Higher Total Bilirubin Levels Research Articles

Turmeric Extract-loaded Selenium Nanoparticles Counter Doxorubicin-induced Hepatotoxicity in Mice via Repressing Oxidative Stress, Inflammatory Cytokines, and Cell Apoptosis.

Doxorubicin (DOX) is an antitumor anthracycline used to treat a variety of malignancies; however, its clinical use is associated with noticeable hepatotoxicity. Therefore, the current study was designed to delineate if biosynthesized SeNPs with turmeric extract (Tur-SeNPs) could alleviate DOX-induced hepatic adverse effects. Mice were orally post-treated with Tur extract, Tur-SeNPs, or N-acetyl cysteine after the intraperitoneal injection of DOX. Our findings have unveiled a remarkable liver attenuating effect in DOX-injected mice post-treated with Tur-SeNPs. High serum levels of ALT, AST, ALP, and total bilirubin induced by DOX were significantly decreased by Tur-SeNPs therapy. Furthermore, Tur-SeNPs counteracted DOX-caused hepatic oxidative stress, indicated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and mRNA expression levels of Nrf-2. Noteworthily, decreased hepatic IL-1β, TNF-α, and NF-κB p65 levels in addition to downregulated iNOS gene expression in Tur-SeNPs-treated mice have indicated their potent antiinflammatory impact. Post-treatment with Tur-SeNPs also mitigated the hepatic apoptosis evoked by DOX injection. A liver histological examination confirmed the biochemical and molecular findings. In brief, the outcomes have demonstrated Tur loaded with nanoselenium to successfully mitigate the liver damage induced by DOX via blocking oxidative stress, and inflammatory and apoptotic signaling.

Liver iron overload and fat content analyzed by magnetic resonance contribute to evaluatingthe progression of chronic hepatitisB.

Chronic hepatitis B (CHB) and its complications still have a major role in liver-related mortality. It has been indicated that hepatic iron and steatosis may influence liver fibrosis and carcinogenesis. The present study aimed to assess the liver iron and fat in patients with CHB by MRI in order to estimate the associations among liver iron, fat and the severity and progression of liver fibrosis. In the present retrospective study, consecutive patients with CHB examined from August 2018 to August 2020 were analyzed. Liver iron and fat content were assessed by MRI, which was measured as liver iron content (LIC) and proton density fat fraction (PDFF). A total of 340 patients were included in the current study. For LIC, the median value was 1.68 mg/g and elevated LIC was seen in 122 patients (35.9%). For liver fat content, the median value of PDFF was 3.1%, while only 15.0% of patients had liver steatosis (PDFF ≥5%). Age, total bilirubin and sex were independent predictive factors of liver iron overload [odds ratio (OR)=1.036, 1.005 and 8.834, respectively]. A higher platelet count (OR=1.005) and no portal hypertension (OR=0.381) independently predicted liver steatosis. The areas under the receiver operating characteristic curves of PDFF for the identification of liver cirrhosis estimated by different non-invasive tools ranged from 0.629 to 0.704. It was concluded that iron overload was common in patients with CHB, particularly in those with older age, male sex and high total bilirubin level, and liver steatosis was less common in CHB. Liver iron and fat content analyzed by MRI may contribute to the evaluation of the severity and progression of CHB.

Risk factors for coronary artery abnormalities and resistance to immunoglobulin plus ciclosporin A therapy in severe Kawasaki disease: subanalysis of the KAICA trial, randomized trial for cicrosporin A as the first-line treatment.

To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with Kawasaki disease (KD) receiving intravenous immunoglobulin (IVIG) plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a phase 3, randomized study (JMA-ILA00174). All data of the patients enrolled in the KAICA trial, who had a Gunma score ≥5 at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including genotypes of KD susceptibility genes were compared between subgroups of patients for CAA or treatment response for each treatment group. Backword-forward stepwise logistic regression analyses were performed. Pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was higher in patients with CAA in both treatment groups and was associated with CAA in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. High serum total bilirubin level was relevant to treatment resistance only in the IVIG plus CsA group (OR = 2.34). Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.

Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries.

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.

Correlation between pre-treatment serum total blood bilirubin and unconjugated bilirubin and prognosis in patients with colorectal cancer.

Epidemiological studies have found that unconjugated bilirubin (UCB) levels are positively correlated with the incidence of colorectal cancer (CRC). Therefore, bilirubin may also play an important role in the prognosis of CRC. To investigate the predictive value of total bilirubin (TBIL) and UCB in the prognosis of patients with CRC. A total of 142 CRC patients were selected as the research subjects in Jingxian Hospital, from October 2014 to May 2021. General and tumour-related clinical data at admission and the overall survival at 3 years after surgery were collected. The optimal cut-off values of TBIL and UCB were determined by receiver operating characteristic curve analysis. Univariate and multivariate Cox regression were used to analyse the effect of bilirubin level on the survival of CRC patients. The Kaplan-Meier method was used to assess the survival time. The 3-year overall survival rate of CRC patients was significantly higher in the high TBIL (> 13.45 μmol/L) group than in the low TBIL (≤ 13.45 μmol/L) group (76.4% vs 37.1%; P < 0.05). The 3-year overall survival rate of CRC patients in the high UCB (> 10.75 μmol/L) group was significantly higher than that in the low UCB (≤ 10.75 μmol/L) group (83.3% vs 34.2%; P < 0.05). Multivariate Cox regression analysis showed that higher TBIL levels were an independent predictor of better prognosis in CRC patients (hazard ratio = 0.360, 95% confidence interval: 0.159-0.812, P = 0.014). TBIL levels can be used as a prognostic indicator for CRC patients.

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study

BackgroundWeekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified.MethodsThis retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS).ResultsAmong 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216–124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052–477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141–137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0–5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8–13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9–15.7 month, P < 0.01 vs RF-2).ConclusionsCareful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.

Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis.

Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

STUDY TO KNOW THE EFFECT OF PHOTOTHERAPY ON SERUM CALCIUM LEVEL IN NEONATAL HYPERBILIRUBINEMIA

Background: Phototherapy is the most common method to treat neonatal jaundice. The effect of phototherapy on serum calcium levels is a questionable issue. Objective: To study to know the effect of phototherapy on serum calcium level in neonatal hyperbilirubinemia. Methods: Cohort study compared total serum calcium level before and after phototherapy in neonates with hyperbilirubinemia. Study was conducted on 54 neonates with high total serum bilirubin levels, according to the Bhutani curve and was treated with phototherapy at neonatal intensive care unit in the Department of Pediatrics at Mayo Institute of Medical Sciences from November 2021 to April 2022. Results: Hypocalcaemia was observed in 33.33% of neonates after phototherapy. The difference between pre- and post-phototherapy serum calcium levels was found to be statistically significant (p&lt;0.005). Conclusion: Hypokalcemia has a significant association with phototherapy.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body’s antioxidant defense system, reducing inflammation, and suppressing apoptosis.Graphical

Efficacy and predictors of immune checkpoint inhibitors in patients with gallbladder cancer.

