Clinical and microbiological profile of health care-associated infections in a tertiary hospital: Comparison between a cohort of hospitalized patients during prepandemic and COVID-19 pandemic periods.

BACKGROUND: During the COVID-19 pandemic, health service practices underwent significant changes, impacting the occurrence of health care-associated infections (HAIs). This study presents the epidemiology of bacterial infections and compares clinical data on nosocomial infections in hospitalized patients before and during the pandemic. METHODS: A unicentric, observational, retrospective cohort study was conducted with descriptive analyses on the microorganism identification and resistance profile. Patient's clinical data who had hospital-acquired infection (HAI), during their hospitalization in a tertiary hospital before and during the COVID-19 pandemic was compared by descriptive and inferential analyses. RESULTS: A total of 1,581 bacteria were isolated from 1,183 hospitalized patients. Among patients coinfected with COVID-19, there was a statistically significant increase in HAI-related deaths (P < .001) and HAI caused by multidrug-resistant organisms (P < .001), mainly by Acinetobacter baumannii and Staphylococcus aureus. A higher odds ratio of HAI-related deaths compared to the prepandemic period was observed (odds ratio 6.98 [95% confidence interval 3.97-12.64]). CONCLUSIONS: The higher incidence of multidrug-resistant bacteria and increased deaths due to HAI, especially in patients with COVID-19 coinfection, might be related to various factors such as increased workload, broad-spectrum antibiotic use, and limited resources. The pandemic has changed the profile of circulating bacteria and antimicrobial resistance. Prevention strategies should be considered to reduce the impact of these infections.

Assessing the impact of the Gamma variant on COVID-19 patient admissions in a southern Brazilian tertiary hospital-A comparison of dual pandemic phases.

Since the first case of COVID-19, Brazil has undergone infection waves with distinct characteristics. The description of new variants has alerted the emergence of more contagious or virulent viruses. The variant of concern Gamma emerged in Brazil and caused an epidemic wave, but its spread outside the country was limited. We report the clinical-epidemiological profile of hospitalized patients with COVID-19 by comparing two periods. A retrospective cohort study was performed. The primary outcome was to assess individuals with COVID-19 admitted in wards and intensive care units at the academic hospital of the Federal University of Parana (CHC-UFPR) between March 2020 and July 2021, correlating demographic, clinical-epidemiologic, and survival data with the most prevalent viral variant found in each period. We used Kaplan-Meier analysis to estimate the probability of survival and ROC curves to evaluate laboratory tests to find a cutoff point for poor outcomes. Data from 2,887 individuals were analyzed, 1,495 and 1,392 from the first and second periods, respectively. Hospitalization predominated among males in both periods, and the median age was significantly lower in the second one. The frequency of comorbidities was similar. Various demographic factors, clinical assessments, and laboratory tests were examined in relation to greater severity. When comparing the two periods, we observed predominance of the Wild virus during the first wave and the Gamma variant during the second, with no significant difference in outcomes. The findings suggest that despite the association of many factors with increased severity, the temporal variation between the two periods did not result in a notable divergence in the measured outcomes. The COVID-19 pandemic has lasted for a long time, with periods marked by peaks of cases, often caused by the emergence of viral variants, resulting in higher infection rates and rapid dissemination but, for variant Gamma, no apparent greater virulence.

Fear of childbirth: prevalence and associated factors in pregnant women of a maternity hospital in southern Brazil.

BACKGROUND: The fear of childbirth (FOC) harms maternal and fetal health, however it has been little studied in Brazil. This research aimed to determine the prevalence of FOC in a maternity hospital in southern Brazil and identify its associated factors. METHODS: The Wijma Delivery Expectancy Questionnaire - W-DEQ(A) was used to assess the prevalence of FOC, and its relationship with sociodemographic variables, gestational history, aspects of the current pregnancy, knowledge about childbirth, anxiety symptoms (Beck Anxiety Inventory), depressive symptoms (Edinburgh Postnatal Depression Scale), and perception of social support (Multidimensional Scale of Perceived Social Support) was investigated. Questionnaires about the content of FOC and information sources regarding childbirth were also applied. RESULTS: We interviewed 125 pregnant women between 28 and 36 weeks of pregnancy between July and September of 2021, and 12% of them scored ≥ 85 on the W-DEQ(A), indicating severe FOC. There was a significant correlation between FOC and anxiety symptoms (r = 0.50, p < 0.001), depressive symptoms (r = 0.34, p < 0.001), and poor social support (r = -0.23, p = 0.008). FOC was lower in pregnant women with complete elementary education when compared to those with higher education (p = 0.003), however, those with negative experiences in previous deliveries had more FOC than those who had had positive experiences (p = 0.001). More than 85% of them fear fetal distress. CONCLUSIONS: FOC is a prevalent condition that impacts the mental health of pregnant women. Therefore, health professionals should recognize and address it during prenatal care to provide integral maternal-fetal care and improve the childbirth experience.

