Elevated Aspartate Aminotransferase Research Articles

Metformin alleviates doxorubicin-induced hepatic damage by modulating oxidative stress: a molecular, biochemical, and histopathological approach in a rat model.

Doxorubicin (DOX) is one of the most commonly prescribed anti-cancer drugs. However, DOX-induced hepatotoxicity is a dose-limiting side effect. This study aimed to clarify the potential protective effects of metformin on DOX-induced hepatotoxicity in rats. The animals were divided into six groups (n = 6 each): Control Group, DOX group, metformin 200mg/kg group, DOX + metformin 50mg/kg group, DOX + metformin 100mg/kg group, and DOX + metformin 200mg/kg group. Hepatic injury was induced by a single intraperitoneal injection of DOX (20mg/kg). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in serum were determined. Furthermore, the hepatic histopathological changes were evaluated. To identify the markers of oxidative stress, the level of malondialdehyde (MDA) and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver tissue were measured. Results showed that DOX provoked a marked elevation in ALT, AST, and ALP serum levels. In addition, oxidative stress was significantly boosted in DOX-treated rats compared to control rats. All these were abolished with the metformin administration. Histological examination also showed that metformin could substantially reduce DOX-induced alterations. The most prominent effect was observed by high-dose metformin.

A phase II study of fruquintinib plus sintilimab as a second-line therapy for advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results.

407 Background: Preliminary results of the open-label, single-arm phase II study (NCT05625737) had demonstrated the combination of fruquintinib and sintilimab as a second-line therapy had a promising anti-tumor activity and an acceptable safety profile in pts with advanced GC/GEJC (ASCO-GI 2024. Poster 332). Here, we update the results with a focus on subgroup analyses. Methods: Patients (pts) aged 18-75 years who were HER2-negative and had failed first-line standard treatment were enrolled. Eligible pts received 4mg of fruquintinib orally once daily on days 1-14 and 200 mg of sintilimab intravenously on day 1, with treatment repeated every 3 weeks. An optimal Simon two-stage design was employed. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: At data cut-off (August 25, 2024), 29 pts (7 in the first stage; 22 in the second stage) with median age 51 (range 33–73) years old had been enrolled. 41.4% were male, 37.9% had ECOG PS 1, 69% had lymph node metastasis and 72.4% had previously received immunotherapy. Among the 24 efficacy evaluable pts, the ORR was 33.3% (95% CI 15.6–55.3) and DCR was 66.7% (95% CI 44.7–84.4). After a median follow-up of 13.14 months, the median PFS was 5.13 (95% CI: 2.73–7.03) months and OS result was pending maturity. Pts who had lymph node metastasis exhibited higher ORR compared to pts without lymph node metastasis (ORR-47.1 vs 0%). In particular, pts without prior immunotherapies were more likely to achieve higher response rate (37.5 vs 33.3%) and had an obvious trend for longer PFS than pts with prior immunotherapies (9.00 vs 5.13 months). Majority of treatment-emergent adverse events (TEAEs) were grade 1-2 and the most frequently reported ones (≥20%) were white blood cell decreased (33%), hypertriglyceridemia (25%), lymphocyte count decreased (21%), abdominal pain (21%) and decreased appetite (21%). Grade 3/4 TEAEs occurred in only one patient, consisting of increased blood bilirubin levels, aspartate transaminase elevation, and alanine transaminase elevation. Conclusions: Fruquintinib combined sintilimab was well tolerated, with encouraging antitumor activity as second-line treatment for advanced GC/GEJC, especially in pts without prior immunotherapies. Further studies in larger cohorts to validate these findings are warranted. Clinical trial information: NCT05625737 .

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.

