Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Lower bone density and microarchitecture alterations in HIV-infected Brazilian men aged 50 years and older are associated with estradiol levels.

OBJECTIVE: Combination antiretroviral treatment (cART) allows for longer survival for people living with HIV and hence long-term complications of both disease and treatment are common. Our purpose was to evaluate bone alterations in men living with HIV (MLWH) and receiving cART and to identify associated factors that can be corrected or mitigated. PATIENTS AND DESIGN: Thirty MLWH and 36 healthy controls (≥50 years) were studied for areal bone mineral density (aBMD) and body composition (dual-energy X-ray absorptiometry), volumetric bone mineral density (vBMD) and bone microstructure (high-resolution peripheral quantitative computed tomography [HR-pQCT]), serum calcium, phosphate, parathyroid hormone, 25(OH)D, testosterone (T), estradiol (E2 ), glucose, creatinine, and albumin levels. RESULTS: The proportion of patients classified as osteoporosis (according to the lowest aBMD T-score) was higher among MLWH as compared to controls (17.9% vs. 5.9%, p = .011). The MLWH showed significant alterations in cortical and trabecular bone on HR-pQCT, which were not associated with the duration of HIV infection or cART. These differences in vBMD and bone microstructure seen in HR-pQCT persisted in the nonosteoporotic MLWH as compared to nonosteoporotic control subjects. Body mass index (BMI) and fat mass were lower in MLWH and positively associated with total vBMD, cortical bone area, and thickness. E2 and E2 /T ratios were lower in MLWH than in controls and significantly correlated with several cortical and trabecular bone parameters. Multivariate regression analysis entering simultaneously age, BMI, and E2 defined that E2 is an independent influence on bone parameters evaluated by HR-pQCT. CONCLUSION: MLWH have alterations in bone volumetric density and microstructure when compared with controls, irrespective of aBMD, which are associated with lower E2 and BMI.

Geographic Distribution and Time Trends of Colorectal Cancer in Brazil from 2005 to 2018.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death in the world. The aim of this study was to investigate the geographic distribution and time trends of CRC in Brazil. METHODS: Data were retrospectively retrieved from January 2005 to December 2018 from the Brazilian Public Health System. The incidence and lethality rates of CRC per 100,000 inhabitants in each municipality were estimated from hospitalizations and in-hospital deaths and were classified by age, sex, and demographic features. RESULTS: During the study period, the mean incidence of CRC estimated from hospitalizations and adjusted to available hospital beds more than tripled from 14.6 to 51.4 per 100,000 inhabitants (352%). Increases in CRC incidence were detected in all age ranges, particularly among people aged 50-69 years (266%). Incidence rates increased in all 5 macroregions, with a clear South to North gradient. The greatest changes in incidence and lethality rates were registered in small-sized municipalities. CRC lethality estimated from in-hospital deaths decreased similarly in both sexes, from 12 to 8% for males and females, from 2005 to 2018. The decline in lethality rates was seen in all age ranges, mainly in people aged 50 to 69 years (- 38%). CONCLUSIONS: CRC incidence is increasing, predominantly above fifty years of age, and also in areas previously considered as having low incidence, but the increase is not paralleled by lethality rates. This suggests recent improvements in CRC screening programs and treatment, but also supports the spread of environmental risk factors throughout the country.

Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial.

BACKGROUND: Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: In a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also assessed. RESULTS: From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo (p=0.006). The percentage viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. CONCLUSIONS: In patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Prevalence, Indirect Costs, and Risk Factors for Work Disability in Patients with Crohn's Disease at a Tertiary Care Center in Rio de Janeiro.

