Estimation of the graft failure by current value joint model, and extension to alternative parameterization structures: Cohort study.

In clinical practice, individuals are followed up to predict the outcome event of interest, and their longitudinal measurements are collected on a regular or irregular basis. We aimed to examine the classical approach, joint model (JM), and alternative parameterization structures using data on the effect of time-varying longitudinal measurements on survival. The motivating cohort dataset included 158 consecutive kidney transplant recipients who had baseline and follow-up data. Although the longitudinal log-transformed estimated glomerular filtration rate (log[eGFR]) measurements and graft failure have an association clinically, the 2 processes are analyzed separately in the classical approach. In addition to the extended Cox model, the current value JM, the weighted cumulative effect JM, and dynamic predictions were performed in the study, by taking advantage of R codes. Of the 158 patients, 34.8% were males. The mean age was 29.8 ±â€…10.9 years, and the median age was 26 years at the time of transplantation. The hazard ratio for graft failure was 8.80 for a 1-unit decrease in log(eGFR) in the extended Cox model, 10.58 in the current value JM, and 3.65 in the weighted cumulative effect JM. The presence of coronary heart disease was also found to be associated with log(eGFR): 0.199 (P = .03) for the current value JM and 0.197 (P = .03) for the weighted cumulative effect JM. The current value JM was identified as a better model than the extended Cox model and the weighted cumulative effect JM based on parameter and standard error comparison and goodness of fit criteria. JMs should be preferred, as they facilitate better clinical decisions by accounting for the varying slopes and longitudinal variation of estimated glomerular filtration rate among patients. Suitable types of models should be practiced depending on baseline biomarker levels, their trends over time, the distribution of the biomarkers, and the number of longitudinal biomarkers.

Evaluation of Salmonella biofilm attachment and hydrophobicity characteristics on food contact surfaces.

Salmonella forms biofilms, and persist on food contact surfaces. Once a biofilm is formed cleaning and sanitation protocols may be inadequate for effective removal. This study evaluated attachment characteristics, surface properties, and structure of Salmonella biofilms on food contact surfaces commonly used in the tree-fruit industry. Multi-strain Salmonella biofilms were grown in a Centers for Disease Control and Prevention (CDC) biofilm reactor at 22 ± 2 °C and sampling was conducted at 2, 24 and 96-h. After each incubation period, coupons weregently rinsed and the remaining cells enumerated. Biofilms were analyzed with Laser Scanning Confocal Microscopy (LSCM). Hydrophobicity was evaluated by measuring the contact angles of reference liquids method using a drop tensiometer instrument. Material type and biofilm age significantly influenced attachment and biofilm hydrophobicity (P < 0.05). The strength of attachment, across all time points, was highest on nylon followed by wood and high-density polyethylene. The highest contact angle measurements were observed after 96-h of biofilm formation for each material. All the results and observations from this study contribute to a better understanding of the attachment and hydrophobicity characteristics of Salmonella and might help producers make informed decisions when selecting containers for harvesting and storing in order to minimize biofilm formation and potential for cross-contamination.

Sexual dysfunction among female patients with rheumatic diseases.

To demonstrate the burden of sexual dysfunction (SD) among females with rheumatic diseases, we conducted a cross-sectional comparative study in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Behçet's syndrome (BS) along with suitable healthy controls (HCs). Age-matched female patients with SSc (n = 50), SLE (n = 49), and BS (n = 54), along with 52 female HCs were included in this study between April and October, 2021. Sociodemographic features were recorded, and psychometric tests, i.e., female sexual function index (FSFI), Beck depression inventory (BDI), body cathexis scale, and marital adjustment test (MAT) were performed. Scale scores were compared, and binary logistic regression was used to identify predictors for SD in the whole group. The total FSFI and body cathexis scores among the patient groups were significantly lower than those of the HCs (p < 0.001). Depression was significantly more frequent in the patient groups. MAT scores did not differ significantly between the study groups. Patients with SSc had the worst scores in each psychometric index, including MAT. Decreased body cathexis score [OR 0.974, 95% CI (0.957-0.991), p = 0.003] and low MAT score [OR 0.937, 95% CI (0.896-0.980), p = 0.005], and being diagnosed with SSc [OR 6.6, 95% CI (1.975-22.498), p = 0.002], SLE [OR 2.7, 95% CI (0.998-7.753), p = 0.050], and BS [OR 2.8, 95% CI (1.100-7.359), p = 0.031], were identified as independent predictors for SD. Body cathexis seems to be the most important independent predictor for SD, and the burden of SD appears heavier in patients with SSc, probably due to poor body image satisfaction.

[When should a liver disease patient be admitted to the intensive care unit?] / Wann soll ein Leberkranker auf die Intensivstation?

