypriot ICUs. Urgent implementation of comprehensive dysphagia education programs within the units is necessary, and interdisciplinary collaboration among nurses, intensivists, and speech and language therapists is crucial to improve the quality of care provided.

Abstract ObjectivesThe aim of this perspective is to report the use of synthetic data as a viable method in women’s health given the current challenges linked to obtaining life-course data within a short period of time and accessing electronic healthcare data. Methods We used a 3-point perspective method to report an overview of data science, common applications, and ethical implications. Results There are several ethical challenges linked to using real-world data, consequently, generating synthetic data provides an alternative method to conduct comprehensive research when used effectively. The use of clinical characteristics to develop synthetic data is a useful method to consider. Aligning this data as closely as possible to the clinical phenotype would enable researchers to provide data that is very similar to that of the real-world. Discussion Population diversity and disease characterisation is important to optimally use data science. There are several artificial intelligence techniques that can be used to develop synthetic data. ConclusionSynthetic data demonstrates promise and versatility when used efficiently aligned to clinical problems. Therefore, exploring this option as a viable method in women’s health, in particular for epidemiology may be useful.

Abstract Aim: The study aimed to evaluate the clinical laboratory features of moderate and severe COVID-19 patients among a cohort of the Egyptian population. The study also aimed to assess the accuracy—sensitivity, specificity, and area under the curve (AUC) of various detected parameters in predicting the severity of COVID-19 infection. Patients and methods: One hundred diagnosed COVID-19 patients and fifty healthy participants in total were involved in current study. COVID-19 patients were categorized based on how severe their symptoms into two groups. Estimates were made for serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, lactate dehydrogenase (LDH) and C-reactive protein (CRP) as well as white blood cells (WBCs) count, lymphocytes count, and hemoglobin content (Hb) content. Results: COVID-19 patients displayed increased serum levels of liver enzymes and CRP as well as WBCs count when compared to healthy individuals. On the other hand, Hb content, lymphocytes count, and albumin level fell in all COVID-19 patients. The severe group showed a statistically significant rise in liver enzymes, WBCs, and CRP levels, compared with moderate group. WBCs and lymphocytes counts were closely correlated with age, ALT, LDH, and CRP in all cases. WBCs and lymphocytes counts also had a negative correlation with albumin Level. Additionally, WBCs count, lymphocytes count, LDH activity and CRP level have higher AUC in severe than in moderate cases. WBCs count, LDH activity and CRP level have AUC above 0.80 in the severe group. Conclusion: The current investigation found a significant correlation between WBCs count, lymphocytes count, CRP level and liver injury in COVID-19 patients. WBCs count, lymphocytes count, LDH activity and CRP level were effective indicators for determining the severity of COVID-19.

Breast cancer is the foremost common in women, and its early diagnosis will help treat and increase patients' survival. This review article aims to studies on recent findings of standard imaging techniques and their characteristics for breast cancer diagnosis and recent nanoparticles (NPs) which are used for breast cancer detection. Herein, The search was performed in the literature through scientific citation websites, including Google Scholar, PubMed, Scopus, and Web of Science until May 2023. A comprehensive study on different imaging modalities and NPs for breast cancer diagnosis is reviewed, and their successes, challenges, and limitations are discussed.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no GE product has been approved, as opposed to 22 GT products that cost up to millions of dollars per dose. The FDA has recently added a guideline specific to gene editing that should be understood to enable faster development of GE products; at the same time, the FDA also needs to bring more clarification and make several amendments to this guideline to make it more rational.

Background: Early rehabilitation is an important strategy for the treatment of severe diseases. The study aimed to assess the efficacy of early rehabilitation of patients with mild-to-moderate COVID-19. Methods: The retrospective single-center study with propensity score matching. Results: 180 patients (54 (44 - 62.3) yo) divided into three equal groups: 1 - physical exercises; 2 - physical exercises and chest massage in an electrostatic field; 3 - no rehabilitation. The length of stay (LOS) in the hospital in group 1 was 14 (11-15) days, group 2 - 13 (11-15) days, group 3 - 15 (13-18) days, p=0.0026. Physical exercises for patients with CT-1 improved the quality of life, assessed by the EQ-5D questionnaire, by reducing the level of anxiety and depression. The Hazard Ratio (HR) for desaturation (<93%) was 2.34 (95% Confidence Interval (CI) 1.18-4.63) for group 2, p=0.001. The HR for C-reactive protein level above 50 mg/l in patients with CT-2 was 2.33 (95% CI 1.56-3.47), p=0.0001. Conclusions: Rehabilitation programs are safe for СOVID-19-patients; reduce hospital LOS; improve the quality of life. Continuous monitoring of a patient's condition during rehabilitation is essential. ClinicalTrials.gov ID: NCT0580836

Introduction: The need for therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remains unmet. Previous work has shown that a combination of three aromatic plants’ essential oil (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticosa Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care. Methods: 69 adult patients were included in a clinical, Proof-of-Concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention and control group) during three study periods (IG2020, n=13, IG2021/22, n=25 and CG2021/22, n=31). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture, was administered daily for 14 days, per os in the intervention group, while the control group received usual care. Results: The PoC study, found that the number and frequency of general symptoms, including general fatigue, weakness, fever and myalgia, decreased following CAPeo administration. The average presence (number) of symptoms decreased in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1) by Day 7 compared to Day 1, representing a significant decrease in cumulative presence in IC (-3.3 vs. -0.9, p<0.001; η2=0.20) on Day 7 and on Day 14 (-4.2 vs. -2.9, p=0.027; η2=0.08). Discussion/Conclusion: Our findings suggest that CAPeo, possesses potent antiviral activity, in addition tο the Influenza A and B and the human rhinovirus HRV14 strains against SARS-CoV-2. The early and effective impact in alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for mild COVID-19 patients

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

There is a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI), and other patient-reported outcomes (PROs), such as the visual analog scale (VAS) for symptoms and EULAR sicca score (ESS), are used to assess the disease activity of primary Sjögren’s syndrome (pSS). Recently, Clinical ESSDAI (ClinESSDAI) and Clinical Trials ESSDAI (ClinTrialsESSDAI) were developed for objective clinical disease activity indexes. However, the relationship of ClinESSDAI and ClinTrialsESSDAI with PROs as well as that between ESSPRI and other PROs and the objective parameters of glandular function in pSS have not been established. Herein, we investigated the correlation of ESSPRI and other PROs with the objective parameters of glandular function and the relationship of PROs with ClinESSDAI and ClinTrialsESSDAI in 66 patients with pSS. Correlations were calculated with Spearman’s correlation coefficient. ClinTrialsESSDAI was correlated with ESSPRI, dryness (ESSPRI-Dryness), fatigue, and pain domains of ESSPRI, VAS for oral dryness (oral-VAS), and patient’s global assessment. Although ESSPRI did not correlate with the objective parameters of glandular function, ESSPRI-Dryness, ESS, and oral- and ocular-VAS did. These results suggest that ESSPRI-Dryness, ESS, and VAS for symptoms, but not ESSPRI, reflect the glandular dysfunction and that ClinTrialsESSDAI correlates with PROs for dryness in pSS.

Objective To measure, exposure to PM2.5 particles in outdoor smoking areas and changes in breathing rates in patients with asthma or chronic obstructive pulmonary disease (COPD). Setting Sixty venues in Czechia, Ireland and Spain, in an open, non-randomised, clinical trial. Participants We studied 60 patients-30 asthma patients (Female 63.3%), with a mean age (+/-standard deviation [SD]) of 47.4 (19.0 SD), and 30 COPD patients (Female 51.6%), mean age 63.5 (10.1 SD), smokers, non-smokers or ex-smokers, recruited through medical clinics. Intervention Patients wore a PM2.5 particle monitor (AirSpeck), and a breath monitor (RESpeck) for 24 hours to determine changes in breathing rates (Br) at rest and during a visit to an outside smoking area. Spirometry and breath CO were measured before and the day after visiting an outdoor smoking area. Results PM2.5 levels in the 60 venues were highly variable, in 1 premises levels of PM2.5 were sustained for at least 15 minutes at ≥ 2,000 µg/m3, in 4 premises, ≥ 500 (range 1,933-539) µg/m3, in 8 premises, ≥ 200(range 480-203) µg/m3, in 9 premises, ≥ 100 (range 170-108) µg/m3, in 8 premises, ≥ 40 (range 80.5- 40.1) µg/m3, in 9 premises, ≥ 25 µg/m3, in 10 premises, ≥ 10 µg/m3, in 8 premises, and ≤10 µg/m3 in only 3 premises, with a single wall. The overall breathing rates/minute (Br)did not change significantly but in 28 patients mean Br increased from 21.47 (1.74 SD) to 22.8 (2.29 SD), change of -1.35 (-1.80-0.91 C.I), p value 0.00 and mean in 29 patients Br decreased from 21.95(2.43 SD) to 20.38(2.79 SD), 1.57(1.03-2.12 C.I), p value 0.00. Conclusion Exposure to high levels of PM2.5, and associated alteration of patients’ breathing rates occurred in outdoor smoking areas despite national comprehensive smokefree laws. These exposure levels support the abolition of such areas. (Words 295) ClinicalTrials.gov ID: NCT03074734 Ethics: Approval Number: Ref: 15-103

