Higher Total Bilirubin Levels Research Articles

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.
 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).
 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 > 0.05).
 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.

Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma.

An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC. Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020. The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05). Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.

The iron deficiency anemia in association to Helicobacter pylori infection in Najran city, Saudi Arabia

Despite previous studies showing that Helicobacter pylori influences iron consumption, it is unknown what causes iron deficiency anemia in response to H. pylori infection. The goal of the study was to find out whether having an infection with H. pylori was linked to a drop-in serum iron level. Detection of H. pylori infection presented by serological test to detect titers of IgG and IgA in blood serum. The determination of iron serum level was performed by using biochemistry spectrophotometry test. Additionally, a full blood count was done to assess the haemoglobin concentration and establish whether the patient was anemic. Data analysis included descriptive statistics, Chi-square, and Mann–Whitney U test. Approximately 35% of the H. pylori group reported a low serum iron level against a 5% only in the control group. Also, the total bilirubin levels were 2.6-fold more among H. pylori positive cases than controls. H. pylori can cause a decrease in serum iron levels in infected individuals and eventually lead to iron deficiency anemia. Moreover, high total bilirubin levels are recorded among H. pylori-infected patients.

Clinical and CT comparative study of invasive and non-invasive Klebsiella pneumoniae liver abscesses

To investigate the clinical and CT features of invasive and non-invasive Klebsiella pneumoniae liver abscesses (KPLA). Fifty-one patients with KPLA diagnosis including 26 invasive and 25 non-invasive KPLA cases were analysed retrospectively. All patients underwent routine abdominal unenhanced and three-phase enhanced CT examinations. The CT images were assessed by two experienced radiologists by examining location, number, size, septa, texture, gas in the pus cavity, portal phlebitis, thrombophlebitis, and abnormal perfusion during the arterial phase. Statistical differences for continuous characteristics were analysed with independent samples t-test or Wilcoxon's test, while the chi-square test or Fisher's exact test was used for categorical variables. A logistic regression analysis was performed to determine the independent related factors of invasive KPLA and receiver operating characteristic (ROC) curves were used for assessment. Age and type 2 diabetes were significantly different between the patients with invasive and non-invasive KPLA. In addition, patients with invasive KPLA had lower levels of platelet and total protein (p<0.05) and higher total bilirubin compared to patients with non-invasive KPLA. Throughout the regression analysis, total bilirubin, platelets, and total protein demonstrated an area under the ROC curves of 0.717, 0.745, and 0.728, respectively. Invasive KPLA occurs predominantly in younger patients with type 2 diabetes. Laboratory tests revealed low platelet and total protein levels and high total bilirubin levels. If the patient with KPLA exhibits hepatic venous thrombophlebitis with no abnormal enhancement around the abscess in the arterial phase of enhanced CT, it indicates that the abscess has invaded.

Factors independently associated with prognosis in patients operated for pancreatic cancer: Assessing the role of various parameters including red cell distribution width, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio

Objective: We aimed to assess whether, among other parameters, preoperative red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) values were associated with prognosis in patients operated for pancreatic cancer (PC).&#x0D; Material and Method: This retrospective cohort was conducted from February 1, 2016 to February 1, 2021 at the general surgery department of a university hospital in Turkey. A total of 75 patients histologically diagnosed with PC who had undergone surgery were included in the study. &#x0D; Results: The PLR values of patients with poorly differentiated and undifferentiated tumors were found to be higher than those with moderately and highly differentiated tumors. Also, there was a significant relationship between PLR values and the length of hospital stay. PLR values increased as the length of hospital stay increased. There was a statistically significant positive correlation between CA 19-9 levels and NLR and PLR. High total bilirubin level was related with increased risk of death, while adjuvant chemotherapy recipients had 4.049-fold lower risk of death than those without adjuvant chemotherapy.&#x0D; Conclusion: Our results indicate that preoperative NLR, PLR and RDW cannot be used as prognostic indicators of mortality in patients with operated PC, but high PLR appears to be associated with lower level of tumor differentiation and prolonged hospital stay. We also found that high total bilirubin was a poor prognostic factor, while adjuvant chemotherapy was a good prognostic factor. Further multicenter, prospective studies with larger sample sizes will help to verify these results.

Analysis of the Bacterial Spectrum and Key Clinical Factors of Biliary Tract Infection in Patients with Malignant Obstructive Jaundice after PTCD.