Liver diseases are a significant global cause of morbidity and mortality. Liver cirrhosis can result in severe complications such as bleeding, hepatic encephalopathy (HE), and infections. Implementing a clear strategy for intensive care unit (ICU) admission management improves patient outcomes. Hemodynamically significant esophageal/gastric variceal bleeding (E/GVB) and grade 4 HE, when accompanied by the need for renal replacement therapy (RRT), are definitive indications for ICU admission. E/GVB, spontaneous bacterial peritonitis (SBP), and infections with multidrug-resistant organisms (MDRO) require close and stringent critical assessment. Patients with severe hepatorenal syndrome (HRS) or respiratory failure have increased baseline mortality and most likely benefit from early ICU treatment. Rapid identification of sepsis in patients with liver cirrhosis is a crucial criterion for ICU admission. Prioritizing cases based on mortality risk and clinical urgency enables efficient resource utilization and optimizes patient management. In addition, "Liver Units" provide an intermediate care (IMC) level for patients with liver diseases who require close monitoring but do not need immediate intensive care.

Association of Metabolic Dysfunction-Associated Fatty Liver Disease with Cognitive Impairment and All-Cause Dementia: A Comprehensive Review.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant public health concern, affecting one-third of the global population and posing a risk for progressive liver disease. MAFLD is characterized by hepatic steatosis and impaired metabolic status, which not only impact the liver but also other systems of the human body, making it a multisystemic disorder. Emerging evidence suggests that MAFLD and its associated pathological pathways may contribute to cognitive impairment, potentially through neuroinflammation and neurodegeneration. Studies have detected cognitive impairment in patients with MAFLD using magnetic resonance imaging, which revealed decreased brain volume and cerebral perfusion, in addition to self-reported cognitive tests. While numerous studies have demonstrated an association between MAFLD and cognitive impairment, the relationship between MAFLD and all-cause dementia remains controversial. However, the shared pathological pathways between MAFLD and dementia, such as systemic inflammation, insulin resistance, gut dysbiosis, hyperammonemia, and vascular dysfunction, indicate the possibility of a common prevention strategy for both diseases. In this review, we provide a summary of the current evidence regarding the association between cognitive impairment, all-cause dementia, and MAFLD.

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease Cross Talk.

Nonalcoholic fatty liver disease is a multisystem condition with effects beyond the liver. The identification of chronic kidney disease as an independent mediator of nonalcoholic fatty liver disease or associated entity with shared cardiometabolic risk factors remains controversial and continues to draw scientific interest. With increasing prevalence of nonalcoholic fatty liver disease and lack of Food and Drug Administration approved therapies, these shared cardiometabolic risk factors have drawn significant attention. In this article, we review shared pathophysiological mechanisms between nonalcoholic fatty liver disease and chronic kidney disease along with current treatment strategies that might be useful for both disease processes.

Prevalence of metabolic dysfunction-associated fatty liver disease in kidney transplant recipients: A cross-sectional study using FibroScan.

Background and Aim: Metabolic dysfunction-associated fatty liver disease (MAFLD) is expected to be prevalent among kidney transplant recipients (KTRs). In this study, we evaluated the prevalence of MAFLD among KTRs, data that have not been investigated by any clinical study to date. Materials and Methods: We included a total of 52 KTRs and 53 age-, sex-, and BMI-matched individuals as the control group through prospective consecutive recruitment. We detected the presence of hepatic steatosis and liver fibrosis using the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) defined by FibroScan. Results: Among the KTRs, 18 (34.6%) had metabolic syndrome. The prevalence of MAFLD among the KTRs and controls was 42.3% and 51.9%, respectively (p=0.375). The CAP and LSM values did not differ significantly between the KTRs and controls (p=0.222 and p=0.119). Among the KTRs, patients with MAFLD had significantly higher age, BMI, waist circumference, LDL, and total cholesterol levels (p<0.001, p=0.011, p=0.033, p=0.022, and p=0.029, respectively). In multivariable analysis, age was the only independent factor for MAFLD among the KTRs (OR: 1.120, 95% confidence interval (CI): 1.039-1.208). Conclusion: MAFLD among KTRs did not show a significantly higher prevalence compared to the normal population. Further clinical studies with larger populations are needed.

Changes in the etiology of chronic liver disease by referral to a FibroScan center: Increasing prevalence of the nonalcoholic fatty liver disease.