Human Epidermal Growth Factor Receptor 2(HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced Non-Small Cell Lung Cancer (NSCLC). In the 2023 NCCN guidelines for NSCLC, Antibody-Drug Conjugate(ADC) Trastuzumab emtansine (T-DM1) is recommended for the treatment of HER2-mutant Lung Cancer (LC). However, this medication is currently not approved in certain regions.So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients.In our study of a patient with HER2 exon 20ins Lung Adenocarcinoma who had previously failed multiple TKI treatments, we discovered that Sunvozertinib could stabilize the patient's condition, achieving a progression-free survival (PFS) of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20ins patients who have failed TKI therapy.

Coronavirus 19 disease (COVID-19) may be complicated by thrombotic events, particularly venous thromboembolism (VTE), which have been reported both in critically ill hospitalized patients and in individuals with mild symptoms. It is known that the chronic use of oral contraceptive pills (OCPs) is associated with higher risk of VTE. To date, there are only few reports concerning the association of OCPs and VTE/pulmonary embolism (PE) in COVID-19 patients. Given that during the convalescent phase of disease, a state of endothelial dysfunction, hypercoagulability and a low-grade inflammation may be persistent, the occurrence of thromboembolic events following acute COVID-19 infection may be not surprising. Herein, we report a case of high-risk PE detected in a post-COVID-19 young woman under hormonal contraception, which required thrombolytic treatment. A number of prothrombotic phenomena, such as overweight, hormonal contraceptive therapy, recent COVID-19 infection and prolonged immobilization, might have synergically contributed to the development of a sublethal thromboembolic event.

Obesity is invariably accompanied by autonomic dysfunction, although data in pediatric populations are conflicting. We conducted a systematic review and meta-analysis of 12 studies (totaling 1102 participants) comparing obese and normal-weight subjects (5-18 years of age), defined as body mass index &gt;95th or &lt;85th percentile, respectively. Using a random-effects model, we report the standardized mean differences (SMD) of sympathetic and vagal indices, calculated by heart rate variability. Autonomic dysfunction was present in the obese group, based on the average SMD in the standard deviation of sinus intervals (at -0.5340), and on the ratio of low (LF) to high (HF) frequency spectra (at 0.5735). There was no difference in sympathetic activity, but the heterogeneity among the relevant studies weakens this result. SMD in HF (at 0.5876), in the root mean square of successive differences between intervals (at -0.6333), and in the number of times successive intervals exceeded 50ms divided by the total number of intervals (at -0.5867) indicated lower vagal activity in the obesity group. Thus, autonomic dysfunction is present in obese children and adolescents, attributed to lower vagal activity. Further studies on autonomic function are needed in various pediatric cohorts, placing emphasis on sympathetic activity.

Background: Recommended CKD first-line diagnostics is based on GFR-determination by Creatinine. Cystatin C-use may provide better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination in first-line di-agnostic of 112 hospital patients aged >60 years (median=76 years). Patients were judged kid-ney-sane according to first-line diagnostic recommendations (N=61, eGFR (CKD-EPI) ≥60ml/min/m2, total urine protein <150mg/g creatinine, urinary red and white blood cells not increased) or classified at-risk for kidney insufficiency due to aortic valve dysfunction (N=51). Plausibility of eGFR-values was evaluated retrospectively by final case diagnoses. Results: eGFR (CAPA) was found linearly correlated to eGFR (CKD-EPI) (R2=0.5, slope=0.69, p<0.0001). In 93/112 (>80%) cases, eGFR (CAPA) yielded lower values (on average ≈20%). In 55/112 (49%) cases CKD-stage decreased. CKD-reclassification from kidney-sane to kid-ney-insufficient state (i.e. CKD1/2 to CKD3a/b or 4) or reclassification to more severe kidney in-sufficiency (i.e. CKD3a3b/4 or 3b4) was found in 41/112 (37%) cases. Worsening of CKD-classification (kidney-sanekidney-insufficient) based on eGFR (CAPA) was in 30% of cases plausible in the light of final case-diagnoses. Conclusion: In elderly patients (>60 years), renal function appears systematically overestimated by creatinine-based eGFR (CKD-EPI) heralding for this group employment of cystatin C-based eGFR (CAPA) as first-line diagnostic.

Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, as well as allograft rejection. Specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.

Patients with sAID are a population at high risk of severe COVID outcomes but evidence on the efficacy of SARS-CoV-2 vaccination in this group of patients is scarce. To investigate the efficacy of SARS-CoV-2 vaccination in patients with systemic autoinflammatory diseases (sAID) receiving interleukin-1 inhibition is important. Vaccination responses from 100 sAID patients most of whom were treated with IL-1inhibitors (N=96) and 100 healthy controls (HC) were ana-lyzed. After 2nd SARS-CoV-2 vaccination, sAID patients showed similar anti-SARS-CoV-2 anti-body responses (mean (SD): 6.7 (2.7)) compared to HC (5.7 (2.4)) as well as similar neutralizing antibodies (85.1 ±22.9% vs. 82.5 ±19.7%). Anti-SARS-CoV-2 antibody responses and neutralizing antibodies were similar in sAID patients after SARS-CoV-2 infection and double vaccination. Furthermore, while antibodies increased after 1st and 2nd vaccination in sAID patients they did not further increase after 3rd and 4th vaccination. No difference was found in antibody responses between anakinra and anti-IL-1 antibody treatments and also the additional use of colchicine or other drugs did not impair vaccination responses. Primary and booster SARS-CoV-2 vaccination lead to protective antibody responses in sAID patients, which are at the same level of vaccination responses in HC and in sAID patients after SARS-CoV-2 infection. Immunomodulatory treatments used in sAID do not seem to affect antibody responses to the SARS-CoV-2 vaccine.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Background: The aim of this study was to examine cervical multifidus muscle morphology and its impact on postural balance in patients with post-stroke. Methods: This is a pilot study. A convenience sample of 24 volunteers of 67 ±8.5 years (12 with hemiparesis due to post-stroke, 12 healthy) was recruited for this study. The outcomes measured were the thickness of the multifidus muscle using ultrasonography, Modified Functional Reach Test (MFRT), Timed Up and Go (TUG) test and Berg Balance scale (BBS). Results: No significant differences in the ultrasound values between stroke patients' paretic and non-paretic sides were found. Similarly, there were no significant differences between the non-paretic side of stroke patients and the non-paretic side of the control group, (all, p>0.05). Additionally, no significant correlations between the ultrasonographic variables of the multifidus muscles and the main outcome measures were identified. Conclusions: In conclusion, our study did not find significant differences in cervical multifidus muscle morphology between healthy individuals and post-stroke patients in relation to postural balance.

Intellectual disability with speech delay and behavioural abnormalities as well as hypotonia, seizures, feeding difficulties and cra-niofacial dysmorphism are the main symptoms associated with pathogenic variants of ZMYND11 gene. The range of clinical mani-festations of ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present 2 previ-ously unreported paediatric patients with neurodevelopmental features diagnosed with missense variants in ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinemic hypoglycaemia (HH), a symptom that was not de-scribed before in published works. Although the reason for the occurrence of HH in our proband is not clear, it is likely that it broadens the spectrum of symptoms characteristic of ZMYND11 syndrome. Thus, this paper contributes to extending the range of possible manifestations of ZMYND disease and further supports its association with neurodevelopmental challenges.