BACKGROUND AND AIMS: Crohn's disease (CD) can lead to work disability with social and economic impacts worldwide. In Brazil, where its prevalence is increasing, we assessed the indirect costs, prevalence, and risk factors for work disability in the state of Rio de Janeiro and in a tertiary care referral center of the state. METHODS: Data were retrieved from the database of the Single System of Social Security Benefits Information, with a cross-check for aid pension and disability retirement. A subanalysis was performed with CD patients followed up at the tertiary care referral center using a prospective CD database, including clinical variables assessed as possible risk factors for work disability. RESULTS: From 2010 to 2018, the estimated prevalence of CD was 26.05 per 100,000 inhabitants, while the associated work disability was 16.6%, with indirect costs of US$ 8,562,195.86. Permanent disability occurred more frequently in those aged 40 to 49 years. In the referral center, the prevalence of work disability was 16.7%, with a mean interval of 3 years between diagnosis and the first benefit. Risk factors for absence from work were predominantly abdominal surgery, anovaginal fistulas, disease duration, and the A2 profile of the Montreal classification. CONCLUSIONS: In Rio de Janeiro, work disability affects one-sixth of CD patients, and risk factors are associated with disease duration and complications. In the context of increasing prevalence, as this disability compromises young patients after a relatively short period of disease, the socioeconomic burden of CD is expected to increase in the future.

Increasing pancreatic cancer is not paralleled by pancreaticoduodenectomy volumes in Brazil: A time trend analysis.

BACKGROUND: Currently, surgical resection represents the only curative treatment for pancreatic cancer (PC), however, the majority of tumors are no longer resectable by the time of diagnosis. The aim of this study was to describe time trends and distribution of pancreaticoduodenectomies (PDs) performed for treating PC in Brazil in recent years. METHODS: Data were retrospectively obtained from Brazilian Health Public System (namely DATASUS) regarding hospitalizations for PC and PD in Brazil from January 2008 to December 2015. PC and PD rates and their mortalities were estimated from DATASUS hospitalizations and analyzed for age, gender and demographic characteristics. RESULTS: A total of 2364 PDs were retrieved. Albeit PC incidence more than doubled, the number of PDs increased only 37%. Most PDs were performed in men (52.2%) and patients between 50 and 69 years old (59.5%). Patients not surgically treated and those 70 years or older had the highest in-hospital mortality rates. The most developed regions (Southeast and South) as well as large metropolitan integrated municipalities registered 76.2% and 54.8% of the procedures, respectively. LMIM PD mortality fluctuated, ranging from 13.6% in 2008 to 11.8% in 2015. CONCLUSIONS: This study suggests a trend towards regionalization and volume-outcome relationships for PD due to PC, as large metropolitan integrated municipalities registered most of the PDs and more stable mortality rates. The substantial differences between PD and PC increasing rates reveals a limiting step on the health system resoluteness. Reduction in the number of hospital beds and late access to hospitalization, despite improvement in diagnostic methods, could at least in part explain these findings.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study.

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

Effects of Dietary Supplementation with Brazil Nuts on Microvascular Endothelial Function in Hypertensive and Dyslipidemic Patients: A Randomized Crossover Placebo-Controlled Trial.

OBJECTIVE: To investigate the effects of dietary supplementation with GBNs on microvascular endothelial function in hypertensive and dyslipidemic patients. METHODS: Ninety-one patients of both sexes aged 62.1 ± 9.3 years received 13 g/day of GBNs or a placebo for three months with a washout period of one month between treatments. Microvascular endothelial function was assessed using LSCI coupled with iontophoresis of ACh and PORH. We also used skin video capillaroscopy to measure capillary density and recruitment at rest and during PORH. Plasma concentrations of NOx were also measured as a marker of nitric oxide bioavailability. RESULTS: Supplementation with GBNs significantly increased the plasma levels of Se (p < 0.05) and NOx (p < 0.05). However, we did not observe any effects of GBN consumption on microvascular vasodilator responses to ACh or PORH (p > 0.05), and GBNs did not improve capillary density at baseline or recruitment during PORH (p > 0.05). CONCLUSIONS: Supplementation with GBNs induced significant increases in the plasma Se concentration and systemic bioavailability of nitric oxide. Nevertheless, GBN supplementation did not lead to any improvement in systemic microvascular reactivity or density in patients with arterial hypertension and dyslipidemia who were undergoing multiple drug therapies.

Intake of partially defatted Brazil nut flour reduces serum cholesterol in hypercholesterolemic patients--a randomized controlled trial.