Predictors of liver fibrosis progression in cohort of type 2 diabetes mellitus patients with MASLD

AimTo investigate predictors of liver fibrosis progression in patients with T2DM over a minimum follow-up duration of three years. MethodsTwo hundred and thirty-three patients completed the follow-up period and their clinical, laboratory and liver FibroScan data are reported. Patients were categorized into progressors 42 (18.0 %) and non-progressors 191 (82.0 %) based on liver fibrosis progression. Factors influencing fibrosis progression were identified by comparing these groups. ResultsProgressors showed significantly increased aspartate aminotransferase (AST) (p = 0.010), increased alkaline phosphatase (ALP) (p = 0.001) and decreased platelet count (p = 0.002). Non-progressors exhibited significant decreases in diastolic blood pressure (DBP) (p = 0.050), body mass index (BMI) (p < 0.001), waist circumference (p < 0.001), gamma-glutamyl transferase (GGT) (p < 0.001), albumin (p < 0.001), alanine aminotransferase (ALT) (p = 0.022), glycosylated haemoglobin (HbA1c) (p = 0.002) and fasting blood sugar (FBS) (p = 0.030) with increase in HDL-cholesterol (p < 0.001), creatinine (p < 0.001), bilirubin (p < 0.001), and ALP (p = 0.007). Baseline parameters predictive of liver fibrosis progression included elevated AST and reduced platelet count. Delta changes from baseline to follow-up revealed that increases in ALP, BMI, waist circumference, and reduction in platelet count were correlated with fibrosis progression. Use of GLP-1 receptor agonist was associated with reduced progression. ConclusionIn conclusion, increase in ALP and waist circumference and reduction in platelet count are predictive of liver fibrosis progression in patients with T2DM. GLP-1 receptor agonists use seems to have a promising protective effect against liver fibrosis progression.ClinicalTrials.govID:NCT05697991

Lazertinib-Induced Rhabdomyolysis in a Patient With Non-Small Cell Lung Cancer: A Case Report.

Lazertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor effective in patients with non-small cell lung cancer. Although generally well tolerated, this case report presents a rare occurrence of common terminology criteria for adverse events grade 3 rhabdomyolysis in a 69-year-old Korean woman after taking lazertinib. The patient exhibited general weakness and tea-coloured urine with elevated levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), serum myoglobin and hyperkalemia. Lazertinib was temporarily discontinued, and urine alkalization was initiated. After the patient's condition improved, lazertinib was restarted at a reduced dose (80 mg) without any adverse effects. This case highlights the importance of assessing CPK and LDH levels in patients undergoing treatment with lazertinib, particularly in those with myalgia and elevated AST levels. Further studies are required to clarify the mechanisms underlying lazertinib-induced rhabdomyolysis.

P-1922. Liver Function Test Abnormalities near Admission Predict Mortality for Patients with COVID-19: A Single-Center Study

Abstract Background Early data from the COVID-19 pandemic shows patients commonly present with abnormal liver function tests (LFTs) upon admission. This phenomenon is multifactorial and is associated with increased in-hospital mortality and disease severity. There is limited data describing COVID-19 LFT derangements in the United States, and few comparisons of LFT derangements between variants. Methods This is a retrospective cohort study that includes non-pregnant adults admitted at Parkland Health and Hospital System from 03/01/2020 to 12/31/2021 with laboratory confirmed or ICD-10-documented COVID-19. We examine the association of LFT derangement (within 24 hours of admission) and mortality using multivariate logistic regression adjusting for baseline demographics, comorbidities, oxygen requirement, and lab values previously reported to be associated with COVID-19 mortality. We also examine this association after excluding patients with prior liver disease, viral hepatitis, and use of remdesivir prior to measuring LFTs. Finally, we compare LFT derangement patterns between variants (defined by date).Table 2.Multivariate logistic regression of liver function tests as predictors for mortality Results In our cohort of 3587 patients, over 93% had an available LFT. Abnormalities of aspartate aminotransferase (AST) and alkaline phosphatase (AP) are more prevalent in the deceased group (Table 1). Multivariate logistic regression shows that severely elevated AST and abnormal AP are consistently associated with mortality, while severely elevated alanine aminotransferase (ALT) is associated with mortality only in patients with no prior liver disease, viral hepatitis or remdesivir use (Table 2). Our analysis reveals significant differences in the frequency of AST and ALT abnormalities based on the variant, with the delta variant showing the highest occurrence of abnormalities. However, we do not find a significant difference in mortality between variants (Table 3).Table 3.Distribution of liver function tests and mortality rate by SARS-CoV-2 variant Conclusion This study highlights the consistent association between elevated LFTs at admission and mortality in COVID-19 patients, suggesting close monitoring by clinicians. It also demonstrates that COVID-19 is a systemic illness. Further studies are warranted to elucidate variant-specific differences in the association between LFT derangements and mortality. Disclosures Mamta K. Jain, MD, MPH, Abbvie: Grant/Research Support|Gilead Sciences: Grant/Research Support|Laurent: Grant/Research Support

