Elevated Alanine Aminotransferase Research Articles

Sonographic Analysis of Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Correlation with Obesity

Background: NAFLD is strongly associated with obesity and metabolic syndrome, arguably the most common liver disorders worldwide. To provide early diagnosis and prevention, we need to understand its predictors. Objectives: This study aimed to identify the clinical, biochemical and sonographic predictors for NAFLD in a cohort of patients with multivariate analysis. Methods: In our study, 537 patients: 340 with NAFLD as diagnosed by sonography. Clinical parameters (BMI and waist circumference) and biochemical markers (ALT, triglycerides, HDL cholesterol) were compared with demographic characteristics (age, gender and marital status). Sonographic findings involved evaluation of liver echogenicity, hepatomegaly, and steatosis. Multivariate logistic regression was used to identify odds ratios (OR) and 95% confidence intervals (CI) of NAFLD predictors. Results: All three measures (BMI, OR = 3.21, 95% CI: 1.8–5.3; waist circumference, OR = 4.02, 95% CI: 2.5–6.0; and waist/hip ratio, OR = 2.09, 95% CI: 1.3–3.3) were significantly associated with NAFLD. Elevated ALT (OR = 2.55, 95% CI: 1. The associations between NAFLD and 9–3.8), triglycerides (OR = 1.45, 95% CI: 1.2–1.9), and HDL cholesterol (OR = 0.35, 95% CI: 0.18–0.63) were lower. Sonographically, increased liver echogenicity (OR = 3.50, 95% CI: 2. Prevalence of NAFLD patients was 8–4.8 and (OR = 4.85, 95% CI: 3.2–7.1) for steatosis. Conclusion: Strong association exists between NAFLD and obesity, metabolic dysfunction, and characteristic sonographic features. Preventing disease progression requires early detection, via ultrasound, with weight loss and metabolic control interventions.

Genetic Risk, BMI Status, BMI Change Patterns, and the Risk of Steatotic Liver Disease and Liver Enzyme Elevation in Chinese Adults

Background/Objectives: Whether an increased genetic risk of steatotic liver disease (SLD) can be offset by maintaining a healthy weight remains unknown. We aimed to clarify the associations among the body mass index (BMI) and its change patterns with SLD and assess whether genetic susceptibility can modify these associations in Chinese people. Methods: A total of 10,091 and 6124 participants from the Health Omics Preventive Examination (HOPE) Program were enrolled in cross-sectional and follow-up analyses, respectively. BMI change patterns were defined according to the BMI at baseline and the last follow-up visit. Genetic risk was estimated using the polygenic risk score (PRS) derived from variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Data were analyzed using logistic regression models and Cox proportional-hazards models. Results: The analyses of the BMI and genetic risk simultaneously showed a dose–response association with the risk of SLD (p-trend < 0.001). Significant interactions between BMI and PRS were found for alanine aminotransferase (ALT) elevation (p = 0.007) and aspartate aminotransferase (AST) elevation (p < 0.001). Weight loss led to a 71%, 60%, and 67% lower risk of SLD, ALT elevation, and AST elevation, compared with stable overweight/obesity. A significant interaction between the genetic risk and BMI change patterns in ALT elevation was observed (p = 0.008). The absolute risk reductions associated with weight loss were greater for participants at a high genetic risk (26.60, 12.29, and 9.31 per 100 person years for SLD, ALT elevation, and AST elevation, respectively). Conclusions: Maintaining a healthy weight reduces the liver injury risk among all individuals, and the risk reduction is greater among the subset with a high genetic risk of SLD.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B

BackgroundXalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.MethodsWe conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.05 IU per milliliter) at 24 weeks after the end of treatment. Safety was also assessed.ResultsAmong 159 participants (30, 30, 34, 30, and 35 in groups 1 through 5, respectively), the primary end-point event occurred in 7% (95% confidence interval [CI], 1 to 22) of those in group 1, in 3% (95% CI, 0 to 17) of those in group 2, in 12% (95% CI, 3 to 28) of those in group 3, in 23% (95% CI, 10 to 42) of those in group 4, and in none (95% CI, 0 to 10) of those in group 5. In groups 1 through 5, respectively, HBsAg seroconversion occurred in 3%, none, 3%, 20%, and none of the participants at 24 weeks after the end of treatment. HBsAg loss with or without seroconversion occurred only in participants with a screening HBsAg level below 1000 IU per milliliter. In groups 1 through 5, respectively, grade 3 or 4 adverse events occurred in 17%, 10%, 18%, 50%, and 6% of the participants, with the most frequent event being an elevated alanine aminotransferase level.ConclusionsAmong participants with chronic HBV infection who had virologic suppression with NA therapy, treatment with xalnesiran plus an immunomodulator resulted in HBsAg loss at 24 weeks after the end of treatment in a substantial percentage of participants. Grade 3 or 4 adverse events were not uncommon. (Funded by F. Hoffmann–La Roche; Piranga ClinicalTrials.gov number, NCT04225715.)

"Polyethylene Terephthalate Nanoplastics Caused Hepatotoxicity in Mice Can be Prevented by Betaine: Molecular and Immunohistochemical Insights".

Polyethylene terephthalate nanoplastics (PET-NPs) are one of the most frequently distributed nanoplastics in daily life. Betaine is thought to be a promising hepatoprotective agent. The current investigation focused on whether orally administered PET-NPs caused hepatotoxicity and ameliorative effect of betaine. Forty adult male Swiss albino mice were randomly split into four groups: group I control, group II betaine (1000 mg/kg I/P), group III PET-NPs (200 mg/kg orally), and group IV betaine plus PET-NPs at doses similar to group II& III respectively. After 30 days, blood sample were collected then animals were euthanized and liver specimens were dissected out for biochemical and histopathological examination. PET-NPs induced a significant elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), as well as an increase in the inflammatory genes a proto-oncogene (c-FOS) and cyclooxygenase 2 (COX2) (p ≤ 0.05), with a substantial decrease in glutathione (GSH) (p ≤ 0.05). Furthermore, on the level of histopathological analysis PET-NPs caused alterations in hepatic tissue architecture as vascular dilatation and congestion with hepatocytes degeneration, bile duct epithelial hyperplasia and inflammatory cell infiltrations While on the level of immunohistochemistry, PET-NPs trigger positive tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-ҠB) expression in comparison to control. Meanwhile, betaine treatment reduced the deleterious effects of PET-NPs. To summarize, PET-NPs may cause hepatotoxicity in mice, with a belief that betaine could mitigate the detrimental impact.

Impact of Sodium-Glucose Co-Transporter Type-2 Inhibitors on Alanine Aminotransferase Levels in Type-2 Diabetes Patients Having Features of Nonalcoholic Fatty Liver Disease: A Retrospective Cohort Study in Pakistan.

We aimed to elucidate the effectiveness of Sodium-glucose co-transporter-2 inhibitors (SGLT2-I) in the reduction of ALT among Type-2 diabetes patients (T2DM) with Non-alcoholic fatty liver disease (NAFLD). We retrospectively collected data from 120 files of T2DM, aged 30-60 years, with elevated ALT, and documented follow-up for one year from August 2018 - July 2019. The effects of SGLT2Is (Dapagliflozin and Empagliflozin) were evaluated using Generalized Estimating Equation (GEE) for analysis. The overall mean age was 48.9 ± 7.3 years, 57.5% were females, and the mean duration of diabetes was 8.5 ± 5.6 years. At baseline, the mean BMI was 32.5 ± 5.7 kg/m2, mean ALT was 51.6 IU/L ± 17.8 IU/L, and mean HbA1c was 8.5% ± 1.5%. There was a statistically significant reduction in mean ALT of 2.2 IU/L (p-value 0.02) with every 10 mg/dl increase in LDL among females using 10 mg Empagliflozin as compared to males not on SGLT2i. We observed an average reduction in mean ALT levels when SGLT2Is was initiated in T2DM patients having NAFLD. Apart from encouraging diet and lifestyle modification, early intervention with SGLT2Is may decrease liver-related morbidity and mortality resulting from NAFLD.

