Pigmentary abnormality without significant drusen as a risk factor for late age-related macular degeneration

We investigated the incidence and risk factors of late age-related macular degeneration (AMD) in the fellow eye (FE) without significant drusen of patients with unilateral exudative macular neovascularization (MNV). In this retrospective study, 241 eligible patients who were followed-up for more than 3 years were enrolled. We analyzed the incidence and hazard ratios (HRs) of late AMD in the FE according to demographic and ophthalmologic variables. Hypopigmentation on color fundus photography (CFP) corresponds to shallow irregular RPE elevation (SIRE), so-called “double-layer sign” and/or “attenuation or disruption of RPE and/or ellipsoid zone” on OCT. The 5-year incidence of FE exudative MNV conversion was 8.6%. The 5-year incidence of FE exudative MNV of large hypopigmentation (≥ 0.5 disc area; DA) and small hypopigmentation (< 0.5 DA) on CFP, and SIRE (≥ 1000 µm) and small RPE elevation (< 1000 µm) on OCT were 36.2%, 14.2%, 55.0%, and 15.6%, respectively. The multivariate Cox proportional hazard model revealed that large hypopigmentation, small hypopigmentation, SIRE, and small RPE elevation showed HRs of 23.230, 8.037, 132.589, and 41.823 for FE exudative MNV occurrence, respectively. Hypopigmentation on CFP and SIRE on OCT could represent the same lesion. Even small hypopigmentation and small RPE elevation were significant risk factors for progression to exudative MNV.

Irradiation of the Subventricular Zone and Subgranular Zone in High- and Low-Grade Glioma Patients: an Atlas-based Analysis on Overall Survival

Background Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p&lt;0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p&lt;0.001; multivariate: 1.055/Gy, p&lt;0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (&gt;30.33 Gy) vs 14.0 months (&lt;30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (&gt;29.11 Gy) vs 15.5 months (&lt;29.11 Gy) median OS, p&lt;0.001). No correlations between dose and OS were found for LGG patients. Conclusion Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

Variability, mean, and baseline values of metabolic parameters in predicting the risk of type 2 diabetes

Context Impact of baseline and alteration of metabolic parameters (MPs), including plasma glucose (PGs) testing, insulin resistance surrogates, and lipid profile and their mutual interactions on the development of type 2 diabetes (T2DM) has not been investigated systematically. Objective To access the association of the past variability (V), past mean (M), and the baseline (B) values of various MPs and their mutual interaction with the risk of T2DM. Design Longitudinal analysis from the Korean Genome and Epidemiology Study. Setting Community-based Participants 3829 non-diabetic participants with completed MPs measurements during three biannually visits were followed up over the next 10 years. Outcomes Incidence of T2DM during the follow up. Results Among predictors, PG concentrations measured during the oral glucose tolerance test were the most prominent T2DM determinants, in which the M of the average value of fasting PG, 1-h, and 2-h PGs had the strongest discriminative power (hazard ratios and 95% CI for an increment of SD: 3.00 (2.5–3.26), AUC: 0.82). The M values of MPs were superior to their B and V values in predicting T2DM, especially among post-load PGs. Various mutual interactions between indices and among MPs were found. The most consistent interactants were the M values of high-density lipoprotein cholesterol and the M and V values of fasting PG. The findings were similar in normal tolerance glucose participants and were confirmed by sensitivity analyses. Conclusion The post-load PGs, past alteration of measurements, and mutual interactions among indices of MPs are important risk factors for T2DM development.

COVID-19 is associated with higher risk of venous thrombosis, but not arterial thrombosis, compared with influenza: Insights from a large US cohort