Objective To analyze the bacterial spectrum and key clinical factors associated with biliary tract infections following percutaneous transhepatic cholangial drainage (PTCD) for malignant obstructive jaundice (MOJ). Methods This retrospective study comprised patients with MOJ who were treated with PTCD from 1st June 2016 to 31st December 2020. Patient clinical data, development of postprocedure biliary tract infections, spectrum of pathogenic bacteria, and drug sensitivity were analyzed, focusing on antibiotic drug resistance and identifying key associated risk factors for postoperative biliary tract infections. Results Of the 528 study patients, 80 were diagnosed with postoperative biliary tract infections, 58 of whom had pathogenic bacteria detected in their bile samples. A total of 90 strains of pathogenic bacteria and 3 strains of fungi were detected; the top 4 were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, and Pseudomonas aeruginosa. By univariate analysis, a positive bile culture following PTCD was closely correlated with both the location and degree of preoperative obstruction and the preoperative bilirubin level. Moreover, the results of logistic regression analysis concluded that complete obstruction and a high preoperative total bilirubin level prior to PTCD were independent risk factors for a positive bile culture following PTCD. Conclusion Biliary tract infections following PTCD for MOJ were principally due to Escherichia coli, and bacteria in the bile were statistically more likely to be detected in patients with complete obstruction and high preoperative bilirubin levels.

Serum total bilirubin and new-onset hypertension in perimenopausal women: a cross-sectional study.

Previous studies have shown negative associations between total bilirubin (TBIL) and hypertension. However, the association of TBIL with new-onset hypertension in perimenopausal women is unknown. A total of 196 perimenopausal women were included in this cross-sectional study of which 85 had new-onset hypertension. All participants underwent 24-hour ambulatory blood pressure monitoring and a clinical assessment including anthropometrics. Sociodemographic, lifestyle, and menopausal symptoms (modified Kupperman Index [mKI]) were measured by questionnaire. A fasting blood sample was taken to measure a wide range of biomarkers and hormone levels. Restricted cubic spline regression was used to investigate potential nonlinearity. Multivariable logistic and robust linear regression analyses adjusting for minimal sufficient adjustment sets based on directed acyclic graphs were performed to test the association of TBIL with hypertension/blood pressure. We examined mKI-stratified analyses and a TBIL-mKI interaction term to explore potential effect modification by number of menopausal symptoms. Hypertensive women had significantly lower TBIL levels than did normotensive women (11.15 vs 12.55 μmol/L, P = 0.046). Univariate restricted cubic spline regression showed nonsignificant nonlinearity ( P value for nonlinearity, 0.339). Multivariable regression analyses adjusted for minimal sufficient adjustment sets revealed that higher TBIL level was associated with lower odds of hypertension (odds ratio, 0.91 per μmol/L TBIL; 95% confidence interval [CI], 0.84-0.98; P = 0.019). Total bilirubin showed a significant inverse association with average 24-hour diastolic blood pressure ( β = -0.36 mm Hg per μmol/L TBIL; 95% CI, -0.62 to -0.10; P = 0.008) but not with 24-hour systolic blood pressure ( β = -0.37 mm Hg per μmol/L TBIL; 95% CI, -0.79 to 0.06; P = 0.090). Stratified analyses suggested stronger inverse associations of TBIL with hypertension and 24-hour blood pressure in women with fewer menopausal symptoms (mKI ≤10), although the TBIL-mKI interaction was not significant. In perimenopause, TBIL was inversely associated with diastolic blood pressure and new-onset hypertension, diagnosed using 24-hour ambulatory blood pressure monitoring.

Ficus exasperata Attenuates Acetaminophen-Induced Hepatic Damage via NF-κB Signaling Mechanism in Experimental Rat Model.

