A robust platform for integrative spatial multi-omics analysis to map immune responses to SARS-CoV-2 infection in lung tissues.

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies. METHODS: Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients. RESULTS: Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza. CONCLUSION: Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.

COVID-19 and Lung Mast Cells: The Kallikrein-Kinin Activation Pathway.

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein-kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.

Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.

The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease's mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1ß, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients.

MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including those caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional enrichment analysis, miR-26a-5p, miR-29b-3p, and miR-34a-5p were identified as regulators of mRNA targets involved in endothelial and inflammatory signaling pathways, as well as viral diseases. A miRNA/mRNA network, constructed based on protein-protein interactions of the miRNA targets and the inflammatory biomarkers characterized in the patients, revealed a close interconnection of these miRNAs in association to the endothelial activation/dysfunction. Reduced expression levels of selected miRNAs were observed in the lung biopsies of COVID-19 patients (n = 9) compared to the Controls (n = 10) (P < 0.01-0.0001). MiR-26a-5p and miR-29b-3p presented the best power to discriminate these groups (area under the curve (AUC) = 0.8286, and AUC = 0.8125, respectively). The correlation analysis of the miRNAs with inflammatory biomarkers in the COVID-19 patients was significant for miR-26a-5p [IL-6 (r2 = 0.5414), and ICAM-1 (r2 = 0.5624)], and miR-29b-3p [IL-4 (r2 = 0.8332) and IL-8 (r2 = 0.2654)]. Altogether, these findings demonstrate the relevance and the non-random involvement of miR-26a-5p, miR-29b-3p, and miR-34a-5p in endothelial dysfunction and inflammatory response in patients with SARS-CoV-2 infection and the occurrence of severe lung injury and immunothrombosis.

Physical health-related quality of life at higher achieved hemoglobin levels among chronic kidney disease patients: a systematic review and meta-analysis.

BACKGROUND: The impact of anemia treatment with erythropoietin stimulating agents (ESA) on health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients is controversial, particularly regarding optimal hemoglobin (Hb) target ranges. METHODS: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCT) with ESA to estimate the effect of different achieved Hb values on physical HRQOL and functionality. We searched PubMed, EMBASE, CENTRAL, PEDro, PsycINFO and Web of Science databases, until May 2020. Two authors independently extracted data from studies. We included observational and RCTs that enrolled CKD patients undergoing anemia treatment with ESA with different achieved Hb levels among groups. We excluded studies with achieved Hb < 9 g/dL. For the meta-analysis, we included RCTs with control groups achieving Hb 10-11.5 g/dL and active groups with Hb > 11.5 g/dL. We analyzed the standardized mean difference (SMD) between groups for physical HRQOL. RESULTS: Among 8496 studies, fifteen RCTs and five observational studies were included for the systematic review. We performed the meta-analysis in a subset of eleven eligible RCTs. For physical role and physical function, SMDs were 0.0875 [95% CI: - 0.0025 - 0.178] and 0.08 [95% CI: - 0.03 - 0.19], respectively. For fatigue, SMD was 0.16 [95% CI: 0.09-0.24]. Subgroup analysis showed that trials with greater achieved Hb had greater pooled effects sizes - 0.21 [95% CI: 0.07-0.36] for Hb > 13 g/dL vs. 0.09 [95% CI: 0.02-0.16] for Hb 11.5-13 g/dL. Proportion of older and long-term diabetic patients across studies were associated with lower effect sizes. CONCLUSION: Achieved hemoglobin higher than currently recommended targets may be associated with small but potentially clinically significant improvement in fatigue, but not in physical role or physical function. Younger and non-diabetic patients may experience more pronounced benefits of higher Hb levels after treatment with ESAs.