A new approach to the treatment of wound lesions, which are complicated by the presence of polyresistant microflora and a possible immunodeficiency background has been proposed. It involves treating the wound surface with high-intensity pulsed optical radiation of a continuous spectrum, continuously covering the entire UV range (from 200 to 400 nm), visible and near infrared region of the spectrum. A pulsed xenon lamp is used as a radiation source. A description of the design and technical characteristics of the developed device for high-intensity optical irradiation "Zarnitsa-A", which implements the proposed medical technology for wound therapy, is represented. The results of preclinical studies of the apparatus in vitro and in vivo are represented hereinafter. The article shows that the apparatus exposure has pronounced bactericidal and wound-healing properties. The apparatus action reliably provides higher rates of wound healing compared to the use of only a typical antibacterial and wound healing agent – “Levomekol” ointment.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Insufficient oral ridge tissue presents a challenge in the treatment of dental implants. One method to enhance alveolar crest dimensions is guided bone regeneration (GBR); however, existing membranes have certain limitations. To address this issue, we aimed to compare the effectiveness of a resorbable bilayer membrane composed of poly(l-lactic acid) and poly(-caprolactone) （PLACL）with that of a collagen membrane（COL） in a rat GBR model. The rat calvaria was used as an experimental model by placing a plastic cylinder. Forty male Fisher rats underwent surgery, and micro-computed tomography and histomorphometric analyses were performed to assess bone regeneration. The results showed that bone regeneration was similar across all the groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, occasional partial degradation, and intermittent air bubble formation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. In conclusion, this study shows that the PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane may address the limitations of the current membranes. Further studies and clinical trials are warranted to validate the efficacy and safety of this drug in humans.

Type II pneumocytes are the target of SARS-CoV-2 which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. Here we evaluated whether the treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2–), lipid peroxidation (LPO), and thiols groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), -S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There was a significant increase in LPO and carbonyls (p≤0.03) and a decrease in TAC, NO2–, thiols, GSH, (p&lt;0.001) in COVID-19 patients. The activities of the ecSOD, TrxR, GPx, GST, GR and peroxidases were decreased (p≤ 0.04). The treatment with MT favored the activity of the antioxidant enzymes which contributed to increase TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis functioning as a glycolytic agent and inhibited the Warburg effect. Thus, MT restores the redox homeostasis which is altered in COVID-19 patients and can be used as adjuvant therapy in the SARS-CoV-2 infection.

Introduction and Objective: Caudal block has been used in children for many years and is considered the gold standard for multimodal analgesia in the pediatric age group. Caudal block belongs to the category of central neuraxial blocks, which can provide both visceral and somatic analgesia. With the introduction of ultrasound into the clinical practice of anaesthesia, the caudal block is now performed under USG guidance. In our study, we aimed to compare the efficacy of a single caudal block in postoperative acute pain management, the need for additional analgesics, the incidence of side effects, the timing of initial analgesic administration, and the need for rescue analgesic administration (paracetamol 10 mg/kg) in circumcision surgery. Materials and Methods: 120 patients undergoing circumcision surgery were divided into 3 groups. The caudal block was performed in all cases under USG guidance. Only the caudal block was applied for cases in the Caudal group (Group C). The Caudal + paracetamol group (Group CP) received paracetamol 10 mg/kg intravenously (i.v.) and the caudal block. Patients in the Caudal + meperidine group (Group CM) received 1 mg/kg meperidine intravenously. The caudal block was performed in each case with a 0.5 ml/kg volume of 0.125% bupivacaine. Results: As a result of our study, it was found that the least postoperative pain occurred in 12.50% of the CM group (p=0.011). Significant results were obtained when weight and age variables were analyzed according to the groups (p-values p=0.011 and p=0.003, respectively). Significant differences were found between the input pulse values, 5-minute pulse values, 15-minute pulse values, and input SpO2 values (p values p < 0.001, p < 0.001, p=0.011, p=0.037, respectively). Only Wong-Baker pain scores at the 24th hour differed significantly from the periods measured after the groups (p < 0.001). There was no significant difference between the FLACC and Wong-Baker pain scores in the other periods. There was no difference between the groups regarding the time when postoperative analgesics were administered and the total amount of analgesics administered (rescue analgesic 10 mg/kg oral paracetamol) (p=0.408, p=0.238). Conclusion: Caudal block can be safely applied during circumcision. Ultrasound guidance increases the chances of success and reduces the complication rate. Caudal block can be safely used in pediatric surgery since it does not cause serious complications, has low postoperative pain scores, and reduces the number of postoperative analgesics.

Static and functional occlusal relationships are the well-defined objectives of orthodontic therapy. To accomplish it, the jaws must be positioned in centric relation (CR)/ Central occlusion (CO) and appropriately proportioned in three space planes. Orthodontists have well-established techniques when analyzing the skeletal connection between the maxilla and mandible in both sagittal and vertical planes. Although there exist multiple analyses for the skeletal transverse dimension (STD), their inclusion in conventional orthodontic diagnosis is not widely acknowledged. Transverse tooth compensations have been visually represented in prosthodontic literature using a crosshatch arch that passes through the buccal and palatal cusps of maxillary molars, known as the Wilson curve. An inflated Wilson curve has long been seen as a prosthetic maxim, increasing the possibility of working and non-working side interferences. Research has indicated a connection between higher masticatory muscle activity and posterior occlusal contacts or interferences. When skeletal transverse issues are concealed by dental expansion, there is an elevated susceptibility to gingival recession in orthodontic patients who have a small Maxilla or constricted upper jaw. The temporomandibular joints, muscles, periodontal tissue, and airway might all suffer in a susceptible patient with a transverse insufficiency brought on by a narrow maxilla. As for orthodontists, the objective is to create skeletal connections and functional occlusion that are as near ideal as feasible. This will reduce the likelihood of occlusion-related inconsistencies exacerbating the negative consequences on the dentition, periodontium, or joints. An accurate skeletal and dental diagnostic in all three space planes is required. Our goal is to explain all approaches to enable readers to use a transverse skeletal diagnostic in their practice regardless of the technological level at their disposal. The initial step is to ascertain the kind and presence of deficiencies in the maxilla. Since fewer soft tissue alterations are caused by maxilla hypoplasia in the transverse direction, skeletal transverse dimension (STD) assessment is a more significant challenge than vertical or sagittal discrepancy assessment. Model analysis, clinical assessments, radiographic measurements, and occlusograms have all proven successful in producing accurate assessments. Most of the time, surgically assisted maxillary expansion (SARME) is reported to have higher stability than orthopedic maxillary expansion (OME). We examine and discourse on possible research opportunities using the Collaborative Cross (CC) mouse model as a substitute research model.

Background: Cardiovascular disease (CVD) increases the risk of mortality and morbidity in patients with rheumatoid arthritis (RA). Patients with RA have a 50-60% increased risk for CVD compared with the general population. Cardiovascular risk is commonly meas-ured using the Systemic Coronary Risk Estimation 2 calculator modified for patients with RA. Traditional modifiable risk factors for CVD include arterial hypertension, dyslipidemia, insulin resistance, diabetes, cigarette smoking, and low physical activity. In this study, we analyzed the effects of smoking and the risk of CVD in patients with RA. Methods: This was a prospective, clinical, cohort study with an eight-year follow-up pe-riod. A total of 201 patients, 124 with RA (study group) and 77 with osteoarthritis (OA) (control group), were included in this study. However, only 137 patients (82 with RA and 55 with OA) completed the study. Fifty-eight patients (41 with RA and 17 with OA) died during the study period. We compared the prevalence of smoking and its association with the risk for CVD and RA. Results: The prevalence of smoking in the RA group was higher than that in the OA group (p<0.0001). Trends in the prevalence of smoking in both groups did not change signifi-cantly during the follow-up period. In the RA group, smoking was associated with the in-cidence of CVD in current smokers (p=0.028) and in patients with a history of smoking (p=0.016). These results suggest that smokers have an increased risk for RA. The trend of continued smoking in patients with RA may be attributed to attempts to reduce stress caused by RA symptoms. Conclusions: Previous studies have shown that current and former smokers with RA have more severe symptoms, more joint damage, and poorer response to therapy than those who have never smoked. However, the reason underlying the trend of continued cigarette smoking in patients with RA remains unclear. Further studies are needed to clarify the trend of continued smoking in patients with RA.