Clinical features of abnormal α-fetoprotein in 15 patients with chronic viral hepatitis B after treatment with antiviral drugs.

Liver function of chronic hepatitis B (CHB) patients is essentially normal after treatment with antiviral drugs. In rare cases, persistently abnormally elevated α-fetoprotein (AFP) is seen in CHB patients following long-term antiviral treatment. However, in the absence of imaging evidence of liver cancer, a reasonable explanation for this phenomenon is still lacking. To explore the causes of abnormal AFP in patients with CHB who were not diagnosed with liver cancer. From November 2019 to May 2023, 15 patients with CHB after antiviral treatment and elevated AFP were selected. Clinical data and quality indicators related to laboratory testing, imaging data, and pathological data were obtained through inpatient medical records. All patients had increased AFP and significantly elevated IgG. Cancer was excluded by imaging examination. Only four patients had elevated alanine aminotransferase, 10 had elevated aspartate aminotransferase, nine had elevated total bilirubin, and two had antinuclear antibodies. The liver biopsy and histopathological examination indicated that 14 patients had rosette, moderate, or higher interfacial inflammation, lymphocyte infiltration, and severe hepatic fibers (11 cases), which was consistent with the pathological features of autoimmune hepatitis (AIH). After 8-12 week of hormone therapy, the levels of AFP and IgG, and liver function returned to normal (P < 0.05). For patients with CHB and elevated AFP after antiviral treatment, autoimmune hepatitis should be considered. CHB with AIH is clinically insidious and difficult to detect, and prone to progression to cirrhosis. Liver puncture pathological examination should be performed when necessary to confirm diagnosis.

Efficacy and safety of first-line nivolumab plus ipilimumab treatment in elderly patients (aged ≥ 75 years) with non-small cell lung cancer

PurposeNivolumab plus ipilimumab (Nivo-Ipi) combination therapy is an effective first-line treatment for advanced non-small cell lung cancer (NSCLC). However, its effectiveness and feasibility in elderly patients (aged ≥ 75 years) remain unclear. This study aimed to investigate the efficacy and safety of first-line Nivo-Ipi therapy in elderly patients with NSCLC.MethodsThis retrospective study included 57 patients with NSCLC (52 men and 5 women), aged ≥ 75 years (range: 75–86) who received first-line Nivo-Ipi therapy from December 2020 to November 2022 at four institutes in Japan. Patient characteristics, therapeutic efficacy, and the incidence and severity of adverse events (AE) were assessed.ResultsThe overall response rate was 42.1%, the disease control rate was 73.6%, the median progression-free survival (PFS) was 7.1 months, and the median overall survival (OS) was 14.1 months. Common Grade ≥ 3 AEs included pneumonitis, elevated aspartate transaminase, elevated alanine transaminase, adrenal insufficiency, and colitis. No treatment-related deaths were reported. PFS and OS were longer in patients who experienced treatment-related AEs. Patients with and without AEs had a median PFS of 11.7 and 2.8 months, respectively. Similarly, the median OS of patients with and without AEs was 20.4 and 9.0 months, respectively.ConclusionFirst-line Nivo-Ipi therapy is effective in elderly patients with NSCLC. Although there was an increased incidence of pneumonitis, the treatment was manageable and presented as a viable treatment option. Notably, the occurrence of treatment-related AEs was associated with improved clinical outcomes, suggesting a potential prognostic value of AEs in this population.

