Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age.

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

No effect of acidification or freezing on urinary metanephrine levels.

BACKGROUND: Urinary metanephrine is a reliable method to estimate catecholamine secretion. Traditionally, urinary metanephrines are collected into chilled containers containing hydrochloric acid (HCl) and most laboratories freeze urinary samples before analysis. It is uncertain if these pre-analytic procedures alter metanephrine values. AIM: To evaluate if acidifying and freezing urine samples affect the accuracy of urinary metanephrine measurements. METHODS: Random urine samples from healthy individuals were collected. Urine samples were distributed into two containers: with HCl 50% homogenized with urine to obtain pH < 2, and without HCl. Each container was divided again into aliquots for immediate measurement or freezing. One aliquot with acid (group 1) and another without acid (group 2) were sent immediately to the laboratory for testing (HPLC), while the other two aliquots, one with acid (group 3) and another without it (group 4) were frozen for 3 months at - 20 °C. Bland-Altman's test was used to analyze inter-assay agreement between measurements. RESULTS: A total of 15 individuals were included (mean age 27.5 ± 5.9 years, 8 male and 14 white). No difference was observed on mean urinary metanephrine/creatinine ratio between groups: group 1: 0.23 ± 0.11, group 2: 0.22 ± 0.07, group 3: 0.25 ± 0.13, group 4: 0.25 ± 0.15 mg/g creatinine; P > 0.05 for all the comparisons). Bland-Altman's analysis showed agreement between the standard method (group 1) and the experimental method (group 4). CONCLUSION: Measurement of urinary metanephrines by HPLC method is not influenced by sample acidification nor freezing at - 20 °C for 3 months.

Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials.

Topiramate was associated with weight loss in clinical trials. We summarize the evidence on the efficacy and safety of topiramate in the treatment of overweight/obesity. The databases Medline, Embase, and Cochrane were searched. Randomized controlled studies with at least 16 weeks of duration that report the effect of topiramate on weight loss and adverse events were eligible for inclusion. Ten studies were included (3320 individuals). Patients treated with topiramate lost an average of 5.34 kg (95% confidence interval [95%CI]-6.12 to -4.56) of additional weight as compared with placebo. According to meta-regression analysis, treatment duration and dosage were associated with the efficacy of topiramate treatment. Evaluating trials using topiramate 96-200 mg day(-1) , the weight loss was higher in trials with >28 weeks of duration (-6.58 kg [95%CI -7.48 to -5.68]) than in trials with ≤28 weeks (-4.11 kg [95%CI -4.92 to -3.30]). Data of 6620 individuals were available for adverse events evaluation and those more frequently observed were paraesthesia, taste impairment and psychomotor disturbances. The odds ratio for adverse events leading to topiramate withdrawal was 1.94 (95%CI 1.64-2.29) compared with the control group. In conclusion, topiramate might be a useful adjunctive therapeutic tool in the treatment of obesity as long as proper warnings about side effects are considered.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 ± 10.1 years and 313 (37.2 percent) patients were males. MetS was detected in 662 (78.6 percent) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 ± 30.8; two: 92.9 ± 28.1; three: 84.0 ± 25.1; four: 83.8 ± 28.5, and five: 79.0 ± 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL·min-1·1.73 (m²)-1) 2.82-fold (95 percentCI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95 percentCI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95 percentCI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus.

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 +/- 10.1 years and 313 (37.2%) patients were males. MetS was detected in 662 (78.6%) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 +/- 30.8; two: 92.9 +/- 28.1; three: 84.0 +/- 25.1; four: 83.8 +/- 28.5, and five: 79.0 +/- 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL x min(-1) x 1.73 (m2)(-1)) 2.82-fold (95%CI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95%CI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95%CI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Degree of catecholamine hypersecretion is the most important determinant of intra-operative hemodynamic outcomes in pheochromocytoma.

Pheochromocytoma resection is often complicated by intra-operative hypertension and post-resection hypotension. Factors associated with these hemodynamic alterations are not well defined. The aim of this study was to analyse the clinical-laboratory features associated with hemodynamic parameters during pheochromocytoma resection. Twenty-seven patients submitted to tumor resection - either open (no.=18) or video laparoscopic - between 1978-2007 were included. Nineteen received pre-operative alpha-blockers. Intra-operative hemodynamic data analysed were: maximum and minimum mean arterial blood pressure (MABP), no. of severe hypertensive (systolic BP >200 mmHg) and hypotensive episodes (MABP <60 mmHg), maximum and minimum heart rate (HR), no. of episodes of tachycardia and bradycardia, need to receive iv intra-operative treatment for hypertension and hypotension and the volume of fluids administered during surgery. Patients were 39.4+/-14.4-yr-old, 66% women. Intra-operative hemodynamic parameters were not different in patients submitted to open or video laparoscopic resection. Maximum intraoperative HR and the percentage of patients with HR>100 beats/min were higher in patients without pre-operative alpha- blocker treatment (no.=8). Pre-operative urinary vanylmandelic acid was positively associated with intra-operative maximum MABP (r=0.535, p=0.047) and with maximum transoperative systolic BP (r=0.805, p=0.016). Pre-operative urinary catecholamine (Pearson correlation r=0.575, p=0.03) and vanylmandelic acid (Pearson correlation r=0.605, p=0.04) levels were associated with maximum intra- operative MABP, adjusted for the presence of pheochromocytoma symptoms, surgical approach and pre-operative alpha-blockers. In conclusion, the degree of pre-operative catecholamine secretion was the most important aspect of transoperative BP control.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95 percentCI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95 percentCI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95 percentCI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100 percent to the odds for diabetic retinopathy (OR = 2.01, 95 percentCI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9 percent, KQ = 48.2 percent, and QQ = 25.9 percent) and BD (KK = 22.0 percent, KQ = 53.8 percent, and QQ = 24.2 percent) compared to European descendant type 2 DM patients (KK = 62.7 percent, KQ = 33.3 percent, and QQ = 4.1 percent) and BD (KK = 61.0 percent, KQ = 35.6 percent, and QQ = 3.4 percent). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

