Lower Bilirubin Levels Research Articles

Association between elevated serum bilirubin levels with preserved lung function under conditions of exposure to air pollution

BackgroundHigh serum bilirubin levels have been shown to be associated with an improved pulmonary function test results. Their potential ability to similarly benefit pulmonary function in an environment of polluted air has not been tested. We retrospectively analyzed data of 15,605 apparently healthy individuals in order to evaluate the effect of serum bilirubin levels on forced expiratory volume in 1 s (FEV1).MethodsIndividuals attended the Tel-Aviv Medical Center Inflammatory Survey for a routine annual health check between February, 2002 and June, 2009 and were divided into low, medium and high serum bilirubin levels. Their FEV1 results were compared under various levels of air pollution. Air pollution and weather data were obtained from air pollution monitoring stations of the Israeli Ministry of Environmental Protection.ResultsThe elevated serum bilirubin concentrations on FEV1 were evaluated under moderate and high pollution levels FEV1 and were significantly higher in participants with high blood bilirubin levels compared to medium or low levels (p < 0.001 and p = 0.018, respectively). Participants with high levels of bilirubin had preserved FEV1 under exposure to high and medium pollution levels of both Nitrogen Oxide (NOx) and Carbon Monoxide (CO) pollutants (p = 0.003 and p = 0.022, respectively). The multivariate regression analysis revealed that the influence of bilirubin under conditions of air pollution remained significant even after adjustment for FEV1 confounders, but the interaction was not significant.ConclusionsElevated serum bilirubin concentrations are associated with preserved lung function in healthy individuals in Israel exposed to high levels of air pollution.

P45 Effect of One Anastomosis Gastric Bypass on Liver Function Tests: A comparison between 150 cm and 200 cm Bilio-Pancreatic Limb

IntroductionThe effect of One Anastomosis Gastric Bypass (OAGB) on Liver Function Tests (LFTs) is unclear. The purpose of this study was to find out the effect of OAGB on LFTS and also if a Bilio-Pancreatic Limb (BPL) of 150 cm (OAGB-150) would deliver better outcomes than that with a BPL of 200 cm (OAGB-200).MethodsWe investigated our prospectively maintained records to obtain information on patients who underwent an OAGB-200 or OAGB-150 until 31st July 2018 in our unit.ResultsA total of 405 patients underwent an OAGB-200 (n = 234) or OAGB-150 (n = 171) in our unit between October 2012 -July 2018. There were significant improvements in Gamma-Glutamyl-Transpeptidase (GGT) levels at 1 and 2 years after OAGB-200 and significant worsening in the levels of Alkaline Phosphatase (ALP) and albumin at 1 and 2 years follow up. There was a significant improvement in GGT levels at 1 and 2 years after OAGB-150, and in Alanine Transaminase (ALT) levels at 1 year follow up. There was a significant worsening in ALP and albumin levels at both follow-up points in this group. There was no significant increase in the number of abnormal values for any of the tests in either group at both follow-up points. OAGB-150 group had a significantly lower bilirubin level at 1 year and significantly fewer abnormal ALP values at 2 years in comparison with OAGB-200 patients.ConclusionThis study demonstrates the overall safety of OAGB with regards to its effect on LFTs with no remarkable difference between OAGB-150 and OAGB-200.

Plasma bilirubin levels are reduced in first-episode psychosis patients and associates to working memory and duration of untreated psychosis

Schizophrenia is a severe mental disorder and one of its characteristics is cognitive impairments. Findings regarding levels of the heme metabolite and plasma antioxidant bilirubin in schizophrenia are inconclusive. However, a recently published study indicate that low levels of bilirubin may be implicated in the memory impairments seen in the disorder. The aim of this cross-sectional study was to investigate the levels of bilirubin in individuals with a first-episode psychosis (FEP) and to examine if bilirubin levels were associated to cognitive impairments, symptoms and duration of untreated psychosis (DUP). Bilirubin levels were reduced in 39 individuals with FEP compared with 20 HC (median [IQR]: 11.0 [9.0–13.0] µM vs. 15.0 [11.5–18.5] µM). In individuals with FEP, bilirubin levels were also positively correlated to two working memory tests (r = 0.40 and r = 0.32) and inversely correlated to DUP (r = − 0.36). Findings were not influenced by confounding factors. The results confirm the antioxidant deficit previously seen in schizophrenia, but also indicate that these changes may be related to DUP. The study also confirms that bilirubin may be implicated in the cognitive deficits that accompanies the disorder, here for the first time presented in individuals with FEP.