e16124 Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) has shown promising efficacy in multiple cancers including biliary tract cancers (BTCs). However, the data focusing on the efficacy of ICIs in patients with gallbladder cancer (GBC) is still limited. This study aims to assess the efficacy of ICIs in GBC and explore the clinicopathological and molecular markers of ICI benefit. Methods: This was a single center, retrospective study, including 80 GBC patients who had received ICI (anti-PD-1 monoclonal antibody) therapy at Eastern Hepatobiliary Surgery Hospital (Shanghai, China) between January 2016 and December 2020. Tumor samples from 31 of these patients who had previously underwent surgical resection before ICI therapy were obtained and conducted for whole exome sequencing and immunohistochemical analysis. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR) and disease control rate (DCR). The associations between efficacy with clinicopathological factors, genetic variations and PD-L1/CD8 expression were further explored. Results: Of 80 patients with GBC, 36 were male, the median age was 61 years (range, 30-79). The median PFS and OS was 4.5 months (95% CI, 2.99-5.95) and 8.7 months (95% CI, 7.07-10.26) respectively. Multivariate analysis indicated that alcohol intake history (HR, 2.66; 95% CI, 1.31-5.40; p=0.007), extrahepatic metastasis (HR, 2.03; 95% CI, 1.15-3.59; p=0.015), carcinoma embryonic antigen (CEA) level ≥100U/mL (HR, 3.58; 95% CI, 1.65-7.74; p=0.001) and immune-related adverse events (irAEs) (HR, 0.24; 95% CI, 0.10-0.57; p=0.001) were independent prognostic factors for PFS. Extrahepatic metastasis (HR, 2.42; 95% CI, 1.37-4.31; p=0.003), CEA level ≥100U/mL (HR, 2.82; 95% CI, 1.33-5.95; p=0.007) and irAEs (HR, 0.32; 95% CI, 0.14-0.72; p=0.006) were independent prognostic factors for OS. ORR and DCR were 13.75% and 37.5%, respectively. Patients with irAEs (85.7%, OR, 16.00; 95% CI, 3.26-78.61; p&lt;0.001), high CD8+ T-cells-infiltrated GBCs (87.5%, OR, 19.83; 95% CI, 2.00-196.38; p=0.011), immune inflamed phenotype (66.7%, OR, 5.60; 95% CI, 1.16-27.08; p=0.032) had higher DCR, while patients with high level of total bilirubin (TBIL&gt;34.2μmol/L) (8.3%, OR, 0.12; 95% CI, 0.01-0.97; p=0.048) had lower DCR. Patients with high CD8+ T-cells-infiltrated or immune inflamed GBCs also had a notably improved PFS and OS. Conclusions: ICIs were effective in patients with GBC. Alcohol intake history, extrahepatic metastasis, CEA level ≥100U/mL, irAEs, high positivity of CD8+ T-cells and immune inflamed phenotype may be useful for predicting the efficacy of ICIs in GBC.

Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease.

The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

The Impact of Patient Age and Corticosteroids in Patients With Sulfonamide Hepatotoxicity.

Sulfonamides are widely used to treat and prevent various bacterial and opportunistic infections. The aim of this study was to describe the clinical presentation and outcomes of a large cohort of patients with sulfonamide hepatotoxicity. Between 2004 and 2020, 105 patients with hepatotoxicity attributed to trimethoprim/sulfamethoxazole (TMP-SMZ) (n = 93) or other sulfonamides (n = 12) were enrolled. Available liver biopsies were reviewed by a single hepatopathologist. Among the 93 TMP-SMZ cases, 52% were female, 7.5% younger than 20 years, and the median time to drug-induced liver injury (DILI) onset was 22 days (range: 3-157). Younger patients were significantly more likely to have rash, fever, eosinophilia, and a hepatocellular injury pattern at onset that persisted at the peak of liver injury compared with older patients ( P < 0.05). The 18 (19%) TMP-SMZ patients treated with corticosteroids had more severe liver injury and a higher mortality but a trend toward more rapid normalization of their laboratory abnormalities compared with untreated patients. During follow-up, 6.2% of the TMP-SMZ patients died or underwent liver transplantation. Chronic DILI developed in 20% and was associated with cholestatic injury at onset and higher peak total bilirubin levels. Sulfonamide hepatotoxicity is characterized by a short drug latency with frequent hypersensitivity features at onset. Subject age is an important determinant of the laboratory profile at presentation, and patients with cholestasis and higher total bilirubin levels were at increased risk of developing chronic DILI. Corticosteroids may benefit a subgroup of patients with severe injury, but further studies are needed.