THE EVALUATION OF INFLIXIMAB TROUGH LEVEL FAVORS MAINTENANCE THERAPY OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases that result from the deregulation of the mucosal immune system of the gastrointestinal tract. The use of biological therapies, including infliximab (IFX), is one of the strategies to treat both CD and UC. The IFX treatment is monitored by complementary tests, namely: fecal calprotectin (FC); C-reactive protein (CRP); and endoscopic and cross-sectional imaging. Besides, serum IFX evaluation and antibody detection are also used. OBJECTIVE: To evaluate trough levels (TL) and antibodies in a population with inflammatory bowel (IBD) disease undergoing treatment with IFX, and the factors that might impact the treatment effectiveness. METHODS: Retrospective, cross-sectional study with patients with IBD that were assessed for TL and antibody (ATI) levels in a southern Brazilian hospital, from June 2014 to July 2016. RESULTS: The study assessed 55 patients (52.7% female) submitted to serum IFX and antibody evaluations (95 blood samples, 55 first test; 30 second test, and 10 as third testing. Forty-five (47.3%) cases were diagnosed with CD (81.8%), and ten with UC (18.2%). Serum levels were adequate in 30 samples (31.57%), subtherapeutic in 41 (43.15%), and supratherapeutic in 24 (25.26%). IFX dosages were optimized for 40 patients (42.10%), maintained for 31 (32.63%), and discontinued for 7 (7.60%). The intervals between infusions were shortened in 17.85% of the cases. In 55 tests (55.79%), the therapeutic approach was exclusively defined according to IFX and/or serum antibody levels. The assessment of patients one year later indicated that: the approach was maintained with IFX for thirty-eight patients (69.09%); the class of biological agent was changed for eight (14.54%); changes using the same class of biological agent occurred for two patients (3.63%); the medication was discontinued and not replaced for three patients (5.45%), and four patients (7.27%) were lost to follow-up. CONCLUSION: There were no differences in TL between groups with or without immunosuppressants, serum albumin (ALB), erythrocyte sedimentation rate (ESR), FC, CRP, and endoscopic and imaging examinations. Current therapeutic approach could be maintained for almost 70% of patients. Thus, serum and antibody levels are a useful tool in the follow-up of patients undergoing maintenance therapy and after treatment induction in patients with inflammatory bowel disease.

Donor-Specific HLA Antibodies Are Associated with Graft Failure and Delayed Hematologic Recovery after Unrelated Donor Hematopoietic Cell Transplantation.

Graft failure (GF) is one of the major concerns after allogeneic hematopoietic cell transplantation (allo-HCT) and remains a significant cause of morbidity and mortality. Although previous reports have associated the presence of donor-specific HLA antibodies (DSAs) with an increased risk of GF after unrelated donor allo-HCT, recent studies have failed to confirm this association. We sought to validate the presence of DSAs as a risk factor for GF and hematologic recovery in the unrelated donor allo-HCT setting. We retrospectively evaluated 303 consecutive patients who underwent their first unrelated donor allo-HCT at our institution between January 2008 and December 2017. DSA evaluation was performed using 2 single antigen bead (SAB) assays; DSA titration with 1:2, 1:8, and 1:32 dilutions; C1q-binding assay; and absorption/elution protocol to assess possible false-positive DSA reactivity. The primary endpoints were neutrophil and platelet recovery and GF, and the secondary endpoint was overall survival. Multivariable analyses were performed using Fine-Gray competing risks regression and Cox proportional hazards regression models. The median patient age was 14 years (range, 0 to 61 years), 56.1% were male, and 52.5% underwent allo-HCT for nonmalignant disease, Eleven patients (3.63%) were DSA-positive, including 10 with preexisting DSAs and 1 with post-transplantation de novo DSAs. Nine patients had 1 DSA, 1 patient had 2 DSAs, and 1 patient had 3 DSAs, with a median mean fluorescent intensity (MFI) of 4334 (range, 588 to 20,456) and 3581 (range, 227 to 12,266) in LABScreen and LIFECODES SAB assays, respectively. Overall, 21 patients experienced GF, including 12 with primary graft rejection, 8 with secondary graft rejection, and 1 with primary poor graft function. The cumulative incidence of GF was 4.0% (95% confidence interval [CI], 2.2% to 6.6%) at 28 days, 6.6% (95% CI, 4.2% to 9.8%) at 100 days, and 6.9% (95% CI, 4.4% to 10.2%) at 365 days. In the multivariable analyses, DSA-positive patients had significantly delayed neutrophil recovery (subdistribution hazard ratio [SHR], .48; 95% CI, .29 to .81; P = .006) and platelet recovery (SHR, .51; 95% CI, .35 to .74; P = .0003) compared to patients without DSAs. In addition, only DSAs were significant predictors of primary GF at 28 days (SHR, 2.78; 95% CI, 1.65 to 4.68; P = .0001). The Fine-Gray regression also demonstrated that the presence of DSAs was strongly associated with a higher incidence of overall GF (SHR, 7.60; 95% CI, 2.61 to 22.14; P = .0002). DSA-positive patients with GF had significantly higher median MFI values than DSA-positive patients who achieved engraftment in the LIFECODES SAB assay using neat serum (10,334 versus 1250; P = .006) and in the LABScreen SAB at 1:32 dilution (1627 versus 61; P = .006). All 3 patients with C1q-positive DSAs failed to engraft. DSAs were not predictive of inferior survival (HR, .50; 95% CI, .20 to 1.26; P = .14). Our results validate the presence of DSAs as a significant risk factor for GF and delayed hematologic recovery after unrelated donor allo-HCT. Careful pretransplantation DSA evaluation may optimize unrelated donor selection and improve allo-HCT outcomes.

Effects of High-Intensity Interval Training and Continuous Training on Exercise Capacity, Heart Rate Variability and Isolated Hearts in Diabetic Rats. / Efeitos do Treinamento Intervalado de Alta Intensidade e do Treinamento Contínuo na Capacidade de Exercício, Variabilidade da Frequência Cardíaca e em Corações Isolados em Ratos Diabéticos.

