Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

Percepção Inadequada do Risco Cardiovascular e Baixo Conhecimento sobre Hipercolesterolemia Familiar em Indivíduos com Hipercolesterolemia Grave

BackgroundIndividuals with severe hypercholesterolemia are at a high risk of developing atherosclerotic cardiovascular disease (ASCVD). Many of them have familial hypercholesterolemia (FH).ObjectivesTo assess from a patient perspective the degree of awareness about severe hypercholesterolemia, especially FH, ASCVD risk perception, cascade screening performance, and treatment of individuals participating in a routine health evaluation program.MethodsFrom a database of 70,000 Brazilian individuals evaluated between 2006 and 2016, 1,987 (2.8%) met the inclusion criteria (age ≥ 18 years and LDL-C ≥ 190 mg/dL or ≥ 160 mg/dL, respectively, if not in use of statins or on statin therapy). Two-hundred individuals were randomly invited to complete an extensive questionnaire. FH was diagnosed if suspected by the attending physician.ResultsAlthough 97% of the sample (age 48±9 years; 16% women; 95% college/university education; 88% primary prevention; LDL-C 209±47 mg/dL) had severe hypercholesterolemia, only 18% and 29.5% believed to be at high ASCVD risk and reported knowledge of their recommended LDL-C goal, respectively. Fifty-eight percent reported being informed that high cholesterol could be a family disease, 24.5% (n = 49) had ever heard about FH, and merely 14% (n = 29) had been previously identified as suspected of having FH (age at FH diagnosis 35±12 years; 79% and 31% diagnosed, respectively, > 30 and > 40 years old). Only 2.5% underwent genetic tests, 17% underwent cascade screening, and 17% were not in use of pharmacological treatment.ConclusionsAn important gap in risk perception, cholesterol management, and aspects related to FH was encountered in individuals with severe hypercholesterolemia. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)     

Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation

We made the hypothesis that donor and recipient gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplantation (BMT). HLA-identical BMT was performed for patients with acute (n = 39) or chronic leukemia (n = 68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines (tumor necrosis factor-alpha [TNF-alpha] and TNF-beta, interleukin-1 receptor antagonist [IL-1Ra], IL-6, and IL-10), adhesion molecules (CD31 and CD54), Fcgammareceptors (FcgammaRIIa, IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infection were studied retrospectively for 180 days after BMT. Univariate and multivariate analyses, using death as a competing event, were performed to study risk factors. In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that (1) time to neutrophil recovery was shorter when donors were FcgammaRIIIb HNA-1a/HNA-1b (HR = 1.77; P =.002); (2) donor IL-1Ra (absence of IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD) (II-IV) (HR = 2.17; P =.017); and (3) recipient IL-10 (GG) and IL-1Ra genotypes increased the risk for chronic GVHD (P =.03 and P =.03, respectively). Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004). In conclusion, donor and recipient gene polymorphisms are informative genetic risk factors for selecting donor/recipient pairs and could help in the understanding of mechanisms involved in host defenses of BM transplant recipients.     

The reproducibility of clinical OSA subtypes: a population-based longitudinal study

Purpose

The identification of subgroups of obstructive sleep apnea (OSA) is critical to understand disease outcome and treatment response and ultimately develop optimal care strategies customized for each subgroup. In this sense, we aimed to perform a cluster analysis to identify subgroups of individuals with OSA based on clinical parameters in the Epidemiological Sleep Study of São Paulo city (EPISONO). We aimed to analyze whether or not subgroups remain after 8 years, since there is not any evidence showing if these subtypes of clinical presentation of OSA in the same population can change overtime.

Methods

We used data derived from EPISONO cohort, which was followed over 8 years after baseline evaluation. All individuals underwent polysomnography, answered questionnaires, and had their blood collected for biochemical examinations. OSA was defined according to AHI?≥?15 events/h. Cluster analysis was performed using latent class analysis (LCA).

Results

Of the 1042 individuals in the EPISONO cohort, 68% agreed to participate in the follow-up study (n?=?712), and 704 were included in the analysis. We were able to replicate the OSA 3-cluster solution observed in previous studies: disturbed sleep, minimally symptomatic and excessively sleepy in both baseline (36%, 45% and 19%, respectively) and follow-up studies (42%, 43%, and 15%, respectively). The optimal cluster solution for our sample based on Bayesian information criterion (BIC) was 2 cluster for baseline (disturbed sleep and excessively sleepy) and 3 clusters for follow-up (disturbed sleep, minimally symptomatic, and excessively sleepy). A total of 45% of the participants migrated clusters between the two evaluations (and the factor associated with this was a greater delta-AHI (B?=????0.033, df?=?1, p?=?0.003).