Timosaponin B II as a novel KEAP1-NRF2 inhibitor to alleviate alcoholic liver disease:Receptor structure-based virtual screening and biological evaluation.

Oxidative stress induced by excess ethanol is an important factor in the progression of alcoholic liver disease (ALD). In recent years, inhibiting Kelch-like ECH-associated protein 1 (KEAP1) to activate the antioxidant regulator Nuclear factor erythroid 2-related factor 2 (NRF2) has been considered an effective strategy for treating oxidative stress-related diseases, but its application in ALD remains insufficiently explored. This study aims to discover high-affinity inhibitors targeting the KEAP1 receptor. We conducted virtual screening of a compound library based on a structure-based pharmacophore model, ultimately identifying the candidate compound Timosaponin B II (TBII). Subsequently, we established ALD models in AML-12 cells and C57BL/6 mice, and evaluated the therapeutic effects and mechanisms of TBII on ALD using methods including Immunofluorescence, Western blotting, RT-qPCR, Biochemical assays, and histological staining. Results indicate that TBII significantly improved ethanol-induced liver injury, inhibited the elevation of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Cholesterol (T-CHO), and Triglycerides (TG) levels, and reduced lipid droplet accumulation in liver tissues. Furthermore, TBII treatment enhanced the antioxidant capacity of AML-12 cells and mouse liver, increasing Glutathione (GSH) and Superoxide Dismutase (SOD) levels while reducing Malondialdehyde (MDA) and Reactive Oxygen Species (ROS) levels. Mechanistic studies indicated that TBII inhibited the ethanol-induced increase in KEAP1 and reversed the ethanol-induced changes in NRF2 and its downstream targets. In conclusion, this study suggests that TBII may become a potential therapeutic agent for ALD by modulating the KEAP1-NRF2 pathway to alleviate oxidative stress and lipid metabolism abnormalities.

Ten Machine Learning Models for Predicting Preoperative and Postoperative Coagulopathy in Patients With Trauma: Multicenter Cohort Study.

Recent research has revealed the potential value of machine learning (ML) models in improving prognostic prediction for patients with trauma. ML can enhance predictions and identify which factors contribute the most to posttraumatic mortality. However, no studies have explored the risk factors, complications, and risk prediction of preoperative and postoperative traumatic coagulopathy (PPTIC) in patients with trauma. This study aims to help clinicians implement timely and appropriate interventions to reduce the incidence of PPTIC and related complications, thereby lowering in-hospital mortality and disability rates for patients with trauma. We analyzed data from 13,235 patients with trauma from 4 medical centers, including medical histories, laboratory results, and hospitalization complications. We developed 10 ML models in Python (Python Software Foundation) to predict PPTIC based on preoperative indicators. Data from 10,023 Medical Information Mart for Intensive Care patients were divided into training (70%) and test (30%) sets, with 3212 patients from 3 other centers used for external validation. Model performance was assessed with 5-fold cross-validation, bootstrapping, Brier score, and Shapley additive explanation values. Univariate logistic regression identified PPTIC risk factors as (1) prolonged activated partial thromboplastin time, prothrombin time, and international normalized ratio; (2) decreased levels of hemoglobin, hematocrit, red blood cells, calcium, and sodium; (3) lower admission diastolic blood pressure; (4) elevated alanine aminotransferase and aspartate aminotransferase levels; (5) admission heart rate; and (6) emergency surgery and perioperative transfusion. Multivariate logistic regression revealed that patients with PPTIC faced significantly higher risks of sepsis (1.75-fold), heart failure (1.5-fold), delirium (3.08-fold), abnormal coagulation (3.57-fold), tracheostomy (2.76-fold), mortality (2.19-fold), and urinary tract infection (1.95-fold), along with longer hospital and intensive care unit stays. Random forest was the most effective ML model for predicting PPTIC, achieving an area under the receiver operating characteristic of 0.91, an area underthe precision-recallcurve of 0.89, accuracy of 0.84, sensitivity of 0.80, specificity of 0.88, precision of 0.88, F1-score of 0.84, and Brier score of 0.13 in external validation. Key PPTIC risk factors include (1) prolonged activated partial thromboplastin time, prothrombin time, and international normalized ratio; (2) low levels of hemoglobin, hematocrit, red blood cells, calcium, and sodium; (3) low diastolic blood pressure; (4) elevated alanine aminotransferase and aspartate aminotransferase levels; (5) admission heart rate; and (6) the need for emergency surgery and transfusion. PPTIC is associated with severe complications and extended hospital stays. Among the ML models, the random forest model was the most effective predictor. Chinese Clinical Trial Registry ChiCTR2300078097; https://www.chictr.org.cn/showproj.html?proj=211051.