Objective: To describe the methodology used and the results found in the implementation of Lean in Emergencies in the Emergency sector of the Hospital de Clínicas of the Federal University of Uberlândia (HC-UFU), verifying the difficulties and particularities that involved the process, as well as the result obtained. Material and methods: For the comparison between the periods before (T1), contemporary (T2) and after (T3) the implementation of Lean, hospital data were used , and the indicators corresponding to 10 variables were analyzed: Male Hospitalization and Female Hospitalization; High Male and High Female; Male Transfer and Female Transfer, Male Death <24h and Female Death <24h; Male Death >24h and Female Death >24h and general occupancy rate. All raw data related to the 36 months of evaluation were provided by the HC-UFU Statistics sector in spreadsheets without identifying patients. The indicators were compared to each other in the three analyzed periods, with the study directed as follows: Previous stage - Pre -intervention (T1): considered between the months of April 2017 to March 2018, completing 12 months before the implementation of Lean; Intra-intervention stage - contemporary (T2): considered between the months of April 2018 to March 2019, in a total of 12 months which was the implementation period; Post-Intervention Stage (T3): later: considered between the months of April 2019 to March 2020, completing 12 months after the implementation of Lean. The Lean in Emergencies scores (NEDOCS and LOS) were only recorded during the period that the implementation team was able to record and were used only to demonstrate trend over time. Comparison of the indicators with those found in other hospital units that also implemented Lean was carried out based on bibliographical research. Results and Discussion: The analysis of the behavior of the indicators did not demonstrate effectiveness related to the implementation of the system in the emergency sector. The failure to obtain better indicators can be attributed to discontinuity in monitoring the project, the lack of involvement of the clinical staff and alignment with the needs of the staff training academy, the difficulty of understanding the project by local and regional public entities. geographical location where the hospital is located, and by users of the health system who were not properly informed about the development of the project. These aspects should be considered in future management projects that may be implemented in the hospital. Despite the result of the implementation of Lean in the emergency sector not having reached the expected goals, the attempt showed windows of opportunity for future action on points that can improve the hospital management process and that should be tested in the next experiences. Conclusion: The methodology followed for the implementation of Lean in Emergencies in the emergency sector of the hospital did not produce improvement in hospital indicators.

Background: The gold standard for the diagnosis of sleep bruxism (SB) and obstructive sleep apnea (OSA) is Polysmnography (PSG). At the end of the apnea episodes there is frequently a final hy-permotor muscle activity that could act as a confusion factor in the diagnosis of SB with the elec-tromyography portable devices. The aim of this study was to compare the concordance on the number of episodes of SB in a population with OSA, between the diagnosis obtained by PSG, an-alyzed manually by a neurophysiologist and that obtained manually and automatically by a portable electromyography (EMG) and electrocardiography (EKG) device. Methods: Twenty-three subjects underwent one night of polysomnographic study with simulta-neous recording with the EMG-EKG device. The variables referring to the number of episodes and the SB index measured with both tools and analyzed in the manual and automatic modes were compared. Masticatory muscle activity was scored according to published criteria. The sample was segmented by severity of OSA according to AASM criteria. ANOVA, correlations, and the Bland–Altman plot were used to quantify the agreement between both methods. The concordance was calculated through the ICC. Results: The total events of SB per night in the PSG study were on average (8.17), lower than the one obtained with EMG-EKG manual analysis (14.13) and automatic (29.26). Both the SB PSG and Manual EMG-EKG episodes decrease from non-OSA (PSG = 16 ± 13,55, EMG-EKG = 16,83 ±11,58) to severe OSA (PSG = 3,14 ± 4,26, EMG-EKG = 9,86 ± 8,09). However, in the case of automatic EMG-EKG mode: the number of SB episodes in severe OSA doubled (41,23 ± 12,50) with respect to non OSA (24,50 ± 12,19). On average: the EMG-EKG device Automatic analysis measures 21.08 units more than PSG. The results with the manual EMG-EKG analysis improved. Conclusion: There is no concordance between the results obtained in the PSG neurophysiologic analysis and those obtained by means of the EMG-EKG device automatic and manual analysis for the diagnosis of SB in a population mostly with OSA. The OSA could act as a confusion factor in the diagnosis of SB with the electromyography portable devices, but further study is needed.

Abstract: Background: Patients with diabetes are particularly susceptible to COVID-19 infection, which can result in severe respiratory illness. Methods: This study conducted a comparative as-sessment of the impact of antiviral therapy using molnupiravir and favipiravir in COVID-19 pa-tients with underlying diabetes. A cohort of one hundred individuals infected with SARS-CoV-2, diagnosed with diabetes, and consecutively admitted, was included in the present study. These patients were treated with antivirals according to local guidelines: Group F (51 cases) was treated with favipiravir – 10 days and Group M (49 cases) was treated with molnupiravir – 5 days. Re-sults: In Group F, the average hospitalization was higher than in Group M (11.29±2.27 vs. 7.14±3.16, p

(1) Background: This study aimed to evaluate whether the implementation of a modified blood sampling protocol, which focused on need-based laboratory testing and minimized venous sampling by replacing it with point-of-care testing (POCT) via capillary puncture, successfully reduced iatrogenic blood loss, incidence of anemia, and frequency of blood transfusion in extremely low birth weight infants (ELBWIs) without negatively affecting neonatal outcomes. (2) Methods: A retrospective analysis was conducted on 313 ELBWIs of gestational age (GA) between 23 and 28 weeks, born between 2013 and 2019. The infants were divided into two groups: before (period I) and after (period II) the implementation of the modified blood sampling protocol in January 2016. Propensity score matching was conducted to minimize selection bias. Clinical data, including the frequency and amount of blood sampling, frequency and volume of blood transfusion, and clinical characteristics, such as gestational age, birth weight, and neonatal outcome data, were collected and compared between the two groups. (3) Results: No significant differences in the GA or birth weight between the two periods were observed. The total sampling volume during a month after birth (16.7 ± 4.1 mL vs. 15.6 ± 4.4 mL, P=0.03) and total sampling volume during hospital days (51.4 ± 29.7 mL vs. 44.3 ± 27.5 mL, P=0.04) in period II were significantly lower than that in period I. There were no differences in the mortality or morbidity between the two periods. Although the transfusion frequency and amount did not have significant differences between the periods, we observed a positive correlation between the transfusion frequency and sampling volume (coefficient: 0.09, 95% CI: 0.08–0.11). (4) Conclusions: The modified blood sampling protocol effectively reduced the iatrogenic blood loss without negatively affecting the neonatal outcomes.

Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The electromechanical, inflammatory, and autonomic changes due to amyloid deposition result in arrhythmias. Atrial fibrillation is by far the most common arrhythmia. Rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted irrespective of CHA2DS2Vasc score in patients with favorable bleeding profile; data on left appendage closure devices is still insufficient. Ventricular arrhythmias are also not uncommon and the role of implantable cardioverter-defibrillator in cardiac amyloidosis is controversial. There is no evidence of improvement in outcomes when used for primary prevention in these patients. Bradyarrhythmia is most commonly associated with sudden cardiac death in cardiac amyloidosis. Pacemaker implantation can help provide symptomatic relief but does not confer mortality benefit.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Background: Mood disorders, especially depression, and emotional difficulties such as anxiety are very common problems among patients with spinal cord injury (SCI). The loss of physical training may deteriorate their mental state, which in turn has a significant impact on the improvement of functioning. The aim of the present study was to examine the influence of innovative rehabilitation approaches involving robotic assisted gait therapy (RAGT) on mood and anxiety symptoms in pa-tients with SCI. Methods: To this single-centre, single-blinded, single-arm, prospective study, 110 participants with subacute SCI were enrolled; patients were divided into experimental (robotic assisted gait therapy -RAGT) and control (conventional gait therapy with dynamic parapodium - DPT) groups. They received five training sessions per week over 7- weeks. The severity of de-pression was assessed by Depression Assessment Questionnaire (KPD) and anxiety symptoms by State - Trait Anxiety Inventory (STAI X-1) on the beginning and end of therapy. Results: SCI patients experienced significantly lower levels of anxiety and depression-related symptoms after completing the seven-week rehabilitation program (KPD: Z=6.35; p<0.001; r=0.43; STAI X-1: Z=-6.20; p<0.001; r=0.42) in both group of patients. In the RAGT group, post-rehabilitation measurements also indicated an improvement in psychological functioning, i.e., a decrease in depression and anxiety, and an increase in self-regulation. Significant results were noted for each variable (STAI X-1: Z = -4.93; KPD: Z = -5.26; SR: Z = -3.21). In the control group, there was also a decrease in the effect on the depression, anxiety-state and an increase in self-regulation ability (STAI X-1: Z=-4.01; KPD: Z=-3.65; SR: Z=-2.83). Rehabilitation modality did not appear to have a statistically significant relationship with the magnitude of improvement in KPD (including SR) and STAI scores. However, there were some significant differences when comparing the groups by extent and depth of injury and type of paralysis. The study also did not find a significant rela-tionship between improvements in physical aspects and changes in psychological factors. Conclusion: Subjects in RAGD and DPT groups experienced a decrease in anxiety and depres-sion after a 7-week rehabilitation program. However, the rehabilitation modality (DPT vs. RAGT) did not differentiate patients with SCI in terms of the magnitude of this change. Our results may suggest that individuals with severe neurological condition and complete spinal cord injury (AIS A) may experience more benefit in terms of change in psychological parameters after rehabilitation with RAGT.