Ficus exasperata has been used to treat ulcer, diabetes, fever, and a variety of stress-related disorders. Acetaminophen (APAP) overdose is the most common cause of drug-induced acute liver injury. In this study, we evaluated the hepatoprotective effect and antioxidant capacity of ethanolic extract of F. exasperata (EFE) on acetaminophen-induced hepatotoxicity in albino rats. Rats were pretreated with EFE (150, 250, 500 mg/kg) and thereafter received 250 mg/kg APA intraperitoneally (i.p.). The normal control group received distilled water, while the negative control group received 250 mg/kg APAP, respectively. Hepatotoxicity and oxidative stress-antioxidant parameters were then assessed. Flavonoids, saponins, steroids, and glycosides, but not phenolics were detected by EFE phytochemical analysis. No mortality was recorded on acute exposure of rats to varying concentrations of APAP after 24 h; however, a dose-dependent increase in severity of convulsion, urination, and hyperactivity was observed. APAP overdose induced high AST, ALT, ALP, and total bilirubin levels in the serum, invoked lipid peroxidation, depleted GSH, decreased CAT, SOD, and GST levels, respectively. Nitric oxide (NO) level, myeloperoxidase activity, TNF-α, IL-1β, NF-κB, COX-2, MCP-1, and IL-6 were also increased. Importantly, pretreatment of rats with EFE before acetaminophen ameliorated and restored cellular antioxidant status to levels comparable to the control group. Our results show and suggest the hepatoprotective effect of F. exasperata and its ability to modulate cellular antioxidant status supports its use in traditional medicine and renders it safe in treating an oxidative stress-induced hepatic injury.

Features of serum bilirubin in non ST elevation acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Even though, bilirubin is known to be an endogenous antioxidant, there is conflicting evidence whether level of serum bilirubin is associated with non-ST elevation acute coronary syndrome (NSTE ACS). Purpose We aimed to assess the possible impact of bilirubin level non-ST elevation acute coronary syndrome. Methods 128 patients with NSTEACS were enrolled in the study (Aged 38-75 years; mean age 56.2±16.85 years; male 53%). Patients were divided into two groups in terms of level of total bilirubin. Group I included 56 patients (total bilirubin was higher 19 mMol/L) and Group II 72 patients with NSTA ACS (total bilirubin was lower 19 mMol/L). Anthropometric, laboratory including serum total, direct, indirect bilirubin level and instrumental data were obtained at baseline while admission prior to percutaneous coronary intervention. Follow-up was conducted via telephone in six months. Statistical analysis were performed by STATA software. Results Patients presenting with NSTE ACS having high level of bilirubin tended to have more severe course of the disease (62% vs. 53%, P&amp;lt;0.05), high level of high sensitive troponin level (55ng/mL vs. 43 ng/mLK, P=0.001), multi-vessel disease (35% vs. 21%, P=0.001) and high rate of new revascularization (82% vs. 65%, P=0.001) than those ones with lower level of total bilirubin. Patients with high level of total bilirubin at admission with NSTE ACS had worse outcomes both in 1 month (1.24; 1.12-1.75; CI 95%; P&amp;lt;0.05) and 6 months follow-up period than those NSTE ACS patients with lower bilirubin level at admission (1.512; 1.24-1.95; CI 95%; P&amp;lt;0.05). Conclusion Total serum bilirubin level seems to be an independent predictor for severity of the disease and adverse outcomes in patients with NSTE ACS.

Association of serum total bilirubin with survival outcomes in patients with cancer cachexia: A prospective, multicenter cohort study

ObjectivesCancer cachexia is a systemic paraneoplastic phenomenon involving multiple organs, including the liver. Total bilirubin (TBIL) is an easily obtained blood biomarker that reflects liver homeostasis. The aim of this study was to evaluate the prognostic value of serum TBIL in patients with cancer cachexia. MethodsThis study included 2282 patients from a multicenter research database who were diagnosed with cancer cachexia between June 2012 and December 2019. The hazard ratio (HR) for all-cause mortality was analyzed using Cox proportional hazards regression models. The association of serum TBIL with all-cause mortality was modeled with restricted cubic splines. The optimal cutoff value for TBIL was calculated with maximally selected rank statistics. ResultsOf the participants, there were 1327 (58.2%) men and 955 (41.8%) women. The mean patient age was 60.4 ± 1.5 y. The 12-mo all-cause mortality rate for patients with cancer cachexia was 29.5% (95% confidence interval [CI], 27.6%–31.3%), resulting in a rate of 209.58 events per 1000 patient-years. An inverted L-shaped association between TBIL and all-cause mortality was observed. The cutoff point for TBIL for the prediction of the time to mortality was <21.7 µmol/L. A high TBIL level but not the direct bilirubin or indirect bilirubin level was identified as an independent prognostic factor (HR, 1.60; 95% CI, 1.32–1.93). For patients with digestive system tumors, a high serum TBIL level (≥21.7 µmol/L) was significantly associated with mortality. ConclusionHigh TBIL levels are associated with increased all-cause mortality in patients and might be a promising prognostic indicator in patients with cancer cachexia.