Effects of chronic cold stress and thermal stress on growth performance, hepatic apoptosis, oxidative stress, immune response and gut microbiota of juvenile hybrid sturgeon (Acipenser baerii ♀ × A. schrenkii ♂)

The current study was conducted to investigate the effects of chronic cold stress and thermal stress on the growth performance, hepatic oxidative status, immune response, apoptosis and gut microbiota in juvenile hybrid sturgeon. The fish (initial mean weight: 21.4 ± 0.3 g) was reared at three temperatures (14 °C, 22 °C, and 30 °C) for 16 d, which were termed as low temperature group (LT), moderate temperature group (MT), and high temperature group (HT), respectively, and the second group was regarded as control group in this study. Each group was assigned randomly to three tanks with 15 fish per replica. The results indicated that cold stress resulted in a significant reduction of growth metrics and a significant increase of feed conversion ratio in fish compared with MT group. Interestingly, cold stress increased hepatocyte apoptosis revealed by TUNEL staining, along with nuclear disappearance in H&E-stained sections and elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Transcriptional levels of apoptosis-related genes and toll-like receptor signaling pathway components were significantly up-regulated in liver under cold stress. Compared with control group, in terms of thermal stress, the growth performance and feed utilization of fish were declined to some extent compared with MT group. Moreover, high temperature significantly elevated hepatic productions of malondialdehyde and hydrogen peroxide, as well as increased activities of some antioxidant enzymes in liver. In addition, low and high temperature induce changes in the composition of gut microbiota. Overall, the results suggested that cold stress decelerated growth performance, induced hepatocyte apoptosis, and enhanced innate immunity in hybrid sturgeon to cope with additional stressors. Whereas, thermal stress resulted in hepatic oxidative stress in liver and the protective responses in the antioxidant enzymes in fish were activated. These results provided insights into the different physiological adaptation strategies in responsive to cold stress and thermal stress in this cold-water fish.

Protective effects of nutrients and antioxidant-rich seed oil and sprouted seed oil of Benincasa hispida against formaldehyde-induced hepatic and renal damage

IntroductionIn traditional Chinese medicine (TCM), Benincasa hispida, commonly referred to as wax gourd, winter melon, or ash gourd, has been used extensively for managing fever, urinary dysfunction, cough with viscous mucus, pulmonary and periappendicular abscesses, edema, spermatorrhea, gonorrhea, discharge pus, and expel dampness. In this study, we investigated the antioxidant, macro- and micronutrients as well as the protective effects of Benincasa hispida seed oil (BHSO) and sprouted seed oil (BHSSO) against formaldehyde (FA)-induced liver and kidney damage in mice. MethodsThe in vitro antioxidant activity was evaluated using the DPPH radical scavenging assay. Protein, fat, fiber, and total carbohydrate contents were assessed, and micronutrients were determined using flame atomic absorption spectrophotometry. BHSO, BHSSO, and Vitamin E (3485 mg/kg, 3485 mg/kg, and 30 mg/kg p.o., respectively) were administered once daily shortly after formaldehyde exposure (10 mg/kg, I.P.) to separate groups of Swiss albino male mice for a period of 26 days to investigate their protective effects against hepatic and renal damage. The normal control group was given access to sterile tap water and a balanced diet, whereas the disease control group was given only 10 mg/kg of formaldehyde intraperitoneally. Results and DiscussionSerum ALT, AST, and creatinine levels were significantly elevated after formaldehyde (FA) administration. Histopathological examinations of liver and kidney tissue revealed degenerative changes in both organs. However, mice pretreated with BHSO and BHSSO showed a significant reduction in FA-induced elevations of serum ALT, AST, and creatinine levels and retained normal liver and kidney tissue histology. BHSO and BHSSO exhibited the ability to scavenge free radicals, as shown in vitro antioxidant studies. Essential micronutrients like zinc (Zn), copper (Cu), calcium (Ca), and chromium (Cr) were also found in both oils. These micronutrients may prevent the inactivation of antioxidant enzymes, thereby increasing free radical scavenging and preserving oxidation and antioxidant equilibrium. Moreover, both oils were found to contain crude fat and carbohydrates that are essential in safeguarding against formaldehyde-induced hepatic and renal damage by offering structural and metabolic support to cells and preserving membrane integrity. ConclusionBenincasa hispida seed oil and sprouted seed oil have significant protective effects against formaldehyde-induced hepatic and renal damage and serve as a valuable source of antioxidants, as well as macro- and micronutrients.