OBJECTIVE: Thyroid hormones can lower levels of atherogenic lipoproteins, and selenium is important in thyroid hormone homeostasis. We aimed to investigate the effects of a healthy diet associated with the Brazil nut (Bertholletia excelsa) in dyslipidemic and hypertensive patients. METHODS: This study was a randomized, placebo-controlled, double-blind trial. Seventy-seven dyslipidemic and hypertensive patients already receiving lipid-lowering drugs received either a dietary treatment associated with partially defatted Brazil nut flour (13 g/day providing 227,5 µg of selenium/day),or with dyed cassava flour as a placebo. All patients received a personalized dietary guideline with nutritional recommendations for dyslipidemia and hypertension and were followed for 90 days. RESULTS: The Brazil nut group showed reductions in total cholesterol (-20.5 ± 61.2 mg/dL, P = 0.02), non HDL-cholesterol (-19.5 ± 61.2 mg/dL, P = 0.02) and Apo A-1 (-10.2 ± 26.7 mg/dL, P = 0.03) without significant alterations in the Apo B/Apo A-1 ratio. The placebo group showed a reduction in FT3 levels (-0.1 ± 0.4, P = 0.03) and increased Lp(a) levels (5.9 ± 18.0 mg/dL, P = 0.02). There were no statistical differences in blood pressure and serum lipids between Brazil nut and placebo group. CONCLUSIONS: Supplementation with Brazil nuts seems to favor the maintenance of FT3 levels and contributes to lipemia reduction in hypercholesterolemic and euthyroid patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01990391.

Improvement of antioxidant status after Brazil nut intake in hypertensive and dyslipidemic subjects.

OBJECTIVES: To investigate the effect of partially defatted Granulated Brazil nut (GBN) on biomarkers of oxidative stress and antioxidant status of hypertensive and dyslipidemic patients on nutrition and drug approaches. METHODS: Ninety one hypertensive and dyslipidemic subjects of both genders (51.6 % men), mean age 62.1 ± 9.3 years, performed a randomized crossover trial, double-blind, placebo controlled. Subjects received a diet and partially defatted GBN 13 g per day (≈227.5 µg/day of selenium) or placebo for twelve weeks with four-week washout interval. Anthropometric, laboratory and clinic characteristics were investigated at baseline. Plasma selenium (Se), plasma glutathione peroxidase (GPx3) activity, total antioxidant capacity (TAC), 8-epi PGF2α and oxidized LDL were evaluated at the beginning and in the end of each intervention. RESULTS: GBN intake significantly increased plasma Se from 87.0 ± 16.8 to 180.6 ± 67.1 µg/L, increased GPx3 activity in 24,8% (from 112.66 ± 40.09 to 128.32 ± 38.31 nmol/min/mL, p < 0,05), and reduced 3.25% of oxidized-LDL levels (from 66.31 ± 23.59 to 60.68 ± 20.88 U/L, p < 0.05). An inverse association between GPx3 and oxidized LDL levels was observed after supplementation with GBN by simple model (ß -0.232, p = 0.032) and after adjustment for gender, age, diabetes and BMI (ß -0.298, p = 0.008). There wasn't association between GPx3 and 8-epi PGF2α (ß -0.209, p = 0.052) by simple model. CONCLUSION: The partially defatted GBN intake has a potential benefit to increase plasma selenium, increase enzymatic antioxidant activity of GPx3 and to reduction oxidation in LDL in hypertensive and dyslipidemic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01990391; November 20, 2013.

Intermediate fibrosis staging in hepatitis C: a problem not overcome by optimal samples or pathologists' expertise.