Conclusions

The results replicate and confirm previously identified clinical clusters in OSA which remain in the longitudinal analysis, with some percentage of migration between clusters.

     

Neutral lipid composition changes in the fat bodies of engorged females Rhipicephalus microplus ticks in response to fungal infections

The tick’s fat body plays an essential role in energy storage and utilization. This study aimed to analyze the fat body neutral lipid composition in Rhipicephalus microplus engorged females. In the first study (physiological profile of untreated ticks), the lipid analysis took place over the course of 4 days; the engorged females were incubated at optimal conditions and their fat bodies were dissected daily. Fat body lipid analysis after fungal infection with Metarhizium anisopliae sensu lato (s.l.) or Beauveria bassiana s.l. was performed with four groups: one without any treatment, one that was inoculated with a solution of 0.1 % Tween 80 in water, and two groups that were inoculated with M. anisopliae or B. bassiana conidial suspensions. The fat bodies were dissected 24 and 48 h after infection. Lipid analysis was conducted by thin-layer chromatography on a silica plate. The results of the physiological profile showed that the amounts of triacylglycerol (TAG) and free cholesterol (CHO) decreased with time, whereas cholesterol ester (CHOE) increased on the second and fourth days. Following M. anisopliae or B. bassiana infection, there was an increase in the amount of CHO after 24 h, whereas the other lipid classes were not altered. M. anisopliae caused an increase in CHOE and TAG and a reduction in CHO at 48 h after infection; however, B. bassiana infection did not cause significant alterations in the concentrations of these lipids. M. anisopliae and B. bassiana infection changed the fat body metabolism of engorged female R. microplus ticks. This study provides the first report of changes in the neutral lipid composition of the R. microplus fat body.     

Accuracy of computer-aided image analysis in the diagnosis of odontogenic cysts: A systematic review

Background This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing odontogenic cysts. Material and Methods A systematic review was conducted according to the PRISMA statements and considering eleven databases, including the grey literature. Protocol was registered in PROSPERO (CRD 42020189349). The PECO strategy was used to define the eligibility criteria and only studies involving diagnostic accuracy were included. Their risk of bias was investigated using the Joanna Briggs Institute Critical Appraisal tool. Results Out of 437 identified citations, five papers, published between 2006 and 2019, fulfilled the criteria and were included in this systematic review. A total of 5,264 images from 508 lesions, classified as radicular cyst, odontogenic keratocyst, lateral periodontal cyst, glandular odontogenic cyst, or dentigerous cyst, were analyzed. All selected articles scored low risk of bias. In three studies, the best performances were achieved when the two subtypes of odontogenic keratocysts (solitary or syndromic) were pooled together, the case-wise analysis showing a success rate of 100% for odontogenic keratocysts and radicular cysts, in one of them. In two studies, the dentigerous cyst was associated with the majority of misclassifications, and its omission from the dataset improved significantly the classification rates. Conclusions The overall evaluation showed all studies presented high accuracy rates of computer-aided systems in classifying odontogenic cysts in digital images of histological tissue sections. However, due to the heterogeneity of the studies, a meta-analysis evaluating the outcomes of interest was not performed and a pragmatic recommendation about their use is not possible. Key words:Computer-assisted diagnosis, computer-assisted image analysis, computer-assisted image processing, odontogenic cysts, keratocysts, radicular cysts.     

Immune response to Helicobacter pylori infection and gastric cancer development

Gastric adenocarcinoma is a global health concern, and Helicobacter pylori (H. pylori) infection is the main risk factor for its occurrence. Of note, the immune response against the pathogen seems to be a determining factor for gastric oncogenesis, and increasing evidence have emphasized several host and bacterium factors that probably influence in this setting. The development of an inflammatory process against H. pylori involves a wide range of mechanisms such as the activation of pattern recognition receptors and intracellular pathways resulting in the production of proinflammatory cytokines by gastric epithelial cells. This process culminates in the establishment of distinct immune response profiles that result from the cytokine-induced differentiation of T naïve cells into specific T helper cells. Cytokines released from each type of T helper cell orchestrate the immune system and interfere in the development of gastric cancer in idiosyncratic ways. Moreover, variants in genes such as single nucleotide polymorphisms have been associated with variable predispositions for the occurrence of gastric malignancy because they influence both the intensity of gene expression and the affinity of the resultant molecule with its receptor. In addition, various repercussions related to some H. pylori virulence factors seem to substantially influence the host immune response against the infection, and many of them have been associated with gastric tumorigenesis.