Background and Aim: Chronic liver disease (CLD) is a leading cause of morbidity and mortality worldwide with a wide etiological spectrum. FibroScan® is used for follow-up of fibrosis and steatosis. This single-center study aims to review the distribution of indications by referral to FibroScan®. Materials and Methods: Demographic characteristics, CLD etiologies, and FibroScan® parameters of the patients who were referred to our tertiary care center between 2013 and 2021 were retrospectively evaluated. Results: Out of 9345 patients, 4946 (52.93%) were males, and the median age was 48 [18-88] years. Nonalcoholic fatty liver disease (NAFLD) was the most common indication (N=4768, 51.02%), followed by hepatitis B (N=3194, 34.18%) and hepatitis C (N=707, 7.57%). Adjusting for age, sex, and CLD etiology, the results revealed that patients with older age (Odds ratio (OR)=2.908; confidence interval (CI)=2.597-3.256; p<0.001) and patients with hepatitis C (OR=2.582; CI=2.168-3.075; p<0.001), alcoholic liver disease (OR=2.019; CI=1.524-2.674, p<0.001), and autoimmune hepatitis (OR=2.138; CI=1.360-3.660, p<0.001) had increased odds of advanced liver fibrosis compared to NAFLD. Conclusion: NAFLD was the most common indication for referral to FibroScan®.

Epidemiology, natural history, and diagnosis of metabolic dysfunction-associated fatty liver disease: a comparative review with nonalcoholic fatty liver disease.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide - with an estimated global prevalence of 37%. Different from nonalcoholic fatty liver disease (NAFLD), which is an exclusion diagnosis, MAFLD is defined by a set of positive criteria. This recent change in terminology is challenging because MAFLD and NAFLD denote two similar, albeit not identical, clinical populations. When the diagnostic criteria for MAFLD are applied, liver histology appears more severe and clinical outcomes are less favorable. However, the clinical management of MAFLD and NAFLD remains similar. While liver biopsy is still the reference standard for achieving a final diagnosis, noninvasive imaging- or biomarker-based diagnostic modalities are currently gaining momentum. However, liver biopsy should be recommended when diagnostic challenges exist. In this review, we compared the epidemiology, natural history, and diagnosis of MAFLD with respect to the traditional NAFLD definition.

Prevention of hepatocellular carcinoma and monitoring of high-risk patients.

Hepatocellular carcinoma (HCC) accounts for some 80% of primary liver tumors. According to recent data, HCC is the sixth most common type of cancer and the third leading cause of cancer-related mortality worldwide. Risk factors for HCC include the presence of the hepatitis B virus, hepatitis C virus, non-alcoholic fatty liver disease, and exposure to noxious agents, such as alcohol, or toxins, such as aflatoxin, which are considered preventable etiologies of HCC. Monitoring strategies are needed for patients at risk of developing HCC. There is a consensus on routine monitoring of cirrhotic patients due to definitive evidence of a significantly high rate of progression to HCC; however, the appropriate surveillance of patients with advanced fibrosis remains a topic of discussion. Nevertheless, adherence to a strict observation protocol is the cornerstone of early detection and treatment with curative options for patients with a high risk of developing HCC. This review examines prevention strategies, risk factors, and surveillance based on current guidelines.

Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver.

Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, awareness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.

The Effect of Plant Metabolites on Coronaviruses: A Comprehensive Review Focusing on their IC50 Values and Molecular Docking Scores.

Coronaviruses have caused worldwide outbreaks in different periods. SARS (severe acute respiratory syndrome) was the first emerged virus from this family, followed by MERS (Middle East respiratory syndrome) and SARS-CoV-2 (2019-nCoV or COVID 19), which is newly emerged. Many studies have been conducted on the application of chemical and natural drugs for treating these coronaviruses and they are mostly focused on inhibiting the proteases of viruses or blocking their protein receptors through binding to amino acid residues. Among many substances which are introduced to have an inhibitory effect against coronaviruses through the mentioned pathways, natural components are of specific interest. Secondary and primary metabolites from plants, are considered as potential drugs to have an inhibitory effect on coronaviruses. IC50 value (the concentration in which there is 50% loss in enzyme activity), molecular docking score and binding energy are parameters to understand the ability of metabolites to inhibit the specific virus. In this study we reviewed 154 papers on the effect of plant metabolites on different coronaviruses and data of their IC50 values, molecular docking scores and inhibition percentages are collected in tables. Secondary plant metabolites such as polyphenol, alkaloids, terpenoids, organosulfur compounds, saponins and saikosaponins, lectins, essential oil, and nicotianamine, and primary metabolites such as vitamins are included in this study.

Accuracy of Fibrosis-4 index and non-alcoholic fatty liver disease fibrosis scores in metabolic (dysfunction) associated fatty liver disease according to body mass index: failure in the prediction of advanced fibrosis in lean and morbidly obese individuals.