Isotretinoin and Hepatotoxicity in Patients with Acne: A Narrative Review

Acne vulgaris is a prevalent dermatological condition that is often treated with isotretinoin, a potent medication effective in moderate to severe cases. However, its use requires careful monitoring because of its potential hepatotoxic effects. Isotretinoin has been associated with transient elevations in liver enzyme levels, with mild abnormalities observed in up to 11% of cases. Severe elevations (grade ≥ 3), indicating potential liver dysfunction, occur infrequently, with an incidence of approximately 0.2% to 0.5%. The mechanisms underlying isotretinoin-induced liver injury involve oxidative stress and genetic susceptibility, primarily manifesting as idiosyncratic drug-induced liver injury. Most enzyme abnormalities occur within the initial months of treatment, and their clinical significance varies, with many cases resolving without intervention. A review of large cohort studies highlighted the incidence of abnormal liver function tests, including elevated alanine aminotransferase and aspartate aminotransferase levels. These abnormalities are often present within the first 3 months of therapy, particularly at higher cumulative doses. The role of routine liver function monitoring is debated, with recommendations favoring baseline and early follow-up tests and further testing guided by clinical indicators. Alanine aminotransferase may serve as a more specific marker for liver injury compared to other markers, such as aspartate aminotransferase. This review highlights the importance of evidence-based guidelines to balance effective acne treatment with the risk of isotretinoin-induced hepatotoxicity. Standardizing monitoring protocols and integrating genetic and oxidative stress markers may enhance safety and therapeutic outcomes. Further research is essential to refine these strategies and address gaps in long-term hepatotoxicity data.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks. Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment. In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT;68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause. Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.

Utility of ursodiol prophylaxis against sinusoidal obstruction syndrome (SOS)/ veno-occlusive disease (VOD) in acute leukemia patients receiving gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO).

Sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication in hematopoietic stem-cell transplant (HSCT) patients. Gemtuzumab-ozogamicin (GO) and InO are known to cause SOS/VOD in leukemic and transplant populations. Due to limited data on ursodiol prophylaxis in non-HSCT patients, we aimed to assess hepatotoxicity, SOS/VOD incidences, time to hepatotoxicity, and confirmed SOS/VOD in adults receiving GO or InO ± ursodiol. A multicenter, retrospective chart review of adult acute leukemia patients who received ≥1 dose of GO or InO at DFCI/some of the Harvard Cancer Centers during 4-year period (9/1/2017-9/1/2021). Acute promyelocytic leukemia patients and post-GO or InO HSCT-recipients (100-day follow-up period) were excluded. Descriptive summaries are provided, direct comparisons were made using Student T-test (continuous variables) and Fisher's exact test (categorical variables). In our population (N = 82), 87.8% received ursodiol and 12.2% did not. There were no significant differences in baseline to peak hepatic labs. The No-Ursodiol Group had higher incidence of Grade 3 aspartate aminotransferase (AST) transaminitis vs. the Ursodiol Group (60% vs. 20.8%; p = 0.015), and a trend towards shorter mean time to Grade 3 AST transaminitis (18.5 vs. 23.8 days; p = 0.30). Moreover, 4.2% of Ursodiol Group developed SOS/VOD vs. 0% in the No-Ursodiol Group (NS). Three patients developed SOS/VOD: 2 received GO, 1 received InO, and 2 were alive by the end of the follow-up period. In our cohort, ursodiol prophylaxis in adults receiving GO/InO is not associated with lower incidences of hepatotoxicity, SOS/VOD, or time to Grade 3 AST transaminitis, but is associated with decreased incidence of AST elevations.

Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria

BackgroundNumerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, particularly immune checkpoint...

Body Condition and Blood Biochemistry of Free-Range Caiman latirostris in Northeast Brazilian Atlantic Forest.

The Atlantic Forest broad-snouted caiman (Caiman latirostris) inhabits regions within one of the world's most ecologically diverse ecosystems, yet few studies have explored the relationship between body condition, blood biochemistry, and environmental factors in the wild. Our study investigated the effects of sex, ontogeny, habitat, and environmental variables on the body condition and blood biochemistry of free-ranging caimans from the state of Alagoas, Northeast Brazil. From 2020 to 2022, we captured 75 caimans across three sites in different seasons. Results revealed sex-specific responses to seasonal and Interannual weather changes, with females showing higher body condition in the wet season, while males peaked in the dry season. Elevated glucose, total protein, albumin, triglycerides, and fructosamine were linked to higher body condition and larger individuals, while elevated aspartate aminotransferase to low body condition. Seasonal rainfall influenced blood parameters, with the dry season associated with higher creatinine, calcium, and alanine aminotransferase levels, and the wet season with higher total protein, sodium, and potassium. Differences in glucose, alkaline phosphatase, and gamma-glutamyl transferase across sites pointed to physiological effects of human activities. Blood biochemical values varied widely, with some exceeding reported species ranges. These findings highlight the need to interpret physiological data within the context of local habitat and environmental conditions. Conservation strategies should go beyond species presence and habitat preservation, incorporating pollution control. Our study advances understanding of Caiman latirostris ecophysiology, offering valuable insights for the conservation and management of crocodilian populations in both wild and captive environments.

Bicalutamide does not raise transaminases clinically significantly compared to alternative anti-androgen regimens among transfeminine adolescents and young adults: a retrospective cohort study

Background Bicalutamide is a potential anti-androgen for transgender individuals with feminizing embodiment goals, but use is limited because of hepatotoxicity in cisgender men with prostate cancer. This study compared transaminase changes in transfeminine adolescents and young adults (AYA) using low dose bicalutamide with individuals using another androgen blockade. Methods A retrospective analysis was conducted using electronic health record data for patients starting gender affirming hormone therapy with at least 10 months of follow-up between 2015 and 2023. The primary outcome was change in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline. Linear mixed models compared change in ALT and AST from baseline and maximum ALT and AST values in bicalutamide and comparison groups. Secondary outcomes included % individuals with ALT and AST elevation more than 1, 2, or 3 times the upper limit of normal (ULN) (Fisher’s exact test), standardized mean estradiol dose by group (t test), and Tanner staging of breast tissue by group (Fisher’s exact test). Results Eighty-four transfeminine AYA (median age 18) taking bicalutamide were compared to 69 transfeminine AYA (median age 19) taking GnRH agonists, spironolactone or no agent in addition to estradiol. In linear mixed models adjusted for baseline age, race, BMI, baseline ALT or AST, and alcohol use, there were no clinically significant differences in delta or maximum ALT or AST in bicalutamide and comparison groups. No individuals had AST or ALT levels > 3x ULN though % with AST > ULN was higher for bicalutamide (10.7 v 1.5%, p = 0.02). Estradiol doses and Tanner stages were similar between groups among individuals receiving pediatric care. Conclusion Bicalutamide was not associated with a clinically significant change in transaminases as compared with other anti-androgen regimens over one year. Bicalutamide appears to be a safe anti-androgen for transfeminine individuals at low dose with close monitoring and deserves further study.

