A possible case of bictegravir-associated severe unconjugated hyperbilirubinemia.

BACKGROUND: Bictegravir (BIC) co-formulated with emtricitabine (FTC) and tenofovir alafenamide (TAF) is approved by Federal Food and Drug Administration in 2018 for both treatment-naïve and experienced persons living with HIV (PLWH). CASE PRESENTATION: A young man with recently diagnosed human immunodeficiency virus (HIV) infection presented with jaundice. Blood work was significant for mild anemia and grade 4 unconjugated hyperbilirubinemia. A comprehensive evaluation for hemolytic anemia failed to reveal any etiology. Other causes of hyperbilirubinemia were negative. Four months prior, patient was started on antiretroviral therapy with a single tablet regimen containing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), brand name Biktarvy®, and the medication was suspected to be the cause. The medication was held, and the hyperbilirubinemia improved. CONCLUSION: Severe hyperbilirubinemia can be found in the patient using BIC/FTC/TAF. The data for this adverse reaction is scarce, and more studies are needed on this possible side effect. The mechanism of unconjugated hyperbilirubinemia by INSTI remains undefined.

Transradial versus Transfemoral Access and the Risk of Acute Kidney Injury following Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Propensity-Score-Matched Studies.

Objectives: The aim of this study is to examine the association between vascular access sites and the incidence of AKI in patients with STEMI undergoing primary PCI. Background: Emerging evidence has suggested that transradial access (TRA) may be associated with lower rates of acute kidney injury (AKI) as compared with transfemoral access (TFA). However, most of these studies have included a nonselected study population undergoing diagnostic cardiac catheterization or percutaneous coronary intervention (PCI). Data on the association between TRA and AKI in this setting of STEMI are limited and with conflicting results. Methods: We systematically searched PubMed, Embase, and Scopus for abstracts and full-text articles from inception to July 13th of 2021. Studies included were randomized controlled trials (RCTs) and propensity-score-matched (PSM) studies evaluating the association of TRA versus TFA access with AKI in patients undergoing primary PCI for STEMI. Data were integrated using the random effects model and generic inverse-variance method of DerSimonian and Laird. Results: A total of 10,093 studies were found. After applying our inclusion criteria, 5 studies from 2014 to 2021 with a total of 8,536 STEMI patients were included. TRA was not significantly associated with a reduced risk for AKI compared with TFA (odds ratio 0.85, 95% CI 0.71-1.01, p 0.07, I 2 = 40%). Conclusions: Transradial access was not significantly associated with lower risk of AKI in patients undergoing primary PCI for STEMI compared with TFA. Larger studies are needed to clarify this outcome.

Risk factors and outcomes of post-transplant erythrocytosis among adult kidney transplant recipients: a systematic review and meta-analysis.

Post-transplant erythrocytosis (PTE) can occur in up to 10-16% after kidney transplant (KT). However, the post-transplant outcomes of recipients with PTE in the literature were conflicting. We performed systematic review and meta-analysis of published studies to evaluate risk factors of PTE as well as outcomes of recipients who developed PTE compared with controls. A literature search was conducted evaluating all literature from existence through February 2, 2021, using MEDLINE and EMBASE. Data from each study were combined using the random-effects model. (PROSPERO: CRD42021230377). Thirty-nine studies from July 1982 to January 2021 were included (7,099 KT recipients). The following factors were associated with PTE development: male gender (pooled RR = 1.62 [1.38, 1.91], I2 = 39%), deceased-donor KT (pooled RR = 1.18 [1.03, 1.35], I2 = 32%), history of smoking (pooled RR = 1.36 [1.11, 1.67], I2 = 13%), underlying polycystic kidney disease (PKD) (pooled RR=1.56 [1.21, 2.01], I2 =44%), and pretransplant dialysis (pooled RR=1.6 [1.02, 2.51], I2 =46%). However, PTE was not associated with outcomes of interest, including overall mortality, death-censored graft failure, and thromboembolism. Our meta-analysis demonstrates that male gender, deceased-donor KT, history of smoking, underlying PKD, and pretransplant dialysis were significantly associated with developing PTE. However, with proper management, PTE has no impact on prognosis of KT patients.

The utility of drug challenge testing in Brugada syndrome: A systematic review and meta-analysis.