Hepatic Flare Following Effective Antiretroviral Therapy Is Associated With HBsAg Seroclearance in HBV/HIV-1 Co-Infection.

Little is known about the clinical significance of hepatic flare following effective antiretroviral therapy (ART) on HBsAg seroclearance and prognosis in HBV/HIV co-infection. This observational cohort study recruited HBV/HIV-1 co-infected patients from the China National Free Antiretroviral Treatment Program. We obtained longitudinal information on demographic characteristics, clinical indicators, and treatment outcomes. Hepatic flare was defined as an elevation of ALT of more than five times the upper limit of the normal range without an upsurge of HBV DNA or HBsAg at any time point between ART initiation and 12 months. Among the 1354 enrolled patients, 98.7% received two anti-HBV drugs containing ART and 95.1% achieved good viral control. Hepatic flare was observed in 88 (6.5%) patients and was more frequent in those with lower baseline immune function but subsequently enhanced immune reconstitution. Over a median follow-up of 4.7 years, we observed 99 HBsAg seroclearance, 9 hepatic events, 6 HIV-associated malignancy, 3 non-HIV-associated malignancy, and 3 all-cause mortality. The 3-, 5-, and 10-year cumulative incidence of HBsAg seroclearance was 6.4%, 8.9%, and 12.9%, respectively. Compared to patients without hepatic flare, patients with hepatic flare had significantly higher rates of HBsAg seroclearance (13.6% vs. 6.9%, p = 0.018) but had no recorded adverse outcome. Multivariate analysis with different models indicated that hepatic flare was independently associated with HBsAg seroclearance especially in patients with low immune function, normal ALT, and high levels of HBV DNA and HBsAg at baseline. In HBV/HIV-1 co-infection, hepatic flare following effective ART is associated with HBsAg seroclearance. HBV-specific T cells immune reconstitution may represent a potential mechanism which deserves further investigation.

The application of hepatopancreatoduodenectomy in advanced gallbladder carcinoma: Patients’ selection, surgical outcome and influence on survival compared to radical cholecystectomy

Aimto investigate hepatopancreatoduodenectomy (HPD) application in gallbladder carcinoma (GBC) and compare it to radical cholecystectomy (RC) regarding patients’ characteristics, surgical outcome and survival. MethodsPatients treated in our center were included. Three groups (HPD, RC, no-surgery) were compared. Comparisons included basic characteristics, liver function, tumor biomarkers, surgical complications, outcome, and survival. Differences in severity, surgical risks and survival were investigated. ResultsIn total, 19 patients in HPD, 89 in RC and 20 in no-surgery groups were included. Median follow-up was 42.0 months. Compared to RC, HPD group revealed increased severity represented by significantly higher rates of elevated ALT, AST, TB, DB, preoperative biliary decompression, T3/4, N1/2, stage III/IV, and MVI. Similar severity was observed between HPD and no-surgery groups. Additionally, HPD presented higher risks of perioperative bleeding, transfusion and complications (grade III/IV). Pancreatic fistula and delayed gastric emptying were most encountered in HPD and only one mortality was recorded. Although HPD had shorter survival in general population (HPD: 17 ± 5.804, RC: 49 ± 11.433,P < 0.001); however, in matched (PSM) advanced stages, its benefits matched RC (HPD: 17 ± 4.793, RC: 11 ± 1.169, P = 0.966). Significant survival advantages were observed when comparing HPD to no-surgery group (HPD: 17 ± 5.804, no-surgery: 7 ± 0.836, P = 0.013). ConclusionCases benefiting from HPD are usually severe and comparable to unresectable cases. Although HPD complexity and complication risks are higher than RC, the survival benefits of HPD in advanced GBC stages are not inferior. Thus, HPD is a valuable option in such patients and can be the only approach to achieve R0 resection.