Clinical and biochemical abnormalities in a feline model of GM2 activator deficiency

Though it has no catalytic activity toward GM2 ganglioside, the GM2 activator protein (GM2A) is essential for ganglioside hydrolysis by facilitating the action of lysosomal ß-N-acetylhexosaminidase. GM2A deficiency results in death in early childhood due to rapid central nervous system deterioration similar to the related GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease. This manuscript further characterizes a feline model of GM2A deficiency with a focus on clinical and biochemical parameters that may be useful as benchmarks for translational therapeutic research. The GM2A deficient cat has clinical features consistent with the human condition, including isointensity of gray and white matter of the brain on T2-weighted MRI; MR spectroscopic changes of brain metabolites consistent with gliosis, neuronal injury and demyelination; rhythmical slowing of cerebral cortical activation on electroencephalography; and elevation of aspartate aminotransferase and lactate dehydrogenase in cerebrospinal fluid. Biochemically, the brain of GM2A deficient cats has storage of GM2 and GA2 ganglioside coincident with increased hexosaminidase activity toward a standard synthetic substrate. Also, the brain of GM2A deficient cats has increased levels of lyso-platelet activating factor and lyso-phosphatidylcholine, which may serve as novel biomarkers of disease progression and provide insights into pathogenic mechanisms.

Efficacy and safety of camrelizumab for the treatment of cervical cancer: a systematic review and meta-analysis.

Cervical cancer (CC) is a prevalent malignancy in women and ranks fourth in global cancer-related mortality. The prognosis for women with metastatic or recurring cervical cancer is unfavorable. Camrelizumab is a humanized high-affinity IgG4-kappa monoclonal antibody targeting programmed cell death 1 (PD-1), which has been progressively documented as a therapy for advanced cervical cancer with good result metrics. Nonetheless, a comprehensive investigation of Camrelizumab's efficacy in treating cervical cancer has yet to be conducted. We conducted a search across PubMed, Ovid Medline, Embase, Web of Science, Cochrane Library, Scopus, ProQuest, CNKI, Wan Fang, VIP database, and CBMdisc, restricting the establishment date of the databases to October 2024. The ROBINS-I Scale was utilized to evaluate the methodological quality of the included studies. Furthermore, information about CR, PR, SD, PD, ORR, DCR, median OS, median PFS, adverse events (AEs), and other relevant data was obtained. A meta-analysis was performed utilizing a random-effects model and effect size for illness. This meta-analysis included six trials, including 238 people with CC. The aggregated outcomes for patients were as follows: CR (0.097, 95% CI: 0.032-0.186), PR (0.465, 95% CI: 0.291-0.638), SD (0.264, 95% CI: 0.124-0.403), PD (0.174, 95% CI: 0.051-0.296), ORR (0.577, 95% CI: 0.354-0.799), DCR (0.784, 95% CI: 0.652-0.916), AEs (all grades: 0.836, 95% CI: 0.629-1.000, ≥grade III: 0.472, 95% CI: 0.111-0.834). The predominant treatment-related adverse events included anemia (≤grade II: 0.295, 95% CI: 0.187-0.402; ≥grade III: 0.124, 95% CI: 0.018-0.230), elevated aspartate aminotransferase (≤grade II: 0.196, 95% CI: 0.013-0.380; ≥grade III: 0.030, 95% CI: 0.007-0.053), neutropenia (≤grade II: 0.206, 95% CI: 0.150-0.261; ≥grade III: 0.114, 95% CI: 0.066-0.162), thrombocytopenia (≤grade II: 0.295, 95% CI: 0.187-0.402), and fatigue (≤grade II: 0.174, 95% CI: 0.046-0.303). This meta-analysis demonstrates that camrelizumab is efficacious and well-tolerated in patients with cervical cancer. https://www.crd.york.ac.uk/prospero/, identifier CRD42024527065.

