Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

BACKGROUND: HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins. METHODS: We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins. RESULTS: High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67). CONCLUSIONS: High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes.

Facial reconstruction with thinned anterolateral thigh free flap.

Facial reconstruction is challenging for plastic surgeons, as it can be difficult to decide the best approach. One technique that has been widely used is the anterolateral thigh (ALT) flap due to its numerous benefits. However, its thickness can be a drawback, especially regarding facial reconstruction. The thinning technique is not a new novel, but how to apply it to the ALT flap to get the best result hasn't been reported yet. Our study involved 117 patients, and we used 73 thinned ALT flaps to determine the best method to increase the flap's safety. After thinning, we significantly reduced the flap's thickness from an average of 22.5 mm to 5.9 mm, making it more suitable for contouring purposes. We apply a thinned ALT flap for coverage, contouring, and recreating the facial 3D structure. The 12/45 flap has the chance to make the multiple-paddle ALT flap, which helps to reconstruct difficult positions even more flexibly. The key to successfully thinning the ALT flap is understanding the perforator's structure and pathway through the fascia. With the thinning technique, we have overcome the limitations of the flap's thickness, making it suitable for use in whole-body reconstruction. The ALT flap can overcome the restriction of its thickness and can be applied even more extensively in whole-body reconstruction.

Nucleos(t)ide analogs to treat patients with positive hepatitis B virus deoxyribonucleic acid and normal alanine transaminase: protocol for an open-label single-center randomized parallel controlled trial.

BACKGROUND: Direct high-quality evidence remains absent on the benefits of HBeAg-negative chronic hepatitis B patients (CHB) with normal alanine transaminase (ALT) and positive HBV DNA after nucleos(t)ide analogs (NAs) treatment. METHODS: This is a single-center, open-label, randomized parallel controlled trial with a follow-up duration of 96 weeks. An estimated 300 patients will be recruited at West China Hospital of Sichuan University, China. After stratified by serum HBV DNA (< 2000 vs. ≥ 2000 IU/ml), eligible patients will be randomized (allocation ratio 1:1) to receive either antiviral therapy (the treatment group) or regular examination alone (the control group). The primary outcomes are rates of virological response and changes in the levels of serum HBV pregenomic RNA (pgRNA) and scores of health-related qualities of life. DISCUSSION: This randomized controlled trial focuses on HBeAg-negative patients with normal ALT, including those of the inactive carrier phase and the grey zone, whose antiviral treatment remains controversial. Additionally, a health-related quality of life scale is introduced to comprehensively estimate the benefit of antiviral treatment apart from virological response and adverse liver events. Meaningfully, the study findings will provide high-quality and direct evidence for optimal clinical management in such populations. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300069391) on 15 March 2023.

D-dimer is a prognostic marker for 1-year mortality in patients with chronic liver failure and hepatic encephalopathy.

Background and Aim: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver failure with poor outcomes. The present study aimed to evaluate the predictive values of D-dimer in patients with HE. Materials and Methods: Patients with chronic liver failure (CLF) and HE were enrolled. Univariate and multivariate logistic analysis was performed to investigate the risk factors for 1-year mortality of HE. Results: During the first year after diagnosis, 39.2% (65/166) of the patients died. D-dimer was significantly higher in non-survivors (Z=2.617, p<0.01). Both D-dimer and international normalized ratio (INR) positively correlated with Child-Pugh and MELD scores, and negatively correlated with sodium (all p<0.01). Moreover, there was a negative relationship between D-dimer and HE grades (r=-0.168, p=0.031), while the relationship between INR and HE grades was not significant (r=0.083, p=0.289). Multivariate analysis showed that age (odds ratio (OR):1.035, 95% CI:1.004-1.067, p=0.03), D-dimer (OR=1.138, 95% CI:1.030-1.258, p=0.01), ALT (OR=1.012, 95% CI:1.001-1.022, p=0.03), and sodium (OR=0.920, 95% CI:0.858-0.986, p=0.02) were independent risk factors for 1-year mortality. Then, a new model Model(Age_DD_ALT_Na) incorporating age, D-dimer, ALT, and sodium was developed. AUROC of Model(Age_DD_ALT_Na) was 0.732, which was significantly higher than MELD and Child-Pugh scores (AUROC: 0.602 and 0.599, p=0.013 and 0.022). Conclusion: D-dimer is a prognostic marker for 1-year mortality in patients with CLF and HE.