BACKGROUND AND AIMS: The prediction of intermediate stage of fibrosis in chronic hepatitis C represents a prognostic factor for disease progression. Studies evaluating biopsy performance in intermediate stage considering current patterns of liver samples and pathologists' variability are scarce. We aimed to evaluate the effect of optimal liver specimens (≥ 20 mm and/or ≥ 11 portal tracts) and pathologists' expertise on agreement for intermediate stage of fibrosis in chronic hepatitis C. MATERIAL AND METHODS: Guided biopsies with large TruCut needle were initially scored by four pathologists with different expertise in liver disease and posteriorly reviewed by a reference hepatopathologist to evaluate fibrosis agreement. RESULTS: Of the 255 biopsies initially selected, 240 met the criteria of an optimal fragment (mean length 24 ± 5 mm; 16 ± 6 portal tracts) and were considered for analysis. The overall agreement among all fibrosis stages was 77% (κ = 0.66); intraobserver and interobserver agreement was, respectively, 97% (k = 0.96) and 73% (κ = 0.60). Excluded samples (< 20 mm and < 11 portal tracts) presented a lower agreement (40%; κ = 0.24). Stratifying fibrosis stages, an interobserver agreement of 42% was found in intermediate stage (F2), ranging from 0 to 56% according to pathologists' expertise, compared to 97% in mild (F0-F1) and 72% in advanced fibrosis (≥ F3) (p < 0.001). Of the 23% misclassified cases, fibrosis understaging occurred in 82% of specimens, predominantly in F2, even when evaluated by a hepatopathologist. CONCLUSIONS: Liver biopsy presents intrinsic limitations to assess intermediate stage of fibrosis not overcome by optimal samples and experienced pathologists' analysis, and should not be considered the gold standard method to evaluate intermediate fibrosis in chronic hepatitis C.

Prevalence of anaemia and associated factors among children below five years of age in Cape Verde, West Africa.

This study estimated the prevalence of anaemia and associated factors in a probability sample of 993 chil- dren aged 6-59 months in Cape Verde, West Africa. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated from a hierarchical model for multiple analysis to assess the association between anaemia and explanatory variables. The prevalence of anaemia was 51.8% (95% CI 47.7-55.8). Children who resided within poor household conditions (OR 1.99; 95% CI 1.06-3.71) were below 24 months of age (OR 3.23; 95% CI 2.03-5.15) and recently experienced diarrhoea (OR 1.58; 95% CI 0.99-2.50) were at high risk of anaemia. Anaemia should be considered a serious public-health concern in Cape Verde, mainly for chil- dren below 24 months. Further, special consideration should be given to children who have experienced recent diarrhoea and belong to families residing in poor household conditions.

Common mental disorders among civil aviation flight attendants.

INTRODUCTION: The purpose of the current study was to estimate the prevalence of common mental disorders (CMDs) among Brazilian civil aviation flight attendants and to investigate associations between CMDs and sociodemographic and work-related variables. METHODS: This was a quantitative cross-sectional study conducted between October 2009-October 2010 using a self-reporting questionnaire about sociodemographic and work-related data and a screening instrument for the detection of psychiatric morbidity. RESULTS: A total of 453 flight attendants were evaluated. The prevalence of CMDs was found to be 29.8% (N = 135/453; 95% CI 25.7-34.10%). Female flight attendants presented higher prevalence (36.0%) than male flight attendants (19.7%). The prevalence among individuals who had completed their training more than 5 yr earlier was 35.7% versus 19.2% among those who had qualified less than 5 yr earlier. In the final adjusted model, only the following variables maintained a statistically significant association: sex (OR 2.83); regular physical activity practice (OR 1.68); time since completion of training (OR 2.56); involvement with religious belief (OR 1.66); and type of flight route (OR 1.71). DISCUSSION: Flight attendants are subjected to stressful situations determined both by specific occupational risks and by the form of work organization. Studies with civil aviation pilots found lower values for CMD prevalence (6.7%). This shows that although both categories are classified as aircrew members and share various similarities of occupational risks, they are also, at the same time, profoundly different regarding their professional profiles.

Healing complications of traumatized permanent teeth in pediatric patients: a longitudinal study.

BACKGROUND: Traumatic dental injuries (TDI) can affect soft and hard dental tissues and supporting structures in different ways and severity. AIM: This study describes the complications associated with health in traumatized permanent teeth (TPT) over a 12-month period and assesses the relationships between TDI, involved tissues, and root development (RD). DESIGN: The study enrolled 294 patients with 548 TPT. Data were collected on the TDI, RD, and the healing complication (HC) and when they were examined (03, 06, and 12 months). Frequencies are described and analyzed using the chi-squared test, relative risk (RR), and Mantel-Haenszel analysis (P≤0.05). RESULTS: Healing complications were present in 201 (36.68%) teeth and were more frequently diagnosed 3 months (63.68%) after the TDI. Pulp necrosis was the most common HC (38.3%), and it was significantly associated with avulsion (P=0.023). Teeth with complete RD showed a tendency of developing HC over time, independent of TDI (P=0.05). HC in teeth with complete RD related to support tissue trauma (P=0.005) and avulsion (P<0.001) appeared more frequently after 3 months. CONCLUSION: Healing complications are more common in teeth that have suffered trauma in supporting tissues and avulsion, especially in teeth with complete RD. The HC occur more frequently in the first 3 months, and a necrotic pulp was the most common complication.