BACKGROUND: High-intensity interval training (HIIT) has been suggested as an alternative for continuous training (CT) in people with diabetes mellitus (DM) due to its short duration and potential to improve adherence to exercise. However, data on its impact on heart rate variability (HRV) are scarce. OBJECTIVES: To assess and compare the effects of HIIT and CT on exercise capacity, HRV and isolated hearts in diabetic rats. METHODS: DM (intravenous streptozotocin, 45 mg.kg -1 ) and control (C) animals performed 20 sessions (5 days/week, 50 min, for 4 weeks) of CT on a treadmill (70% of maximal exercise capacity) or HIIT (cycles of 1:1min at 50% and 90% of maximal exercise capacity). HRV was assessed by continuous electrocardiogram, and cardiac function assessed in isolated perfused hearts. For data analysis, we used the framework of the multivariate covariance generalized linear model or one-way ANOVA followed by Tukey's test, considering p<0.05 as significant. RESULTS: Higher exercise capacity (m/min) was achieved in HIIT (DM-HIIT: 36.5 [IQR 30.0-41.3]; C-HIIT: 41.5 [37.8-44.5], both n=10) compared to CT (DM-CT: 29.0 [23.8-33.0]; C-CT: 32.0 [29.5-37.0], both n=10) (p<0.001). Heart rate (bpm) was lower in DM compared to controls (p<0.001) both in vivo (DM-HIIT:348±51, C-HIIT:441±66, DM-CT:361±70, C-CT:437±38) and in isolated hearts. There were no differences in HRV between the groups. Maximum and minimal dP/dt were reduced in DM, except +dP/dt in DM-HIIT vs. C-HIIT (mean difference: 595.5±250.3, p=0.190). CONCLUSION: Short-term HIIT promotes greater improvement in exercise performance compared to CT, including in DM, without causing significant changes in HRV.

FUNDAMENTO: O treinamento intervalado de alta intensidade (HIIT) tem sido sugerido como alternativa ao treinamento contínuo (TC) em indivíduos com diabetes mellitus (DM) devido à sua curta duração e potencial para melhorar a adesão ao exercício. No entanto, dados sobre seu impacto sobre a variabilidade da frequência cardíaca (VFC) são escassos. OBJETIVOS: Avaliar e comparar os efeitos do HIIT e TC sobre a capacidade no exercício, VFC e corações isolados em ratos diabéticos. MÉTODOS: Animais diabéticos (estreptozotocina intravenosa, 45 mg.kg -1 ) e controles (C) realizaram 20 sessões de TC (5 dias/semana, 50 min, por quatro semanas) em esteira (70% da capacidade máxima de exercício) ou HIIT (ciclos de 1:1min a 50% e 90% da capacidade máxima de exercício). A VFC foi avaliada por eletrocardiograma contínuo, e a função cardíaca foi avaliada em corações isolados perfundidos. Para a análise dos dados, utilizamos a matriz do modelo linear generalizado de covariância multivariada ou o teste one-way ANOVA seguido pelo teste de Tukey, considerando um valor de p<0,05 como significativo. RESULTADOS: A capacidade de exercício (m/min) foi maior no grupo submetido ao HIIT [DM-HIIT: 36,5 (IIQ 30,0-41,3); C-HIIT: 41,5 (37,8-44,5), ambos n=10) em comparação ao grupo submetido ao TC [DM-TC: 29,0 (23,8-33,0); C-TC: 32,0 (29,5-37,0), ambos n=10) (p<0,001). A frequência cardíaca (bpm) foi mais baixa no grupo DM em comparação aos controles (p<0,001) tanto in vivo (DM-HIIT: 348±51, C-HIIT:441±66, DM-TC:361±70, C-TC:437±38) como nos corações isolados. Não houve diferenças na VFC entre os grupos. Os valores máximos e mínimos de dP/dt foram reduzidos no DM, com exceção da +dP/dt no grupo DM-HIIT vs. C-HIIT (diferença média: 595,5±250,3, p=0,190). CONCLUSÃO: O HIIT de curto prazo promoveu melhora superior no desempenho no exercício em comparação ao TC, sem causar mudanças significativas na variabilidade da frequência cardíaca.

A avaliação de níveis sérios de infliximabe favorece a manutenção do tratamento em pacientes com doença inflamatória intestinal / The evaluation of infliximab trough level favors maintenance therapy of patients with inflammatory bowel disease

ABSTRACT Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases that result from the deregulation of the mucosal immune system of the gastrointestinal tract. The use of biological therapies, including infliximab (IFX), is one of the strategies to treat both CD and UC. The IFX treatment is monitored by complementary tests, namely: fecal calprotectin (FC); C-reactive protein (CRP); and endoscopic and cross-sectional imaging. Besides, serum IFX evaluation and antibody detection are also used. Objective: To evaluate trough levels (TL) and antibodies in a population with inflammatory bowel (IBD) disease undergoing treatment with IFX, and the factors that might impact the treatment effectiveness. Methods: Retrospective, cross-sectional study with patients with IBD that were assessed for TL and antibody (ATI) levels in a southern Brazilian hospital, from June 2014 to July 2016. Results: The study assessed 55 patients (52.7% female) submitted to serum IFX and antibody evaluations (95 blood samples, 55 first test; 30 second test, and 10 as third testing. Forty-five (47.3%) cases were diagnosed with CD (81.8%), and ten with UC (18.2%). Serum levels were adequate in 30 samples (31.57%), subtherapeutic in 41 (43.15%), and supratherapeutic in 24 (25.26%). IFX dosages were optimized for 40 patients (42.10%), maintained for 31 (32.63%), and discontinued for 7 (7.60%). The intervals between infusions were shortened in 17.85% of the cases. In 55 tests (55.79%), the therapeutic approach was exclusively defined according to IFX and/or serum antibody levels. The assessment of patients one year later indicated that: the approach was maintained with IFX for thirty-eight patients (69.09%); the class of biological agent was changed for eight (14.54%); changes using the same class of biological agent occurred for two patients (3.63%); the medication was discontinued and not replaced for three patients (5.45%), and four patients (7.27%) were lost to follow-up. Conclusion: There were no differences in TL between groups with or without immunosuppressants, serum albumin (ALB), erythrocyte sedimentation rate (ESR), FC, CRP, and endoscopic and imaging examinations. Current therapeutic approach could be maintained for almost 70% of patients. Thus, serum and antibody levels are a useful tool in the follow-up of patients undergoing maintenance therapy and after treatment induction in patients with inflammatory bowel disease.