Migraine and cognitive function: Baseline findings from the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

Background The association between migraine and cognitive performance is unclear. We analyzed whether migraine is associated with cognitive performance among participants of the Brazilian Longitudinal Study of Adult Health, ELSA-Brasil. Methods Cross-sectional analysis, including participants with complete information about migraine and aura at baseline. Headache status (no headaches, non-migraine headaches, migraine without aura and migraine with aura), based on the International Headache Society classification, was used as the dependent variable in the multilinear regression models, using the category "no headache" as reference. Cognitive performance was measured with the Consortium to Establish a Registry for Alzheimer's Disease word list memory test (CERAD-WLMT), the semantic fluency test (SFT), and the Trail Making Test version B (TMTB). Z-scores for each cognitive test and a composite global score were created and analyzed as dependent variables. Multivariate models were adjusted for age, gender, education, race, coronary heart disease, heart failure, hypertension, diabetes, dyslipidemia, body mass index, smoking, alcohol use, physical activity, depression, and anxiety. In women, the models were further adjusted for hormone replacement therapy. Results We analyzed 4208 participants. Of these, 19% presented migraine without aura and 10.3% presented migraine with aura. All migraine headaches were associated with poor cognitive performance (linear coefficient ß; 95% CI) at TMTB -0.083 (-0.160; -0.008) and poorer global z-score -0.077 (-0.152; -0.002). Also, migraine without aura was associated with poor cognitive performance at TMTB -0.084 (-0.160, -0.008 and global z-score -0.077 (-0.152; -0.002). Conclusion In participants of the ELSA-study, all migraine headaches and migraine without aura were significantly and independently associated with poorer cognitive performance.

Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis.

Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15-4.52) for CHD incidence, 2.09 (95% CI 1.51-2.89) for stroke incidence, 2.76 (95% CI 1.62-4.71) for CVD mortality and 2.22 (95% CI 1.92-2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67-0.80) for overall CVD, 0.71 (95% CI 0.67-0.75) for CHD, 0.77 (95% CI 0.70-0.85) for stroke, 0.70 (95% CI 0.58-0.84) for CVD mortality and 0.71 (95% CI 0.65-0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56-0.91) for CHD, 0.63 (95% CI 0.57-0.71) for CVD mortality and 0.80 (95% CI 0.76-0.84) for all-cause mortality. For women with BMI 30-35 kg/m2 the risk was 1.67 (95% CI 1.24-2.25) for CHD and 2.3 (95% CI 1.56-3.40) for CVD mortality, compared to normal weight. Each 5 kg/m2 increase in BMI was associated with 24% (95% CI 16-33%) higher risk for all-cause mortality. This meta-analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality. Smoking and higher BMI were associated with an increased risk of these endpoints. Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women. However, this review highlights important gaps, as lack of standardized methods in assessing lifestyle factors and lack of accurate information on menopause status, which should be addressed by future studies in order to understand the role of menopause on the association between lifestyle factors and cardiovascular events.

Achieved systolic blood pressure in older people: a systematic review and meta-analysis.

BACKGROUND: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts' opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment. METHODS: We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design. RESULTS: Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. CONCLUSIONS: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.

Effects of non-pharmacological interventions on urinary citrate levels: a systematic review and meta-analysis.