Impact of donor transaminases on liver transplant utilisation and unnecessary organ discard: national registry cohort study.

Background: Donor liver transaminases (ALT and AST) have been used to decline livers for transplant, despite evidence that they do not influence transplant outcomes. This study assesses the effect that raised donor transaminases have on the unnecessary decline of livers. Methods: This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019). Logistic regression models were built to assess the impact of donor transaminases on the utilisation of organs donated following brain stem death (DBD) and circulatory death (DCD). A further model was used to simulate the impact on liver decline if raised donor ALT was not used to make utilisation decisions. Results: 5,424 adult livers were offered for transplant, of which 3,605 were utilised (2,841 DBD, 764 DCD). In multivariable analysis, adjusted for key factors, increasing peak donor ALT independently increased the odds of liver decline (DBD aOR = 1.396, 1.305-1.494, p < 0.001, DCD aOR = 1.162, 1.084-1.246, p < 0.001). AST was also a significant predictor of liver decline. 18.5% of livers from DBD donors with ALT > 40 U/L (n = 1,683) were declined for transplantation. In this group, our model predicted a 48% (38%-58%) decrease in decline if raised donor ALT was excluded from these decisions. This represents an additional 37 (30-45) liver transplants every year in the UK. Conclusions: Raised donor ALT increased the likelihood of liver decline. As it does not influence transplant outcome, avoiding donor ALT-based organ decline is an immediate and effective way to expand the donor pool.

Role of oral hypoglycaemic drugs in preventing complication in non-alcoholic fatty liver disease with type 2 diabetes mellitus.

Objective: To determine the prevalence of non-alcoholic fatty liver disease, and the effect of oral hypoglycaemic drugs and lifestyle modifications in reducing fatty liver changes and liver enzymes in these patients. METHODS: The comparative, observational study was conducted at the Department of Pharmacology, Sohail University, Karachi, from October 2022 to October 2023, and comprised patients of either gender having elevated liver enzymes and ultrasound finding of fatty liver changes along with raised glycated haemoglobin, transaminases, total cholesterol and triglycerides. The participants were prescribed oral hypoglycaemic agents by endocrinologists. Those given empaglifazolin + metformin were in group A, empaglifazolin + linglaptin in group B, sitaglaptin + metformin in group C, metformin alone in group D and sitaglaptin alone in group E. Lifestyle modifications were advised in all the treatment groups, while control group F was only advised lifestyle modifications. The intervention lasted 3 months. Investigations included B-mode ultrasound liver, liver enzymes and glycated haemoglobin, which were done at baseline and after the intervention. Data was analysed using SPSS 25. RESULTS: Of 200 patients, 40 were males and 160 were females in ratio of 1:4. The overall mean age was 48±16 years. There were 154(77%) patients who had non-alcoholic fatty liver disease with type 2 diabetes mellitus, while 46(23%) had only fatty liver changes. There were 50(25%) patients in group A, 30(15%) in group B, 30(15%) in group C, 40(20%) in group D, 10(5%) in group E and 40(20%) in group F. Post-intervention improvement was noted in 48(24%) patients, with 20(41.7%) of them being in group A. Conclusion: The prevalence of non-alcoholic fatty liver disease with type 2 diabetes was high. Combination of empagliflozin + metformin along with lifestyle modifications was highly effective in reducing fatty changes and the level of liver enzymes.

Elevated Alanine Transaminase-to-Platelet Index (APRI) Is Associated with Obesity and Distinct Forms of Dyslipidemia: A Retrospective Cross-Sectional Study.