Early Biomarkers for Detecting Subclinical Exposure to Fumonisin B1, Deoxynivalenol, and Zearalenone in Broiler Chickens.

Identifying biomarkers of mycotoxin effects in chickens will provide an opportunity for early intervention to reduce the impact of mycotoxicosis. This study aimed to identify whether serum enzyme concentrations, gut integrity, and liver miRNAs can be potential biomarkers for fumonisin B1 (FB1), deoxynivalenol (DON), and zearalenone (ZEA) toxicity in broiler birds as early as 14 days after exposure. A total of 720 male broiler chicks were distributed to six treatment groups: T1: control group (basal diet), T2 (2 FB1 + 2.5 DON + 0.9 ZEA), T3 (5 FB1 + 0.4 DON + 0.1 ZEA), T4 (9 FB1 + 3.5 DON + 0.7 ZEA), T5 (17 FB1 + 1.0 DON + 0.2 ZEA), and T6 (21 FB1 + 3.0 DON + 1.0 ZEA), all in mg/kg diet. On d14, there were no significant differences in the body weight gain (BWG) of mycotoxin treatment groups when compared to the control (p > 0.05), whereas on d21, T6 birds showed significantly reduced BWG compared to the control (p < 0.05). On d14, birds in T6 showed significant upregulation of liver miRNAs, gga-let-7a-5p (14.17-fold), gga-miR-9-5p (7.05-fold), gga-miR-217-5p (16.87-fold), gga-miR-133a-3p (7.41-fold), and gga-miR-215-5p (6.93-fold) (p < 0.05) and elevated serum fluorescein isothiocyanate-dextran (FITC-d) concentrations, aspartate aminotransferase (AST), and creatine kinase (CK) levels compared to the control (p < 0.05). On d21, T2 to T6 birds exhibited reduced serum phosphorus, glucose, and potassium, while total protein, FITC-d, AST, and CK levels increased compared to control (p < 0.05). These findings suggest that serum FITC-d, AST, CK, and liver miRNAs could serve as biomarkers for detecting mycotoxin exposure in broiler chickens.

The Effect of Administration of Centella asiatica (Pegagan) Leaf Extract on Clinical Outcomes of Adolescent Tuberculosis

Tuberculosis (TB) ranks among the top 10 causes of mortality worldwide. Indonesia stands third in Southeast Asia for the highest prevalence of TB cases. One of the adverse effects of Anti-Tuberculosis Drugs (ATD) is hepatotoxicity. Approximately 20% of patients treated with Isoniazid show elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels in their plasma. Despite the direct efficacy of ATD in managing TB, hepatotoxicity necessitates discontinuation of drug administration, leading to complications such as Multidrug-Resistant Tuberculosis (MDR-TB). Pegagan leaves (Centella asiatica) contain alkaloids with antibacterial properties. Extracts from Pegagan leaves have been shown to enhance expression of Cluster of Differentiation (CD)4, CD8, and macrophages. Furthermore, this extract can increase cytokine production, including Tumor Necrosis Factor-alpha (TNF-α) and Interferon-gamma (IFN-γ). Based on these premises, this study aims to investigate whether administration of Pegagan leaves extract significantly impacts levels of Hypoxia-Inducible Factor 1-alpha (HIF-1α), TNF-α, IFN-γ, Serum Glutamic Oxaloacetic Transaminase (SGOT), and Serum Glutamic Pyruvic Transaminase (SGPT) in teenage TB patients.