Association between Serum Total Bilirubin Level and Patients with Primary Open-Angle Glaucoma in China: A Cross-Sectional, Case-Control Study.

To investigate the relationship between peripheral blood total bilirubin (TBIL) levels and the risk of primary open-angle glaucoma (POAG). This study was a cross-sectional, case-control study design. Between April 2021 and January 2022, 198 POAG patients and 205 healthy subjects were recruited from the EENT Hospital of Fudan University. Their clinical information (intraocular pressure, central corneal thickness, vertical cup-disk ratios (VCDR), and axial length) and demographic data were collected. Serum levels of TBIL were measured in enzymes using a Roche C702 biochemical analyzer. The POAG subgroups were classified by gender and VCDR: mild (VCDR ≤ 0.64), moderate (VCDR ≤ 0.85), and severe (VCDR > 0.85). Univariate and multivariate logistic regression analyses were performed. The level of TBIL (11.58 ± 5.16 μmol/L) in the POAG group was higher than that in the control group (10.18 ± 3.38 μmol/L; p < 0.05). In the male subgroup, TBIL was also significantly higher than in the normal control group; TBIL levels were lower in the mild subgroup (10.82 ± 4.48 μmol/L), followed by the moderate subgroup (12.00 ± 5.55 μmol/L) and the severe subgroup (14.47 ± 5.45 μmol/L). The results of the multivariate logistic regression analysis showed that high TBIL levels were a risk factor for male POAG, at 1.126 (95% CI 1.009-1.256). Pearson's analysis revealed that TBIL was positively correlated with intraocular pressure (r = 0.134, p = 0.012), VCDR (r = 0.142, p = 0.046), anterior chamber depth (r = 0.190, p = 0.014), and axial length (r = 0.179, p = 0.019) in the patients. However, no statistical difference (p < 0.05) was observed in the female patients with POAG. The results showed that high levels of TBIL may be related to the pathogenesis of POAG and that the severity of the disease is positively correlated, especially in male patients.

A new, simple marker for predicting complicated appendicitis in patients with normal white blood cell count indicator; LUC.

The aim of this study was to investigate the ability of a new marker that could be easily obtained to differentiate between complicated and uncomplicated appendicitis in a patients with a white blood cell (WBC) count within the normal range. The patients who underwent surgery with histopathologically proven acute appendicitis (AA) between January 2021 and October 2022 were evaluated retrospectively. Patients were classified into two groups as uncomplicated and complicated appendicitis, based on the surgical and histopathological findings. Groups were compared in terms of laboratory parameters at the time of hospital admission. During the study period, 2589 patients underwent an appendectomy, among these 612 patients who had a WBC count within the normal range at the time of admission were analyzed. Uncomplicated appendicitis was detected in 79.6% of the patients and complicated appendicitis in 20.4%. Neutrophil%, neutrophil-to-lymphocyte ratio, C-reactive protein, and total bilirubin levels were significantly higher, whereas lymphocyte%, lymphocyte count, lymphocyte-to-monocyte ratio, sodium levels, and large unstained cells (LUC)% were significantly lower in patients with complicated appendicitis. Multiple logistic regression analysis revealed that lower LUC% (Odds Ratio [OR]: 0.45; 95% Confidence Intervals [CI]: 1.08-2.09; P=0.01) and higher total bilirubin levels (OR: 1.50; 95% CI: 1.08-2.09; P=0.01) were independent risk factors for complicated appendicitis. In patients with a diagnosis of AA with a normal WBC value, LUC% obtained from the complete blood count can be used as a new parameter predicting the diagnosis of complicated appendicitis.

Left ventricular assist device bridging to heart transplantation: Comparison of temporary versus durable support.

