Skin accumulation of advanced glycation end-products predicts kidney outcomes in type 2 diabetes: results from the Brazilian Diabetes Study.

The accumulation of advanced glycation end-products (AGEs) elicits morphofunctional kidney impairment. AGEs levels can be noninvasively estimated by skin autofluorescence (SAF). We explored whether high SAF predicts kidney outcomes in type 2 diabetes (T2D) individuals. The study was conducted as a predefined analysis of the Brazilian Diabetes Study, a prospective single-center cohort of T2D adults. Data from 155 individuals followed for up to 1716 days were considered. The incidence of major adverse kidney events (MAKE) was 9.6%. Individuals with above-median SAF had a higher incidence of MAKEs (4.6% vs. 21%; p = 0.002), with an HR of 3.39 [95% CI: 1.06-10.85; p = 0.040] after adjustment by age and gender. The mean adjusted eGFR change was 1.08 units (SE: 1.15; 95%CI: -1.20, 3.37) in the low SAF and -5.19 units [SE: 1.93; 95%CI: -9.10, -1.29] in the high SAF groups (between-subject difference: F: 5.62, p = 0.019). The high-SAF group had a greater prevalence of rapid decliners than the low-SAF group (36.7% vs. 15.8%; p = 0.028). In conclusion, high SAF was related to increased incidence of MAKEs and faster decline in eGFR among T2D subjects. This should be considered by healthcare providers when identifying individuals more prone to diabetes-related kidney complications.

Resistance training improves cardiac function in older women: a randomized controlled trial.

This investigation aimed to determine the effects of 24 weeks of resistance training (RT) on cardiac function in older women. Seventy-three physically independent older women were selected for this investigation. Participants were randomized into a training group (TG, n = 38) and a control group (CG, n = 35). The RT program was conducted over 24 weeks and consisted of three sessions a week. Participants performed eight exercises for the whole body in three sets of 8-12 repetitions. Tissue Doppler echocardiography was performed, according to current guidelines, before and after 24 weeks of the intervention. One-repetition maximum (1-RM) tests were used to assess muscular strength. A group vs. time interaction (P < 0.05) was shown for left ventricular end-diastolic volume (TG = - 8.3% vs. CG = - 0.6%), left ventricular end-systolic volume (TG = - 10.6% vs. CG = + 1.1%), and left atrial volume index (TG = - 9.1% vs. CG = + 3.9%). A main time effect (P < 0.05) was found for left ventricular mass index (TG = + 4.9% vs. CG = - 0.6%), septal thickness (TG = + 3.3% vs. CG = - 1.7%), left ventricular ejection fraction (TG = + 3.7% vs. CG = - 0.5%), E'/E septal (TG = - 4.8% vs. CG = + 0.5%), deceleration time (TG = - 4.1% vs. CG = + 3.9%), E septal (TG = + 4.6% vs. CG = - 0.6%), and E lateral (TG = + 5.2% vs. CG = - 1.1%). These results suggest that 24 weeks of RT improves cardiac morphological and functional variables in older women.

Cutoffs for white-coat and masked blood pressure effects: an ambulatory blood pressure monitoring study.