BACKGROUND: Hypocitraturia is a known risk factor for nephrolithiasis, present in 20-60% of stone-forming patients. The administration of citrate or other alkali preparations has been demonstrated to benefit hypocitraturic stone formers. Dietary modifications that include citrate-containing fluids can be an alternative option to pharmacological agents. We aimed to systematically review, summarize and quantify available evidence on the effects of non-pharmacological interventions on urinary citrate and nephrolithiasis. METHODS: Manual and electronic database searches (MEDLINE/PubMed, Embase, Cochrane Library, Scopus, Scielo, LILACS) were performed for studies published up to July 2014. Two reviewers independently identified studies for inclusion and extracted data on study characteristics, outcomes and quality assessments. We included controlled studies with non-pharmacological interventions that assessed urinary citrate levels or nephrolithiasis pre- and post-intervention. Meta-analysis was performed by random effects and subgrouped by the type of intervention, and heterogeneity was analysed by I(2). RESULTS: Of the 427 studies identified, 13 studies were included (18 samples), involving 358 participants with a mean age of 43 ± 11.0 years across the studies. Interventions were grouped as commercial fruit juices, soft drinks, calcium-/magnesium-rich mineral water, high-fiber diet, low-animal-protein diet and plant extract. Almost half of the studies (6/13; 8/18 samples) reported effects in non-stone formers. Two studies included stone formers and non-stone formers. Commercial fruit juice interventions showed high I(2) (88.1%, P = 0.000) and an increase in citraturia levels ( 95% confidence interval) of 167.2 (65.4; 269) mg/day. Other types of intervention did not show important heterogeneity; however, pooled estimates were not significant. CONCLUSION: Our review indicates that further larger scale trials are required to analyze whether non-pharmacological interventions can increase urinary citrate levels and act in kidney stone prevention.

Acute modification in plasma lipid levels in ultramarathon runners.

We aimed to evaluate the effects of a 24-h ultramarathon, an aerobic test of high physical load, on lipid profile and apolipoproteins B (ApoB) and A1 (ApoA1) levels, minimally modified low-density lipoprotein (LDL), and oxidised LDL. Prospective evaluation of 16 male athletes who participated in an ultramarathon run, where the objective was to run the greatest distance possible in 24 h. Fourteen participants completed the run. The mean distance achieved was 133.1 km (maximum of 169.6 km). There was a trend in reduction of triglycerides and total cholesterol (P = 0.06 and 0.05, respectively), without significant modifications in high-density lipoprotein, LDL and ApoA1 levels (P = 0.16; 0.55 and 0.67). There was a marked reduction in ApoB levels (P < 0.001), correlated directly to the distance covered (Pearson R = 0.68). Accordingly, an increase in the LDL/ApoB ratio was observed. The stress of this physical activity was not associated to an increase in minimally modified LDL or oxidised LDL. Lipid profile levels were not acutely altered by prolonged physical activity. Similarly, there was no evidence of greater oxidation of LDL over a 24-h period of physical activity. The reduction in ApoB was directly proportional to the distance covered, suggesting an acute positive change in phenotype of LDL molecules.

Health-related quality of life in Guillain-Barré syndrome patients: a systematic review.

Guillain-Barré syndrome (GBS) encompasses a broad spectrum of health-related quality of life (HRQL) determinants, including mobility, fatigue, pain, and depression. We systematically reviewed the literature on functional outcome domains in which GBS patients experience limitations in the short and long terms and evaluated determinants of HRQL in GBS patients. MEDLINE and EMBASE were systematically searched by two independent reviewers for articles covering HRQL data of GBS patients. Of 730 abstracts screened, 17 articles covering data of 14 studies matched the selection criteria. The included articles showed that many GBS patients experienced physical limitations, even years after the acute phase of the disease, while results were inconsistent for perceived levels of pain, fatigue, and general mental well-being. Only three papers covered HRQL assessments at more than one time point, generally showing large improvements in HRQL in the first year after GBS onset, but not thereafter. We appraised the methodological quality of included studies using a 13-item checklist; none of the articles fulfilled all items and only seven articles presented data on correlations between HRQL and determinants. In conclusion, the majority of studies on HRQL in GBS patients are cross-sectional and of low methodological quality. This paper provides guidance for much needed high-quality studies on patterns of patient-perceived recovery after GBS onset.

First year of COVID-19 in Brazil: Factors associated with the spread of COVID-19 in small and large cities.