Effect of one anastomosis gastric bypass on liver function tests: A comparison between 150 cm and 200 cm biliopancreatic limbs.

Context:Some studies have shown that one anastomosis gastric bypass (OAGB) results in the derangement of liver function tests (LFTs). We wanted to study this in our patients.Aims:The aims are to study the effect of OAGB on LFTs and to compare the effect of a biliopancreatic limb (BPL) of 150 cm (OAGB-150) to a BPL of 200 cm (OAGB-200).Settings and Design:The study was a retrospective cohort study conducted at a university hospital.Materials and Methods:Information was obtained from our prospectively maintained database and hospital's computerised records.Statistical Analysis:A P < 0.05 was regarded statistically significant; however, given the number of variables examined, findings should be regarded as exploratory.Results:A total of 405 patients underwent an OAGB-200 (n = 234) or OAGB-150 (n = 171) in our unit between October 2012 and July 2018. There were significant improvements in gamma-glutamyl transpeptidase (GGT) levels at 1 and 2 years after OAGB-200 and significant worsening in the levels of alkaline phosphatase (ALP) and albumin at 1 and 2 years. There was a significant improvement in GGT levels at 1 and 2 years after OAGB-150 and in alanine transaminase levels at 1 year. There was a significant worsening in ALP and albumin levels at both follow-up points in this group. OAGB-150 group had a significantly lower bilirubin level at 1 year and significantly fewer abnormal ALP values at 2 years in comparison with OAGB-200 patients.Conclusions:This exploratory study demonstrates the overall safety of OAGB with regard to its effect on LFTs, with no remarkable difference between OAGB-150 and OAGB-200.

Liver Drains after Surgery, a Real-life Snapshot among the HPB Community: the LI.DR.A.S. World-wide Survey

Background: Although several trials have been conducted, the management of liver drains remains controversial among HPB surgeons. We conducted a world-wide survey to define actual clinical drain practices adopted by liver surgeons in the EA-HPBA, A-HPBA and AP-HPBA communities. Methods: An open survey consisting of 30 questions was prepared and then published on Google – Form, which was then delivered by email to members of the three major chapters of the international hepato-pancreato-biliary association (IHPBA). Results: 191 HPB surgeons responded to the web-survey. Twenty (10.5%) respondents were from the Asian-Pacific region, while 15 (7.9%) were from North America, 13 (6.8%) from South America and 143 (74.9%) from Europe and Africa. One hundred-twelve surgeons (58.6%) reported routine use of abdominal drains liver resection. Eighty-eight (46.1%) respondents responded that drain removal was driven by low volume and low bilirubin levels in the drains; 85 (44.5%) surgeons usually consider removal of the drain on 2-3 post-operative days (POD). In case of minor liver resection, 97 (50.8%) surgeons reported using drains only in select cases. When a major resection (>=3 liver segments) is performed, 134 (70.2%) surgeons preferred to always use a drain. Among patients with cirrhosis, 87 (45.5%) surgeons reported the routine use of drains, while 84 (44.0%) respondents considered drains only selectively. The lack of drains was most prevalent among surgeons from North America (12, 80%); in contrast, 14 (70.0%) surgeons in Asian-Pacific region, 87 (60.8%) in Europe and Africa and 8 (61.5%) in South America were more inclined to employ liver drains routinely (p=0.014). Among surgeons whose practice is mostly mini-invasive liver surgery (n=31), 23 (74.2%) reported draining only in selected cases, while the proportion of surgeons who use drains selectively among surgeons who performed mainly open liver resections was lower (n=56, 35.0%)(p<0.001). Conclusion: Despite several RCTs, use of drains at the time of liver resection remains highly variable. In particular, surgeons from North America, as well as surgeons who predominantly perform minimally-invasive hepatectomy, are much less likely to employ abdominal drains at the time of liver resection.