BACKGROUND AND AIM: While non-invasive scores are increasingly being used to screen for advanced fibrosis in metabolic (dysfunction) associated fatty liver disease (MAFLD), the effect of BMI on their clinical utility remains uncertain. This study assessed the usefulness of the Fibrosis-4 index (FIB-4) and the non-alcoholic fatty liver disease fibrosis score (NFS) in lean, overweight, obese, severely obese, and morbidly obese patients with biopsy-proven MAFLD. METHODS: A total of 560 patients (28 lean, 174 overweight, 229 obese, 89 severely obese, 40 morbidly obese) were included. Diagnostic performances and optimal cut-off values for FIB-4 and NFS were calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: In both lean and morbidly obese patients with MAFLD, both FIB-4 and NFS failed to discriminate advanced fibrosis. Conversely, both scores showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients. FIB-4 was able to exclude advanced fibrosis with the highest diagnostic accuracy in the subgroup of overweight patients (area under the ROC curve: 0.829, 95% confidence interval: 0.738-0.919). CONCLUSION: FIB-4 and NFS can confidently be used to exclude advanced fibrosis in overweight, obese, and severely obese patients. However, they do not appear clinically useful in lean and morbidly obese patients.

A Review of the Epidemiology, Pathophysiology, and Efficacy of Anti-diabetic Drugs Used in the Treatment of Nonalcoholic Fatty Liver Disease.

In recent years, epidemiological studies have consistently demonstrated that the coexistence of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is strongly associated with increased mortality and morbidity related to hepatic- and extrahepatic causes. Indeed, compared with the general population, patients with T2DM are more likely to be diagnosed with more severe forms of NAFLD (i.e., nonalcoholic steatohepatitis (NASH) with liver fibrosis). There is an ongoing debate whether NALFD is a consequence of diabetes or whether NAFLD is simply a component and manifestation of the metabolic syndrome, since liver fat (steatosis) and even more advanced stages of liver fibrosis can occur in the absence of diabetes. Nevertheless, insulin resistance is a key component of the mechanism of NAFLD development; furthermore, therapies that lower blood glucose concentrations also appear to be effective in the treatment of NAFLD. Here, we will discuss the pathophysiological and epidemiological associations between NAFLD and T2DM. We will also review currently available anti-diabetic agents with their regard to their efficacy of NAFLD/NASH treatment.

Feasibility of Fibroscan in Assessment of Hepatic Steatosis and Fibrosis in Obese Patients: Report From a General Internal Medicine Clinic.

BACKGROUND: In metabolic associated fatty liver disease (MAFLD) vibration controlled transient elastography (VCTE) by Fibroscan has emerged as a non-invasive diagnostic tool for the measurement of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are surrogate markers for hepatic steatosis and fibrosis, respectively. However, obesity constitutes a limitation in terms of creating unreliable examinations due to increased skin to liver capsule distance. Here, we aimed to investigate the feasibility of VCTE in the evaluation of hepatic steatosis and fibrosis in obese individuals. METHODS: A total of 126 consecutive obese patients (body mass index ≥30 kg/m2) without a known history of MAFLD enrolled in the study. We performed CAP and LSM measurements and calculated Fibrosis-4 Index for each patient and included data of those patients to the analysis, from whom valid measurements were able to be taken. RESULTS: Reliable VCTE measurements were able to be obtained in 122 patients (97%), from those in 34 patients with M and 88 patients in XL probe (median age: 50 [18-75], 45 males and 77 females). In 1 patient VCTE failed to take any measurements and in 3 the measurements were classified as unreliable. The mean CAP value was 323 ± 48 dB/m and the median LSM value 5.3 [1.8-34.3] kPa. CONCLUSION: CAP and LSM assessments by Fibroscan are reliable diagnostic tools for the early diagnosis of hepatic steatosis and fibrosis in obese individuals.

Macro- and micronutrients in metabolic (dysfunction) associated fatty liver disease: association between advanced fibrosis and high dietary intake of cholesterol/saturated fatty acids.

BACKGROUND AND AIM: There is still no approved pharmacotherapy for metabolic (dysfunction) associated fatty liver disease (MAFLD). Although dietary and lifestyle modifications for weight loss remain the mainstay for disease management, the association between macro- and micronutrients and fibrosis stage in patients with MAFLD remains unclear. This study was undertaken to address this issue. METHODS: This is a retrospective analysis of prospectively collected data from patients in whom MAFLD was diagnosed with vibration controlled transient elastography. Steatosis was defined by a controlled attenuation parameter ≥238 dB/m, whereas a liver stiffness measurement ≥11 kPa was considered to indicate advanced fibrosis. RESULTS: The study sample consisted of 106 patients with MAFLD (mean age 49 ± 10 years, 52 men and 54 women). Among the different micro- and macronutrients tested, only the dietary intake of cholesterol and saturated fatty acid (SFA) was independently associated with the presence of advanced fibrosis. CONCLUSION: Our findings suggest that cholesterol/SFA-restricted dietary regimens - as exemplified by the traditional Mediterranean diet - may reduce the risk of advanced fibrosis in patients with MAFLD.