AIM: To test the association between sociodemographic and social characteristics with COVID-19 cases and deaths in small and large Brazilian cities. METHODS: This ecological study included COVID-19 data available in State Health Secretaries (managed by brasil.io API) and three national databases (IBGE, DATASUS and Embrapa). Temporal spread of COVID-19 in Brazil during the first year considered as outcome: a) days until 1st case in each city since 1st in the country; b) days until 1,000 cases/100,000 inhabitants since 1st case in each city; c) days until 1st death until 50 deaths/100,000 inhabitants. Covariates included geographic region, city social and environmental characteristics, housing conditions, job characteristics, socioeconomic and inequalities characteristics, and health services and coverage. The analysis were stratified by city size into small (<100,000 inhabitants) and large cities (≥100,00 inhabitants). Multiple linear regressions were performed to test associations of all covariates to adjust to potential confounders. RESULTS: In small cities, the first cases were reported after 82.2 days and 1,000 cases/100,000 were reported after 117.8 days, whereas in large cities these milestones were reported after 32.1 and 127.7 days, respectively. For first death, small and large cities took 121.6 and 36.0 days, respectively. However, small cities were associated with more vulnerability factors to first case arrival in 1,000 cases/100,000 inhabitants, first death and 50 deaths/100,000 inhabitants. North and Northeast regions positively associated with faster COVID-19 incidence, whereas South and Southeast were least. CONCLUSION: Social and built environment characteristics and inequalities were associated with COVID-19 cases spread and mortality incidence in Brazilian cities.

Fever as a Predictor of COVID-19 Outcomes in Hospitalized Patients.

INTRODUCTION: With the advent of the COVID-19 pandemic, numerous questions have arisen regarding the screening, diagnosis, treatment, and prognosis of infected patients. Among these, screening infected patients through body temperature measurement has proven ineffective. However, doubts persist regarding the role of fever as a prognostic factor in the disease. OBJECTIVE: To assess the prevalence of fever and its relevance as a marker of mortality in COVID-19. METHODOLOGY: This prospective and longitudinal cohort study was conducted between April 2020 and December 2021 and analyzed 1400 COVID-19 patients systematically admitted to the emergency department of a reference hospital during the period from April 2020 to December 2021, in the city of Curitiba, Brazil. [LG1] The study evaluated [LG2] the presence of fever (body temperature above 37,7ºC) upon admission and/or during hospitalization, patient profiles, and outcomes (in-hospital death, discharge, admission at the intensive care unit, need of mechanical ventilation). RESULTS: Fever was present in 128 participants (9.1%), with a higher prevalence in males (71%) and obese individuals (42.9%). Among the febrile patients, 39 required intubation (30.4%), with two intubated upon admission (1.5%), 104 were discharged (81.2%), and 24 deceased (18.7%). Fever was not associated with a higher mortality rate. CONCLUSION: Fever showed low prevalence, is more common in males and obese individuals, and is not related to worse clinical outcomes.

Aging and the COVID-19 pandemic: The inter-related roles of biology, physical wellbeing, social norms and global health systems.

The coronavirus disease 2019 (COVID-19) pandemic has had a devastating and disproportionate impact on the elderly population. As the virus has swept through the world, already vulnerable elderly populations worldwide have faced a far greater burden of deaths and severe disease, crippling isolation, widespread societal stigma, and wide-ranging practical difficulties in maintaining access to basic health care and social services - all of which have had significant detrimental effects on their mental and physical wellbeing. In this paper, we present an overview of aging and COVID-19 from the interrelated perspectives of underlying biological mechanisms, physical manifestations, societal aspects, and health services related to the excess risk observed among the elderly population. We conclude that to tackle future pandemics in an efficient manner, it is essential to reform national health systems and response strategies from an age perspective. As the global population continues to age, elderly-focused health services should be integrated into the global health systems and global strategies, especially in low- and middle-income countries with historically underfunded public health infrastructure and insufficient gerontological care.

Longitudinal Relationship Between Handgrip Strength and Cognitive Function in a European Multicentric Population Older Than 50 Years.