RESUMO Contexto: A doença de Crohn e a colite ulcerativa são doenças crônicas nas quais existem desregulação do sistema imune da mucosa do trato gastrointestinal. Uma das terapias usadas no tratamento dessas doenças são as medicações biológicas, entre elas o Infliximabe. A monitorização do tratamento dos pacientes com Iinfliximabe é feita por exames complementares: calprotectina fecal, pesquisa de atividade inflamatória, exames endoscópicos e imagem. Utiliza-se, também a dosagem do nível sérico do Infliximabe e a pesquisa de anticorpos. Objetivo: Analisar uma população com doenças inflamatórias intestinais, em tratamento com Infliximabe, submetida a avaliação do nível sérico do Infliximabe e do anticorpo, além de possíveis fatores que possam alterar ou contribuir no tratamento. Métodos: Trata-se de estudo retrospectivo, transversal, realizado por meio da revisão dos prontuários dos pacientes com doença inflamatória intestinal, em um hospital sul-brasileiro, no período de junho de 2014 até julho de 2016, que foram submetidos a avaliação dos níveis séricos de Infliximabe e do anticorpo. Resultados: Foram incluídos 55 pacientes, submetidos a dosagem do Infliximabe e do anticorpo, totalizando 95 coletas sanguíneas. Destes, 55 realizaram uma primeira coleta, 30 tiveram uma segunda amostra coletada e 10 coletaram uma terceira vez. Vinte e nove pacientes eram do sexo feminino (52,7%) e vinte e seis do sexo masculino (43.2%). Quarenta e cinco (47,3%) casos tinham diagnóstico de doença de Crohn (81,8%) e 10 de colite ulcerativa (18,2%). Em relação ao nível sérico encontrou-se nível adequado em 30 coletas (31,57%), subterapêutico em 41 coletas (43,15%) e supraterapêutico em 24 coletas (25,26%). A prescrição foi otimizada em 40 (42,10%) casos, mantida em 31 (32,63%) pacientes, suspensa em 7 (7,60%) ou que o intervalo entre as infusões fosse aumentado (17,85%). Na análise geral, em 53 coletas (55,79%) a conduta foi definida em função exclusivamente da dosagem sérica do Infliximabe e/ou do anticorpo, já em relação, apenas a primeira coleta obteve-se 33 (60%) pacientes. Avaliando-se os pacientes um ano após, obteve-se: em 38 (69,09%) pacientes a conduta foi mantida com Infliximabe e, em 8 (14,54%) foi optado por troca de classe, em 2 (3,63%) foi optado por troca da medicação na mesma classe, em 3 (5,45%) pacientes a medicação foi suspensa e não foi substituída e, em 4 (7,27%), perdeu-se o seguimento. Conclusão: Não encontrou-se diferença entre os níveis de Infliximabe entre os grupos com ou sem imunossupressor, albumina sérica, velocidade de hemossedimentação, Calprotectina, Proteína C reativa, exames endoscópicos e exames de imagem. A conduta atual pode ser mantida em quase 70% dos pacientes. Concluindo, a dosagem do nível sérico e do anticorpo é ferramenta útil no acompanhamento dos pacientes em terapia de manutenção e após a indução de tratamento em pacientes com Doença Inflamatória Intestinal.

Efeitos do Treinamento Intervalado de Alta Intensidade e do Treinamento Contínuo na Capacidade de Exercício, Variabilidade da Frequência Cardíaca e em Corações Isolados em Ratos Diabéticos / Effects of High-Intensity Interval Training and Continuous Training on Exercise Capacity, Heart Rate Variability and Isolated Hearts in Diabetic Rats

Resumo Fundamento O treinamento intervalado de alta intensidade (HIIT) tem sido sugerido como alternativa ao treinamento contínuo (TC) em indivíduos com diabetes mellitus (DM) devido à sua curta duração e potencial para melhorar a adesão ao exercício. No entanto, dados sobre seu impacto sobre a variabilidade da frequência cardíaca (VFC) são escassos. Objetivos Avaliar e comparar os efeitos do HIIT e TC sobre a capacidade no exercício, VFC e corações isolados em ratos diabéticos. Métodos Animais diabéticos (estreptozotocina intravenosa, 45 mg.kg -1 ) e controles (C) realizaram 20 sessões de TC (5 dias/semana, 50 min, por quatro semanas) em esteira (70% da capacidade máxima de exercício) ou HIIT (ciclos de 1:1min a 50% e 90% da capacidade máxima de exercício). A VFC foi avaliada por eletrocardiograma contínuo, e a função cardíaca foi avaliada em corações isolados perfundidos. Para a análise dos dados, utilizamos a matriz do modelo linear generalizado de covariância multivariada ou o teste one-way ANOVA seguido pelo teste de Tukey, considerando um valor de p<0,05 como significativo. Resultados A capacidade de exercício (m/min) foi maior no grupo submetido ao HIIT [DM-HIIT: 36,5 (IIQ 30,0-41,3); C-HIIT: 41,5 (37,8-44,5), ambos n=10) em comparação ao grupo submetido ao TC [DM-TC: 29,0 (23,8-33,0); C-TC: 32,0 (29,5-37,0), ambos n=10) (p<0,001). A frequência cardíaca (bpm) foi mais baixa no grupo DM em comparação aos controles (p<0,001) tanto in vivo (DM-HIIT: 348±51, C-HIIT:441±66, DM-TC:361±70, C-TC:437±38) como nos corações isolados. Não houve diferenças na VFC entre os grupos. Os valores máximos e mínimos de dP/dt foram reduzidos no DM, com exceção da +dP/dt no grupo DM-HIIT vs. C-HIIT (diferença média: 595,5±250,3, p=0,190). Conclusão O HIIT de curto prazo promoveu melhora superior no desempenho no exercício em comparação ao TC, sem causar mudanças significativas na variabilidade da frequência cardíaca.