Background: Resistance to antimalarial drugs often used in emerging countries, including combination therapies, has forced scientists to search for and develop drugs with novel mechanisms of action, especially resistance to Plasmodium falciparum and Plasmodium vivax, which are highly prevalent in Southeast Asia, Africa, and South America. Objective: evaluate whether there is a relationship between urinalysis and resistance to in-hospital treatment of malaria in Angola. Methodology: This was a cross-sectional, prospective study with a quantitative approach. Results: of the 214 patients, the resistance rate was 24.1%, men (53.6%), between 21 and 40 years old (72.7%), employees (46.4%), from peri-urban regions (77.7%), treated with artemether (90.9), with high parasitemia (57.7%) and after 5 days of treatment, remained hospitalized (61.4%). Was a significant relationship between resistance in unemployed individuals [OR: 0.03 (95% CI: 0.01-0.29), p =0.003] and high levels of parasitemia [OR: 1.09 (95% CI: 1.09-3.95), p=0.040], remained hospitalized for more than 5 days [OR: 5.28 (95% CI: 0.65-43.1), p=0.121] and death [OR: 2.59 (95% CI: 0.32-20.9), p=0.371] when compared with other subgroups. Was a significant relationship between resistance to clear urine [OR: 5.55 (95% CI: 0.72-42.7), p =0.016], few urinary crystals [OR: 11.3 (95% CI: 5.07-25.3), p <0.001] and who presented some microorganisms that were not bacteria or fungi [OR: 3.02 (95% CI: 1 .32-6.90), p=0.009]. Conclusion: urine results, especially the appearance of cloudy urine, the presence of few crystals, and the presence of other microorganisms that are not bacteria or fungi, may be clear signs of resistance to hospital treatment with injectable antimalarials.

Functional neurological disorders (FND) are relatively frequent disabling conditions. Given their complexity, multidisciplinary rehabilitation is envisaged. Whole-body cryostimulation (WBC) represents a promising adjuvant treatment, mainly because of its anti-inflammatory and exercise-mimicking effects. Here, we propose a novel use of WBC in a wheelchair-ridden 61-year-old woman diagnosed with FND and other comorbidities, who, after several therapeutic and rehabilitation failures, underwent a multidisciplinary rehabilitation program including WBC. The 4-week program included physiotherapy, nutritional intervention, psychological support, and WBC. Questionnaires to assess disease impact, pain level, perceived fatigue and sleep quality were administered. At discharge, improvements in body composition, haematological biomarkers, physical performance, and questionnaire scores were observed. The patient was able to walk with a walker for medium distances, even outdoors. We observed unprecedented improvements, particularly in functional parameters and questionnaire scores. Although we cannot ascertain to which extent WBC per se contributed to the improvements measured, subjective reporting and our clinical observation were that WBC, the only intervention not previously experienced by the patient, acted as a booster for the rehabilitation interventions. Further research will be necessary to rule out any possible placebo effect and to assess the effects of WBC on FND.

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.

Background &amp; Aim: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. Methods: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between Dec 1st, 2017, and May 1st, 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid, surgical, and hospitalization-free treatment. Results: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p=0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p=0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p=0.593). Conclusion: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

Background: Post-Covid condition can reduce activity and quality of life, resulting in a significant socioeconomic and health burden. Understanding its impact on patients' health is important for the development of personalized rehabilitation interventions. An independent association between obesity and post-covid condition was found because of complications and comorbidities. Methods: Sixteen patients with obesity and post-COVID symptoms (i.e., dyspnea, pain, poor sleep quality, muscle fatigue) admitted to the Istituto Auxologico Italiano, Piancavallo (VB), Italy, were recruited for a four-week rehabilitation program including conventional exercise therapy, nutritional intervention, psychological support and whole-body cryostimulation (WBC). Results: All participants attended all sessions of the program. Anthropometric data showed statistically significant changes in weight, waist circumference and body mass index. Biochemical analyses showed significant reductions in lipid and inflammatory profiles. There was a significant improvement in physical performance, reduction in pain and improvement in psychological well-being. Conclusion: A multidisciplinary rehabilitation protocol including WBC designed for patients with obesity and post-covid condition is safe and feasible. The overall improvements demonstrate that multidisciplinary rehabilitation was effective on post COVID patients and suggest that the use of WBC is safe and could play a role as a booster in rehabilitation programs.

Most recent studies of doxycycline PEP have assessed doxycycline's effect on antimicrobial resistance by measuring the proportion of colonies of the target species with AMR as the outcome measure. In this study, we show that this method is insufficiently sensitive to detect shifts in MIC distribution.

Tunneled central venous catheters (CVC) are mainly considered as rescue vascular access option in dialysis but still used in about one quarter of prevalent patients worldwide as being associated with poor performances and higher risks. Study design. In this retrospective single-center study, we aimed to report on clinical performances achieved with high-flow tunneled CVC (DualCath, DCath) and compared it with arteriovenous accesses (AVAs; AV fistula, AV graft, Thomas Shunt) in a hospital-based dialysis unit. Methods. Sixty-eight stage 5 chronic kidney disease dialysis dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-up of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V and total Kt, ultrafiltration volume and percent reduction of ß2-M were measured monthly as part of quality control in our unit. Results. At baseline, effective blood flow with DCath was close to 400 ml/min, similar to AVAs. Recirculation with DCath (7%, 6-13%) was higher than AVAs. Diffusive dialysis dose delivered with DCath (spKt and eKt/V) and convective dialysis dose achieved with DCath were slightly lower than AVAs, but still much higher than recommended by guidelines. Percent reduction of ß2-M achieved with DCath was also 4 to 10% lower than AVAs. On longitudinal follow-up, main clinical performance indicators of DCath (total Kt and total ultrafiltration volume, L/session) were maintained very stable over time and close to those achieved with AVAs. Conclusions. As shown in this study, high-flow DualCath tunneled two single lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performances. These results rely from the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Background: Here, we investigated the inflammaging and physical performance in older adults before and after the COVID-19 pandemic. Methods: Women(n=18) and men(n=7) older were evaluated before the COVID-19 pandemic(PRE), 12 months after the lockdown(POST), and 10 months after resuming exercise training(POS-TR). Physical tests [gait speed(GS) and timed-up-and-go(TUG)]; muscle strength (handgrip-HG), and serum cytokine levels were assessed. Results: The older women showed higher GS and TUG at POST than PRE and POST-TR, besides lower HG at POST-TR than PRE, whereas older men exhibited lower HG at POST and POST-TR than PRE. Both groups presented (1)lower IL-10 and IL-12p70 values in contrast to higher IL-6/IL-10 and IL-8/IL-10 ratios at POST than PRE; (2)higher IL-10 values and lower IL-8/IL-10 ratio at POST-TR than POST; (3)higher IL-12p70/IL-10 ratio at POST-TR than PRE and POST. Particularly older women showed: (4)lower IL-6 values at POST and POST-TR than PRE; (5)lower IL-8 and IL-10 values at POST-TR than POST; (6)and higher TNF-α/IL-10 and IFN-γ/IL-10 ratios at POST than PRE and POST-TR. Significant correlations between the variables were found in both groups. Conclusion: During the COVID-19 pandemic, detraining and resumption of exercise training promoted distinct alterations in physical capacity and inflammaging among older women and older men population.

