Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation.

Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; P = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; P = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; P = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reduced-intensity conditioning (HR, 1.69: P = .04) and in patients with acute GVHD (HR, 1.88; P = .02), and lower in those who received higher doses of CD34 cells (HR, .55; P = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease.

INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

Importance: There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective: To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants: This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions: Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures: Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results: Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance: The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04323527.

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease

Abstract INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

Haploidentical Transplantation with Post-Transplant Cyclophosphamide versus Unrelated Donor Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

Hematopoietic stem cell transplantation (HSCT) is the standard treatment for patients with high-risk hematologic malignancies. Only approximately 25% of siblings are HLA-matched, and thus alternative donors-unrelated or haploidentical-are usually the only options available. This meta-analysis aimed to compare haploidentical HSCT with post-transplantation cyclophosphamide and unrelated donor (URD) HSCT. We searched the PubMed and Cochrane databases for pertinent studies indexed between 2008 and 2018. Twenty observational studies (with a total of 1783 haploidentical HSCT recipients and 6077 URD HSCT recipients) were included. Results for overall survival, graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and relapse incidence were pooled. Measures of association used were hazard ratios and risk differences. The median age was 51 years for haploidentical transplant recipients and 52 years for URD transplant recipients. Peripheral blood stem cell (PBSC) grafts were more frequent in the URD transplant recipients (85%) than in the haploidentical transplant recipients (31%). Overall survival was not different between the 2 groups. NRM was lower for haploidentical transplantation. All forms of GVHD (acute grades II-IV and III-IV and moderate, severe, and extensive chronic) were lower with haploidentical donor HSCT. The risk of chronic GVHD was fairly proportional to the differential use of PBSC grafts across studies, however. All included studies were retrospective, representing the major limitation of this meta-analysis. In conclusion, haploidentical HSCT for hematologic malignancies achieved the same overall survival as URD HSCT, with a lower incidence of GVHD and NRM. The increased frequency of PBSC use in the unrelated donor group could partially explain the higher cGVHD rate. Haploidentical transplantation with post-transplantation cyclophosphamide should strongly be considered as the first option for adult patients with hematologic malignancies who do not have matched sibling donors in experienced centers. This systematic review has been registered at PROSPERO (65790).

The impact of pilates exercises on the postural alignment of healthy adults / Efeito dos exercícios do método pilates no alinhamento postural de adultos saudáveis / Efecto de los ejercicios del método pilates en la alineación postural de adultos sanos

ABSTRACT Introduction: Exercises of Pilates method have been widely used to improve postural alignment. There is strong evidence favoring their use in improving flexibility and balance, as well as some evidence of improvement in muscle strength. However, the benefits related to posture are not well established. Objective: To investigate in healthy adults, the impact of the Pilates method in the postural alignment through some angles in the sagittal plane and the occurrence of pain before and after an exercise session, and after the completion of a 16-session program. Methods: This is a quasi-experimental study of pre and post-intervention type. Healthy adults (n = 37) interested in starting Pilates were evaluated for acute effects on posture after a Pilates session (n = 37) and after a 16-session program, for a period of 10 weeks (n = 13). Using the postural assessment software (SAPO), six angles were analyzed: head horizontal alignment (HHA), pelvis horizontal alignment (PHA), hip angle (HA), vertical alignment of the body (VAB), thoracic kyphosis (TK), and lumbar lordosis (LL). The occurrence of pain was investigated to control adverse effects. Results: Statistically significant (p<0.05) differences found after one session include increased HHA (left view), decreased VAB (left view) and TK (both side views). After 16 sessions, we observed an increase of HHA, and a decrease of TK, LL (both side views) and HA (right view). All the differences point to an improvement of postural alignment. A significant reduction of prevalence of pain was verified after the first session (40.5% vs. 13.5%; p=0.004) and after the full program (30.8% vs. 15.3%; p=0.02). Conclusions: Our results suggest that the Pilates method has a positive impact on postural alignment in healthy adults, besides being a safe exercise.