Background: Obesity is a pathological condition and a major risk factor for dyslipidemia, type 2 diabetes, and non-alcoholic fatty liver disease. Recent research highlighted the association of non-invasive serum markers with these conditions but the clinical utility of ALT APRI in obesity and its relationship with dyslipidemia remain unexplored. Methods: We examined the association of ALT APRI in 165 non-diabetic adults stratified by BMI and serum lipid parameters. Results: Obese subjects had significantly higher APRI than lean subjects, with an area under the curve (AUC) of 0.65 (p = 0.019). Medians of APRI were significantly increased in subjects with high TG, TG/HDL, TC/HDL, and LDL/HDL and low HDL. Notably, all lipid parameters and ratios were significantly elevated in the highest APRI tertile, compared with patients in the lowest tertile. APRI was weakly yet significantly correlated with BMI (R2 = 0.032, p = 0.022), HDL (R2 = 0.071), TG/HDL (R2 = 0.031), TC/HDL (R2 = 0.063), LDL/HDL (R2 = 0.072), and TyG index (R2 = 0.081). While APRI only showed a discriminating capacity for HDL (AUC: 0.69, p = 0.003), TG/HDL (AUC: 0.63, p = 0.020), LDL/HDL (AUC: 0.68, p < 0.001), and TyG index (AUC: 0.65, p = 0.037), the highest diagnostic performance of APRI was observed with TC/HDL (AUC: 0.74, p < 0.001). Additionally, APRI was a risk factor for high TG (OR: 1.6, p = 0.028), low HDL (OR: 2.7, p = 0.0002), high TG/HDL (OR: 1.94, p = 0.0011), high TC/HDL (OR: 2.3, p < 0.0001), high LDL/HDL (OR: 2.2, p = 0.0001), and high TyG index (OR: 2.1, p = 0.008). Conclusions: Our findings argue for the role of APRI as a potential marker for obesity and dyslipidemia, which requires further confirmation in longitudinal studies.

Glucagon-Producing Pancreatic Neuroendocrine Tumors (Glucagonomas) are Enriched in Aggressive Neoplasms with ARX and PDX1 Co-expression, DAXX/ATRX Mutations, and ALT (Alternative Lengthening of Telomeres).

Glucagonomas are functioning pancreatic neuroendocrine tumors (PanNETs) responsible for glucagonoma syndrome. This study aims to shed light on the clinicopathological and molecular features of these neoplasms. Six patients with glucagonomas were identified. All neoplasms were investigated with immunohistochemistry for neuroendocrine markers (Synaptophysin, Chromogranin-A), ATRX, DAXX, ARX, and PDX1 transcription factors. Fluorescent in situ hybridization (FISH) for assessing alternative lengthening of telomeres (ALT), and next-generation sequencing (NGS) for molecular profiling were performed. All cases were large single masses (mean size of 8.2 cm), with necrolytic migratory erythema as the most common symptom (6/6 cases, 100%). All neoplasms were well-differentiated G1 tumors, except one case that was G2. The tumors consistently showed classic/conventional histomorphology, with solid-trabecular and nested architecture. Lymphatic and vascular invasion (6/6, 100%), perineural infiltration (4/6, 66.6%), and nodal metastasis (4/6, 66.6%) were frequently observed. Transcription factors expression showed strong ARX expression in all tumors, and PDX1 expression in 5/6 cases (83.3%), indicating co-occurring alpha- and beta-cell differentiation. NGS showed recurrent somatic MEN1 and ATRX/DAXX biallelic inactivation. Cases with ATRX or DAXX mutations also showed matched loss of ATRX or DAXX protein expression and ALT. One case harbored somatic MUTYH inactivation and showed a high tumor mutational burden (TMB, 41.0 mut/Mb). During follow-up, one patient died of the disease, and four patients developed distant metastasis. Pancreatic glucagonomas are distinct PanNETs with specific clinicopathological and molecular features, including histological aspects of biological aggressiveness, co-occurring alpha- and beta-cell differentiation, MEN1 and DAXX/ATRX mutations enrichment, and the possible presence of high-TMB as an actionable marker.

Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic, and it is the most common cause of liver diseases. The patients with severe insulin-resistant diabetes having high body mass index (BMI), high-grade adipose tissue insulin resistance, and high hepatocellular triacylglycerols (triglycerides; TAG) content develop hepatic fibrosis within a 5-year follow-up. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol (DAG), fatty acyl CoA, or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/nonalcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with an increase in saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in the liver tissue of patients with NASH. Hepatocyte lipoapoptosis is a critical feature of NASH. In the "second hit," reduced glutathione levels due to oxidative stress lead to the overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused at least by two ineffectual cyclical pathways. First is the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and the second is the Kelch like-ECH-associated protein 1 (Keap1)-nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. In clinical practice, on ultrasonographic examination, the elevation of transaminases, γ-glutamyltransferase, and the aspartate transaminase to platelet ratio index indicates NAFLD. Fibrosis-4 index, NAFLD fibrosis score, and cytokeratin18 are used for grading steatosis, staging fibrosis, and discriminating the NASH from simple steatosis, respectively. In addition to ultrasonography, "controlled attenuation parameter," "magnetic resonance imaging proton-density fat fraction," "ultrasound-based elastography," "magnetic resonance elastography," "acoustic radiation force impulse elastography imaging," "two-dimensional shear-wave elastography with supersonic imagine," and "vibration-controlled transient elastography" are recommended as combined tests with serum markers in the clinical evaluation of NAFLD. However, to confirm the diagnosis of NAFLD, a liver biopsy is the gold standard. Insulin resistance-associated hyperinsulinemia directly accelerates fibrogenesis during NAFLD development. Although hepatocyte lipoapoptosis is a key driving force of fibrosis progression, hepatic stellate cells and extracellular matrix cells are major fibrogenic effectors. Thereby, these are pharmacological targets of therapies in developing hepatic fibrosis. Nonpharmacological management of NAFLD mainly consists of two alternatives: lifestyle modification and metabolic surgery. Many pharmacological agents that are thought to be effective in the treatment of NAFLD have been tried, but due to lack of ability to attenuate NAFLD, or adverse effects during the phase trials, the vast majority could not be licensed.

Elucidating the role of hepatic enzymes in spontaneous abortion: a Mendelian randomization approach.

Background: While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA. Methods: Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis. Results: The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899). Conclusion: The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA.

Management of a Complex, Recurrent Case of Medial Thigh Sarcoma With Pedicled Deep Inferior Epigastric Artery Perforator (DIEP) Lymphatic Flow-Through (LyFT) Flap and Secondary Anterolateral Thigh (ALT) Free Flap With Innervated Vastus Lateralis Anastomosed to Synthetic Artery Graft: A Case Report.

Soft-tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin and account for only 1% of adult malignancies. They tend to occur most commonly in the lower extremities. Reconstruction after sarcoma resection can be challenging, especially when important structures are involved and recurrences occur. Additionally, more attention is now being paid to reconstructing the lymphatic system to prevent lymphatic complications. In this case report, we presented the management of recurrent medial thigh sarcoma that necessitated multiple challenging reconstructions to provide valuable insights for lectures on similar cases. A 50-year-old male patient was diagnosed with an undifferentiated pleomorphic cell sarcoma (UPS) of the anteromedial thigh. After preoperative radiotherapy, a mass of 23 × 15 cm was removed, and reconstruction with a pedicled deep inferior epigastric artery perforator (p-DIEP) flap-based lymphatic flow through (LyFT) was performed. Six months later, the patient developed the first local recurrence with the presence of a distant metastasis. Following the tumor resection, the medial part of the DIEP flap was de-epithelized and buried in the defect for dead space obliteration. Another local recurrence arose 7 months after the second surgery. Therefore, a major debulking surgery involving the femoral neurovascular bundle was performed. The femoral artery was reconstructed with a synthetic graft, and the femoral vein with the great saphenous vein harvested from the contralateral thigh. A composite myocutaneous neurotized anterolateral thigh (ALT) flap from the contralateral thigh was used to obliterate the defect and restore the loss of function of the quadriceps femoris. Two lymphaticovenular anastomoses (LVAs) were performed at the ankle to reduce the risk of lymphatic sequelae. This case report highlights the importance of integrating various techniques to create a tailored approach that effectively addresses complex surgical requirements to avoid limb amputation and maintain functionality.