Postcardiotomy Extracorporeal Membrane Oxygenation Support in Patients with Congenital Heart Disease.

BackgroundThis study investigated mortality and morbidity in patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) support after operations for congenital heart disease (CHD).MethodsCHD patients requiring postoperative ECMO support between May 2011 and May 2021 were retrospectively reviewed. Patients were divided into non-survivors and survivors to hospital discharge. Survival outcomes and associations of various factors with in-hospital death were analyzed.ResultsFifty patients required postoperative ECMO support. Patients’ median age and weight at the time of ECMO insertion were 1.85 months (interquartile range [IQR], 0.23–14.5 months) and 3.84 kg (IQR, 3.08–7.88 kg), respectively. Twenty-nine patients (58%) were male. The median duration of ECMO support was 6 days (IQR, 3–12 days). Twenty-nine patients (58%) died on ECMO support or after ECMO weaning, and 21 (42%) survived to hospital discharge. Postoperative complications included renal failure (n=33, 66%), bleeding (n=11, 22%), and sepsis (n=15, 30%). Prolonged ECMO support (p=0.017), renal failure (p=0.005), continuous renal replacement therapy (CRRT) application (p=0.001), sepsis (p=0.012), bleeding (p=0.032), and high serum lactate (p=0.002) and total bilirubin (p=0.017) levels during ECMO support were associated with higher mortality risk in a univariate analysis. A multivariable analysis identified CRRT application (p=0.013) and a high serum total bilirubin level (p=0.001) as independent risk factors for death.ConclusionPostcardiotomy ECMO should be considered as an important therapeutic modality for patients unresponsive to conventional management. ECMO implementation strategies and management in appropriate patients without severe complications, particularly renal failure and/or liver failure, are crucial for achieving positive outcomes.

Phylogenetic exploration and haemato-biochemical significance of Anaplasma marginale infection in water buffalo (Bubalus bubalis)

During 2017-2020, a total of 8352 buffalo blood samples were screened microscopically for Anaplsma species and 104 positive samples were found. Later on same samples were confirmed positive using genomic DNA PCR technique. For efficiency of PCR technique, a total of 335 blood samples were randomly chosen. Microscopy revealed Anaplasma species in erythrocytes of 1.19% (4 samples) of the total blood samples (n=335). Initially PCR assay was standardized targeting 16S rRNA for detection of genus Anaplasma with expected amplicon size 781 bp. Thereafter, msp1 β gene was targeted for species level identification of Anaplasma (Anaplasma marginale) with expected amplicon size 407 bp. A total of fourteen samples out of 335 samples (4.17%) found positive by PCR. Randomly, two confirmed positive samples were sent for bidirectional sequencing. The sequencing results, submitted in GenBank(MW269530, MW269531), further confirm the Anaplasma marginale infection in buffalo. The study show higher specificity and sensitivity of PCR test above blood smear examination. Erythron of infected animals showed significantly low level of mean Hb, PCV, RBC count, MCH, MCHC and high level of mean MCV, indicating regenerative hypochromic macrocytic anaemia. Infected animals had a significantly low mean level of total protein, albumin and globulin and significantly high level of phosphorus, total bilirubin, direct and indirect bilirubin. The current study provides indication of the association between A. marginale infection and probable liver damage or hepatic fatty degeneration. Nevertheless advanced studies are warranted to explain the precise pathophysiological mechanism of this association.

Restoration of the gut microbiota is associated with a decreased risk of hepatic encephalopathy after TIPS