Intestinal failure (IF) is characterized by a critical reduction of functional gut mass below the minimum needed for optimal growth in children. It requires parenteral nutrition (PN) and home-PN (HPN) which is challenging in terms of meeting nutritional needs according to age, growth velocity, clinical situation, and rapid changes in fluid and electrolyte requirements. Due to these complex requirements, age-adapted multi-chamber bags (MCBs) are important additions to the nutrition armamentarium. The launch of composite fish oil (FO)-containing intravenous lipid emulsions (ILEs) heralded the development of MCBs containing these ILEs in combination with a crystalline amino acids solution (CAAS) adapted for pediatric use. The safety and efficacy of lipid and amino acid components in this context have been widely documented in numerous published studies. This manuscript includes a review of the articles published in PubMed, Embase, and Google Scholar until June 2022, exploring studies in the age groups from term infants to children and adolescents. Preterm infants with their highly specific demands are not included. It aims to offer an overview of the clinical experience regarding the use of a composite FO-based ILE and a specific CAAS developed

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting patient’s quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and need for blood transfussions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5-1mg) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. Epistaxis severity score (ESS) and hemoglobin levels were parameters used to evaluate tacrolimus impact. The occurrence of side effects was also recorded. Results: Tacrolimus was well tolerated in most of the patients, except in 2 which abandoned the treatment. The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced comparing the ESS before and after treatment. Hemoglobin levels were significantly increased overcoming the anemia in the course of the treatment. Conclusion: Tacrolimus at low doses should be considered as a promising treatment for bleeding derived of epistaxis and GI in HHT.

Polycystic ovary syndrome (PCOS) usually comes along with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is frequently not investigated. We evaluated 99 PCOS and 41 non-PCOS women. Clinical biomarkers of glucose-, liver-, and endothelial-related metabolic alterations were measured; participants were categorized into four groups according with obesity (OB) and hyperandrogenemia (HA) statuses: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were highly frequent in PCOS women (70%). BMI correlated with all biomarkers, while free testosterone (FT) only with glucose- and hepatic-related indicators. Despite insulin sensitivity and liver enzymes were associated with FT, women with obesity exhibited lower M [coeff = 8.56 – 0.080(FT) –3.71(Ob); p &lt;0.001)] and higher aspartate aminotransferase (coeff = 26.27 + 0.532(FT) + 8.08(Ob); p = 0.015)] than lean at the same level of FT. Women with obesity exhibited greater risk of metabolic disorders than lean, independently of hyperandrogenemia. Clinicians are compelled to search for metabolic alterations in PCOS women; obesity must be handled in all cases, but hyperandrogenemia needs to be managed also in those with glucose- or liver-related disturbances.

Based on previous studies of our group in which we demonstrated that dalbavancin loaded in bone cement had good elution capacity for the treatment of biofilm-related periprosthetic infections, we now assess the anti-biofilm activity of dalbavancin and compare it with that of vancomycin up to a 3-month period. We performed an in vitro model based on calculation of percentage reduction of log cfu/ml counts of sonicated steel discs contaminated with Staphylococci and further exposed to bone cement discs loaded with 2.5% or 5% vancomycin and dalbavancin at each study period (24 hours, 48 hours, 1 week, 2 weeks, 6 weeks, 3 months). In addition, we tested the anti-biofilm activity of eluted vancomycin and dalbavancin at each study period based on a 96-well plate model assessing percentage reduction of metabolic activity. Overall, dalbavancin showed a significant concentration decrease from 2 weeks of incubation and maintain its anti-biofilm activity up to 3 months, whereas, despite vancomycin showed a significant decrease at 1w and then it gradually increased, its anti-biofilm activity was significantly lower. Dalbavancin percentage reduction cfu/ml counts were higher than those of vancomycin, both at 2.5% and 5% concentrations. Reduction of log cfu/ml counts were higher for S. epidermidis than for S. aureus, being more notable for 5% dalbavancin at month 3. In addition, percentage reduction of metabolic activity also decreased at 3 months in 5% dalbavancin and 5% vancomycin, being more notable in the last.

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. Neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. This systematic review provides an overview on the value of NfL in early detection of neuropathy, central nervous system involvement, monitoring of neuropathy progression, and treatment effect in systemic amyloidosis. A literature search in PubMed, Embase and Web of Science was performed on 14-02-2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene variant (TTRv) carriers. Only studies containing original data were included. Included were twelve full-text articles and six abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has potential to be used for early detection of neuropathy, monitoring treatment effect, and monitoring disease progression in patients with systemic amyloidosis.

Background. There is limited evidence on the relationship between chronic kidney disease (CKD) and frailty in older people in Vietnam. This study aimed to examine the prevalence of frailty and its impact on mortality in older patients with end-stage renal disease. Method. This is a prospective, observational study at two large Dialysis Centres in Vietnam from November 2020 to June 2021. Consecutive older patients diagnosed with end-stage renal disease and on dialysis were recruited. Participants’ frailty status was defined by the Clinical Frailty Scale (CFS). The study outcome was all-cause mortality at 6th month. Results. A total of 175 participants were recruited (mean age 72.4 years, 58.9% female). Using the cut-point of CFS ≥4, 87.4% of the participants were frail. Mortality at 6th month was 14.9%, 31.9% in participants with CFS ≥7, 12.8% in participants with CFS=6, 7.5% in participants with CFS from 4 to 5, and 4.5% in participants with CFS ≤3 (p=0.001). Cox regression analysis showed that compared to the non-frail participants, the probability of death over 6 months was nearly 2-fold higher in the mildly frail, 3-fold higher in the moderately frail, and 9-fold higher in the severely frail participants. Conclusion. This study demonstrated a very high prevalence of frailty in older patients with end-stage renal disease and dialysis and the significant impact of frailty severity on mortality. Healthcare providers should consider incorporating frailty screening into routine care for older patients with end-stage renal disease and dialysis.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Identifying reliable biomarkers for early detection, prognostics and therapy is a criti-cal imperative for improving the stroke patient treatment. Metabolomics has been shown as a promising tool for biomarker discovery since many of the post-ischemic metabolites can found in the plasma or serum of the patient. In this research, we have performed comparative targeted metabolomic analysis of stroke thrombi, patient serums and healthy control serums in order to determine the alteration in the patients’ metabolome. The most statistically altered metabolites characterized in patient compared to control serums were glutamate and serotonin, followed by several lipid metabolites (phospholipids and triacylglycerols) and glucose. In stroke thrombi compared to patient’s serums, the most significantly altered metabolites were classified as li-pids, with choline-containing phospholipids and sphingomyelins having the highest discrimi-natory score. The results of this study could help in understanding the roles of different meta-bolic changes occurring during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers of the ischemic stroke.

Infective endocarditis (IE) is a rare but severe disease with high mortality and healthcare burden. Cardiac surgery plays a major role in the contemporary clinical management of IE patients. During cardiac surgery, cardiopulmonary bypass significantly contributes to an increased risk for organ dysfunction and mortality by inducing an acute inflammatory response, vascular endothelial cell injury, impairment of the coagulation cascade, and ischemia‒reperfusion injury. During the past decade, the use of extracorporeal hemoadsorption therapy with the CytoSorb® hemoadsorber has been proposed as an adjuvant therapy to mediate inflammatory responses in IE patients receiving cardiac surgery with cardiopulmonary bypass. However, there is currently a lack of systemic evaluation of the effect of CytoSorb® hemoadsorption on clinical outcomes such as hemodynamics, organ dysfunction, and mortality in patients with IE. Therefore, in this review, we exclusively discuss contemporary findings concerning the rationale, clinical evidence and future perspectives for CytoSorb® hemoadsorption therapy in IE patients.

Circulating miRNA-451a has recently emerged as an important biomolecule with potential clinical values as a diagnostic marker for several diseases. However, to be used as such, it is critical to accurately assay miRNA-451a in the clinic. Yet, pre-analytical factors that can affect such an error-free clinical assay of miRNA-451a have not been explored. This study aimed at investigating several of these pre-analytical factors that may affect the accurate quantification of miRNA-451a in human blood samples. We initially evaluated miRNA-451a levels in red blood cells (RBCs), white blood cells (WBCs), platelets, and plasma by droplet digital PCR (ddPCR). Next, we quantified miRNA-451a levels in whole blood or plasma stored at different temperatures for different time periods by ddPCR and used hemolyzed plasma samples to study the effects of hemolysis on plasma miRNA-451a concentration. We found that WBCs and platelets contain trace amounts of miRNA-451a and that about 99.9% of miRNA-451a in the blood are localized in RBCs. Hemolyzed plasma showed 58.5-fold increase in miRNA-451 concentration as compared to non-hemolyzed plasma. Importantly, plasma stored at room temperature (RT) or 4ºC showed a steady statistically significant decrease in miRNA-451a levels over a 7-day period whereas plasma samples stored at -20 or -80ºC for up to 7 days showed stable miRNA-451a levels. Together, our data indicate that hemolysis and blood storage at RT or 4ºC may have significant negative effects on the levels of circulating miRNA-451a.