Integrated multi-omics analyses combined with western blotting discovered that cis-TSG alleviated liver injury via modulating lipid metabolism.

Background: Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects. The bioactive components responsible for these effects are unknown. This study investigates whether cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (cis-TSG), a stilbene glycoside, has hepatoprotective and/or hepatotoxic effects in a liver injury model. Methods: C57BL/6J mice were administered α-naphthylisothiocyanate (ANIT) to induce cholestasis, followed by treatment with cis-TSG. Hepatoprotective and hepatotoxic effects were assessed using serum biomarkers, liver histology, and metabolomic and lipidomic profiling. Transcriptomic analysis were conducted to explore gene expression changes associated with lipid and bile acid metabolism, inflammation, and oxidative stress. Results and Discussion: ANIT administration caused significant liver injury, evident from elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and dysregulated lipid metabolism. cis-TSG treatment markedly reduced ALT and AST levels, normalized lipid profiles, and ameliorated liver damage, as seen histologically. Metabolomic and lipidomic analyses revealed that cis-TSG influenced key pathways, notably glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis. The treatment with cis-TSG increased monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs), enhancing peroxisome proliferator-activated receptor alpha (PPARα) activity. Transcriptomic data confirmed these findings, showing the downregulation of genes linked to lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. The findings suggest that cis-TSG has a hepatoprotective effect through modulation of lipid metabolism and PPARα activation.

The applications of Ursodeoxycholic acid in infant with cholestasis: A retrospective cohort analysis

Biliary atresia is the predominant etiology of cholestasis in early infancy. Impairment of bile fluid excretion results in elevated bilirubin levels, causing a yellowing of the skin. Ursodeoxycholic acid is well-established to enhance liver function when taken promptly. The application of ursodeoxycholic acid for treating cholestasis in pediatric patients remains contentious. The objective of this study is to assess the impact of ursodeoxycholic acid treatment on liver biomarkers in infant with cholestasis. This was retrospective cohort study in infant with cholestasis who underwent ursodeoxycholic acid treatment for two weeks. Secondary data including aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin were extracted from the medical records of the outpatient clinic in the Department of Child Health at Dr. Soetomo General Hospital, Indonesia (January 2020 - December 2023). The data was devided into two groups based on biopsy and examined utilizing SPSS version 23. This study included 64 participants. Statistics show an equal gender ratio. Ursodeoxycholic acid treatment in paediatric cholestasis patients can lower liver biomarker level. Levels of total bilirubin and direct bilirubin diminished in individuals both groups. Notable levels were recorded in individuals with normal biopsy outcomes (p=0.007 and p=0.012). Administration of ursodeoxycholic acid markedly elevated ALT levels in both the normal and abnormal liver biopsy outcome groups (p=0.031 and p=0.006). Ursodeoxycholic acid has been shown to be effective in improving liver function in infant with cholestasis. In order to avoid negative effects, the medication must be carefully administered to people who already have liver fibrosis.

Prevalence and factors of elevated alanine aminotransferase in central Taiwan – a retrospective study

Prevalence and factors of elevated alanine aminotransferase in central Taiwan – a retrospective study

BIOM-12. ALLIANCE A071401: GENOMICALLY GUIDED PHASE II TRIAL OF ABEMACICLIB IN PATIENTS WITH GRADE 2/3 MENINGIOMAS HARBORING SOMATIC NF2 OR CDK PATHWAY ALTERATIONS