Abstract Background High-intensity interval training (HIIT) has been suggested as an alternative for continuous training (CT) in people with diabetes mellitus (DM) due to its short duration and potential to improve adherence to exercise. However, data on its impact on heart rate variability (HRV) are scarce. Objectives To assess and compare the effects of HIIT and CT on exercise capacity, HRV and isolated hearts in diabetic rats. Methods DM (intravenous streptozotocin, 45 mg.kg -1 ) and control (C) animals performed 20 sessions (5 days/week, 50 min, for 4 weeks) of CT on a treadmill (70% of maximal exercise capacity) or HIIT (cycles of 1:1min at 50% and 90% of maximal exercise capacity). HRV was assessed by continuous electrocardiogram, and cardiac function assessed in isolated perfused hearts. For data analysis, we used the framework of the multivariate covariance generalized linear model or one-way ANOVA followed by Tukey's test, considering p<0.05 as significant. Results Higher exercise capacity (m/min) was achieved in HIIT (DM-HIIT: 36.5 [IQR 30.0-41.3]; C-HIIT: 41.5 [37.8-44.5], both n=10) compared to CT (DM-CT: 29.0 [23.8-33.0]; C-CT: 32.0 [29.5-37.0], both n=10) (p<0.001). Heart rate (bpm) was lower in DM compared to controls (p<0.001) both in vivo (DM-HIIT:348±51, C-HIIT:441±66, DM-CT:361±70, C-CT:437±38) and in isolated hearts. There were no differences in HRV between the groups. Maximum and minimal dP/dt were reduced in DM, except +dP/dt in DM-HIIT vs. C-HIIT (mean difference: 595.5±250.3, p=0.190). Conclusion Short-term HIIT promotes greater improvement in exercise performance compared to CT, including in DM, without causing significant changes in HRV.

High-Flow Nasal Cannula Therapy in Patients With COVID-19: Predictive Response Factors.

BACKGROUND: COVID-19 pneumonia has been responsible for many ICU patients' admissions with hypoxemic respiratory failure, and oxygen therapy is one of the pillars of its treatment. The current pandemic scenario has limited the availability of ICU beds and access to invasive ventilation equipment. High-flow nasal cannula (HFNC) can reduce the need for orotracheal intubation compared with conventional oxygen therapy, providing better results than noninvasive respiratory support. However, HFNC use has been controversial due to concerns about the benefits and risks of aerosol dispersion. In this context, we evaluated the performance of the HFNC therapy in patients with COVID-19 and investigated factors that can predict favorable responses. METHODS: A prospective observational study was conducted, which included hospitalized adult subjects with COVID-19 in the respiratory wards who needed oxygen therapy. Clinical and laboratory parameters were collected to compare HFNC therapy use and the outcomes. RESULTS: In 6 months, 128 subjects were included and the success rate of HFNC therapy was 53%. Logistic regression analysis showed that the Charlson comorbidity score, need for oxygen flow, [Formula: see text], and breathing frequency predicted therapy failure. The mortality rate increased among the non-responders versus the responders (47% vs 3%), 48% of failure occurred in the first 24 h of the HFNC therapy. A ROX (respiratory frequency - oxygenation) index > 4.98 in 6 h and > 4.53 in 24 h predicted success of the HFNC therapy with an area under the curve of 0.7, and a ROX index < 3.47 predicted failure with 88% of specificity. CONCLUSIONS: HFNC in the subjects with COVID-19 was associated with reduced mortality and improved oxygenation in the subjects with respiratory distress. Close monitoring of specific parameters defines eligible patients and rapidly identifies those in need of invasive ventilatory support.

Probable awake bruxism - prevalence and associated factors: a cross-sectional study.

INTRODUCTION: Bruxism is defined as a repetitive activity of masticatory muscles, characterized by the clenching or grinding of the teeth, which can occur during wakefulness (awake bruxism) or during sleep (sleep bruxism). OBJECTIVES: The objectives of the present study were to determine the prevalence of awake bruxism and its associated factors. METHODS: Sample was composed by 50 participants of both genders, aged between 18 and 60 years, submitted to a clinical examination - to observe the presence of tooth wear, marks on the mucosa, or masseter muscles hypertrophy - and self-applied questionnaires, which evaluated the presence of TMD signs and symptoms, oral behaviors, lifestyles, anxiety level and sleep quality. RESULTS: The prevalence of awake bruxism was 48%. Its presence was statistically and significantly associated with the presence of signs and symptoms of TMD (p= 0.002), poor sleep quality (p = 0.032), buccal mucosa indentations (p < 0.001) and tongue (p = 0.011). Age, gender, social characteristics, habits (such as coffee ingestion, smoking, alcoholism and physical activity) and tooth wear were variables that had no significant association with awake bruxism. CONCLUSIONS: It was concluded that awake bruxism shows a high prevalence and a positive association with signs and symptoms of TMD and worst sleep quality. In addition, awake bruxism is more likely to occur in individuals who have buccal mucosa indentation and who present high rates of oral habits and oral behaviors.

Untreated Donor-Specific HLA Antibodies Are Associated With Graft Failure and Poor Survival After Haploidentical Transplantation With Post-Transplantation Cyclophosphamide in Pediatric Patients With Nonmalignant Disorders.