INTRODUCTION: Brugada syndrome (BrS) is associated with ventricular arrhythmia leading to sudden cardiac death. Risk stratification is challenging, as major arrhythmic events (MAEs) are rare. We assessed the utility of drug challenge testing in BrS by a systematic review and meta-analysis. METHODS AND RESULTS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies compared the incidence of MAE between spontaneous and drug challenge-induced Type 1. Mixed-effects Poisson regression was used to calculate the incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were included (4099 patients, mean follow-up: 4.5 years). Pooled annual incidences of MAE in spontaneous, drug challenge induced (regardless of symptoms), asymptomatic drug challenge induced, and symptomatic drug challenge-induced Type 1 were 23.8 (95% confidence interval [CI]: 19.8-27.8), 6.5 (95% CI: 3.9-9.1), 2.1 (95% CI: -0.3 to 4.4), and 19.6 (95% CI: 9.9-29.3) per 1000 person-years, respectively. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was not statistically different (IRR = 1.0; 95% CI: 0.6-1.7). CONCLUSIONS: The incidence of MAE in drug challenge-induced Type 1 in asymptomatic patients is low. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was similar.

Device infections in implantable cardioverter defibrillators versus permanent pacemakers: A systematic review and meta-analysis.

INTRODUCTION: Recent studies suggest that implantable cardioverter defibrillators (ICDs) are associated with increased risk of cardiac implantable electronic device (CIED) infections when compared with permanent pacemakers (PPMs). However, there were controversies among studies. In this study we performed a systematic review and meta-analysis to explore the risk of device infection in ICD versus PPM. METHODS: We searched the databases of MEDLINE and EMBASE from inception to January 2019. Data from each study were combined using the random-effects, generic inverse variance method of Der Simonian and Laird to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Twenty-seven studies involving 202 323 CIEDs (36 782 ICDs and 165 541 PPMs) were included. Infections occurred from 9 days to 6 years postoperatively. When compared with PPM, ICD had a significantly higher risk of device infection in overall analysis (OR = 1.62, 95% CI: 1.29-2.04). The risk was seen in subgroups such as single chamber or dual chamber device (OR = 1.57, 95% CI: 1.18-2.09), de novo implantation (OR = 1.62, 95% CI: 1.29-2.69), revision implantation (OR = 1.63, 95% CI: 1.24-2.13), and cardiac resynchronization therapy (CRT) (OR = 1.75, 95% CI: 1.18-2.60). CRT-defibrillator increased risk of infection over CRT-pacemaker in revision implantation (OR = 1.81, 95% CI: 1.20-2.74) but not in de novo implantation (OR = 1.07, 95% CI: 0.23-4.88). The increased risk of infection among defibrillator was higher in CRT compared to non-CRT but not significant (P = 0.654). CONCLUSIONS: Our meta-analysis demonstrates a statistically significant increased risk of device infection in CIED patients who received ICD when compared to PPM.

PROGNOSIS OF DIFFERENTIATED THYROID CARCINOMA IN PATIENTS WITH GRAVES DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model. Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I2, 6.5%; P = .381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I2, 0.0%; P = .497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up. Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD. Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone.

Atrial fibrillation and risk of major arrhythmic events in Brugada syndrome: A meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is a common cause of sudden cardiac death (SCD). There is recent evidence that atrial fibrillation (AF) is associated with increased risk of SCD in general population. However, whether AF increases a risk of major arrhythmic events (MAE) in patients with BrS is still unclear. We performed a systematic review and meta-analysis to explore the effect of AF on MAE in BrS population. METHODS: We searched the databases of MEDLINE and EMBASE from inception to March 2019. Included studies were published cohort studies reporting rates of MAE (ventricular fibrillation, sustained ventricular tachycardia, SCD, or sudden cardiac arrest) in BrS patients, with and without previous documented AF. Data from each study were combined using the random-effects model. RESULTS: Six studies from 1,703 patients were included. There was a significant association between AF and an increased risk of MAE in patients with BrS (pooled OR = 2.37, 95% CI = 1.36-4.13, p-value = .002, I2  = 40.3%). CONCLUSIONS: Our meta-analysis demonstrated that AF is associated with an increased risk of MAE in patients with BrS.

Baseline fragmented QRS is associated with increased all-cause mortality in heart failure with reduced ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Recent studies suggested that fragmented (fQRS) is associated with poor clinical outcomes in heart failure with reduced ejection fraction (HFrEF) patients. However, no systematic review or meta-analysis has been done. We conducted a systematic review and meta-analysis to assess the association between baseline fQRS and all-cause mortality in HFrEF. METHODS: We comprehensively reviewed the databases of MEDLINE and EMBASE from inception to February 2018. Published studies of HFrEF that reported fQRS and outcome of all-cause mortality and major arrhythmic event (sudden cardiac death, sudden cardiac arrest, ventricular fibrillation, or sustained ventricular tachycardia) were included. Data were integrated using the random-effects, generic inverse-variance method of DerSimonian and Laird. RESULTS: Ten studies from 2010 to 2017 were included. Baseline fQRS was associated with increased all-cause mortality (risk ratio [RR] 1.63, 95% confidence interval [CI] 1.22-2.19, p < 0.0001, I2  = 73%) as well as major arrhythmic events (RR = 1.74, 95% CI 1.09-2.80, I2  = 89%). Baseline fQRS increased all-cause mortality in both Asian and Caucasian cohorts (RR = 2.17 with 95% CI 1.33-3.55 and RR = 1.45 with 95% CI 1.05-1.99, respectively) as well as increased major arrhythmic events in Asian cohort (RR = 1.50, 95% CI 1.05-2.13). Baseline fQRS also increased all-cause mortality in patients who had not received implantable cardioverter-defibrillator, significantly more than in patients who had received implantable cardioverter-defibrillator (RR = 2.46 with 95% CI 1.56-3.89 and 1.36 with 95% CI 1.08-1.71, respectively). CONCLUSION: Baseline fQRS is associated with increased all-cause mortality up to 1.63-fold in HFrEF patients. Fragmented QRS could be a predictor of clinical outcome in patients with HFrEF.

SCN5A mutation status increases the risk of major arrhythmic events in Asian populations with Brugada syndrome: systematic review and meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmic disease linked to SCN5A mutations. It is controversial whether SCN5A mutation carriers possess a greater risk of major arrhythmic events (MAE). We examined the association of SCN5A mutations and MAE in BrS patients. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published cohort and case-control studies that compared MAE in BrS patients with and without SCN5A mutations. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Seven studies from March 2002 to October 2017 were included (1,049 BrS subjects). SCN5A mutations were associated with MAE in Asian populations (RR = 2.03, 95% CI: 1.37-3.00, p = 0.0004, I2  = 0.0%), patients who were symptomatic (RR = 2.66, 95% CI: 1.62-4.36, p = 0.0001, I2  = 23.0%), and individuals with spontaneous type-1 Brugada pattern (RR = 1.84, 95% CI: 1.05-3.23, p = 0.03, I2  = 0.0%). CONCLUSIONS: SCN5A mutations in BrS increase the risk of MAE in Asian populations, symptomatic BrS patients, and individuals with spontaneous type-1 Brugada pattern. Our study suggests that SCN5A mutation status should be an important tool for risk assessment in BrS patients.

Ultrasound surveillance for cholangiocarcinoma in an endemic area: A prove of survival benefits.

BACKGROUND AND AIM: Cholangiocarcinoma (CCA) is an aggressive malignancy with rapid progression and poor prognosis. Abdominal ultrasound surveillance may detect early-stage malignancy and improve surgical outcome. However, little data exist on the benefits of abdominal ultrasound surveillance in populations at high risk for CCA development in an endemic area. This study compared survival outcomes of CCA patients recruited through abdominal ultrasound surveillance program and those presented to the hospital independent of surveillance. METHODS: The surveillance population-based cohort was 4225 villagers in Northern Thailand, aged 30-60 years, who consented to a 5-year abdominal ultrasound surveillance program, which included interval ultrasound examinations every 6 months. The non-surveillance cohort was hospital-based CCA patients diagnosed during April 2007 to November 2015. Numbers of operable tumors, percentages of R0 resection, and survival analyses were compared between the two cohorts. RESULTS: There were 48 and 192 CCA patients in the surveillance and the non-surveillance cohorts, respectively. Of these, 37/48 (77.1%) and 22/192 (11.5%) were in an operable stage and R0 resections performed in 36/48 (97.3%) and 14/192 (63.6%), respectively. The median survival in each group was 31.8 and 6.7 months, respectively (with correction of lead time bias) (P < 0.0001). By multivariate analysis, abdominal ultrasound surveillance (hazard ratio [HR] = 0.41; P = 0.012), operable stage (HR = 0.11; P < 0.001), and serum albumin ≥ 3.5 g/dL (HR = 0.42; P < 0.001) were significantly associated with decreased mortality, whereas size of CCA (HR = 1.11; P < 0.001), serum alanine aminotransferase > 40 IU/L (HR = 1.71; P = 0.017), and tumor recurrence (HR = 4.86; P = 0.017) were associated with increased mortality. CONCLUSION: Abdominal ultrasound surveillance provided survival benefits and should be considered in areas highly endemic for CCA to reduce mortality.