Post-menopausal women are at risk of osteoporotic vertebral fractures (OVFs), which if undetected and untreated, can lead to significant pain and morbidity. However, OVFs are often not reported by radiologists on routine chest radiographs. Artificial Intelligence (AI) is increasingly used in medical applications with improvements in detection and diagnosis. This study aims to investigate the clinical value of a newly developed AI tool, Ofeye 1.0 for automated detection of OVFs on lateral chest radiographs in post-menopausal women (&gt;60 years) who were referred to undergo chest x-rays for other reasons. A total of 510 de-identified lateral chest radiographs from three clinical sites were retrieved and analysed by Ofeye1.0 tool. These images were then reviewed by a consultant radiologist to decide whether there is any fracture present or not with findings served as the reference standard for determining the diagnostic performance of the AI tool. The percentage of radiologist reports which included the OVF was analysed by comparing diagnostic reports with AI findings, while the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) of the AI tool were calculated. Out of all the original radiologist reports, missed OVFs were found in 14% images but were detected by the AI tool. The AI tool demonstrated a relatively high specificity 92.8% (95% CI: 89.6, 95.2%), moderate accuracy 80.3% (95% CI: 76,3, 80.4%), PPV 73.7% (95% CI: 65.2, 80.8%) and NPV 81.5% (95%CI: 79, 83.8%), but low sensitivity 49% (95%CI: 40.7, 57.3%). The high false negative results were mainly due to mild OVFs with &lt;20% vertebral height loss. The new AI software tool has high specificity with a low false positive rate of 5.1%, showing that it can be used as a complimentary tool to the routine diagnostic reports for reduction of missed OVF in elderly women. The low sensitivity with high false negative rates indicate the necessity of radiologist’s in identifying and reporting early OVFs.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse variance-weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113 %, standard error (SE) = 0.03 %, P-value = 2E-04; glucosamine, eGFR change beta = -0.240 %, SE = 0.035 %, P-value = 6E-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426 %, SE = 0.136 %, P-value = 1E-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here we analysed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a posthoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, taper/stop) as the predictor. 282 patients were analysed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that functional decline after tapering or stopping DMARDs in RA patients with stable remission is small and related to relapses but to on overall functional decline.

Ebstein anomaly, a congenital heart condition, can manifest across a broad age spectrum, including adulthood. We present a unique case of a 67-year-old woman with no significant medical history who sought medical attention for severe headaches, vomiting, and respiratory distress, accompanied by elevated blood pressure and rapid pulse. Initial investigations, including troponin T levels, yielded unremarkable results. However, an electrocardiogram unveiled a right bundle branch block (RBBB) pattern, prompting further assessment. A subsequent chest X-ray disclosed an enlarged heart, indicating cardiomegaly, prompting echocardiography. The echocardiogram confirmed the diagnosis of Ebstein anomaly, revealing a 26 mm apical displacement of the tricuspid valve (TV). The patient was managed conservatively with supplemental oxygen and exhibited gradual improvement. This case underscores the infrequent occurrence of Ebstein anomaly in adulthood and underscores the necessity for thorough evaluation in cases of unexplained cardiopulmonary symptoms.

Abstract: Arterial hypertension is the main preventable risk factor for premature death and stroke worldwide and anxiety is a real public health problem. Stress is the common denominator for both cases. In the last 3 years, the aggressive exposure of the population to negative emotions (fear of disease in a pandemic, fear of war, financial instability) was the trigger factor. The psycho-neuro-endocrine mechanisms include the hypothalamic-pituitary-adrenal axis and induce sympathetic-parasympathetic imbalance, hypercortisolemia, endothelial dysfunction, oxidative stress, inflammation, cytokine growth, and atherosclerosis. The individual’s vulnerability to stress depends on many factors, but the key role in the perception of stress belongs to immunogenic personality traits. Among them, self-efficacy is a protective factor against stress. Our research aimed to evaluate the connections between psycho-emotional factors and hypertension, using psychometric tests, to identify vulnerability to stress, perceived stress level, anxiety, self-efficacy, and psychobehavioral type, for 215 patients, 104 hypertensive and 111 non-hypertensive patients. The results of the study confirmed that there is a statistically significant difference, which requires psychological screening measures to identify patients vulnerable to stress, as well as medical education courses for doctors in the field of psychology.

Vaccines are an important tool of preventive medicine. Organized vaccination programs have saved numerous people from serious infectious diseases. Surprisingly, there is a considerable portion of the population who oppose vaccinations. In particular, the existence of anti-vaccination perceptions among travelers to countries with endemic diseases is a major public health concern. Although hesitancy towards vaccinations is not a novel phenomenon, it came back to the forefront during the fight against the COVID-19 pandemic. This review explored the etiology of anti-vaccination beliefs among travelers and drew conclusions about their impact on public health and society in general. For this purpose, a purposeful search for data on the causative factors of vaccine hesitancy and their impact on people’s health was conducted. A descriptive analysis of the findings and conclusions about possible implications in health policy and clinical practice are presented. Fear of side effects, lack of credence in the necessity of vaccines, and mistrust of medical authorities are important causative factors. Their interplay shapes hesitancy towards vaccines. However, anti-vaccination beliefs can also be an aspect of a more general unconventional stance of life. Health care professionals and organizations must be ready to tackle vaccine hesitancy by making the necessary interventions. Correcting misconceptions about vaccinations is a prerequisite for ensuring personal and public health, especially in the context of a pandemic or epidemic. Moreover, ensuring the efficacy and safety of vaccines, especially in cases of modern technology applications, is a fundamental factor in addressing people’s concerns about vaccines. For this purpose, medical authorities and organizations must provide accurate and clear information on vaccines so as to eliminate misinformation. Furthermore, clinicians should cultivate their communication skills in order to convey the appropriate messages to prospective recipients of vaccinations.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

Background: Advances in additive manufacturing and the development of antimicrobial biopolymers facilitate the production of critical medical devices with strong and safe biocidal properties. The purpose of this study was to assess the antimicrobial efficacy, safety, and longevity of a polylactic acid-based biopolymer supplemented with a copper-based composite additive. Methods: An antimicrobial polylactic acid-based biopolymer was tested against several inoculants including Staphylococcus Aureus, MRSA, E. coli, Listeria, HCoV-229E (a SARS-CoV-2 surrogate), and HIV-1. Material safety was evaluated according to international testing standards for in vitro cytotoxicity. Results: The main findings of the present investigation showed a strong and long-lasting biocidal effect of a polylactic acid-based biopolymer embedded with a copper-based composite additive against Staphylococcus Aureus, MRSA, E. coli, Listeria, HCoV-229E (a SARS-CoV-2 surrogate), and HIV-1. Furthermore, the cytotoxicity and safety assessment of the antimicrobial biopolymer was found to be “non-toxic” and safe for human skin contact. Conclusions: The present investigation showed that the antimicrobial biopolymer exhibits strong and long-lasting biocidal properties against an array of viral and bacterial inoculants.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Visual Patient Avatar ICU is an innovative approach to patient monitoring enhancing the user's situation awareness in intensive care settings. It dynamically displays the patient's current vital signs through changes in color, shape and animation. The technology can also indicate patient-inserted devices, such as arterial lines, central lines and urinary catheters, along with their insertion locations. We conducted an international, multi-center study using a sequential qualitative-quantitative design to evaluate users' perception of Visual Patient Avatar ICU among physicians and nurses. Twenty-five nurses and twenty-five physicians from the ICU participated in the structured interviews. Forty of them completed the online survey. Overall, ICU professionals expressed a positive outlook on Visual Patient Avatar ICU. They described Visual Patient Avatar ICU as a simple and intuitive tool that improved information retention and facilitated problem identification. However, a subset of participants expressed concerns about potential information overload and a sense of incompleteness due to missing exact numerical values. These findings provide valuable insights into user perceptions of Visual Patient Avatar ICU and encourage further technology development before clinical implementation.