Association between serum bilirubin and albuminuria in type 2 diabetes mellitus and diabetic nephropathy

Introduction: Diabetic nephropathy develops due to oxidative stress and inflammation resulting from chronic hyperglycemia. Bilirubin, a product of heme catabolism is found to have antioxidant and anti-inflammatory properties. Though previous studies have examined the relationship between total bilirubin and diabetic nephropathy, very few studies have focused on indirect and direct bilirubin levels. Hence, the present study aimed to compare serum bilirubin (total, indirect and direct) levels between non-diabetics, type 2 diabetics and diabetic nephropathy subjects and also to correlate albuminuria with serum bilirubin in type 2 diabetics and diabetic nephropathy subjects. Materials and Methods: 50 non-diabetics, 50 type 2 diabetics and 50 diabetic nephropathy subjects were included in the study. Fasting blood glucose, HbA1C, serum bilirubin (total, indirect and direct), serum creatinine, urine microalbumin and urine creatinine were measured. Estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) was calculated. Results: Total bilirubin, direct and indirect bilirubin were significantly decreased in type 2 diabetics and diabetic nephropathy subjects compared to non-diabetics. Total bilirubin and indirect bilirubin were also significantly decreased in diabetic nephropathy subjects compared to type 2 diabetics. Total bilirubin, direct and indirect bilirubin showed significant negative correlation with albuminuria (Urine ACR) in type 2 diabetics and diabetic nephropathy subjects. Conclusion: Our study suggests that low bilirubin levels might be a risk factor for the development of type 2 diabetes and diabetic nephropathy. Bilirubin can be used as a marker to predict the risk of developing type 2 diabetes among general population and diabetic nephropathy among type 2 diabetes patients. Keywords: Albuminuria, Antioxidant, Bilirubin, Diabetes mellitus, Diabetic nephropathy

Bilirubin as a metabolic hormone: the physiological relevance of low levels.

Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors. Studies are now revealing that low plasma bilirubin levels, defined as "hypobilirubinemia," are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction. Hypobilirubinemia is most commonly seen in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke. We address the clinical significance of low bilirubin levels. A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious. We present mechanisms by which bilirubin may be protective at mildly elevated levels and research directions that could generate treatment possibilities for patients with hypobilirubinemia, such as targeting of pathways that regulate its production or turnover or the newly designed bilirubin nanoparticles. Our review here calls for a shift in the perspective of an old molecule that could benefit millions of patients with hypobilirubinemia.

Evaluasi Tingkat Pengetahuan Perawat tentang Terapi Stimulasi Fisik pada Hiperbilirubinemia Neonatus

Background. Infants with hyperbilirubin have management in lowering bilirubin levels. Management of the physiological management of jaundice is regular drinking with frequent breastfeeding and light therapy if possible. WHO guidelines for the pathological management of jaundice can be carried out by phototherapy and pharmacology. Physical stimulation therapy is a complementary therapy in the form of passive Range of Motion (ROM) movements. The aim of the study was to evaluate the level of knowledge of nurses about physical stimulation therapy in hyperbilirubinemia neonates.&#x0D; Methods. This study used a quasi-experiment with a one-group pretest-posttest design approach. The research was conducted in May-August 2020 in virtual or online due to the Covid 19 pandemic situation. The number of respondents was 30 people. Data collection using a modified questionnaire by the researcher. The data were then processed and analyzed using univariate analysis and bivariate analysis using the Paired Sample T-Test.&#x0D; Results. The mean pre-test score was 77.18 and the post-test mean score was 93.74. The statistical test results showed a difference in knowledge before and after education with a p-value of 0.000 (p &lt;0.05).&#x0D; Conclusion. Nurses' level of knowledge about physical stimulation therapy increased after being given an education.

Socioeconomic correlates and biochemical profiles of smokers in Poland: a cross-sectional study.

Epidemiological studies have shown a fairly constant association between the socioeconomic status and smoking. However, associations between smoking and the biological indicators of health status have not been well described yet. This study aimed to determine the relationship among smoking, biochemical risk factors, and sociodemographic characteristics in the Polish population. A survey was carried out in a representative sample of Polish residents aged 18 to 79 years. A total of 2413 randomly selected subjects participated in the survey. Logistic regression analysis as well as parametrical and nonparametrical tests were performed. Significantly higher cholesterol, apolipoprotein B, and potassium levels were observed in smoking women and men compared with the nonsmoking population. Significantly lower bilirubin levels were noted in smoking individuals. Higher C‑reactive protein and lower creatinine levels were reported only in the smoking male population compared with nonsmokers. There was a significant inverse gradient in the relationship between income and smoking. Single women and men were at greater risk of being smokers (odds ratio [OR], 1.9 and 2.39, respectively). Individuals from small towns (less than 50 000 inhabitants) were at significantly greater risk of smoking compared with those living in rural areas (OR, 1.45 and 1.64 in women and men, respectively). We found differences regarding socioeconomic characteristics and major biochemical parameters between smokers and nonsmokers in Poland. However, it is difficult to establish which associations are causal for cardiovascular risk owing to the cross‑sectional design of this study.