RESUMO Introdução: Os exercícios do método Pilates têm sido amplamente utilizados com a finalidade de melhorar o alinhamento postural. Existem evidências científicas fortes que favorecem seu uso na melhora da flexibilidade e do equilíbrio, bem como alguma evidência de melhora da força muscular. Entretanto, os benefícios relacionados à postura não estão bem estabelecidos. Objetivo: Investigar, em adultos saudáveis, o impacto do método Pilates no alinhamento postural, por meio de alguns ângulos no plano sagital e da ocorrência de dor antes e após uma sessão de exercícios, e também após o término de um programa de 16 sessões. Métodos: Este é um estudo quase-experimental do tipo pré e pós-intervenção. Adultos saudáveis (n = 37) interessados em iniciar Pilates foram avaliados quanto aos efeitos agudos sobre a postura após uma sessão de Pilates (n = 37) e após um programa de 16 sessões, por um período de 10 semanas (n = 13). Usando o software para análise postural (SAPO), seis ângulos foram analisados: alinhamento horizontal da cabeça (AHC); alinhamento horizontal da pelve (AHP), ângulo do quadril (AQ), alinhamento vertical do corpo (AVC), cifose torácica (CT) e lordose lombar (LL). A ocorrência de dor foi investigada para controlar efeitos adversos. Resultados: Diferenças estatisticamente significativas (p < 0,05) encontradas após uma sessão incluem aumento do AHC (perfil esquerdo), redução do AVC (perfil esquerdo) e da CT (ambos os perfis). Depois de 16 sessões, foi observado aumento do AHC e redução da CT, LL (ambos os perfis) e AQ (perfil direito). Todas as diferenças encontradas apontam para a melhora do alinhamento postural. Uma redução significativa de prevalência de dor foi verificada após a primeira sessão (40,5% vs. 13,5%; p = 0,004) e após o programa completo (30,8% vs. 15,3%; p = 0,02). Conclusões: Nossos resultados sugerem que o método Pilates tem impacto positivo sobre o alinhamento postural de adultos saudáveis, além de ser um exercício físico seguro.

RESUMEN Introducción: Los ejercicios del método Pilates se han utilizado ampliamente con el fin de mejorar la alineación postural. Hay una fuerte evidencia científica que favorece su uso para la mejora de la flexibilidad y el equilibrio, así como algunos indicios de mejora de la fuerza muscular. Sin embargo, los beneficios relacionados con la postura no están tan bien establecidos. Objetivo: Investigar en adultos sanos, el impacto del método de Pilates en la alineación postural a través de algunos ángulos en el plan sagital y en la aparición de dolor antes y después de una sesión de ejercicios, y también después de un programa de 16 sesiones. Métodos: Se trata de un estudio cuasi-experimental del tipo antes y después de la intervención. Se evaluaron adultos sanos (n = 37) interesados en iniciar Pilates para efectos agudos sobre la postura después de una sesión de Pilates (n = 37) y después de un programa de 16 sesiones durante 10 semanas (n = 13). Usando el software para el análisis postural (SAPO), se analizaron seis ángulos: alineación horizontal de la cabeza (AHC); alineación horizontal de la pelvis (AHP), el ángulo de cadera (AC), la alineación vertical del cuerpo (AVC), cifosis torácica (CT) y la lordosis lumbar (LL). La aparición de dolor se investigó para controlar los efectos adversos. Resultados: Las diferencias estadísticamente significativas (p < 0,05) encontradas después de una sesión incluyen aumento de AHC (perfil izquierdo), reducción de la AVC (perfil izquierdo) y aumento de la CT (ambos perfiles). Después de 16 sesiones, se observó un aumento de la AHC y reducción de la CT, LL (ambos perfiles) y AC (perfil derecho). Todas las diferencias apuntan a la mejora de la alineación postural. Se observó una reducción significativa en la prevalencia del dolor después de la primera sesión (40,5% vs. 13,5% p = 0,004) y después del programa completo (30,8% vs. 15,3%, p = 0,02). Conclusiones: Nuestros resultados sugieren que el método Pilates tiene un impacto positivo sobre la alineación postural en adultos sanos, además de ser un ejercicio seguro.

Proteomic profiling of skeletal muscle in an animal model of overtraining.

Excessive training (i.e. overtraining, OT) may result in underperformance, which can be characterized by the time needed to re-establish performance (i.e. functional overreaching (FOR), nonfunctional overreaching, OT syndrome). The present study is an initial screening for proteins presenting altered abundance in the red (RG) and white (WG) portions of the gastrocnemius muscle from rats submitted to an OT protocol that induced FOR. In the RG, compared to the nontrained control, FOR demonstrated an increased abundance of proteins normally related to adaptation to endurance training (e.g. proteins of oxidative phosphorylation complexes, proteins related to lipid metabolism, antioxidants, and chaperones). In the WG, spots identified as mitochondrial aconitase and a component of the succinate dehydrogenase complex were downregulated in FOR, as were proteins related to myofibril stabilization; these latter were upregulated in the RG. This initial study shows that skeletal muscles with different fiber-type compositions respond differently to an OT period. Also, it is likely that actin-interacting proteins have an important role in muscle adaptation to endurance exercise.