Anemia and its association with glycemia and transaminitis in patients with type 2 diabetes mellitus: A cross-sectional pilot study.

Background and Aims: Anemia impairs glucose homeostasis, affects glycemic control, and predisposes to complications in diabetics. It correlates with oxidative stress and increases the risk of developing microvascular and macrovascular complications. However, it is an underrecognized comorbidity in diabetics. This study was conducted to assess the prevalence of anemia in diabetic patients and compare the metabolic profiles of anemic and non-anemic diabetics. Methods: This is a cross-sectional study, conducted among type 2 diabetes (T2DM) patients, at the outpatient clinic. Patients with chronic kidney disease (CKD), known hematological disorders, and chronic inflammatory disorders were excluded. Results: Of the 97 patients, 37 (38.14%) were found to be anemic (hemoglobin (Hb): male <13 g/dl, female <12 g/dl). The mean values of fasting blood sugar (FBS) in low and normal mean corpuscular volume (MCV) patients were 265.9 ± 43.7 mg/dl and 157.2 ± 7.2 mg/dl, respectively (P = 0.0026), and those of postprandial blood sugar (PPBS) were 370.3 ± 58.4 mg/dl and 226.3 ± 10.1 mg/dl, respectively (P = 0.0015). It was found that 6 (22.2%) of 27 patients with raised alanine aminotransferase (ALT) had anemia against 27 (45.8%) of 59 patients with normal ALT (P = 0.03). The mean Hb levels in patients with raised and normal ALT were 13.31 ± 2.3 gm% and 12.2 ± 2.0 gm% (P = 0.03), respectively. Conclusions: Blood sugar may have a direct relationship with MCV in T2DM patients. Hb tends to relate to hepatic enzymes likely due to altered dietary patterns in anemics. Further larger studies on the effect of iron supplementation and dietary habits on glycemic control and hepatic steatosis are warranted.

The AST/ALT ratio predicts survival and improves oncological therapy decisions in patients with non-small cell lung cancer receiving immunotherapy with or without radiotherapy.

Background and purpose: Immunotherapy, with or without radiotherapy (iRT or ICIs-nonRT), is the standard treatment for non-small cell lung cancer (NSCLC). Nonetheless, the response to the treatment varies among patients. Given the established role of aspartate aminotransferase/alanine transaminase (AST/ALT) ratio in predicting cancer prognosis, we sought to identify whether the pre-treatment AST/ALT ratio has the potential to serve as a prognostic factor for NSCLC patients receiving ICIs-nonRT and iRT. Materials and methods: We retrospectively analyzed NSCLC patients who received immunotherapy between April 2018 and March 2021. Patients were classified into iRT group and ICIs-nonRT group and further classified based on AST/ALT ratio cut-off values. The Kaplan-Meier (KM) method estimated the time-to-event endpoints (progression-free survival (PFS) and overall survival (OS). Results: Of the cohort, 239 underwent ICIs-nonRT and 155 received iRT. Higher AST/ALT ratios correlated with worse outcomes in the ICIs-nonRT group but indicated better outcomes in those who received iRT. Multivariate analysis validated AST/ALT ratio as an independent prognostic factor. For AST/ALT ratios between 0.67-1.7, both ICIs-nonRT and iRT yielded similar treatment outcomes; with AST/ALT ratios greater than 1.7, iRT could be a more favorable treatment option (P=0.038). Conversely, for ratios less than 0.67, ICIs-nonRT could be a more favorable treatment option (P=0.073). Conclusions: The pre-treatment AST/ALT ratio demonstrates potential as a prognostic marker for treatment outcomes in NSCLC patients receiving either ICIs-nonRT or iRT. This finding could help guide clinicians in selecting more effective treatment protocols, thereby enhancing patient prognosis.

Effectiveness of sarcopenia screening markers in predicting out-of-hospital death in the oldest (≥80 years) older.