Bilirubin Can Be Used as a Prognostic Factor for Lung Adenocarcinoma Patients with EGFR Mutations.

Background and ObjectivesNon-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation demonstrate only a median progression-free survival (PFS) of 8 to 10 months and undergo EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy. For decades, bilirubin has been reported to be associated with the onset and prognosis of lung cancer as a prooxidant. This study aimed to investigate the prediction of pretreatment circulating bilirubin for PFS in lung adenocarcinoma (LAC) patients who underwent EGFR-TKIs targeted therapy.Patients and MethodsLAC cases diagnosed and undergone EGFR-TKIs targeted therapy at The First Affiliated Hospital of Zhengzhou University between 2013 and 2015 were retrospectively reviewed. A total of 180 patients were studied according to inclusion and exclusion criteria. Follow-up data were collected for all patients until the disease progressed.ResultsUnivariate analysis showed that the levels of pretreatment total bilirubin (TBIL), indirect bilirubin (IBIL) and direct bilirubin (DBIL) were related to PFS (all p<0.05). Considering the close relationship among the three factors, we combined TBIL, IBIL and DBIL into one total factor, which is called bilirubin. Kaplan–Meier survival curves and Log rank tests indicated that patients with lower bilirubin levels had a shorter median PFS than those with higher bilirubin levels (8 vs. 15 months; p=0.002). Multivariate analysis demonstrated that pretreatment bilirubin is an independent prognostic factor (HR=0.454, CI: 0.267–0.773, p=0.004).ConclusionThis study confirms that bilirubin can predict the prognosis of LAC patients who had undergone EGFR-TKIs targeted therapy.

Efficacy and Safety of Ledispavir/Sofosbuvir with or without Ribavirin in patients with Decompensated Liver Cirrhosis and Hepatitis C Infection: a Cohort Study.

Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV). We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy. The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7 % with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16). LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR.

Intervention to Reduce Bilirubin Levels in Newborn Babies: A Systematic Review

Hyperbilirubin in newborns requires prompt and prompt intervention. A newborn is categorized as hyperbilirubun if there is an increase in the total serum bilirubin level to&gt; 5 mg / dl. Treatment for lowering bilirubin levels can be done medically and non-medically. The many choices of interventions to reduce bilirubin levels in newborns make researchers feel the need to conduct a systematic literature review. Literature search was performed on reputable data based on google scholar, PubMed, Proquest, Ebsco and Medline using the keyword "Intervention AND to reduce bilirubin levels AND Newborn". In the literature search stage, the researcher found 11,959 articles. The literature collection was carried out using the Joana Briggs Institute Critical Appraisal tools for analytical cross-sectional and analytical case control. The literature selection was carried out using PRISMA: Preferred Reporting Item For Systematic Review and Meta-Analysis. At the stage of selecting literature the researcher found 100 suitable articles. Literature analysis and synthesis were performed using matrix review tables and matrix synthesis tables. In the literature synthesis stage, the researcher found 10 suitable articles. The results of the systematic literature review show that the intervention of infant massage, photo therapy, early initiation of breastfeeding and the use of Billy Blanket can reduce the total serum bilirubin levels of newborns and prevent kernicterus. Infant massage interventions, photo therapy, early initiation of breastfeeding, breastfeeding every 2 hours and the use of Billy Blanket can significantly reduce total serum bilirubin levels and percutaneous bilirubin levels. Health workers need to increase their competence to select and determine the type of intervention that can be used to reduce the serum bilirubin level of newborns appropriately.

"Effect of zinc supplementation on serum bilirubin level in term neonates undergoing phototherapy"

Background: Neonatal jaundice is considered a major health problem in neonates owing to bilirubin deposition. Recently, zinc demonstrated a high efficiency in reduction of low bilirubin level when administrated in association with phototherapy. Aim of the work: To assess efficiency and safety of oral zinc as a therapy in treatment of indirect hyperbilirubinemia in term neonates during phototherapy. Patients and Methods:A total of 100 term neonates with indirect hyperbilirubinemia were divided into two equal groups: Intervention Group (n=50) received oral zinc sulphate preparation, in a dose of 5 mg twice daily in combination with phototherapy. Control group (n=50) received phototherapy without oral zinc supplementation. In both groups, the total serum bilirubin levels were measured at admission, 12 hours, 24 hours and at discharge. Results: Treatment of full-term neonates with hyperbilirubinemia by oral zinc sulfate at a dose of 5 mg given twice-daily induce a significant reduction of total serum bilirubin [TSB] after 12 hours, 24 hours and at discharge when compared to the control group. The duration of phototherapy in intervention group was markedly decreased with statistically significant difference in comparison to the control group. However, there was no significant differences between groups regarding adverse effects of phototherapy and zinc therapy. Conclusion: Oral zinc could play a major role in the management of neonatal jaundice when administrated at dose of ten mg/day as it can decrease the neonatal TSB with subsequent reduction of phototherapy duration.