Cryptococcosis is a leading cause of death among people with HIV in sub-Saharan Africa. Limited diagnostic and therapeutic options significantly impair treatment options in Africa. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective cohort at 1) Adama Hospital Medical College and 2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult HIV-infected patients presenting with suspected sepsis and assessed 28-day survival. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years and 61% being female. Overall, 11(13%) had positive CrAg tests, of which 5 had Cryptococcus detected in blood cultures. Despite high-dose fluconazole (1200mg/d) monotherapy in patients with positive CrAg tests, the 28-day mortality was 64%(7/11), being significantly higher than in CrAg-negative patients (9%(6/71); p&lt;0.001). Cryptococcosis is the leading cause of mortality among HIV-infected sepsis patients. CrAg screening in HIV-infected patients attending emergency department can minimize the cryptococcosis missing case irrespective of CD4 count and viral load. These findings warrant the need of a bundle approach for diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild course; however, about 1% of affected children require a stay in the pediatric intensive care unit (PICU) due to the severe life-threatening course. The risk of respiratory failure, as in adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyze patients admitted to PICUs due to severe course of SARS-CoV-19 infection. Methods: A retrospective multi-center study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection, who were admitted to PICUs, in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, and the endpoint – survival or death. Results: The study analyzed 45 patients (0.075% of all children hospitalized in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n=18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system, Lung Injury Score and Pediatric Sequential Organ Failure Assessment . A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p=0.028). Analyzing patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalization, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As in adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). The co-occurrence of ARMs and CSS in an individual is unexpected since both diseases are very rare. A review of the literature enabled us to identify 12 individuals with both CSS and ARMs. Among these 12 individuals, 9 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are likely a rare consequence of CSS, especially for ARID1A-related CSS.

Robin sequence is a congenital anomaly characterized by a triad of features that include micrognathia, glossoptosis, and airway obstruction. This comprehensive historical review maps the evolution of approaches and appliances for its treatment from the past until current modern possibilities of interdisciplinary combination of modern engineering, medicine, materials, and computer science combined approach with emphasis to design appliances inspired by nature - individual human anatomy. Current biomimetic designs are clinically applied resulting in appliances that are more efficient, comfortable, sustainable, and safer than legacy traditional designs. Review maps the treatment modalities that have been used for patients with Robin sequence over the years. Early management of Robin sequence focused primarily on airway maintenance and feeding support, while current management strategies involve both nonsurgical and surgical interventions and biomimetic biocompatible personalized appliances. The goal of this paper was to provide a review of the evolution of management strategies for patients with Robin sequence that led to the current interdisciplinary biomimetic approaches impacting the future of Robin Sequence treatment with biomimetics at the forefront.

Wide-field (WF) retinal imaging is becoming a standard diagnostic tool for diseases involving the retinal periphery. Technological progress elicited the advent of wide-field optical coherence tomography (WF-OCT) and WF-OCT angiography (WF-OCTA) examinations. This review presents the results of studies that analyzed the implementation of these procedures in clinical practice and refers to them as traditional and ultra-wide-field fluorescein angiography (UWF-FA). The PUBMED search was performed using the terms WF-OCT OR WF-OCTA OR UWF-FA AND the specific clinical entity, including diabetic retinopathy (DR), retinal vein occlusion (RVO), Coats disease, peripheral retinal telangiectasia, peripheral retinal degeneration, lattice degeneration, and posterior vitreous detachment. The analysis only included the studies in which the analyzed field of view for the OCT or OCTA exam was larger than 55 degrees. The evaluation of the extracted studies indicates that WF imaging with OCT and OCTA provides substantial information on retinal disorders involving the retinal periphery. Vascular diseases, such as DR or RVO, can be reliably evaluated using WF-OCTA with results superior to standard-field fluorescein angiography. Nevertheless, UWF-FA provides a larger field of view and still has advantages over WF-OCTA concerning the evaluation of areas of non-perfusion and peripheral neovascularization. Detailed information on the vascular morphology of peripheral changes should be obtained via WF-OCTA, not angiographic examinations. WF-OCT can serve as a valuable tool for the detection and evaluation of vitreoretinal traction, posterior vitreous detachment, and peripheral retinal degeneration, and guide therapeutic decisions on a patient’s eligibility for surgical procedures.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and is-chemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients so as to prevent and minimize the morbidity of HIBI. Further studies aimed at stand-ardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Mucormycosis is an opportunistic fungal infection that is increasingly affecting patients with Coronavirus Disease (COVID-19). This connection is particularly pronounced in specific populations, including individuals with diabetes or those who have recently undergone corticosteroid therapy. Additionally, Cytomegalovirus (CMV) infection is a frequent complication among COVID-19 patients who have previously received corticosteroid or other immune-modulatory treatments. In this case report, we present the clinical details of a 56-year-old male who developed post-COVID pneumonia complicated by both cutaneous mucormycosis and CMV infection.

Introduction. Psoriatic disease (PsD), encompassing psoriasis, psoriatic arthritis, inflammatory bowel disease, and uveitis, presents a significant burden due to its chronic and diverse inflammatory nature, affecting various clinical domains including skin, joints, and internal organs. Psoriasis, affecting up to 3% of the global population, not only poses physical challenges but also profoundly impacts patients' psychological well-being, ranking among the most debilitating chronic conditions. Furthermore, PsD exhibits a spectrum of manifestations ranging from skin lesions like plaque psoriasis to systemic complications such as cardiovascular comorbidities, necessitating comprehensive assessment and management strategies. The increasing understanding of the aetiopathogenic mechanisms of these immune-mediated diseases and of the proinflammatory intracellular signalling pathways involved in Psoriatic disease (PsD) has facilitated the identification and development of new small molecules capable of inhibiting JAK proteins, emerging as effective treatment options for rheumatic and dermatological manifestations JAK inhibitors act rapidly, within a few days, with a striking beneficial class effect on pain. The oral formulation they share makes them a well-tolerated class of drugs, with a clear advantage over FAME in terms of convenience of administration, improving therapeutic compliance. Material and method. This observational, retrospective study conducted in a single-centre dermatology-rheumatology consultation of a second-level hospital in Granada, Spain, focused on patients diagnosed with Psoriatic Arthritis (PsA) over the last two years, who initiated treatment with Tofacitinib or Upadacitinib due to DMARD failure, excluding those with major contraindications to JAK inhibitors. Results: This study analyzed data from 32 patients diagnosed with Psoriatic Arthritis (PsA), focusing on their demographics, disease characteristics, and treatment history. The majority of patients (75%) initiated treatment with Tofacitinib, while the remainder started with Upadacitinib. The mean age of the patients differed between the two treatment groups. All patients met the CASPAR criteria for PsA diagnosis, with predominantly peripheral joint involvement. The average time from PsA diagnosis to initiation of JAKinhib treatment was 6.5 years, slightly longer for Upadacitinib users. Most patients presented with cutaneous psoriasis, and a minority exhibited radiographic erosions. Before JAKinhib therapy, all patients had previously received DMARDs. A subset of patients received concomitant DMARD therapy, predominantly methotrexate. Additionally, a proportion of patients were on low-dose corticosteroids. Baseline CRP and ESR levels were indicative of systemic inflammation. Disease activity measures at baseline indicated moderate disease activity, with a substantial proportion of patients having mild psoriasis involvement. Upadacitinib recipients with psoriasis primarily exhibited mild involvement. This study provides valuable insights into the characteristics and treatment patterns of PsA patients initiating JAKinhib therapy. Discusion. In this study, the efficacy, safety, and real-world outcomes of Janus kinase inhibitors (JAKinhibs) in the treatment of Psoriatic Arthritis (PsA) were assessed and compared with findings from pivotal randomized controlled trials (RCTs). Both Tofacitinib and Upadacitinib demonstrated significant efficacy in PsA patients refractory to DMARDs and TNF inhibitors, with rapid improvement in joint and skin activity indices. Although patients in this cohort exhibited younger age, higher female prevalence, and shorter disease duration compared to those in RCTs, treatment responses were comparable or even superior. Notably, despite fewer concurrent DMARDs and a higher proportion of patients receiving monotherapy, JAKinhibs maintained a favorable safety profile, with a low frequency of mild adverse events leading to treatment discontinuation. These findings emphasize the robust efficacy and tolerability of JAKinhibs in real-world clinical settings, supporting their role as effective therapeutic options for PsA patients.

To compare concentrations of endogenous N-acylethanolamines (NAEs) lipid mediators pal-mitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA) in fresh, decon-taminated, cryopreserved and freeze-dried amniotic membrane (AM) allografts. Thereby deter-mining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chro-matography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPARα receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher val-ues for all NAEs were detected in cryopreserved samples compared to fresh tissue before decon-tamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of PPARα receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue was found in cryopreserved, but not frieze-dried AM. Results in-dicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects of AM allografts.