Background & AimsHepatic encephalopathy (HE) is a major complication after transjugular intrahepatic portosystemic shunt (TIPS) and is primarily influenced by the gut microbiota. We aimed to evaluate alterations in the microbiota after TIPS and the association between such alterations and HE.MethodsWe conducted a prospective longitudinal study of 106 patients with cirrhosis receiving TIPS. Faecal samples were collected before and after TIPS, and the gut microbiota was analysed by 16S ribosomal RNA sequencing.ResultsAmong all patients, 33 developed HE (HE+ group) within 6 months after TIPS and 73 did not (HE- group), and 18 died during follow-up. After TIPS, the autochthonous taxa increased, whereas the potential pathogenic taxa decreased in the HE- group, and the autochthonous taxon Lachnospiraceae decreased in the HE+ group. Furthermore, synergism among harmful bacteria was observed in all patients, which was weakened in the HE- group (p <0.001) but enhanced in the HE+ group (p <0.01) after TIPS. Variations of 5 autochthonous taxa, namely, Coprococcus, Ruminococcus, Blautia, Ruminococcaceae_uncultured, and Roseburia, were negatively correlated with the severity of HE. Notably, increased abundances of Coprococcus and Ruminococcus were protective factors against HE, and the incidences of HE in patients with improved, stable, and deteriorated microbiota after TIPS were 13.3, 25.9, and 68.2%, respectively. Higher total bilirubin level, Child–Pugh score, model for end-stage liver disease score, Granulicatella, and Alistipes and lower Subdoligranulum before TIPS were the independent risk factors for death.ConclusionsAlterations in gut dysbiosis were negatively related to the occurrence and severity of post-TIPS HE, and the pre-TIPS microbiota were associated with death, suggesting the gut microbiota could be a promising potential biological target for screening suitable patients receiving TIPS and prevention and treatment of post-TIPS HE.Lay summaryAlterations in the gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) and the relationship between such alterations and post-TIPS hepatic encephalopathy (HE) remain unclear. We therefore performed this study and found that after TIPS, restoration of the gut microbiota, mainly characterised by expansion of autochthonous taxa, depletion of harmful taxa, and weakening of synergism among harmful bacteria, was inversely related to the occurrence and severity of post-TIPS HE.

Predictors of Spontaneous Rupture of Hepatocellular Carcinoma and Clinical Outcomes Following Hepatectomy.

ObjectiveTo explore the independent predictive factors of spontaneous tumor rupture (STR) in patients undergoing curative resection of hepatocellular carcinoma (HCC), and to evaluate the impact of STRHCC on long-term survival after hepatectomy.MethodsThe clinicopathological parameters of 106 patients with STRHCC and 201 patients with non-ruptured HCC who underwent hepatectomy from January 2007 to November 2011 at the Eastern Hepatobiliary Surgery Hospital and Zhongnan Hospital of Wuhan University were analyzed using propensity score matching (PSM) and a logistic regression model.ResultsFactors including hypertension, cirrhosis, total bilirubin (TB), tumor size, and ascites were independent predictors of STR. For all 307 HCC patients, the 1-, 3- and 5-year overall survival (OS) rates were 54.0%, 37.3% and 33.8%, respectively. After PSM, the 1-, 3-, and 5-year OS rates in the ruptured group remained significantly lower at 41.5%, 23.5%, and 17.5% when compared with the non-ruptured group at 70.8%, 47.1%, and 37.6%, respectively, while the 1-, 3-, and 5-year disease-free survival (DFS) rates between the groups did not differ significantly (50.4%, 35.1%, 27.1% vs 55.4%, 38.2%, 27.4%). STRHCC was significantly associated with increased risk of OS, but not of shorter DFS. No significant difference in postoperative morbidity or hospital death was observed between the groups.ConclusionFactors including hypertension, liver cirrhosis, higher TB levels, tumor size > 5cm, and ascites are significant predictors of STR. The recurrence rate of patients in the ruptured group was significantly higher than that of patients in the non-ruptured group. STR results in poorer OS but not DFS in patients undergoing curative resection for HCC. STRHCC has no impact on postoperative morbidity and mortality after hepatectomy.

Клінічні та біохімічні аспекти хронічного гепатиту С за умови дисбіозу кишківника