Usefulness of routine blood test-driven clusters for predicting acute exacerbation in patients with asthma

AimAcute exacerbation (AE) is a significant burden in the management of asthma. In this study we aimed to investigate whether routine blood test results predicted AE in asthmatics. MethodsWe applied k-means cluster to routine blood test results which included eosinophil counts, total calcium, phosphorus, uric acid (UA), total cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, aspartate transaminase (AST), alanine transferase (ALT), gamma-glutamyltransferase, blood urea nitrogen, creatinine, and high-sensitive C-reactive protein (hsCRP) obtained from 590 asthmatics. AEs collected over the prospective follow-up of one-year were used to evaluate clinical trajectories of these clusters. ResultsThree blood clusters were identified. The essential features of each cluster can be characterized as follows: (i) high eosinophil count, UA, total cholesterol, AST, ALT, and hsCRP levels (Cluster 1); (ii) intermediate features (Cluster 2); (iii) low UA, total cholesterol and total bilirubin levels (Cluster 3). Kaplan-Meier analysis confirmed that clusters were strongly predictive of time to the first AE (log-rank P = 0.001). Hazard ratio for each group was as follows: Cluster 2 = 1, Cluster 1 = 2.67 (1 vs. 2, P = 4.68 × 10−4), and Cluster 3 = 1.69 (2 vs. 3, P = 0.021). ConclusionsWe defined three blood clusters in asthmatics. These blood clusters are easily identifiable from routine test results and may help clinicians to predict the future risk of AE in asthmatics.

Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach.

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.

Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian center.

559 Background: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety however is lacking, more so when used in patients who fall out of standard clinical trial criteria. Methods: We conducted a retrospective review of all patients with advanced HCC seen at our centre who received at least one dose of an ICI between May 2015 - June 2018. Data cutoff was 31 Dec 2018. Responses were evaluated using RECIST v1.1 criteria. Results: 114 patients fulfilled inclusion criteria. Median age was 66 years and 88.6% were male. 96.5% had an ECOG PS of 0 – 1. 64.9% received an ICI within a clinical trial setting. 62.3% received monotherapy ICI. 19.6% of patients had Child-Pugh B disease on initiation of ICI, and 69.3% had an ALBI Grade of 2. 50.0% were known to have hepatitis B and 11.4% had hepatitis C. Baseline HBV VL ranged from undetectable to 8210000 IU/mL. 30.7% received prior systemic treatment, most commonly sorafenib (82.9%). Over a median follow-up duration of 5.7 months (0.03 - 42.4), ORR was 18.4%, and disease control rate (DCR) was 51.8%. Median PFS was 2.6 months (1.7 - 3.9), and median OS was 13.9 months (7.0 - 16.2). 5 patients (23.8%) had response duration of more than 18 months. 35.1% received further systemic therapy after ICI. On multivariable analyses, age ≥ 65 years, higher albumin level and lower bilirubin level were associated with increased OS. 68.0% of patients experienced adverse events (AEs) of any grade, 12.0% of these being grade 3 - 4. No grade 5 adverse events were observed. Use of antiviral therapy was associated with a lower risk of hepatic AEs (p = 0.04) whilst high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AEs. Conclusions: In the real-world setting, responses and adverse event profiles to ICI use are comparable to those observed in clinical trials despite a more heterogenous population base. The expansion of indications for ICI use in advanced HCC beyond current approvals warrants greater study.