Abstract BACKGROUND Patients with meningiomas that have progressed after surgery and/or radiation have limited treatments. Loss of NF2 and CDKN2A/B are common in higher-grade meningiomas and promote meningioma progression. We evaluated the efficacy of abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, as part of Alliance A071401, a genomically-driven phase II trial in recurrent or progressive meningiomas. METHODS Eligible patients (pts) with grade 2/3 tumors and NF2 mutations or CDK pathway alterations were treated with abemaciclib 200 mg orally twice daily. Two co-primary endpoints were used: progression-free survival at 6 months (PFS6) and response rate (RR); the trial would be declared positive if either endpoint was met. Twenty-four evaluable pts provided ≥85% power to detect a PFS6 ≥41.5% (vs. null 15%; alpha=0.02), and ≥89% power to detect RR ≥20% (vs. null 2.5%; alpha=0.021). RESULTS Of 83 pts screened while the abemaciclib arm was open between September 15, 2021 and October 3, 2022, 36 eligible pts received abemaciclib. The observed PFS6 rate in the first 24 evaluable pts was 54% (95% CI 33-75%), thus the study met PFS6 endpoint. Of all 35 evaluable pts, median PFS was 7.6 months (95% CI 3.6-17.1 months), estimated 6-month PFS was 55% (95% CI 40-75%) and estimated 6-month OS was 88% (95% CI 77-100%). No objective responses were observed. Of the 36 pts who started treatment, two had a grade 4 adverse event at least possibly related to treatment which included ALT elevation(1), AST elevation(1) and vomiting(1). Patients with NF2 alterations (n=24) had favorable PFS6 outcomes (58%, 95% CI 37-78%) compared to those with CDK (n=4, 25%, 95% CI 1-81%) and CDK+NF2 alterations (n=7, 29% 95% CI 4-71%), (Fisher’s Exact p=0.036). CONCLUSIONS Abemaciclib was well-tolerated and resulted in improved PFS6, meeting the trial’s co-primary endpoint. Abemaciclib warrants further investigation for the treatment of patients with progressive meningiomas.

Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia.

BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia (Ph)-like subtype, mediates leukemic cell survival. We treated 24 patients with 14 days of BCL-2 inhibitor, venetoclax, 400 mg daily (dose level 1) during induction and consolidation cycles combined with the CALGB 10403 regimen in newly diagnosed adults with Ph-negative B-ALL. Median age was 31 (range: 18-53) years, 92% were Hispanic, and 12 (50%) patients had Ph-like ALL. No dose limiting toxicity occurred in the phase 1 part. Median times to neutrophil and platelet count recovery were 20 and 21 days from start of induction, respectively. The most common grade ≥3 treatment-related adverse events were leukopenia (96%), neutropenia (83%), anemia (83%), thrombocytopenia (79%), lymphopenia (71%), hyperbilirubinemia (38%), and elevated ALT (33%). One patient with non-Ph-like ALL died from asparaginase-associated pancreatitis, and 23 (96%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) following induction with or without extended induction phase. Of 22 patients who started consolidation, 20 (91%) achieved negative minimal residual disease status (MRD-) (.

Efficacy and safety of favipiravir and remdesivir in COVID-19 patients: Clinical data

Aim. To evaluate the efficacy and safety of favipiravir and remdesivir in the infectious disease hospital of the Volgograd region in 2022. Materials and methods. In total, 559 medical records of patients prescribed favipiravir or remdesivir in 2022 were studied. Long-term results of the drug use and disease outcomes after discharge or transfer to another medical institution were assessed using the Federal registry of people with COVID-19. Results. Favipiravir was more frequently prescribed in mild cases of the disease. After excluding patients without signs of lung injury from the analysis, there were no significant differences in mortality and improvement. Patients receiving favipiravir had lower odds of ALT elevations above 5 upper limits of normal and developing drug-induced liver injury with a possible RUCAM score compared with patients receiving remdesivir (OR = 0.40, 95CI 0.20–0.80 and OR = 0.30, 95 CI 0.08–1.08). Conclusion. The limited experience of the use of favipiravir for COVID-19 necessitates further research into its efficacy and safety, particularly when prescribing warfarin and high doses of direct anticoagulants simultaneously.