Introduction Infection with SARS-CoV-2 is typically compared with influenza to contextualize its health risks. SARS-CoV-2 has been linked with coagulation disturbances including arterial thrombosis, leading to considerable interest in antithrombotic therapy for Coronavirus Disease 2019 (COVID-19). However, the independent thromboembolic risk of SARS-CoV-2 infection compared with influenza remains incompletely understood. We evaluated the adjusted risks of thromboembolic events after a diagnosis of COVID-19 compared with influenza in a large retrospective cohort. Methods We used a US-based electronic health record (EHR) dataset linked with insurance claims to identify adults diagnosed with COVID-19 between April 1, 2020 and October 31, 2020. We identified influenza patients diagnosed between October 1, 2018 and April 31, 2019. Primary outcomes [venous composite of pulmonary embolism (PE) and acute deep vein thrombosis (DVT); arterial composite of ischemic stroke and myocardial infarction (MI)] and secondary outcomes were assessed 90 days post-diagnosis. Propensity scores (PS) were calculated using demographic, clinical, and medication variables. PS-adjusted hazard ratios (HRs) were calculated using Cox proportional hazards regression. Results There were 417,975 COVID-19 patients (median age 57y, 61% women), and 345,934 influenza patients (median age 47y, 66% women). Compared with influenza, patients with COVID-19 had higher venous thromboembolic risk (HR 1.53, 95% CI 1.38–1.70), but not arterial thromboembolic risk (HR 1.02, 95% CI 0.95–1.10). Secondary analyses demonstrated similar risk for ischemic stroke (HR 1.11, 95% CI 0.98–1.25) and MI (HR 0.93, 95% CI 0.85–1.03) and higher risk for DVT (HR 1.36, 95% CI 1.19–1.56) and PE (HR 1.82, 95% CI 1.57–2.10) in patients with COVID-19. Conclusion In a large retrospective US cohort, COVID-19 was independently associated with higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared with influenza. These findings may inform crucial knowledge gaps regarding the specific thromboembolic risks of COVID-19.

MicroRNAs as biomarkers for prostate cancer prognosis: a systematic review and a systematic reanalysis of public data

Background Reliable prognostic biomarkers to distinguish indolent from aggressive prostate cancer (PCa) are lacking. Many studies investigated microRNAs (miRs) as PCa prognostic biomarkers, often reporting inconsistent findings. We present a systematic review of these; also systematic reanalysis of public miR-profile datasets to identify tissue-derived miRs prognostic of biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods Independent PubMed searches were performed for relevant articles from January 2007 to December 2019. For the review, 128 studies were included. Pooled-hazard-ratios (HRs) for miRs in multiple studies were calculated using a random-effects model (REM). For the reanalysis, five studies were included and Cox proportional-hazard models, testing miR association with BCR, performed for miRs profiled in all. Results Systematic review identified 120 miRs as prognostic. Five (let-7b-5p, miR-145-5p, miR152-3p, miR-195-5p, miR-224-5p) were consistently associated with progression in multiple cohorts/studies. In the reanalysis, ten (let-7a-5p, miR-148a-3p, miR-203a-3p, miR-26b-5p, miR30a-3p, miR-30c-5p, miR-30e-3p, miR-374a-5p, miR-425-3p, miR-582-5p) were significantly prognostic of BCR. Of these, miR-148a-3p (HR = 0.80/95% CI = 0.68-0.94) and miR-582-5p (HR = 0.73/95% CI = 0.61-0.87) were also reported in prior publication(s) in the review. Conclusions Fifteen miRs were consistently associated with disease progression in multiple publications or datasets. Further research into their biological roles is warranted to support investigations into their performance as prognostic PCa biomarkers.

The “Obesity Paradox” in Patients With HFpEF With or Without Comorbid Atrial Fibrillation

Background: Overweight and mildly obese individuals have a lower risk of death than their normal-weight counterparts; this phenomenon is termed “obesity paradox.” Whether this “obesity paradox” exists in patients with heart failure (HF) or can be modified by comorbidities is still controversial. Our current study aimed to determine the association of body mass index (BMI) with outcomes with patients with HF with preserved ejection fraction (HFpEF) with or without coexisting atrial fibrillation (AF).Methods: Patients with HFpEF from the Americas in the TOPCAT trial were categorized into the 3 groups: normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obesity (≥30 kg/m2). The Cox proportional-hazards models were used to calculate the adjusted hazard ratios (HRs) and CIs.Results: We identified 1,749 patients with HFpEF, 42.1% of which had baseline AF. In the total population of HFpEF, both overweight (HR = 0.59, 95% CI: 0.42–0.83) and obesity (HR = 0.49, 95% CI: 0.35–0.69) were associated with a reduced risk of all-cause death. Among patients with HFpEF without AF, overweight (HR = 0.51, 95% CI: 0.27–0.95) and obesity (HR = 0.64, 95% CI: 0.43–0.98) were associated with a lower risk of all-cause death. In those with AF, obesity (HR = 0.62, 95% CI: 0.40–0.95) but not overweight (HR = 0.81, 95% CI: 0.54–1.21) was associated with a decreased risk of all-cause death.Conclusions: The “obesity paradox” assessed by BMI exists in patients with HFpEF regardless of comorbid AF.Clinical Trial Registration:https://clinicaltrials.gov, identifier: NCT00094302.