Evolução da população e da mortalidade em Niterói, Rio de Janeiro, Brasil, 1979 a 1997 / Demographic and mortality trends in Niterói, Rio de Janeiro, Brazil, 1979 to 1997

A análise da série histórica de 1979-1997 permite perceber a evolução demográfica e da mortalidade no Município de Niterói, Rio de Janeiro, Brasil, ao longo dessas décadas. A população apresentou um declínio na velocidade de crescimento, com alteração significativa de sua estrutura etária. Observa-se, na série temporal, o declínio da mortalidade por doenças do aparelho circulatório, a tendência geral de declínio das doenças infecto-parasitárias, com acentuado aumento a partir de 1996, decorrente da mudança de classificação das doenças (CID-9 para CID-10). Quanto à mortalidade infantil, destaca-se o predomínio dos óbitos na faixa neonatal. O desvendar das doenças e agravos dentro dos grandes grupos revela a importância das doenças isquêmicas do coração e doenças cerebrovasculares, dos homicídios, acidentes de transporte e da AIDS.

[Demographic and mortality trends in Niterói, Rio de Janeiro, Brazil, 1979 to 1997]. / Evolução da população e da mortalidade em Niterói, Rio de Janeiro, Brasil, 1979 a 1997.

An analysis of the 1979-1997 historical series points to demographic and mortality trends in Niterói, Rio de Janeiro State, over the course of those two decades. There was a drop in the rate of population increase, with a significant change in the age structure. In the time series, there was a decline in mortality from cardiovascular diseases and an overall downward trend in mortality from infectious and parasitic diseases, albeit with a sharp increase beginning in 1996 resulting in a change in disease classification (ICD-9 to ICD-10). As for infant mortality, there was a predominance of deaths in the neonatal group. An analysis of major groups of diseases and injuries highlights the importance of ischemic heart disease and cerebrovascular diseases, homicides, traffic accidents, and AIDS.

A implantação da estratégia DOTS na cidade do Rio de Janeiro / Implementation of the DOTS strategy in the city of Rio de Janeiro

Introdução: o objetivo deste estudo foi descrever a implementação da estratégia DOTS (Estratégia de Tratamento Diretamente Observado de Curta duração) nos centros de saúde na cidade do Rio de Janeiro, apresentando os resultados obtidos após dois anos de desenvolvimento de projetos-piloto. Métodos: análise dos dados contidos nos "Livros de Registro e Controle do Tratamento", regularmente notificados à Secretaria Municipal de Saúde do Rio de Janeiro, visando avaliar o impacto do tratamento diretamente observado (DOT) nos índices de cura e o efeito da implementação da estratégia DOTS na qualidade do programa de controle da tuberculose (PCT). Resultados: De Janeiro de 1999 a Dezembro de 2001, 3657 casos de TB foram registrados nas áreas onde a estratégia DOTS foi implantada. Destes, 1730 receberam DOT e 1927 receberam tratamento auto-administrado (TAA). Entre os caos novos, 81% dos que receberam DOT e 71% dos que receberam TAA foram tratados com sucesso (OR 1,66, IC 95%: 1,3 -1,8), p<0,01. As taxas de negativação da baciloscopia do escarro após 2 e 3 meses de tratamento foram de 84% e 91% respectivamente para aqueles que receberam DOT e 75% e 83% para o grupo em TAA. Nos centros de saúde onde a estratégia DOTS foi implantada houve, em 3 anos, melhora geral dos índices de cura e de abandono, assim como dos percentuais de baciloscopias realizadas para acompanhamento do tratamento. Conclusão: Pacientes que receberam DOTS tiveram maior chance de cura do que aqueles que receberam TAA. A implantação da estratégia DOTS melhorou a qualidade do PCT.

Introduction: The objective of this study is to describe the implementation of DOTS (Directly Observed Treatment, Short course) strategy in health centers in the city of the Rio de Janeiro presenting the results 2 years after teh development of pilot projects. Methods: analysis of data recorded on the "TB treatment and outcome registration books", regularly reported to the City Health Secretariat, to evaluate the results of the directly observed therapy (DOT) on the treatment success rates and the effect of DOTS implementation on the equality of the TB control program. Results: From January 1999 to December 2001, 3,657 TB cases were registered in the areas where the DOTS strategy was implemented. Of these, 1,730 received directly observed treatment (DOT) and 1,927 received self-administered treatment (SAT). In the DOT group 81% of the new cases were treated successfully, whereas in the SAT 71% of the new cases were treated successfully (OR1,66, 95% CI:1,3 -1,8, p <0,01). The sputum smear conversion rates for the new cases after 2 and 3 months' treatment were respectively 84% and 91% for the group on DOT and 75% and 83% for those on SAT. In the health centers where the DOTS strategy was implemented there was a general improvement on the cure and default rates, and also on the proportion of patients monitored bacteriologically during treatment. Conclusion: patients receiving DOT were much more likely to complete treatment than those receiving SAT. The implementation of the DOTS strategy improved the quality of the TB control program.