Epidemiology and laboratory testing of Brucella spondylitis

The average age of patients with BS was 52.29 ± 9.46 years, comprising 136 males and 31 females. Risk factors for BS include close contact with cattle and sheep and consumption of unpasteurized food. The positive detection rate using combined Rose Bengal Test (RBT) and Standard Agglutination Test (SAT) was 94.6%, whereas the positive rate for blood culture was only 7.8%. The most common clinical manifestations were fever (81.4%), back pain (88.6%), sweating (61.1%), fatigue (69.5%), and anorexia (65.3%). Hematological examinations often revealed decreased hemoglobin (18.0%), increased platelets (18.0%), elevated erythrocyte sedimentation rate (ESR) (88.0%), elevated C-reactive protein (CRP) (78.4%), elevated Alanine aminotransferase (ALT) (18.6%), and decreased K+(23.4%). The imaging examinations revealed that the lumbar spine, particularly L4/5 (41.3%), is the most frequently affected vertebral level in BS. After treatment, the overall recurrence rate was 3.0%. In endemic areas, clinicians should be vigilant for BS in patients presenting with back pain and unexplained fever, particularly those with a history of close contact with cattle and sheep. The RBT and SAT tests show a high positivity rate of 94.6%, establishing them as the preferred diagnostic methods. This study enhances clinicians’ comprehension of BS characteristics and lays a robust theoretical groundwork for disease prevention and monitoring.

The Efficacy Research of Prophylactic PEG-rhG-CSF in Preventing Neutropenia in Early-Stage Breast Cancer Patients Treated With Docetaxel-Based Chemotherapy: A Retrospective Analysis

PurposeDocetaxel-based chemotherapy regimens (DBRs) are commonly used in the treatment of early-stage breast cancer (EBC). The prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) has been shown to reduce the incidence of neutropenia induced by DBRs. However, the clinical usage of PEG-rhG-CSF in EBC patients undergoing DBRs in China remains unclear. MethodsThis retrospective study was conducted in 137 EBC patients receiving DBRs from September 2022 to February 2024. We compared the incidence of chemotherapy-induced neutropenia (CIN) between patients who was treated with prophylactic PEG-rhG-CSF or not by complete blood counts, evaluating the effectiveness of PEG-rhG-CSF in preventing CIN. Prophylactic PEG-rhG-CSF was given at 100 μg/kg body weight (maximum total dosage of 6 mg) once 24–48 h following chemotherapy. Meanwhile, we also collected basic patient information, the area under time-concentration curve of docetaxel, and liver and kidney function indicators. Multivariate logistic regression and Receiver operating characteristic (ROC) curve analysis were employed to explore independent factors influencing neutropenia. FindingsIn this study, 87 of 137 EBC patients were administrated with prophylactic PEG-rhG-CSF, while 50 were not. Compared to patients who did not receive PEG-rhG-CSF, those who received prophylactic injections had a significantly lower incidence of grade 3–4 CIN (20% vs. 4.6%, P < 0.05). Higher body surface area (BSA), lower body mass index (BMI), elevated alanine aminotransferase (ALT), and nonprophylactic use of PEG-rhG-CSF were found to be positively correlated with CIN occurrence. ROC curve analysis indicated an area under the curve of 0.756 for predicting CIN in EBC patients when BSA was 1.66 m², BMI was 24.8 kg/m², and ALT was 41 U/L, with a sensitivity of 73.08% and specificity of 73.87%. ImplicationsProphylactic use of PEG-rhG-CSF significantly reduces the incidence of CIN, particularly grades 3 and 4. BSA, BMI, ALT, and PEG-rhG-CSF prophylaxis are independent influencing factors for the occurrence of neutropenia.

Comparison of SPISE and METS-IR and Other Markers to Predict Insulin Resistance and Elevated Liver Transaminases in Children and Adolescents.

Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population. Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points. All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point. SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

Predicting mortality of type-2 diabetes mellitus by applying machine learning to electronic medical records in the west of scotland and hong kong