Sex differences in the 10-year survival of patients undergoing maintenance hemodialysis in the Q-Cohort Study

Women have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45–0.58, P < 0.05) and 0.36 (0.27–0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis.

Incidence and predictors of death among adult patients treated for tuberculosis in two regions of Cameroon: 2010 to 2015

Objectives: Mortality during tuberculosis (TB) remains high in Africa. The purpose of our study was to determine the incidence and predictors of death during TB treatment in Cameroon. Materials and Methods: Data of subjects aged ≥15 years were retrospectively extracted from registers in all TB diagnostic and treatment centers in the Western and Northern regions of Cameroon from 2010 to 2015. Cox regression models were used to determine predictors of death during TB treatment. Results: Of the 19,681 patients included, 12,541 (63.7%) were male and their median age (25th-75th percentile) was 34 (26–45) years. The cumulative incidence (95% confidence interval [CI]) of death during TB treatment was 8.0% (7.5–8.5%). The predictors (hazard ratios [95% CI]) of death were: Age >34 years (1.479 [1.295–1.688], P < 0.001), female sex (1.471 [1.286–1.683], P < 0.001), extra-pulmonary TB (1.723 [1.466–2.026], P < 0.001), human immunodeficiency virus infection (3.739 [3.269–4.276], P < 001]), TB treatment in the Western region (2.241 [1.815–2.768], P < 0.001), treatment before 2012 (1.215 [1.073–1.376], P = 0.002)and low body weight (1st quartile and 2nd quartile) (2.568 [2.133–3.092], [P < 0.001]) and (1.569 [1.298–1.896], P < 0.001) respectively. Conclusion: The incidence of death during TB was relatively high in the Western and Northern regions of Cameroon. Recognition of these persons at greatest risk may improve care and reduce death durinng TB treatment.

Surgery vs. Biopsy in the Treatment of Butterfly Glioblastoma: A Systematic Review and Meta-Analysis

Butterfly glioblastomas (bGBM) are grade IV gliomas that spread to bilateral hemispheres by infiltrating the corpus callosum. Data on the effect of surgery are limited to small case series. The aim of this meta-analysis was to compare resection vs. biopsy in terms of survival outcomes and postoperative complications. A systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane databases through March 2021 in accordance with the PRISMA checklist. Pooled hazard ratios were calculated and meta-analyzed in a random-effects model including assessment of heterogeneity. Out of 3367 articles, seven studies were included with 293 patients. Surgical resection was significantly associated with longer overall survival (HR 0.39, 95%CI 0.2–0.55) than biopsy. Low heterogeneity was observed (I2: 0%). In further analysis, the effect persisted in extent of resection subgroups of both ≥80% and <80%. No statistically significant difference between surgery and biopsy was detected in terms of postoperative complications, although these were numerically larger for surgery. In patients with bGBM, surgical resection was associated with longer survival prospects compared with biopsy.

COVID-19 vaccine effectiveness among healthcare workers in Portugal: results from a hospital-based cohort study, December 2020 to November 2021

Introduction: Healthcare workers (HCW) were amongst the first prioritized for COVID-19 vaccination but data on COVID–19 vaccine effectiveness among HCW is still limited. This study aims to estimate the COVID–19 vaccine effectiveness (VE) against SARS–CoV–2 symptomatic infection among HCW from Portuguese hospitals. Methods: In this prospective cohort study, we analysed data from HCW (all professional categories) from two central hospitals in the Lisbon and Tagus Valley and Centre regions of mainland Portugal between December 2020 and November 2021. VE against symptomatic SARS–CoV–2 infection was estimated as one minus the confounder adjusted hazard ratios by Cox models considering age group, sex, presence of chronic disease and occupational exposure to patients diagnosed with COVID–19 as adjustment variables. Results: During the 11 months of follow up, the 2213 HCW contributed a total of 1950 person-years at risk and 171 SARS–CoV–2 events occurred. The COVID–19 incidence rate for unvaccinated HCW was 348.7 per 1000 person-years while for fully vaccinated HCW was 43.0 per 1000 person-years. We observed a VE against symptomatic SARS–CoV–2 infection of 73.9% (95% CI: 26.2–90.8%) for complete vaccination status. Conclusion: This cohort study found a high COVID-19 VE against symptomatic SARS–CoV–2 infection in Portuguese HCW, which is in concordance with previous studies from other countries. Monitoring of VE in this HCW cohort continues during the winter 2021/2022 to evaluate potential VE decay and booster vaccine effect. Keywords: Vaccine effectiveness, SARS–CoV–2 , COVID–19, symptomatic infection, healthcare workers.