Donor-specific HLA antibodies (DSAs) have been recognized as a major risk factor for graft failure (GF) in adult patients with malignancies undergoing haploidentical transplantation with post-transplantation cyclophosphamide (haplo-PTCy). However, the impact of DSAs after pediatric haplo-PTCy for nonmalignant disorders (NMDs) has been poorly reported. We sought to investigate whether preexisting DSAs adversely affect pediatric haplo-PTCy outcomes. We retrospectively analyzed 59 pediatric patients (≤21 years) who received their first haplo-PTCy for NMDs from January 2008 to December 2017. DSA testing was performed using single antigen beads, and mean fluorescence intensity (MFI) >1000 was considered positive, and MFI <1000 and >500 was considered potentially positive, based on HLA epitope reactivity patterns. Primary endpoints were neutrophil and platelet recovery and GF, whereas secondary endpoints included event-free and overall survival. Multivariable analyses were performed using Fine-Gray competing risk regression or Cox proportional hazards regression models. The median age was 10 years, and 66.1% were male. Main indications for haplo-PTCy were Fanconi anemia (n = 33) and severe aplastic anemia (n = 11). All patients received bone marrow as the graft source, and most patients (91.5%) received fludarabine-based conditioning. Overall, 15 patients (25.4%) had DSAs >500 MFI. Four patients had false-positive DSAs with median MFI of 1762. Of the 11 patients with true-positive DSA reactivity, 5 had 1 DSA, 5 had 2 DSAs, and 1 had 3 DSAs, with median MFI of 2372 (range 527-24,200). Four patients received desensitization therapy with rituximab and plasmapheresis, whereas 7 patients were untreated. All patients with treated DSAs achieved donor engraftment. In the multivariable analyses, untreated DSAs were associated with lower neutrophil recovery (subdistribution hazard ratio [SHR] = 0.15; 95% confidence interval [CI], 0.03-0.63; P = .001), increased GF (SHR = 20.57; 95% CI, 6.57-64.43; P < .001), inferior event-free survival (hazard ratio [HR] = 10.09; 95% CI, 3.37-30.22; P < .001), and poor overall survival (HR 5.56; 95% CI, 1.92-16.12; P = .002). Both treated DSAs (SHR = 0.26; 95% CI, 0.10-0.68; P = .006) and untreated DSAs (SHR = 0.13; 95% CI, 0.04-0.37; P < .001) adversely affected platelet recovery. Our results indicate that the presence of DSAs is an independent predictor of poor outcomes after pediatric haplo-PTCy for NMDs. Therefore DSA-positive donors should be avoided whenever possible, and when a DSA-negative donor is unavailable, desensitization therapy must be performed to enhance the likelihood of donor engraftment and improve transplantation outcomes.

Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial.

BACKGROUND: COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is one of the few reports that presents the longest follow-up after MSC treatment in COVID-19 patients. METHODS: This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation-critically ill patients-were included. The patient infusion was three doses of 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. RESULTS: The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in extension of lung damage was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. CONCLUSIONS: UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration Brazilian Registry of Clinical Trials (ReBEC), UTN code-U1111-1254-9819. Registered 31 October 2020-Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr.

The association of breastfeeding and other factors on respiratory virus positivity and severity in hospitalized children.

Acute respiratory infections (ARIs) are the most prevalent diseases in children under 5 years old, and viruses are the leading cause. ARIs arise due to numerous factors, including age, contact with siblings or other children in daycare centers, and environmental pollution. Breastfeeding reportedly confers protection against ARIs through bioactive components related to mucous epithelial immunity. This study aimed to evaluate the frequency and severity of viral ARIs in hospitalized children, together with the status and duration of exclusive breastfeeding (EBF) and other associated factors. It comprised an epidemiological surveillance study to investigate respiratory viruses in hospitalized children, in which demographic and clinical data were collected. Overall, 279 patients were included, 190 (68%) had positive viral results, and 132 (47%) were exclusively breastfed. In an adjusted analysis, it was observed that older children, the parents' educational level, and the presence of chronic disease were significantly related to EBF for more than 6 months. No significant differences were observed in viral positivity and disease severity concerning EBF. Whereas the EBF status was associated with a positive rate of virus detection, the significance did not remain after adjustment, and it was not considered a protective factor against ARIs. On the other hand, young age and exposure to tobacco were confirmed as risk factors of frequency and severity, respectively. Such confounding factors can impact the analysis and should be considered in future studies.

Probable awake bruxism - prevalence and associated factors: a cross-sectional study

ABSTRACT Introduction: Bruxism is defined as a repetitive activity of masticatory muscles, characterized by the clenching or grinding of the teeth, which can occur during wakefulness (awake bruxism) or during sleep (sleep bruxism). Objectives: The objectives of the present study were to determine the prevalence of awake bruxism and its associated factors. Methods: Sample was composed by 50 participants of both genders, aged between 18 and 60 years, submitted to a clinical examination - to observe the presence of tooth wear, marks on the mucosa, or masseter muscles hypertrophy - and self-applied questionnaires, which evaluated the presence of TMD signs and symptoms, oral behaviors, lifestyles, anxiety level and sleep quality. Results: The prevalence of awake bruxism was 48%. Its presence was statistically and significantly associated with the presence of signs and symptoms of TMD (p=0.002), poor sleep quality (p=0.032), buccal mucosa indentations (p<0.001) and tongue (p=0.011). Age, gender, social characteristics, habits (such as coffee ingestion, smoking, alcoholism and physical activity) and tooth wear were variables that had no significant association with awake bruxism. Conclusions: It was concluded that awake bruxism shows a high prevalence and a positive association with signs and symptoms of TMD and worst sleep quality. In addition, awake bruxism is more likely to occur in individuals who have buccal mucosa indentation and who present high rates of oral habits and oral behaviors.