Blood pressure means rather than nocturnal dipping pattern are related to complications in Type 2 diabetic patients.

AIM: To determine whether systolic and diastolic blood pressure (BP) means, during ambulatory BP monitoring (ABPM), are more strongly correlated with microvascular complications and echocardiographic structural alterations than night-time/daytime (N/D) BP ratio. METHODS: A cross-sectional study was conducted in 270 Type 2 diabetes mellitus (DM) outpatients who underwent clinical and laboratory investigations, urinary albumin excretion rate (UAER) determination, echocardiography, office and 24-h ABPM (Spacelabs 90207). RESULTS: UAER, after multivariate adjustments, was associated with office BP (systolic: R(2)(a) 0.162, P < 0.001; diastolic: R(2)(a) 0.124, P < 0.001) and ABPM (24-h systolic: R(2)(a) 0.195, P < 0.001; 24-h diastolic: R(2)(a) 0.197, P < 0.001) but not with N/D BP ratios (systolic: R(2)(a) 0.062, P = 0.080; diastolic: R(2)(a) 0.063, P = 0.069). Similar results were observed for echocardiographic parameters. The presence of retinopathy was associated only with night-time BP values [systolic means: odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03-1.24 and diastolic means: OR 1.21, CI 1.04-1.40 and N/D diastolic BP ratio > 0.90, OR 3.21, CI 1.65-6.25]. CONCLUSIONS: UAER and echocardiographic structural alterations had more consistent correlations of a greater magnitude with systolic BP means than with N/D BP ratios. The nocturnal BP values appear to be more relevant for diabetic retinopathy. BP measurement in patients with Type 2 DM should take into account the 24-h period rather than focusing on a specific time span of BP homeostasis.

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications.

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9%, KQ = 48.2%, and QQ = 25.9%) and BD (KK = 22.0%, KQ = 53.8%, and QQ = 24.2%) compared to European descendant type 2 DM patients (KK = 62.7%, KQ = 33.3%, and QQ = 4.1%) and BD (KK = 61.0%, KQ = 35.6%, and QQ = 3.4%). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes.

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95%CI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95%CI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95%CI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100% to the odds for diabetic retinopathy (OR = 2.01, 95%CI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

[Comparison of coronary arteriosclerosis in patients with myocardial infarction and angina pectoris]. / Comparação da aterosclerose coronária em pacientes com infarto do miocárdio e angina do peito.

PURPOSE: To compare the severity of the coronary heart disease and the presence of coronary risk factors between angina and myocardial infarction (MI) patients. METHODS: We studied 62 patients with MI and 129 with angina through coronary angiography to evaluate occlusion (lesion of 99% or 100%), extent (with a score of 0-5 derived by the number of vessels affected) and severity (3 groups of different stenosis degrees). Two experiment observers blindly interpreted the angiograms. RESULTS: Patients with MI had more occlusions (50% vs 13.2% [p < 0.01]), more severity (79% vs 54.3% with > 90% stenosis [p < 0.02]) and more extent (2.0 vs 0.87; [p < 0.001]), even when controlled for current coronary risk factors and disease duration. Smoking was the only independent risk factor related to MI (p < 0.001). CONCLUSION: Among the studied patients, coronary heart disease extent and severity was greater in the MI group, as well as the prevalence smoking.

Comparação da aterosclerose coronária em pacientes com infarto do miocárdio e angina do peito / Comparison of coronary heart disease extent and severity in patients with myocardial infarction and angina pectoris

OBJETIVO - Comparar a gravidade da doeça coronária e a presença de fatores de risco cardiovasculares entre pacientes com angina e infarto do miocárdio (IM). MÉTODOS - Estudaram-se 62 pacientes com IM e 129 com angina, através de cineangiocoronariografia, avaliando-se a oclusão (lesäo de 99 'por cento' ou 100 'por cento'), a severidade (escore de 0 a 5 de acordo com o número de vasos afetados) e a extensäo (3 grupos com diferentes graus de estenose). Dois observadores experientes interpretaram cegamente os angiogramas. RESULTADOS - Os pacientes com IM tiveram maior oclusão (50 'por cento' vs 13,2 'por cento'[p<0,01]), maior severidade (79 'por cento' vs 54,3 'por cento' com mais de 90 'por cento' de estenose [p<0,02]) e maior extensão (2,0 vs 0,87 [p<0,001]), mesmo quando controlados para os fatores de risco coronários clássicos e para o tempo de doença. O tabagismo foi o único fator de risco independente correlacionado com IM (P<0,01). CONCLUSÄO - Entre os pacientes estudados, a doença coronária foi maior no grupo IM, bem como a prevalência de tabagismo.