Prolonged intestinal dysbiosis (DB) increases the risk of developing metabolic liver diseases, such as nonalcoholic fatty liver disease (NAFLD), cholestasis, hepatocellular dysfunction and dyskinetic disorders of the biliary tract. According to various studies, hepatic steatosis is observed in almost 50% of patients with chronic hepatitis C (HCV). The presence of NAFLD in patients with CHC contributes to the onset and further progression of fibrosis from the initial stages to cirrhosis of the liver within a short time. The purpose of the research is to study the clinical and biochemical features of the course of chronic HCV in the conditions of intestinal dysbiosis. Materials and methods. There were 142 patients with chronic HCV under observation. The control group consisted of 20 healthy people. The diagnosis of chronic HCV was made according to the International Classification of Diseases of the 10th revision and confirmed by the detection of total IgG antibodies to HCV by enzyme-linked immunoassay, as well as the detection of RNA-HCV in the blood by polymerase chain reaction. All patients were determined the functional state of the liver by the level of activity of alanine and asparagine aminotransferases (ALT, AST), alkaline phosphatase (AP), conjugated bilirubin, gammaglutamyl transpeptidase (GGTP), trophological status was assessed and a microbiological study of feces was performed. To determine the degree of steatosis and fibrosis of the liver, a noninvasive diagnostic method – FibroMax was used. The obtained results allowed to divide all patients into two groups: 1 group (n = 84) of patients with chronic HCV + dysbiosis DB and 2 group (n = 58) of patients with chronic HCV without dysbiosis of the intestine. The analysis and processing of the patients’ examination results were carried out using the Statisticsfor Windows v.7.0 computer program (StatSoftInc, USA). Results and Discussion. It was found that the intestinal dysbiosis had 59.2% (84 out of 142) of patients with chronic HCV, and 52 of them had increased body weight, which was 61.9%. Clinical manifestations of intestinal microbiocenosis disorders in 58 patients were predominant constipation (69%) and minimization of typical diarrheal syndrome in 26 people (31%). A large number of patients with chronic HCV with the intestinal dysbiosis (82.1%) complained of decreased ability to work, headaches, depressed mood and sleep disorders, which confirmed the presence of asthenovegetative syndrome. Analysis of biochemical indicators demonstrated that cholestasis syndrome prevails in patients with chronic HCV in the conditions of intestinal dysbiosis, proving significantly higher levels of total bilirubin, AP and GGTP, compared with patients without dysbiosis (p &lt; 0.05). Also, in patients with chronic HCV, in conditions of intestinal dysbiosis in 3.5 times (p &lt; 0.001) were more often detected increased levels of liver enzyme activity (ALT, AST, GGTP), compared to patients without dysbiosis, which characterizes the cytolysis syndrome. In patients with chronic HCV with intestinal dysbiosis, in 1.6 times more often than in patients without dysbiosis, steatosis of the S1-2 degree was registered, and in 2.4 times more often S2-3. Inflammation in different degrees of hepatic steatosis in 2 times more common in patients with chronic HCV with dysbiosis than in patients without dysbiosis. It was found that in patients with chronic HCV combined with intestinal dysbiosis deep stages of liver fibrosis (F2-3 and F3-4) are registered in 3.6 times more often compared to patients only with chronic HCV (53.6% vs. 24.1% and 11, 9% vs. 3.4% p &lt; 0.05). Conclusions. Intestinal dysbiosis is more often recorded in patients with chronic HC with increased body weight and is characterized by an atypical course, in the predominance of constipation (in 69% of patients). In patients with chronic HCV in the conditions of intestinal dysbiosis dyspeptic, asthenovegetative and cholestatic syndrome, as well as high activity of ALT and AST are more often observed, compared to patients without dysbiosis. According to Fibromax, patients with CHC with intestinal dysbiosis are in 2.4 times more likely to have hepatic steatosis of 2–3 degree (S2-3) and steatohepatitis (N2,) which characterizes the existing metabolic disorders.

Bilirubin levels as an independent predictor of myocarditis in patients with COVID-19

BackgroundMyocardial damage worsens the clinical course and prognosis of coronavirus disease 2019 (COVID-19) patients. High total bilirubin levels have been associated with a poor prognosis in COVID-19. This study aimed to investigate the predictive value of the total bilirubin level, a marker of heme oxygenase-1 enzyme activity, in determining myocarditis in patients with COVID-19.ResultsA total of 190 patients diagnosed with COVID-19 were enrolled in the study. The patients were divided into two groups based on their troponin positivity. The study group (n = 95) consisted of patients with high troponin, and the control group (n = 95) consisted of patients without high troponin levels. The D-dimer (727 [572–995] vs. 591 [440–790], p = 0.001), C-reactive protein (CRP) (30.0 [10–48] vs. 10.3 [5.8–15.9], p < 0.001), and total bilirubin (9.5 [8.2–12.1] vs. 7.0 [5.3–8.0], p < 0.001) levels were significantly higher in the study group. In multivariate analysis, CRP (odds ratio [OR]: 1.103; 95% confidence interval [CI]: 1.060–1.148; p < 0.001) and total bilirubin (OR: 1.612; 95% CI: 1.330–1.954; p < 0.001) levels were independent predictors of myocarditis in COVID-19.ConclusionsTotal bilirubin levels can be used as an early predictor of myocarditis in COVID-19 and can contribute to therapy management.