OBJECTIVE: The aim of this study was to analyze the bidirectional association between handgrip strength (HGS) and cognitive performance in different cognitive functions in a European population and to evaluate the predictive validity of HGS for the risk of future cognitive impairment in aging individuals. METHODS: This was a prospective cohort study conducted using data on individuals over 50 years of age from the Survey of Health, Aging and Retirement in Europe (SHARE). HGS measures and scores in numeracy, recall, and verbal fluency were repeated and analyzed biannually for 4 years and were used in generalized estimating equations to test the bidirectional association, categorized by sex. RESULTS: Of the 8236 individuals included, 55.73% were women with a mean age of 67.55 (standard deviation [SD] = 8.4) years and 44.27% were men with a mean age of 68.42 (SD = 7.7) years. HGS predicted cognitive decline in both sexes, except for numeracy in men, even after adjustments. The strongest association with HGS in women was in verbal fluency (ß = .094; 95% CI = 0.039 to 0.151), whereas the strongest association with HGS in men was in delayed verbal recall (ß = .095; 95% CI = 0.039 to 0.151). Conversely, the greatest cognitive predictor of HGS decline was verbal fluency in men (ß = .796; 95% CI = 0.464 to 1.128), and in women (ß = .801; 95% CI= 0.567 to 1.109). CONCLUSION: There is a significant and bidirectional association between HGS and different cognitive functions in a European multicentric population. This bidirectional association differed between sexes. IMPACT: Both men and women who presented with cognitive decline also showed early changes in their HGS measures, and vice versa, but there still were differences between the sexes. These findings reinforce that HGS may be a simple and inexpensive method to identify early signs of cognitive decline, and that studies and rehabilitation strategies should be more sex specific.

Cognitive Performance and Diabetic Retinopathy: What Your Eyes Can Reveal About Your Brain.

BACKGROUND: Diabetic retinopathy (DR) is a chronic diabetes complication. People with Type 2 Diabetes Mellitus (T2DM) have two times the risk for dementia, suggesting it is a new chronic diabetes complication. OBJECTIVE: Evaluate the association of DR with cognitive performance in a T2DM population. METHODS: Cross-sectional study with 400 T2DM adults from whom socio-demographic, clinical, laboratory data were collected, and screening test for depression symptoms (Patient Health Questionaire- 9 (PHQ-9)), Mini-Mental State Examination (MMSE), Semantic Verbal Fluency Test, Trail Making Test A and B, Word Memory test were performed. All cognitive test scores were converted into Global Cognition z-Score (GCS(z)). The association between GCS(z) < 0 with DR was performed using a multivariate binary logistic regression model adjusted for age ≥ 65 years, school years ≤ 6 years, DM duration ≥ 10 years, depression symptoms score > 9 at PHQ-9, arterial hypertension, physical activity, diabetic retinopathy, macular edema, and cardiovascular disease. RESULTS: After exclusions, the 251 eligible patients were 56.6% female, with a mean age of 61.1 (±9.8) years, DM duration of 12.6 (±8.9) years, and 7.6 (±4.2) years of school education. DR prevalence was 46.5%. Multivariate Logistic Regression Model showed an association between DR and GCS(z) < 0, with odds ratio (CI95%) of 2.50 (1.18-5.34), adjusted for age, low education level, arterial hypertension and depression symptoms (OD and CI95% respectively: 5.46(2.42-12.34); 12.19 (5.62-26.46); 2.55 (0.88-7.39); 3.53 (1.55-8.07)). CONCLUSION: In this T2DM population, having DR increased the chance for worse cognitive performance even when adjusted for age, low education level, presence of arterial hypertension, and depression symptoms.

Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis.

Backgroud: Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS. Methods: We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality. Results: Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low. Conclusions: These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability. / Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade.

BACKGROUND: Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability Association of ischemic heart disease (adjusted for traditional risk factors and socioeconomics variables) and income level (A), and walkability z-score (B), and association of walkability z-score and income level (C). BACKGROUND: Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. OBJECTIVES: To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. METHODS: This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. RESULTS: From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = -0.3%). CONCLUSIONS: Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.