Since the revision of the United States heart allocation system, increasing use of mechanical circulatory support has been observed as a means to support acutely ill patients. We sought to compare outcomes between patients bridged to orthotopic heart transplantation (OHT) with either temporary (t-LVAD) or durable left ventricular assist devises (d-LVAD) under the revised system. The United States Organ Network database was queried to identify all adult OHT recipients who were bridged to transplant with either an isolated t-LVAD or d-LVAD from 10/18/2018 to 9/30/2020. The primary outcome was 1-year post-transplant survival. Predictors of mortality were also modeled, and national trends of LVAD bridging were examined across the study period. About 1,734 OHT recipients were analyzed, 1,580 (91.1%) bridged with d-LVAD and 154 (8.9%) bridged with t-LVAD. At transplant, the t-LVAD cohort had higher total bilirubin levels and greater prevalence of pre-transplant intravenous inotrope usage and mechanical ventilation. Median waitlist time was also shorter for t-LVAD. At 1 year, there was a non-significant trend of increased survival in the t-LVAD cohort (94.8% vs 90.1%; p=0.06). After risk adjustment, d-LVAD was associated with a 4-fold hazards for 1-year mortality (hazard ratio 3.96, 95% confidence interval 1.42-11.03; p=0.009). From 2018 to 2021, t-LVAD bridging increased, though d-LVAD remained a more common bridging strategy. Since the 2018 allocation change, there has been a steady increase in t-LVAD usage as a bridge to OHT. Overall, patients bridged with these devices appear to have least equivalent 1-year survival compared to those bridged with d-LVAD.

BIOCHEMICAL EVALUATION OF THE HEPATIC AND KIDNEY FUNCTIONS IN PATIENTS UNDERGOING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AT THE BAFOUSSAM REGIONAL HOSPITAL, CAMEROON

Background: Nowadays, one of the main ways to manage HIV infection is the use of highly active antiretroviral therapy (HAART). Despite the benefit associated with the use of antiretrovirals, these could have side effects on certain vital body functions such as the liver and kidneys.&#x0D; Aim of the Study: The main objective of this study was to assess the liver and kidney functions of people living with HIV (PLWHIV) and undergoing highly active antiretroviral therapy at the Bafoussam Regional Hospital (BRH).&#x0D; Methodology: A cross-sectional study was conducted for three months on 100 HIV-positive patients undergoing HAART at the Regional Hospital of Bafoussam. Sociodemographic, clinical and biological data were recorded for each subject and then analyzed using standard procedures. Liver function was explored by the following biochemical parameters: alanine aminotransferase, aspartate aminotransferase, albumin, total and direct bilirubin. The renal function was explored by measuring the creatinine and the serum uric acid levels. Results: Among the 100 patients who participated in the study, 83 were women (83 %) and 17 patients were men (17 %). The most represented age group was between 41 and 50 years old (37 %). The mean age was 47.66 ± 10.2 years. For the liver function assessment, 6 % had elevated alanine aminotransferase activity (greater than 42 IU/L), 8 % had an increase in the aspartate aminotransferase activity (greater than 38 IU/L) and 17% of patients had hypoalbuminemia (below 35 g/L). In addition, 14% of the patients had a high total bilirubin level (greater than 1 mg/dL) and 62% of the patients had a high direct bilirubin level (greater than 0.3 mg/dL). Patients presenting simultaneously an abnormal level of direct and total bilirubin were following the Zidovudine-Lamivudine-Atazan avir-Ritonavir (ZLAR) second line regimen. For the evaluation of renal function, 18% had a high creatinine level (greater than 14 mg/L) and 24% of patients had an abnormal level of uric acid (greater than 60 mg/L), this variation was not associated with antiretroviral treatment (p &gt; 0.05).&#x0D; Conclusion: No significant association was found between the regimen and the variations of certain biochemical parameters. However, compared to ZLAR, Tenofovir-Lamivudine-Dolutegravir (TLD) was the regimen that recorded the largest number of patients with abnormal variations of biochemical parameters involved in this study.