The values used to define white-coat and masked blood pressure (BP) effects are usually arbitrary. This study aimed at investigating the accuracy of various cutoffs based on the differences (ΔBP) between office BP (OBP) and 24h-ambulatory BP monitoring (ABPM) to identify white-coat (WCH) and masked (MH) hypertension, which are phenotypes coupled with adverse prognosis. This cross-sectional study included 11,350 [Derivation cohort; 45% men, mean age = 55.1 ± 14.1 years, OBP = 132.1 ± 17.6/83.9 ± 12.5 mmHg, 24 h-ABPM = 121.6 ± 11.4/76.1 ± 9.6 mmHg, 25% using antihypertensive medications (AH)] and 7220 (Validation cohort; 46% men, mean age = 58.6 ± 15.1 years, OBP = 136.8 ± 18.7/87.6 ± 13.0 mmHg, 24 h-ABPM = 125.5 ± 12.6/77.7 ± 10.3 mmHg; 32% using AH) unique individuals who underwent 24 h-ABPM. We compared the sensitivity, specificity, positive and negative predictive values and area under the curve (AUC) of diverse ΔBP cutoffs to detect WCH (ΔsystolicBP/ΔdiastolicBP = 28/17, 20/15, 20/10, 16/11, 15/9, 14/9 mmHg and ΔsystolicBP = 13 and 10 mmHg) and MH (ΔsystolicBP/ΔdiastolicBP = -14/-9, -5/-2, -3/-1, -1/-1, 0/0, 2/2 mmHg and ΔsystolicBP = -5 and -3mmHg). The 20/15 mmHg cutoff showed the best AUC (0.804, 95%CI = 0.794-0.814) to detect WCH, while the 2/2 mmHg cutoff showed the highest AUC (0.741, 95%CI = 0.728-0.754) to detect MH in the Derivation cohort. Both cutoffs also had the best accuracy to detect WCH (0.767, 95%CI = 0.754-0.780) and MH (0.767, 95%CI = 0.750-0.784) in the Validation cohort. In secondary analyses, these cutoffs had the best accuracy to detect individuals with higher and lower office-than-ABPM grades in both cohorts. In conclusion, the 20/15 and 2/2 mmHg ΔBP cutoffs had the best accuracy to detect hypertensive patients with WCH and MH, respectively, and can serve as indicators of marked white-coat and masked BP effects derived from 24 h-ABPM.

The influence of sex on left ventricular remodeling in patients with aortic dissection.

AIMS: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection. METHODS: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60 days before or after the diagnosis of aortic dissection from three Brazilian centers. RESULTS: Men and women had similar clinical characteristics, except for higher age (59.4 ±â€Š13.4 vs. 55.9 ±â€Š11.6 years; P  = 0.013) and use of antihypertensive classes (1.4 ±â€Š1.3 vs. 1.1 ±â€Š1.2; P  = 0.024) and diuretics (32 vs. 19%; P  = 0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P  = 0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P  = 0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence interval = 0.42, 0.20-0.87; P  = 0.019) and were more likely to have LVH (odds ratio, 95% confidence interval = 1.91, 1.11-3.27; P  = 0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence interval = 1.16, 0.77-1.75; P  = 0.49). CONCLUSION: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women.

Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Dialysis parameters associated with SARS-CoV-2 infection and prognosis in end-stage kidney disease.

BACKGROUND: The Covid-19 pandemic has affected patients with end-stage kidney disease (ESKD). Whether dialysis parameters have a prognostic value in ESKD patients with Covid-19 remains unclear. MATERIALS AND METHODS: We retrospectively evaluated clinical characteristics, blood pressure (BP) and dialysis parameters in ESKD patients undergoing maintenance outpatient hemodialysis, with (Covid-ESKD) and without (No-Covid-ESKD) Covid-19, at four Brazilian hemodialysis facilities. The Covid-ESKD (n = 107; 54% females; 60.8 ± 17.7 years) and No-Covid-ESKD (n = 107; 62% females; 58.4 ± 14.6 years) groups were matched by calendar time. The average BP and dialysis parameters were calculated during the pre-infection, acute infection, and post-infection periods. The main outcomes were Covid-19 hospitalization and all-cause mortality. RESULTS: Covid-ESKD patients had greater intradialytic and postdialysis systolic BP and lower predialysis weight, postdialysis weight, ultrafiltration rate, and interdialytic weight gain during acute-illness compared to 1-week-before-illness, while these changes were not observed in No-Covid-ESKD patients. After 286 days of follow-up (range, 276-591), there were 18 Covid-19-related hospitalizations and 28 deaths among Covid-ESKD patients. Multivariable logistic regression analysis showed that increases in predialysis systolic BP from 1-week-before-illness to acute-illness (OR, 95%CI = 1.06, 1.02-1.10; p = .004) and Covid-19 vaccination (OR, 95%CI = 0.16, 0.04-0.69; p = .014) were associated with hospitalization in Covid-ESKD patients. Multivariable Cox-regression analysis showed that Covid-19-related hospitalization (HR, 95%CI = 5.17, 2.07-12.96; p < .001) and age (HR, 95%CI = 1.05, 1.01-1.08; p = .008) were independent predictors of all-cause mortality in Covid-ESKD patients. CONCLUSION: Acute Covid-19 illness is associated with variations in dialysis parameters of volume status in patients with ESKD. Furthermore, increases in predialysis BP during acute Covid-19 illness are associated with an adverse prognosis in Covid-ESKD patients.