Blood levels of heme oxygenase-1 versus bilirubin in patients with coronary artery disease

ObjectiveHeme oxygenase-1 (HO-1) degrades heme to CO, iron, and biliverdin/bilirubin. Although serum bilirubin levels were often reported in patients with coronary artery disease (CAD), HO-1 levels in patients with CAD and the association between HO-1 and bilirubin levels have not been clarified. MethodsWe measured plasma HO-1 and serum total bilirubin levels in 262 patients undergoing coronary angiography. ResultsHO-1 levels were higher in patients with CAD than without CAD (median 0.46 vs. 0.35 ng/mL, P < 0.01), but bilirubin were lower in patients with CAD than without CAD (0.69 vs. 0.75 mg/dL, P < 0.02). Notably, HO-1 levels in CAD(−), 1-vessel, 2-vessel, and 3-vessel disease were 0.35, 0.51, 0.45, and 0.44 ng/mL, and were highest in 1-vessel disease (P < 0.05). Bilirubin levels in CAD(−), 1-vessel, 2-vessel, and 3-vessel disease were 0.75, 0.70, 0.68, and 0.66 mg/dL (P = NS). No correlation was found between HO-1 and bilirubin levels. In multivariate analysis, HO-1 levels were a significant factor for CAD independent of atherosclerotic risk factors and bilirulin levels. Odds ratio for CAD was 2.32 (95%CI = 1.29–4.17) for high HO-1 (>0.35 ng/mL). ConclusionsPatients with CAD were found to have high HO-1 and low bilirubin levels in blood, but no correlation was found between HO-1 and bilirubin levels.

Specific Nutritional Biomarker Profiles in Mild Cognitive Impairment and Subjective Cognitive Decline Are Associated With Clinical Progression: The NUDAD Project

ObjectivesNutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Design, setting and participantsWe included 299 patients without dementia (n = 149 SCD; age 61 ± 10 years, female 44%, n = 150 MCI; age 66 ± 8 years, female 38%). Median (interquartile range) follow-up was 3 (2-5) years. MethodsWe measured 28 nutritional biomarkers in blood and 5 in cerebrospinal fluid (CSF), associated with 3 Alzheimer's disease pathologic processes: vascular change (lipids), synaptic dysfunction (homocysteine-related metabolites), and oxidative stress (minerals and vitamins). Nutritional biomarker associations with clinical progression to MCI/dementia and cognitive decline based on the Mini-Mental State Examination score were evaluated using Cox proportional hazard models and linear mixed models. We used partial least squares Cox models (PLS-Cox) to examine nutritional biomarker profiles associated with clinical progression. ResultsIn the total group, high high-density lipoprotein (HDL) levels were associated with clinical progression and cognitive decline. In SCD, high folate and low bilirubin levels were associated with cognitive decline. In MCI, low CSF S-adenosylmethionine (SAM) and high theobromine were associated with clinical progression to dementia and high HDL, cholesterol, iron, and 1,25(OH)2 vitamin D were associated with cognitive decline. PLS-Cox showed 1 profile for SCD, characterized by high betaine and folate and low zinc associated with clinical progression. In MCI, a profile with high theobromine and HDL and low triglycerides and a second profile with high plasma SAM and low cholesterol were associated with risk of dementia. Conclusion and ImplicationsHigh HDL was most consistently associated with clinical progression. Moreover, different nutritional biomarker profiles for SCD and MCI showed promising associations with clinical progression. Future dietary (intervention) studies could use nutritional biomarker profiles to select patients, taking into account the disease stage.

Effects of hyperbilirubinemia on markers of genotoxicity and total oxidant and antioxidant status in newborns

Hyperbilirubinemia is one of the most common diseases in neonates. Slight elevations in bilirubin levels exert antioxidant effects but high levels may cause oxidative damage in newborns. We assessed the effects of hyperbilirubinemia on DNA damage and total oxidant and antioxidant status in newborns receiving phototherapy. A total of 68 term newborn infants exhibiting idiopathic unconjugated hyperbilirubinemia (UCH) requiring phototherapy and 27 age-matched healthy controls were enrolled in the study. Plasma 8-hydroxy-2 deoxy-guanosine (8-OH-dG) levels, total oxidant status (TOS), and total antioxidant status (TAS) were compared between newborns with UCH requiring phototherapy and age-matched healthy controls. The extent of DNA damage, the TOS, and the TAS were significantly higher in the study group than the control group (p < 0.01). The extent of DNA damage and the TOS increased at lower bilirubin levels; this became significant at bilirubin levels >16 mg/dL. A significant increase in TAS was observed even at low bilirubin levels, and the TAS was positively correlated with the bilirubin level to 30 mg/dL. At slightly elevated levels bilirubin serves as a physiological antioxidant. However, the high bilirubin levels evident in the present study increased DNA damage and oxidative stress.

CCRN Across the Life Span.

CCRN Across the Life Span.