OBJECTIVE: The goal of this investigation was to elucidate the correlation between sarcopenia screening indicators (aspartate transaminase/alanine transaminase (AST/ALT) and creatinine/cystatin C*100 (Cr/CysC*100)) and the risk of out-of-hospital (OFH) death among the very advanced age (≥80 years) population. METHODS: We conducted a retrospective cohort investigation, involving internal medicine inpatients aged ≥80 years of age, who sought treatment at a teaching hospital in western China. We obtained OFH mortality information from telephonic interviews. Subsequently, we employed Cox proportional hazards models to analyze the links between AST/ALT and Cr/CysC*100 and OFH all-cause mortality among the very advanced age (≥80 years old) population. RESULTS: In all, we recruited 398 subjects, among which 51.51% were male. The median age of OFH deceased male patients was 85 years, and the same for female patients was 87 years. The total quantity of OFH deaths was 164 (41.21%). Among the oldest male population, those who died OFH exhibited enhanced AST/ALT, relative to those who survived (death vs. survival: 1.5 vs 1.3, P=0.008). However, among the oldest female, there was no difference in AST/ALT between patients who expired OFH, and those who survived. Among the oldest elders (male and female), Cr/CysC*100 did not significantly differ between surviving and OFH deceased patients. Additional analysis involving the Cox proportional hazards model revealed that among the oldest male population, an enhanced AST/ALT denoted an augmented risk of OFH death (hazard ratios (HRs) =1.797, 95%CI: 1.2-2.691). However, Cr/CysC*100 was not correlated with OFH mortality risk. Among the oldest female population, neither AST/ALT nor Cr/CysC*100 was correlated with OFH mortality risk. CONCLUSIONS: Enhanced AST/ALT was correlated with an augmented OFH mortality risk among the oldest male, but not female population. Alternately, Cr/CysC*100 was not linked to OFH mortality risk among any population.

Strong associations between fasting lipids and glucose concentrations and ALT levels strengthened with increasing ALT quantiles.

BACKGROUND: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. METHODS: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. RESULTS: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. CONCLUSIONS: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.

The Past, Present, and Future of Perforator Flaps in Head and Neck Surgery.

A perforator is a vessel that travels through muscle and perfuses the skin. Perforator flaps require intramuscular dissection and can be used as pedicled or free flap. With improved understanding of microvasculature, they can be tailored to have multiple skin paddles, multiple components, or shaped to conform to any defect. Reliable perforator flap-based reconstruction is a meticulous microvascular technique, ultimately allowing the surgeon to harvest any flap in a freestyle fashion and transplant to any recipient vessel. New technologies improve the safety and reproducibility of this type of reconstruction.

Reconstructive management of a patient with Tessier number 10 cleft.

Tessier number 10 cleft is one of the rarest facial clefts. Surgical treatment of this type of cleft is challenging due to the complexity of periorbital and temporal soft tissue deformities. A 23-year-old male patient presented with typical facial deformities of Tessier number 10 cleft. The surgical procedure involved using a free anterolateral thigh flap to reconstruct the eye socket, while the superficial temporal artery pedicle scalp flap was used to reconstruct the eyebrow deformity. The patient had no complications and 16 months after surgery, the patient had good aesthetic results. A hair-bearing scalp flap with a pedicle of the frontal branch of the superficial temporal artery combined with an anterolateral thigh-free flap can effectively resolve most soft tissue deformities of Tessier number 10 cleft and reconstruct the orbital socket in a single surgery. At the same time, it augments the soft tissue of the frontotemporal area and provides good aesthetic results.

Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India.

Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% females and 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereas in the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01). Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However, compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higher bilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift toward prevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHC who are obese and have low platelet counts with higher liver enzymes.

Tailoring of ALT Flap for Optimizing Donor Site Morbidity.

Wide and irregular-shaped defects at the lower trunk region are not uncommon following wide local excision of tumors. Pedicled anterolateral thigh (ALT) perforator flap has been the workhorse for these types of defects. But, in most of the cases flap donor sites cannot be closed primarily due to wide and irregular-shaped flap requirement. We propose a method of harvesting ALT flap in elliptical shape, dividing it into two or more geometrically predesigned islands based on perforators and rearranging them to fit into the defect, and thus achieving primary closure of the flap donor site.