Abstract Introduction Type 2 diabetes mellitus (T2DM) is associated with accelerated development of atherosclerosis and a reduced life expectancy. Using machine learning (ML) to identify novel characteristics from electronic medical records (EMRs) associated with prognosis may increase prognostic precision and find new targets for investigation and treatment. Aim We used a novel ML approach to investigate the use of EMRs to predict all-cause mortality in two ethnically and geographically different populations; one from the West of Scotland (WoS) and the other from Hong Kong. Methods We obtained EMRs including demographics, prior comorbidities, laboratory measurements, medications, and mortality. Multivariable Cox regression and time-dependent random forest model were used to identify predictors of all-cause mortality in patients with T2DM. Subsequently, we applied a state-of-the-art ML interpretability method, to gain further insight into the key predictors. Results In WoS, 46,031 individuals received a new diagnosis of T2DM between 2009 and 2019. Their median age was 66 (IQR: 56 to 75) years. Within 10 years, 11,727 (25%) deaths were recorded. In Hong Kong, 273,876 patients with a first-attendance with T2DM at public hospitals or clinics were included, with follow-up until December 2019. The median age of the patients was 64 (IQR: 57 to 72) years. Within 10 years, 91,155 (33%) deaths were recorded. For both cohorts, the strongest predictor for all-cause mortality was prescription of loop diuretics (Figure 1). For the WoS, other important predictors were greater age, lower serum albumin, elevated alanine transaminase (ALT), increased alkaline phosphatase (ALP), and lower estimated glomerular function rate (eGFR) (c-index: 0.83; Brier score: 0.07). For Hong Kong, predictive variables were remarkably similar and included greater age, lower eGFR, lower haemoglobin and lymphocytes, lower serum albumin, and elevated ALP (c-index: 0.85; Brier score: 0.06). Multivariable Cox regression adjusting for age and sex showed a higher mortality amongst those prescribed loop diuretics compared to those who were not (WoS: hazard ratio: 1.549, 95% CI: 1.521 to 1.575; Hong Kong: hazard ratio: 1.745 (95% CI: 1.721 to 1.769). Only a minority of patients prescribed loop diuretics had a diagnosis of heart failure, end-stage renal disease or resistant hypertension. Conclusion Amongst patients with recent-onset T2DM, prescription of loop diuretics was the most important predictor of all-cause mortality in both WoS and Hong Kong. Prescription of loop diuretics might be a pharmacological marker of congestion and undiagnosed heart failure or loop diuretics might have deleterious effects on the outcome of patients with T2DM.Fig 1:Predictors of all-cause Mortality

High eosinophil counts aid in diagnosing Kawasaki disease in febrile children

Abstract Background Several recent studies have validated the newfound significance of elevated eosinophils in Kawasaki disease (KD). However, this finding was not incorporated into the suggested laboratory criteria outlined by the Kawasaki Disease Committee of the American Heart Association for assessing children with incomplete KD. Purpose We aimed to determine the potential benefits of including eosinophil levels in the laboratory evaluation of KD. Methods A retrospective cohort study involved 77,934 febrile children (FC, not KD) and 1,970 subjects diagnosed with KD. Participants were recruited from four hospitals, comprising two medical centers and two regional hospitals. The AHA recommends specific laboratory tests—white blood cell count, hemoglobin, platelet count, ALT levels, albumin, and urinalysis—for evaluating incomplete KD in children with a higher CRP than 30mg/dL. The first four items are standard blood assays. Additionally, we introduced high eosinophil counts as a new diagnostic criterion for identifying children with KD. Results All these five laboratory findings (anemia for age defined as below the 5th percentile), platelet count &amp;gt;450,000/mm3, white blood cell&amp;gt;15,000/mm3, ALT&amp;gt;40 U/L, and eosinophil count &amp;gt;190/mm3) are significantly different between KD children and FC. The proportion of having these features is higher in KD children than in FC (19.3% vs. 8.0% in anemia for age, 20.5% vs. 10.3% in thrombocytosis, 37.0% vs. 18.1% in leukocytosis, 45.7% vs. 5.8% in elevated ALT, and 62.6% vs. 29.3% in high eosinophils). Elevated eosinophil counts are most commonly associated with KD among these five parameters. Furthermore, when incorporating the parameter of elevated eosinophil counts, the proportion of KD children with at least two abnormalities rose from 35.4% to 60.7%. In a subgroup analysis of children with KD presenting at least two abnormalities, the proportion rose from 38.7% to 63.5% in the high CRP group (≧ 3.0 mg/L) and 21.6% to 49.0% in the low CRP group (&amp;lt; 3.0 mg/L), respectively. Conclusions Higher eosinophil counts are vital markers in KD children. This aids in the identification of additional potential KD cases, especially in those exhibiting low CRP levels.