RESUMO Introdução: O bruxismo é definido como a atividade repetitiva dos músculos mastigatórios, e pode ocorrer durante o período acordado (bruxismo em vigília) ou durante o sono (bruxismo do sono). Objetivo: O presente estudo teve como objetivo avaliar a prevalência de bruxismo em vigília e seus fatores associados. Métodos: A amostra foi composta por 50 participantes, de ambos os sexos, com idades de 18 a 60 anos, avaliados por meio de minucioso exame clínico - para observar se havia presença de sinais como desgaste dentário, indentações na mucosa, hipertrofia do músculo masseter - e de questionários autoaplicáveis que visaram avaliar a presença de sinais e sintomas de disfunção temporomandibular (DTM), os comportamentos orais e hábitos de vida, o nível de ansiedade e a qualidade de sono dos participantes. Resultados: A prevalência de bruxismo em vigília foi de 48%. Sua presença foi associada, estatística e significativamente, com a presença de sinais e sintomas de DTM (p=0,002), má qualidade do sono (p=0,032), e indentações na mucosa jugal (p<0,001) e língua (p=0,011). Por outro lado, a idade, sexo, características sociais, hábitos (como ingestão de café, fumo, álcool e prática de atividade física), e o desgaste dentário foram variáveis que não tiveram associação com o bruxismo em vigília. Conclusão: Diante disso, conclui-se que o bruxismo em vigília possui uma prevalência significativa e uma associação positiva com DTM e qualidade do sono. Além disso, o bruxismo em vigília apresenta maior probabilidade de acontecer em indivíduos com indentação de mucosa jugal e com alta prevalência de hábitos e comportamentos orais.

Osteosarcopenia and trabecular bone score in patients with type 2 diabetes mellitus

ABSTRACT Objective: To evaluate the prevalence of osteosarcopenia and the association of osteosarcopenia with trabecular bone score (TBS) in a group of patients with type 2 diabetes mellitus(T2DMG) compared with a paired control group (CG). Materials and methods: Cross-sectional study with men and women ≥ 50 years recruited by convenience. Patients in both groups answered questionnaires and underwent evaluation of bone mineral density (BMD), handgrip strength (HGS), and TBS. The T2DMG also underwent a gait speed (GS) test. Sarcopenia was defined as low lean mass plus low HGS or GS according to the Foundation for the National Institute of Health Sarcopenia Project, and osteosarcopenia was deemed present when sarcopenia was associated with osteopenia, osteoporosis, or low-energy trauma fractures. Results: The T2DMG (n = 177) and CG (n = 146) had, respectively, mean ages of 65.1 ± 8.2 years and 68.8 ± 11.0 years and 114 (64.4%) and 80 (54.7%) women. T2DMG versus the CG had higher rates of osteosarcopenia (11.9% versus 2.14%, respectively, p = 0.010), sarcopenia (12.9% versus 5.4%, respectively, p < 0.030), and fractures (29.9% versus 18.5%, respectively, p = 0.019), and lower HGS values (24.4 ± 10.3 kg versus 30.9 ± 9.15 kg, respectively, p < 0.001), but comparable BMD values. Mean TBS values were 1.272 ± 0.11 and 1.320 ± 0.12, respectively (p = 0.001). On multivariate analysis, age, greater waist circumference, fractures, and osteoporosis increased the risk of degraded TBS. Osteosarcopenia was associated with diabetes complications (p = 0.03), calcium and vitamin D supplementation (p = 0.01), and all components of osteosarcopenia diagnosis (p < 0.05). Conclusion: Compared with the CG, the T2DMG had a higher prevalence of osteosarcopenia, sarcopenia, and fractures and lower bone quality assessed by TBS.

Multivariate generalized linear mixed models for continuous bounded outcomes: Analyzing the body fat percentage data.

We propose a multivariate regression model to handle multiple continuous bounded outcomes. We adopted the maximum likelihood approach for parameter estimation and inference. The model is specified by the product of univariate probability distributions and the correlation between the response variables is obtained through the correlation matrix of the random intercepts. For modeling continuous bounded variables on the interval (0,1) we considered the beta and unit gamma distributions. The main advantage of the proposed model is that we can easily combine different marginal distributions for the response variable vector. The computational implementation is performed using Template Model Builder, which combines the Laplace approximation with automatic differentiation. Therefore, the proposed approach allows us to estimate the model parameters quickly and efficiently. We conducted a simulation study to evaluate the computational implementation and the properties of the maximum likelihood estimators under different scenarios. Moreover, we investigate the impact of distribution misspecification in the proposed model. Our model was motivated by a data set with multiple continuous bounded outcomes, which refer to the body fat percentage measured at five regions of the body. Simulation studies and data analysis showed that the proposed model provides a general and rich framework to deal with multiple continuous bounded outcomes.

Osteosarcopenia and trabecular bone score in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the prevalence of osteosarcopenia and the association of osteosarcopenia with trabecular bone score (TBS) in a group of patients with type 2 diabetes mellitus(T2DMG) compared with a paired control group (CG). METHODS: Cross-sectional study with men and women ≥ 50 years recruited by convenience. Patients in both groups answered questionnaires and underwent evaluation of bone mineral density (BMD), handgrip strength (HGS), and TBS. The T2DMG also underwent a gait speed (GS) test. Sarcopenia was defined as low lean mass plus low HGS or GS according to the Foundation for the National Institute of Health Sarcopenia Project, and osteosarcopenia was deemed present when sarcopenia was associated with osteopenia, osteoporosis, or low-energy trauma fractures. RESULTS: The T2DMG (n = 177) and CG (n = 146) had, respectively, mean ages of 65.1 ± 8.2 years and 68.8 ± 11.0 years and 114 (64.4%) and 80 (54.7%) women. T2DMG versus the CG had higher rates of osteosarcopenia (11.9% versus 2.14%, respectively, p = 0.010), sarcopenia (12.9% versus 5.4%, respectively, p < 0.030), and fractures (29.9% versus 18.5%, respectively, p = 0.019), and lower HGS values (24.4 ± 10.3 kg versus 30.9 ± 9.15 kg, respectively, p < 0.001), but comparable BMD values. Mean TBS values were 1.272 ± 0.11 and 1.320 ± 0.12, respectively (p = 0.001). On multivariate analysis, age, greater waist circumference, fractures, and osteoporosis increased the risk of degraded TBS. Osteosarcopenia was associated with diabetes complications (p = 0.03), calcium and vitamin D supplementation (p = 0.01), and all components of osteosarcopenia diagnosis (p < 0.05). CONCLUSION: Compared with the CG, the T2DMG had a higher prevalence of osteosarcopenia, sarcopenia, and fractures and lower bone quality assessed by TBS.

Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin.

INTRODUCTION: Direct-acting oral anticoagulants (DOACs) are therapeutic alternatives to warfarin that act independently of vitamin K, thus not affecting bone matrix formation. The aim of this study was to compare bone mineral density (BMD) and microarchitecture in patients treated with DOACs versus warfarin. METHODS: Cross-sectional, observational study in patients using oral anticoagulants for >1 year and a paired control group (CG). Based on the type of anticoagulant used, the patients were grouped into a DOAC (DOACG) or warfarin (WG) group. All patients filled out a questionnaire and underwent BMD evaluation and trabecular bone score (TBS) measurement. RESULTS: In all, 150 patients were included (50 patients in each group). The mean age was 60.49 ± 7.48 years, and most participants were men (64%). The most frequent comorbidities were hypertension, dyslipidemia, and hyperglycemia (comparison between groups p > 0.05). Low bone mass was diagnosed in 42%, 50%, and 66% of the patients in the CG, DOACG, and WG, respectively (p = 0.012). On logistic regression analysis, BMD was associated with body mass index (BMI; odds ratio [OR] 0.846, 95% confidence interval [CI] 0.763-0.926, p = 0.001), creatinine level (OR 0.024, 95%CI 0.001-0.434, p = 0.017), and TBS value (OR 17.777, 95%CI 4.526-96.903, p = 0.000). The mean TBS decreased progressively from the CG to the DOACG and WG (1.328 ± 0.112, 1.264 ± 0.138, and 1.203 ± 0.112, respectively, p < 0.001). On multivariate linear regression, negative predictors of TBS included warfarin use (-0.06, 95%CI -0.11 to -0.02, p = 0.006), BMI (-0.01, 95%CI -0.01 to -0.00, p < 0.001), and hyperglycemia (-0.07, 95%CI -0.11 to -0.03, p = 0.003), while positive predictors were an active IPAQ classification (0.06, 95%CI 0.01-0.11, p = 0.029) and family history of hip fracture (0.07, 95%CI 0.01-0.14, p = 0.029). CONCLUSION: Patients using anticoagulants have lower BMD and TBS values compared with controls. This negative effect on bone was more pronounced with warfarin, but was also seen with DOACs.

The impact of donor-specific anti-human leukocyte antigen antibodies in salvage haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide in patients with nonmalignant disorders.

The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a major risk factor for graft failure (GF) after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (haplo-PTCy). However, the role of DSAs in salvage haplo-PTCy for rescuing patients with nonmalignant disorders (NMDs) has not yet been reported. The present study retrospectively analyzed 22 patients with NMDs who underwent salvage haplo-PTCy from January 2008 to December 2017. The median age at the time of the rescue haplo-PTCy was 9 years (range, 1-26 years). Median time from the first transplant to second haplo-PTCy was 56 days (range, 37-591 days). Among all patients, six (27.3%) had DSAs, with a median DSA strength (mean fluorescence intensity [MFI]) of 5201 (range, 1412-11,543) in the first DSA testing. In addition, the median DSA MFI was 2672 (range, 832-10,498) before the bone marrow infusion. Overall, GF occurred in 5 (25%) of the 20 assessable patients. Three of four (75%) patients with DSAs experienced GF versus 2 of 16 (12.5%) DSA-negative patients (P = 0.032). The median DSA MFI for patients with GF was 6437 (range, 1412-10,498) versus 1845 (range, 832-2672) for those who engrafted or had early death (P = 0.030). One-year event-free survival was significantly lower in DSA-positive patients than in those without DSAs (16.7% vs. 62.5%, P = 0.002). DSA-negative patients had an acceptable 1-year survival of 62.5%. In conclusion, this study suggests that DSAs may be associated with deleterious outcomes after salvage haplo-PTCy in patients with NMDs.

Association between fractures and traditional risk factors for osteoporosis and low bone mineral density in patients with obesity.

OBJECTIVE: To evaluate the reasons for request of bone mineral density (BMD) evaluation and correlate the BMD results with previous fractures, risk factors for osteoporosis, and clinical characteristics in patients with obesity. METHODS: Cross-sectional, retrospective, single-site study including adult patients with body mass index (BMI) ≥ 30 kg/m2 and BMD evaluation between January 2015 and May 2016 selected from a BMD database. Data on demographic characteristics, lifestyle habits, comorbidities, medications, risk factors, previous fractures, and indications for BMD evaluation were collected from the participants' medical records. RESULTS: The study included 619 patients (89.9% women, mean BMI 34.79 ± 4.05 kg/m2). In all, 382 (61.7%), 166 (26.8%), and 71 (11.5%) patients had class 1, 2, and 3 obesity, respectively. The most frequent (29.9%) reason for BMD evaluation was for osteoporosis monitoring. In all, 69.4% of the patients had low BMD. Multivariate analysis showed that age, calcium supplementation, and previous osteoporosis or osteopenia were associated with low BMD, while age, vitamin D supplementation, use of proton pump inhibitors (PPIs), and low BMD were associated with previous fractures (p < 0.05 for all). CONCLUSION: Among patients with obesity identified from a tertiary hospital database, those with low bone mass and risk factors traditionally associated with fractures had an increased history of fractures. Patients with greater BMI had better bone mass and fewer fractures. These findings indicate that the association between reduced weight, risk factors for osteoporosis, and fractures remained despite the presence of obesity in our population.