Pancreatic follicular dendritic cell sarcoma: one case report and literature review

Pancreatic follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with unclear pathological characteristics. In this study, we report one case of pancreatic FDCS and review published cases to summarize the characteristics and treatment of pancreatic FDCS. A man in his early 30 s was admitted for jaundice, abdominal fullness, and weight loss for 15 days. Computed tomography revealed a large capsule solid mass in the pancreatic head together with a dilated bile duct and enlarged retroperitoneal lymph nodes. Serum biochemistry revealed high total bilirubin levels (313.9 μmol/L) and normal tumor marker levels. Pancreatoduodenectomy was performed, but no chemotherapy was administrated at the patient's behest. The pathologic diagnosis was pancreatic FDCS infiltrating the duodenal seromuscular layer and common bile duct. The patient presented with liver metastasis 3 months after surgery and died 8 months after surgery from multiorgan failure. Pancreatic FDCS is a rare disease with high invasiveness. Our previous case exhibited paraneoplastic syndrome together with this disease, and further investigation is needed to confirm whether paraneoplastic syndrome is a typical syndrome of pancreatic FDCS.

Clinical features and prognostic analysis of lymphoma-associated hemophagocytic syndrome: A report of 139 cases.

Lymphoma-associated hemophagocytic syndrome (LAHS) is characterized by rapid onset, rapid progression and a poor prognosis, and is easy to misdiagnose. In order to improve the clinical understanding, diagnosis and treatment of LAHS, the clinical characteristics and risk factors of LAHS were discussed by retrospective data analysis in the present study. The clinical characteristics of 324 patients with newly diagnosed hemophagocytic syndrome (HPS) were retrospectively investigated. The patients were divided into two groups: The LAHS group comprising 139 patients with LAHS and the non-LAHS group comprising 185 patients with HPS that was not associated with lymphoma. The clinical features and prognosis of the two groups were compared. Patients in the LAHS group had higher levels of total bilirubin (P=0.005) and indirect bilirubin (P=0.006). In addition, patients in the LAHS group had a higher early mortality rate (50.4 vs. 34.6%; P=0.004), higher recurrence rate (30.2 vs. 15.1%; P=0.001), reduced 5-year overall survival rate (OS; 21.5 vs. 52.4%; P<0.001) and reduced relapse-free survival rate (RFS; 7.7 vs. 48.3%; P<0.001) compared with those in the non-LAHS group. If patients with early mortality in the two groups were excluded, the 5-year OS rates were improved and also significantly different (43.3 vs. 80.2%; P=0.041). The 5-year OS and RFS of patients in the LAHS group who had received chemotherapy were significantly superior compared with those who had not received chemotherapy (P<0.001). Multivariate analysis showed that an activated partial thromboplastin time of >36.0 sec (P=0.020) and serum lactate dehydrogenase level of >1,000 U/l (P=0.045) were independent risk factors for a poor LAHS prognosis. The outcomes of the patients with LAHS were worse than those of those with other types of HPS due to the higher early mortality rate. Therefore, it may be concluded that the reduction of the early mortality rate of patients with LAHS is of great importance.

Causes and Risk Factors of Early and Late Non-Relapse Mortality after CD19 CAR T-Cell Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): A Lysa Study from the Descar-T Registry