Durability of the improvement of collagen I and collagen III with the use of oral isotretinoin in the treatment of photoaging.

BACKGROUND: Oral isotretinoin (ISO) is the drug of choice for the treatment of severe acne. For photoaging treatment, ISO has been proved to be effective in some controlled and noncontrolled trials and is an alternative to topical retinoic acid (RA) therapy, which causes an expected skin irritation. OBJECTIVE: To evaluate and compare the skin remodeling in patients taking ISO 20 mg 3 times a week for 12 weeks and 12 weeks after the end of the treatment to quantify collagen I and collagen III augmentation. MATERIAL AND METHODS: Immunohistochemical studies were performed to evaluate the expression of collagen I and collagen III, metalloproteinases (MMPs) -1, -3, -7, -9, -12, and the tissue inhibitor of MMP type-1 (TIMP-1) of the skin of 20 45 to 50-year-old women through morphometry in a semiquantitative method. The inclusion criteria were facial aging 2 and 3 of Glogau's classification, with phototypes between II and V who had not entered menopause. Biopsies of the skin of the left preauricular region were performed at three different times: pre-treatment (T0), end of 12-week treatment (T1), and 12 weeks posttreatment (T2). RESULTS: Collagen fibers I and III increased with statistical significance in T1 (50.7%; P = 0.012) but not in T2 (49.7%), which in turn was higher than in T0 (47.2%) for collagen I and T1 (33.3%; P = 0.002) but not in T2 (32.7%), and also was higher than T0 (32.0%) for collagen III. MMP-9 presented a decreased activity with statistical significance in T1 (P = 0.047) and T2 (P = 0.058). MMP-1 showed a reduction in T2 only (P = 0.015). MMPs -3, -7, -12, and TIMP-1 did not present significant modification in their expressions during or after the treatment. CONCLUSIONS: Low-dose ISO is effective in remodeling the extracellular matrix (ECM). This study found that the increase of collagen occurs through the augmentation of both collagen I and collagen III fibers. With originality, it was possible to verify the durability of these fibers for at least 12 weeks. This may be related to the decrease in MMP-9 expression verified at the end of the treatment and 12 weeks posttreatment.

Vital capacity and inspiratory capacity as additional parameters to evaluate bronchodilator response in asthmatic patients: a cross sectional study.

BACKGROUND: Bronchodilator response in patients with asthma is evaluated based on post-bronchodilator increase in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). However, the need for additional parameters, mainly among patients with severe asthma, has already been demonstrated. METHODS: The aim of this study was to evaluate the usefulness of vital capacity (VC) and inspiratory capacity (IC) to evaluate bronchodilator response in asthma patients with persistent airflow obstruction. The 43 asthma patients enrolled in the study were stratified into moderate or severe airflow obstruction groups based on baseline FEV1. All patients performed a 6-minute walk test before and after the bronchodilator (BD). A bipolar visual analogue scale post-BD was performed to assess clinical effect. The correlation between VC and IC and clinical response, determined by visual analogue scale (VAS) and 6-minute walk test (6MWT), was investigated. RESULTS: Patients in the severe group presented: 1) greater bronchodilator response in VC (48% vs 15%, p = 0.02), 2) a significant correlation between VC variation and the reduction in air trapping (Rs = 0.70; p < 0.01), 3) a significant agreement between VC and VAS score (kappa = 0.57; p < 0.01). There was no correlation between IC and the reduction in air trapping or clinical data. CONCLUSIONS: VC may be a useful additional parameter to evaluate bronchodilator response in asthma patients with severe airflow obstruction.

Troponin in COVID-19: To Measure or Not to Measure? Insights from a Prospective Cohort Study.

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial.

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.