Dialysis parameters were influenced by SARS-CoV-2 infection and may have prognostic value in patients with Covid-19.Increases in blood pressure during acute Covid-19 illness and the lack of vaccination for Covid-19 were predictors of hospitalization for Covid-19.Hospitalization for Covid-19 and age were independent risk factors for all-cause death.

The Clinical and Economic Impact of Delayed Reperfusion Therapy: Real-World Evidence. / O Impacto Clínico e Econômico do Atraso na Terapia de Reperfusão: Evidências do Mundo Real.

BACKGROUND: Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: Estimate the clinical and economic consequences of delaying reperfusion in patients with STEMI. METHODS: This retrospective cohort study evaluated mortality rates and the total expenses incurred by delaying reperfusion therapy among 2622 individuals with STEMI. Costs of in-hospital care and lost productivity due to death or disability were estimated from the perspective of the Brazilian Unified Health System indexed in international dollars (Int$) adjusted by purchase power parity. A p < 0.05 was considered statistically significant. RESULTS: Each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% CI: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. The overall expenses were 45% higher among individuals who received treatment after 9 hours compared to those who were treated within the first 3 hours, primarily driven by in-hospital costs (p = 0.005). A multivariate linear regression model indicated that for every 3-hour delay in thrombolysis, there was an increase in in-hospital costs of Int$497 ± 286 (p = 0.003). CONCLUSIONS: The findings of our study offer further evidence that emphasizes the crucial role of prompt reperfusion therapy in saving lives and preserving public health resources. These results underscore the urgent need for implementing a network to manage STEMI cases.

FUNDAMENTO: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). OBJETIVO: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. MÉTODOS: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. RESULTADOS: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). CONCLUSÕES: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Effect of Empagliflozin with or without the Addition of Evolocumab on HDL Subspecies in Individuals with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the EXCEED-BHS3 Trial.

Evolocumab and empagliflozin yield a modest rise in plasma high-density lipoprotein cholesterol (HDL-C) through unknown mechanisms. This study aims to assess the effect of evolocumab plus empagliflozin vs. empagliflozin alone on HDL subspecies isolated from individuals with type 2 diabetes mellitus (T2D). This post hoc prespecified analysis of the EXCEED-BHS3 trial compared the effects of a 16-week therapy with empagliflozin (E) alone or in combination with evolocumab (EE) on the lipid profile and cholesterol content in HDL subspecies in individuals with T2D divided equally into two groups of 55 patients. Both treatments modestly increased HDL-C. The cholesterol content in HDL subspecies 2a (7.3%), 3a (7.2%) and 3c (15%) increased from baseline in the E group, while the EE group presented an increase from baseline in 3a (9.3%), 3b (16%) and 3c (25%). The increase in HDL 3b and 3c was higher in the EE group when compared to the E group (p < 0.05). No significant interactive association was observed between changes in hematocrit and HDL-C levels after treatment. Over a 16-week period, empagliflozin with or without the addition of evolocumab led to a modest but significant increase in HDL-C. The rise in smaller-sized HDL particles was heterogeneous amongst the treatment combinations.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis.

BACKGROUND: Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus. METHODS: Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects. RESULTS: Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low. CONCLUSIONS: Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable. TRIAL REGISTRATION: PROSPERO identifier: CRD42023393020.

High-Density Lipoproteins at the Interface between the NLRP3 Inflammasome and Myocardial Infarction.

Despite significant therapeutic advancements, morbidity and mortality following myocardial infarction (MI) remain unacceptably high. This clinical challenge is primarily attributed to two significant factors: delayed reperfusion and the myocardial injury resulting from coronary reperfusion. Following reperfusion, there is a rapid intracellular pH shift, disruption of ionic balance, heightened oxidative stress, increased activity of proteolytic enzymes, initiation of inflammatory responses, and activation of several cell death pathways, encompassing apoptosis, necroptosis, and pyroptosis. The inflammatory cell death or pyroptosis encompasses the activation of the intracellular multiprotein complex known as the NLRP3 inflammasome. High-density lipoproteins (HDL) are endogenous particles whose components can either promote or mitigate the activation of the NLRP3 inflammasome. In this comprehensive review, we explore the role of inflammasome activation in the context of MI and provide a detailed analysis of how HDL can modulate this process.

Relationship of blood pressure measured in the calf with arm blood pressure and arterial stiffness: a general population study.

AIM: Leg blood pressure (BP) measurement is needed when arm BP evaluation is not feasible, and calf BP, especially when measured in standing position, may have greater association with cardiovascular remodeling than arm BP. This study evaluated the relationship between calf and arm BP, and investigated whether calf BP would be superior to arm BP in predicting increased arterial stiffness [pulse wave velocity (PWV) > 10 m/s]. METHODS: We evaluated clinical and laboratory characteristics, BP measurements, and PWV in 1397 individuals resident in Baependi, Brazil, between 2017 and 2019. Arm BP was measured in the seated and supine positions while calf BP was measured in supine and standing positions using digital oscillometric devices. Carotid-femoral PWV was measured using a noninvasive mechanotransducer. RESULTS: The sample had 62.7% females, age = 48.1 ±â€Š15.4 years and 8.4% with PWV >10 m/s. Results of linear regression analysis showed that BP values of 140/90 mmHg measured in the arm in supine and seated position were equivalent to calf supine BP values of 164/81 mmHg and 166/78 mmHg and calf standing BP values of 217/137 mmHg and 221/137 mmHg, respectively. Calf-arm BP differences were associated with age, glomerular filtration rate, body mass index, smoking, low-density lipoprotein-cholesterol, diabetes and height. Furthermore, stepwise logistic regression analysis revealed that arm supine systolic BP, but not calf BP measurements, was independently associated with increased arterial stiffness. CONCLUSION: Thresholds of ≈165/80 mmHg and ≈220/135 mmHg could be used for diagnosing hypertension when only calf measurements in supine and standing positions, respectively, are available. Conversely, calf BP was not superior to arm BP in predicting increased arterial stiffness.

Diabetes-related distress and quality of life among people with type 2 diabetes at primary care level in Brazil.

PURPOSE: Living with diabetes can be challenging, particularly when it comes to dealing with psychological distress and requiring self-care directives. Patients may feel frustrated, angry, overwhelmed, and discouraged. This study aimed to investigate the diabetes-related distress and quality of life among people with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study carried out at the Clinical Research Centre at the University of Campinas, Brazil, between September 2020 and April 2021. Patients answered data regarding demographic and clinical variables, the Brazilian version of the Diabetes Distress Scale and the Diabetes Quality of Life (QOL) Measure by telephone contact. The data were managed using the RedCap System. For statistical analysis of the data, the Mann-Whitney and Kruskal-Wallis tests were applied for comparisons, and the Chi-square test for associations. The correlations were evaluated using the Spearman correlation coefficient. RESULTS: Out of the 302 participants we recruited, 50.33% exhibited significant diabetes-related distress. Those with elevated diabetes-related distress scores had shorter education levels (p < 0.05), lower HbA1c levels (p < 0.05), and lower total scores in Diabetes QOL Measure (p < 0.0001), particularly in the QOL impact (p < 0.0001), social/vocational worry (p < 0.05), and diabetes worry (p < 0.0001) subscales compared to the group with the lowest diabetes-related distress. CONCLUSION: Elevated diabetes-related stress scores significantly affect patients' QOL. Therefore, early screening of individuals at risk for this condition, using well-coordinated protocols, could mitigate adverse QOL effects and enhance their overall experience during disease management.

Renal osteodystrophy and clinical outcomes: a prospective cohort study.

INTRODUCTION: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. METHODS: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. RESULTS: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. CONCLUSION: The incidence of clinical outcomes did not differ between the types of ROD.