Background CD19 CAR T-cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory diffuse large B-cell lymphomas (DLBCL). However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the non-relapse mortality (NRM) following CAR T-cells. Improving our knowledge of NRM may help guide the selection and management of patients in order to improve their outcome after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM, and identified risk factors of NRM. Methods We retrospectively analyzed patients from the DESCAR-T registry who received commercial CD19 CAR T-cells for DLBCL between July 2018 and April 2022, from 27 French centers. NRM was defined as patients who died of causes unrelated to lymphoma relapse/progression (deaths of unknown origin were excluded) within 28 days from CAR T-cell infusion (early NRM) or beyond (late NRM). Overall NRM was defined as the sum of early and late NRM. Descriptive statistics of early and overall NRM were performed and cumulative incidences calculated. Risk factors for early and overall NRM were identified by comparing the characteristics at lymphodepletion of early and overall NRM population with patients alive at day 28 post-CAR T-cell infusion or alive at 1 year following CAR-T cell infusion, respectively. Results Between July 2018 and April 2022, 977 consecutive patients registered in the DESCAR-T registry received commercial CD19 CAR T-cells for DLBCL, either axicabtagene ciloleucel (axi-cel, N=611) or tisagenlecleucel (tisa-cel, N=366). Median age was 62 years (range, 18-82), 600 (61%) patients were male, 94 (10%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) >1, 55 (5.6%) had an International Prognostic Index (IPI) >3, 459 (47%) had received ≥3 prior lines of treatment, 118 (12%) had failed a prior autologous stem cell transplant. After a median follow-up of 12.4 months, 48 (4.9%) patients had died of causes unrelated to lymphoma and defined the overall NRM population: 9 deaths (0.92% of all patients and 19% of all NRM) occurred before day 28 post-infusion (early NRM population) and 39 deaths (3.99% of all patients and 81% of all NRM) occurred beyond day 28 post-infusion (late NRM population). Causes of early NRM were cytokine release syndrome (CRS) in 5 patients, infections in 3 patients (2 bacterial sepsis and 1 bacterial pneumonia), and acute kidney failure in one patient. Risk factors for early NRM were as follows: older age (median 73 years vs 63 years, p=0.020), lower body mass index (median 22.5 vs 24.4, p=0.040), ECOG PS >1 (56% vs 13%, p=0.003), higher aspartate transaminase levels (median 68 vs 22 IU/L, p=0.012), higher total bilirubin levels (median 10 vs 6 µmol/L, p=0.035), higher LDH levels (median 408 vs 250 IU/L, p=0.019), and higher ferritin levels (median 1837 vs 480 µg/L, p=0.021). Causes of overall NRM were COVID infection in 13 patients, non-COVID infection in 12 patients (6 bacterial sepsis, 4 bacterial pneumonia, one peritonitis, one septic arthritis), CRS in 5 patients, second malignancy in 3 patients, cerebral hemorrhage in 3 patients, stroke in 2 patients, immune effector cell associated neurotoxicity (ICANS) in 2 patients, acute kidney failure in 1 patient and deaths from other causes in 7 patients. Risk factors for overall NRM were as follows: older age (median 67 years vs 63 years, p=0.003), diabetes (23% vs 10%, p=0.025), ECOG PS >1 (23% vs 5%, p<0.001), lower platelet counts (median 156 g/L vs 185 g/L, p=0.034), higher C-reactive protein levels (median 17 vs 5 mg/L, p<0.001), higher ferritin levels (median 732 vs 393 µg/L, p=0.002), and higher gamma-glutamyl transferase (GGT) levels (median 50 vs 30 IU/L, p=0.017). Conclusion To our knowledge, this is the largest study focusing on NRM after CAR T-cell therapy. NRM in patients receiving commercial CAR T-cells for DLBCL is a relatively rare event (4.9%). Most NRM occurs late (81%) and is due to infections (52%). We identified risk factors of early and overall NRM, which can be useful to select patients for CAR T-cell therapy and prevent/reduce the risk of NRM and thus ultimately improve the outcome of patients treated with CAR T-cells. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Role of bilirubin in the prognosis of coronary artery disease and its relationship with cardiovascular risk factors: a meta-analysis

BackgroundBilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients.MethodsAfter identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels.ResultsForty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: − 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD − 0.30 [95%CI: − 0.56, − 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = − 0.17 [95% CI: − 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: − 8.164 [− 14.531, − 1.769]; p = 0.016) in MI patients.ConclusionPrognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis.