Kinetics of interferon‐gamma producing cytomegalovirus (CMV)‐specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation

Background. Deficiencies in cytomegalovirus (CMV)‐specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. A time‐dependent analysis was conducted to determine the association between the percentages and kinetics of interferon‐gamma‐producing CMV‐specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. Results. Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18–3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99–1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early‐1 (HR: 1.2; 95% CI: 1.01–1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0–1.27; P=0.060) were associated with time‐to‐CMV viremia. Furthermore, a higher degree in the decline of CMV lysate‐activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96–1.36; P=0.125) and CMVpp65‐activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03–1.78; P=0.031) was suggestive of or significantly associated with time‐to‐CMV viremia. Conclusions. Higher levels of CMV‐specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV‐specific T lymphocytes suggests that severe disruption in homeostatic CMV‐specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.     

Elevated fetal haemoglobin is a predictor of better outcome in MDS/AML patients receiving 5‐aza‐2′‐deoxycytidine (Decitabine)

Although azanucleoside DNA‐hypomethylating agents (HMAs) are routinely used for the treatment of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), very few outcome predictors have been established. Expression of the β‐like globin gene locus is tightly regulated by DNA methylation, is HMA‐sensitive in vitro, and fetal haemoglobin (HbF) expression is under study as a potential biomarker for response of MDS patients to azacitidine. We determined HbF expression in 16 MDS and 36 AML patients receiving decitabine (DAC). Pre‐treatment HbF was already elevated (>1·0% of total haemoglobin) in 7/16 and 12/36 patients, and HbF was induced by DAC in 81%/54% of MDS/AML patients, respectively. Elevated pre‐treatment HbF was associated with longer median overall survival (OS): 26·6 vs. 8·6 months for MDS (hazard ratio [HR] 8·56, 95% confidence interval [CI] 1·74–42·49, P = 0·008, with similarly longer progression‐free and AML‐free survival), and 10·0 vs. 2·9 months OS for AML (HR 3·01, 95% CI 1·26–7·22, P = 0·014). In a multivariate analysis, the prognostic value of HbF was retained. Time‐dependent Cox models revealed that the prognostic value of treatment‐induced HbF induction was inferior to that of pre‐treatment HbF. In conclusion, we provide first evidence for in vivo HbF induction by DAC in MDS/AML, and demonstrate prognostic value of elevated pre‐treatment HbF, warranting prospective, randomized studies.     

Azacitidine and low‐dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts – a retrospective single‐center experience

We retrospectively analyzed and compared the efficacy and toxicity of azacitidine (AZA) and low‐dose cytarabine (LD‐Ara‐C) in 65 palliative patients with acute myeloid leukemia (AML) showing high bone marrow blast counts (≥30%) before start of treatment. Twenty‐seven and 38 patients received AZA and LD‐Ara‐C, respectively. The median patient age was 71 yr. Patient and disease characteristics did not differ between the treatment groups, except for BM blast counts, and peripheral leukocyte and blast counts which were significantly higher in the LD‐Ara‐C group. AZA and LD‐Ara‐C were first‐line treatment in 12 (44%) and 17 patients (45%), respectively. Response and hematologic improvement rates were low and similar in both treatment groups. In both treatment groups, most common non‐hematologic toxicities included febrile neutropenia, pneumonia, and bleedings without significant differences regarding frequencies. Estimated 1‐yr survival rates were 15% (95% CI 8–22) and 13% (95% CI 7–19) in the AZA and LD‐Ara‐C groups, respectively, without statistically significant difference. In multivariate analysis (n = 65), previous treatment (HR 2.27, 95% CI 1.00–5.22, P = 0.05) and adverse cytogenetics (HR 2.50, 95% CI 1.20–5.22, P = 0.02) were independent predictors of poor survival. In our center and within the limitations of a retrospective study, both treatment regimens showed similar but limited efficacy in palliative patients with AML and high BM blast counts.     

Advanced chronic kidney disease: Relationship to outcomes post‐TAVR,a meta‐analysis

Chronic kidney disease (CKD) is associated with worse outcomes in high‐surgical‐risk patients undergoing transcatheter aortic valve replacement (TAVR). However, it is unclear whether this relationship is apparent in lower‐surgical‐risk patients. We sought to analyze existing literature to assess whether or not advanced CKD is associated with increased mortality or a greater incidence of adverse events (specifically major stroke, bleeding, and vascular complications). We searched PubMed and Embase (2008–2017) for relevant studies. Studies with <1 year follow‐up and those not evaluating advanced CKD or outcomes post‐TAVR were excluded. Our co–primary endpoints were the incidence of short‐term mortality (defined as in‐hospital or 30‐day mortality) and long‐term mortality (1 year). Our secondary endpoints included incidence of major stroke, life‐threatening bleeding, and major vascular complications. Eleven observational studies with a total population of 10709 patients met the selection criteria. Among patients with CKD there was an increased risk of short‐ and long‐term mortality in high‐surgical‐risk patients who underwent TAVR (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.22–1.88 and HR: 1.56, 95% CI: 1.38–1.77, respectively; P < 0.01). However, there was no association between CKD and mortality in low‐ to intermediate‐risk patients (HR: 1.35, 95% CI: 0.98–1.84, P = 0.06 in short‐term and HR: 1.08, 95% CI: 0.92–1.27, P = 0.34 in long‐term). In low‐ to intermediate‐risk TAVR patients, advanced CKD is not associated with increased mortality or poorer safety outcomes. These findings should be factored into the clinical decision‐making process regarding TAVR candidacy.     

Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril,Compared to the Opposite Order: Results of the Randomized CIBIS III Trial

Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β‐Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β‐blocker or angiotensin‐receptor‐blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6–24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol‐first group were sudden, compared to 16 of 32 in the enalapril‐first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21–1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29–1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51–1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71–16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92–7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99–5.75; P= 0.053. There were no significant between‐group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol‐first cohort.     

Life‐threatening bowel perforation while on thalidomide‐based triplet regimen for multiple myeloma: a retrospective case series

The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15·4%), consisting of: need for phlebotomies (3·3%), uncontrolled myeloproliferation (1·6%), failure to reduce massive splenomegaly (0·8%), development of cytopenia at the lowest dose of HC to achieve a response (1·7%) and extra‐haematological toxicity (9%). With a median follow‐up of 4·6 years, 99 patients died, resulting in a median survival of 19 years. Fulfilling any of the resistance/intolerance criteria had no impact on survival but when the different criteria were individually assessed, an increased risk of death was observed in patients developing cytopenia [Hazard ratio (HR): 3·5, 95% confidence interval (CI): 1·5–8·3, P = 0·003]. Resistance/intolerance had no impact in the rate of thrombosis or bleeding. Risk of myelofibrotic transformation was significantly higher in those patients developing cytopenia (HR: 5·1, 95% CI: 1·9–13·7, P = 0·001) and massive splenomegaly (HR: 9·1, 95% CI: 2·3–35·9, P = 0·002). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukaemia (HR: 20·3, 95% CI: 5·4–76·5, P < 0·001). In conclusion, the unified definition of resistance/intolerance to HC delineates a heterogeneous group of PV patients, with those developing cytopenia being associated with an adverse outcome.     

Genetic polymorphisms in oxidative stress‐related genes are associated with outcomes following treatment for aggressive B‐cell non‐Hodgkin lymphoma

Variable survival outcomes are seen following treatment for aggressive non‐Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B‐cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress‐related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline‐based therapies. Their associations with progression‐free survival (PFS) and overall survival (OS) were estimated by Cox proportional hazard regression; associations with hematologic toxicity were estimated by logistic regression. To validate the findings, the top three SNPs were tested in an independent cohort of 572 DLBCL patients. The top SNPs associated with PFS in the discovery cohort were the rare homozygotes for MPO rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14–3.06, P = 0.013), AKR1C3 rs10508293 (HR = 2.09, 95% CI = 1.28–3.41, P = 0.0032) and NCF4 rs1883112 (HR = 0.66, 95% CI = 0.43–1.02, P = 0.06). The association of the NCF4 SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44–1.01, P = 0.05) and the meta‐analysis was significant (HR = 0.66, 95% CI = 0.49–0.89, P < 0.01). The association of the MPO SNP was attenuated in the validation dataset, while the meta‐analysis remained significant (HR = 1.64, 95% CI = 1.12–2.41). These two SNPs showed similar trends with OS in the meta‐analysis (for NCF4, HR = 0.72, 95% CI = 0.51–1.02, P = 0.07 and for MPO, HR = 2.06, 95% CI = 1.36–3.12, P < 0.01). In addition, patients with the rare homozygote of the NCF4 SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in NCF4 may contribute to treatment outcomes for patients with aggressive NHL. Am. J. Hematol. 89:639–645, 2014. © 2014 Wiley Periodicals, Inc.     

Peptic ulcer bleeding patients with Rockall scores ≥6 are at risk of long‐term ulcer rebleeding: A 3.5‐year prospective longitudinal study

Background and Aim

Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long‐term outcomes deserve follow‐up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5‐year longitudinal cohort.

Methods

Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding.

Results

The proportion of patients with rebleeding during the 3.5‐year follow‐up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person‐year, P = 0.004, log–rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5‐fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person‐year, P = 0.012, log–rank test).

Conclusions

Patients with Rockall scores ≥6 are at risk of long‐term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5‐fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6.     

Excessive Access Cannulation Site Bleeding Predicts Long‐Term All‐Cause Mortality in Chronic Hemodialysis Patients

Our group has previously reported that excessive vascular access bleeding during dialysis treatment in stable hemodialysis (HD) patients was associated with anemia and may indicate poorer health. The association between excessive blood loss from access cannulation site and clinical outcomes was unknown. We hypothesized that excessive access bleeding may have an impact on all‐cause and cardiovascular (CV) mortality in this population. We prospectively conducted an observational, longitudinal study of 360 HD patients. Excessive access bleeding was defined as at least an occurrence of blood loss greater than 4 mL per HD session during a study period of one month. During a median follow‐up of 83 months, all‐cause mortality and CV mortality were registered. Outcomes were analyzed by Kaplan–Meier and Cox proportional hazards regression analyses. A total of 118 (32.8%) participants died and 54 of these were from CV death. Using a multivariate Cox proportional hazards regression, access bleeding was found to be an independent predictor of all‐cause mortality (HR 1.67, 95% CI 0.96–2.91, P = 0.070) but not for CV death (HR 1.53, 95% CI 0.88–2.68, P = 0.135). Our study identified that excessive access cannulation site bleeding could be a novel marker for increased risk of death in HD patients.     

Impact of intravascular ultrasound‐guided percutaneous coronary intervention on long‐term clinical outcomes in a real world population

Objectives : To compare long‐term clinical outcomes between intravascular ultrasound (IVUS)‐guided and angiography‐guided percutaneous coronary intervention (PCI) in a large “real world” registry. Background : The impact of IVUS‐guided PCI on clinical outcomes remains unclear. Methods : Between January 1998 and February 2006, 8,371 patients who underwent IVUS‐ (n = 4,627) or angiography‐ (n = 3,744) guided PCI were consecutively enrolled. Three‐year clinical outcomes were compared after adjustment for inverse‐probability‐of‐treatment weighting (IPTW) in the overall population and in separate populations according to stent type. Results : A crude analysis of the overall population showed that the 3‐year mortality rate was significantly lower in the IVUS‐guided group than in the angiography‐guided group (96.4% ± 0.3% vs. 93.6% ± 0.4%, log‐rank P < 0.001). When adjusted by IPTW, patients undergoing IVUS‐guided PCI remained at lower risk of mortality (hazard ratio [HR] 0.627; 95% CI 0.50–0.79, P < 0.001). Similarly, in the drug‐eluting stent (DES) population, the 3‐year risk of mortality was significantly lower in patients undergoing IVUS‐guided PCI (HR 0.46; 95% CI 0.33–0.66, P < 0.001). In contrast, IVUS‐guided PCI did not reduce the risk of mortality in the bare metal stent population (HR 0.82; 95% CI 0.60–1.10, P = 0.185). However, the risks of myocardial infarction (HR 0.95; 95% CI 0.63–1.44, P = 0.810), target vessel revascularization (HR 1.00; 95% CI 0.86–1.15, P = 0.944), and stent thrombosis (HR 0.82; 95% CI 0.53–1.07, P = 0.109) were not associated with IVUS guidance. Conclusions : IVUS‐guided PCI may reduce long‐term mortality when compared with conventional angiography‐guided PCI. This may encourage the routine use of IVUS for PCI in patients undergoing DES implantation. © 2012 Wiley Periodicals, Inc.     

β‐Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta‐analysis

Introduction: Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and β‐blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of β‐blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites. Materials and Methods: Extensive search of the literature including randomized controlled trial (RCT) and non‐RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using β‐blockers were evaluated. We performed a meta‐analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model. Results: Three RCT and three retrospective studies in which β‐blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non‐responders. Conclusions: This analysis suggests a role of β‐blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding.     

The impact of E‐cadherin expression on the prognosis of esophageal cancer: a meta‐analysis

E‐cadherin is a 120‐KD transmembrane calcium‐dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta‐analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta‐analysis was 1.33 (95% CI 1.16–1.52; z = 3.99, P = 0.00). When the study measured by enzyme‐linked immunosorbent assay is excluded, the pooled HR‐evaluated E‐cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22–1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21–1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E‐cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33–2.02). The pooled odds ratio of reduced E‐cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75–3.94), 1.77 (95% CI 1.06 ?2.97), and 3.39 (95% CI 1.85–6.23). Reduced E‐cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E‐cadherin expression is significantly associated with poorer differentiation degree.     

Comparison of single‐ versus two‐stent techniques in treatment of unprotected left main coronary bifurcation disease

Background : This study sought to compare 3‐year outcomes of single‐ versus two‐stent techniques in patients with distal unprotected left main coronary artery (LMCA) disease treated with drug‐eluting stents (DES). Methods and Results : A total of 392 patients with distal unprotected LMCA disease who underwent DES implantation with single‐ (n = 234) or two‐ (n = 158) stent techniques were evaluated. The primary end point was major adverse cardiac events (MACE), defined as the composite of death, myocardial infarction (MI), and target lesion revascularization (TLR). The two‐stent group was more likely to have extensive coronary artery stenosis. After adjustment with weighted Cox model using the inverse probability of treatment weighting, the 3‐year risk of death was similar in the single‐ and two‐stent groups (hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.28–2.13, P = 0.62). However, the 3‐year risks of MI (HR, 0.38, 95% CI, 0.19–0.78, P = 0.008), TLR (HR, 0.16, 95% CI, 0.05–0.57, P = 0.005), and MACE (HR, 0.89, 95% CI, 0.22–0.67, P = 0.0007) were significantly lower in the single‐stent group. Conclusion : Compared with the two‐stent technique, the single‐stent technique showed more favorable long‐term clinical outcomes in patients with distal unprotected LMCA disease who received DES. © 2011 Wiley‐Liss, Inc.     

Association of IFNL3 and IFNL4 polymorphisms with liver‐related mortality in a multiracial cohort of HIV/HCV‐coinfected women

African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver‐related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV‐related outcomes, the impact of these variants on liver‐related mortality has not been investigated. We conducted a cohort study of HIV/HCV‐coinfected women followed in the multicentre, NIH‐funded Women's Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN‐λ region were associated with liver‐related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver‐related death by race/ethnicity (ascertained by self‐report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver‐related deaths during up to 18 years of follow‐up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95% CI 0.14–0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95% CI 0.45–0.99, P = 0.047) were most strongly associated with liver‐related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95% CI 0.16–1.04, P = 0.060 and HR 0.78, 95% CI 0.51–1.19, P = 0.25, respectively). African American women had persistently lower liver‐related death independent of IFN‐λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV‐coinfected women is not explained by genetic variation in the IFN‐λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver‐related mortality.     

Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia,Spain

The use of some anti‐hypertensive drugs in the current COVID‐19 pandemic has become controversial. This study investigated possible relationships between anti‐hypertensive medications use and COVID‐19 infection risk in the ambulatory hypertensive population. This is a population‐based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID‐19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID‐19 infection. Across study period, 205 PCR‐confirmed COVID‐19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons‐period. In multivariable analyses, only age (HR: 1.03; 95% CI: 1.02‐1.05; P < .001) and nursing home residence (HR: 19.60; 95% CI: 13.80‐27.84; P < .001) appeared significantly associated with increased risk of COVID‐19. Considering anti‐hypertensive drugs, receiving diuretics (HR: 1.22; 95% CI: 0.90‐1.67; P = .205), calcium channel blockers (HR: 1.29; 95%CI: 0.91‐1.82; P = .148), beta‐blockers (HR: 0.97; 95% CI: 0.68‐1.37; P = .844), and angiotensin‐converting enzyme inhibitors (HR: 0.83; 95% CI: 0.61‐1.13; P = .238) did not significantly alter the risk of PCR‐confirmed COVID‐19, whereas receiving angiotensin II receptor blockers was associated with an almost statistically significant reduction risk (HR: 0.67; 95% CI: 0.44‐1.01; P = .054). In conclusion, our data support that receiving renin‐angiotensin‐aldosterone system inhibitors does not predispose for suffering COVID‐19 infection in ambulatory hypertensive people. Conversely, receiving angiotensin II receptor blockers could be related with a reduced risk.     

Factors associated with the presence of multiple Lugol‐voiding lesions in patients with esophageal squamous‐cell carcinoma

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol‐voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence‐specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84–122.45: P = 0.011), presence of the ALDH2‐2 allele (OR 4.5, 95% CI 1.55–13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02–6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13–88.44: P = 0.038) and presence of the ALDH2‐2 allele (OR 4.56, 95% CI 1.4–14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2‐2 allele (OR 17.5, 95% CI 1.97–155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2‐2 allele (OR 8.85, 95% CI 1.68–46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2‐2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2‐2 allele (OR 4.0, 95% CI 0.54–29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2‐2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2‐2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.     

Relationship between IL‐10 gene −1082A/G and −592C/A polymorphisms and the risk of hepatitis C infection: a meta‐analysis

Increasing evidence suggests that interleukin‐10 (IL‐10) gene promoter polymorphisms may be associated with chronic hepatitis C virus (HCV) infection and HCV clearance. To more precisely estimate the association between these variants and the risk of HCV infection, we performed a meta‐analysis of 26 studies describing the IL‐10–1082A/G, –819C/T, –592C/A genotypes, including 4039 chronic HCV infection cases and 2902 controls. When compared with a healthy population, the –1082GG allele had a 43% increased risk of chronic HCV infection in combined populations (GG vs GA + AA: odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.052–1.952, P = 0.023). In subgroup analysis by ethnicity, a significant increased risk was associated with the ?1082GG genotype in the Caucasian population (GG vs AA: OR = 1.390, 95% CI: 1.108–1.744, P = 0.004; GG vs GA + AA: OR = 1.621, 95% CI: 1.267–2.075, P = 0.000). However, no significant association was found in Asian, African or Chinese populations. Moreover, a higher distribution of ?592A was found in the spontaneously recovered population (AA vs CC: OR = 0.585, 95% CI = 0.387–0.884, P = 0.011; AA + AC vs CC: OR = 0.738, 95% CI = 0.551–0.988, P = 0.041; AA vs AC + CC: OR = 0.788, 95% CI = 0.664–0.935, P = 0.006) than that in the chronic HCV infection population. In conclusion, the IL‐10–1082GG allele may increase the risk of chronic HCV infection in Caucasian population, and people carrying the IL‐10–592A allele are more likely to clear HCV spontaneously.     

Comparison of overall survival between antiviral‐induced viral suppression and inactive phase chronic hepatitis B patients

Nucleot(s)ide analogues (NAs) reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. However, the risk of HCC is reportedly higher for NA‐treated patients than for patients in the inactive CHB phase. This study aimed to compare the long‐term outcomes of CHB patients with NA‐induced viral suppression and those of patients with inactive CHB. This retrospective study involved 1118 consecutive CHB patients whose HBV DNA level was continuously <2000 IU/mL during follow‐up with/without antiviral agents. The patients were classified into inactive CHB (n = 373) or NA groups (n = 745). The primary endpoint was overall survival. Secondary endpoints included development of HCC and other liver‐related events. The median duration of follow‐up was 41.0 (interquartile range = 26.5‐55.0) months. The difference in overall survival between the NA group vs. the inactive CHB group was not significant (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.33‐1.85; P = .57). The NA group showed a significantly higher risk of HCC (HR = 3.44; 95% CI = 1.82‐6.52; P < .01), but comparable risk for non‐HCC liver‐related events (HR = 1.02; 95% CI = 0.66‐1.59; P = .93), compared with the inactive CHB group. Among patients with cirrhosis, the NA group showed a significantly lower risk of death (HR = 0.31; 95% CI = 0.097‐0.998; P = .05) and non‐HCC liver‐related events (HR = 0.51; 95% CI = 0.31‐0.83; P < .01), but a slightly higher risk of HCC (HR = 2.39; 95% CI = 0.85‐6.75; P = .09), compared to the inactive CHB group. The overall survival of untreated patients with inactive CHB and of CHB patients achieving viral suppression with NA was comparable. However, NA treatment of cirrhotic patients was significantly associated with longer overall survival and lower risk of liver‐related events.     

Recipient single nucleotide polymorphisms in Paneth cell antimicrobial peptide genes and acute graft‐versus‐host disease: analysis of BMT CTN‐0201 and ‐0901 samples

Host genetics shape the gut microbiota, and gut dysbiosis increases the risk of acute graft‐versus‐host disease (aGVHD). Paneth cells and microbiota have interactions that contribute to immune regulation. α‐defensin‐5 (HD5) and regenerating islet‐derived protein 3 alpha (Reg3A) are the most abundant Paneth cell antimicrobial peptides (AMPs). We hypothesized that single nucleotide polymorphisms (SNPs) in the genes for HD5 (DEFA5) and Reg3A (REG3A) predict aGVHD risk. We analysed pre‐transplant recipient peripheral blood mononuclear cell samples from randomized Blood and Marrow Transplant Clinical Trials Network (BMT CTN) studies 0201 (94 patients with bone marrow and 93 with peripheral blood grafts) and 0901 (86 patients with myeloablative and 77 with reduced‐intensity conditioning; all using peripheral blood grafts). In multivariable analysis (with a SNP × graft source interaction term in CTN‐0201 and a SNP × conditioning intensity term in CTN‐0901), DEFA5 rs4415345 and rs4610776 were associated with altered incidence of aGVHD grade II–IV [rs4415345 G vs. C: hazard ratio (HR) 0·58, 95% confidence interval (95% CI) 0·37–0·92, P = 0·02; rs4610776 T vs. A: HR 1·53, 95% CI 1·01–2·32, P = 0·05] in CTN‐0201, but not CTN‐0901, suggesting a stronger effect in bone marrow allografts. REG3A SNP was not associated with aGVHD. Host genetics may influence aGVHD risk by modulating Paneth cell function.