Bacillus pumilus cellulitis with bacteremia in a person who injects drugs, living with HIV-HCV co-infection: a case report.

Bacillus pumilus (B. pumilus) is a ubiquitous spore-forming bacteria that has rarely been implicated in extraintestinal infections, mostly in immunocompromised hosts. The authors report a case of B. pumilus cellulitis with bacteremia in a person who injects drugs living with human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infection. Although similar cases have been reported for some species of the genus, namely Bacillus anthracis (B. anthracis) and Bacillus cereus (B. cereus), this case reinforces the importance of considering other Bacillus spp. as potential pathogens in skin and soft tissue infections and bloodstream infections related to intravenous drug use.

Viral immunogenic footprints conferring T cell cross-protection to SARS-CoV-2 and its variants.

COVID-19 brought scenes from sci-fi movies into real life. Infected individuals include asymptomatic cases to severe disease leading to death, suggesting the involvement of the genetic constitution of populations and pathogens contributing to differential individuals' outcomes. To investigate shared immunogenic features between SARS-CoV-2 targets and other coronaviruses, we modeled their peptides in 3D structures of HLA-A*02:01 (pMHC), comparing their molecular surfaces These structures were also compared with a panel of epitopes from unrelated viruses, looking for potential triggers conferring cross-protection in uninfected individuals. As expected, SARS-CoV 1 and 2 peptides share molecular and physicochemical features, providing an explanation for the verified experimental immunogenicity among them. Surprisingly, even discordant sequences from human coronaviruses 229E, OC43 and epitopes from unrelated viruses involved in endemic human infections exhibit similar fingerprints of immunogenicity with SARS-CoV-2 peptides. The same approach indicates a conserved CD8+ T cell recognition between Wuhan SARS-CoV-2 sequences and altered peptides from Variants of Concern. Examination of structural data over epitope sequence analysis here could explain how previous infections may produce a heterologous immunity response in a global scale against emergent diseases such as Covid-19, mitigating its full lethal potential, and paves the way for the development of wide spectrum vaccine development.

Unveiling the influence of factor VIII physicochemical properties on hemophilia A phenotype through an in silico methodology.

BACKGROUND AND OBJECTIVES: Hemophilia A (HA) is an X-linked blood disorder. It is caused by pathogenic F8 gene variants, among which missense mutations are the most prevalent. The resulting amino acid substitutions may have different impacts on physicochemical properties and, consequently, on protein functionality. Regular prediction tools do not include structural elements and their physiological significance, which hampers our ability to functionally link variants to disease phenotype, opening an ample field for investigation. The present study aims to elucidate how physicochemical changes generated by substitutions in different protein domains relate to HA, and which of these features are more consequential to protein function and its impact on HA phenotype. METHODS: An in silico evaluation of 71 F8 variants found in patients with different HA phenotypes (mild, moderate, severe) was performed to understand protein modifications and functional impact. Homology modeling was used for the structural analysis of physicochemical changes including electrostatic potential, hydrophobicity, solvent-accessible/excluded surface areas, disulfide disruptions, and substitutions indexes. These variants and properties were analyzed by hierarchical clustering analysis (HCA) and principal component analysis (PCA), independently and in combination, to investigate their relative contribution. RESULTS: About 69% of variants show electrostatic changes, and almost all show hydrophobicity and surface area modifications. HCA combining all physicochemical properties analyzed was better in reflecting the impact of different variants in disease severity, more so than the single feature analysis. On the other hand, PCA led to the identification of prominent properties involved in the clustering results for variants of different domains. CONCLUSIONS: The methodology developed here enables the assessment of structural features not available in other prediction tools (e.g., surface distribution of electrostatic potential), evaluating what kind of physicochemical changes are involved in FVIII functional disruption. HCA results allow distinguishing substitutions according to their properties, and yielded clusters which were more homogeneous in phenotype. All evaluated properties are involved in determining disease severity. The nature, as well as the position of the variants in the protein, were shown to be relevant for physicochemical changes, demonstrating that all these aspects must be collectively considered to fine-tune an approach to predict HA severity.

Y380Q novel mutation in receptor-binding domain of SARS-CoV-2 spike protein together with C379W interfere in the neutralizing antibodies interaction.

We aimed to describe the SARS-CoV-2 lineages circulating early pandemic among samples with S gene dropout and characterize the receptor-binding domain (RBD) of viral spike protein. Adults and children older than 2 months with signs and symptoms of COVID-19 were prospectively enrolled from May to October in Porto Alegre, Brazil. All participants performed RT-PCR assay, and samples with S gene dropout and cycle threshold < 30 were submitted to high-throughput sequencing (HTS). 484 out of 1,557 participants tested positive for SARS-CoV-2. The S gene dropout was detected in 7.4% (36/484) and a peak was observed in August. The B.1.1.28, B.1.91 and B.1.1.33 lineages were circulating in early pandemic. The RBD novel mutation (Y380Q) was found in one sample occurring simultaneously with C379W and V395A, and the B.1.91 lineage in the spike protein. The Y380Q and C379W may interfere with the binding of neutralizing antibodies (CR3022, EY6A, H014, S304).

Variants p.Pro2063Ser and p.Arg324* co-segregate in type 3 von Willebrand disease patients from Southern Brazil.

INTRODUCTION: von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the disease, leads to complete quantitative VWF deficiency. AIM: The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil. METHODS: The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next-generation sequencing using Ion Torrent PGM. RESULTS: In 25 patients, we were able to identify both disease-causing variants. We identified 72 different variants: 31 intronic and 41 exonic. Five novel variants were found: c.6976+5G>T; c.6885_6886insC; c.3378C>T (p.Cys1126); c.3346_3347insCCA; and c.2503G>T (p.Glu835*). Variants p.Pro2063Ser and p.Arg324* co-segregated in 17 patients, 15 of them in homozygosity. CONCLUSION: Our results may contribute to the discussion on whether the variant p.Pro2063Ser is pathogenic or not. Finally, the presence of a common haplotype in patients bearing these two variants suggests a founder effect for this variant in our region.

Acute Heart Failure Comorbidome: The Impact of Everything Else.

INTRODUCTION: Heart failure frequently coexists with several comorbidities. Our aim is to evaluate the prognostic role of various comorbidities in the risk of acute heart failure development. MATERIAL AND METHODS: Comorbidities of patients with acute heart failure were, retrospectively, compared to a control group of patients with chronic heart failure admitted to an Internal Medicine unit in a 2-year period. Logistic regression models were constructed to determine their association with acute heart failure and to develop a comorbidome. RESULTS: We identified 229 patients with acute heart failure and 201 patients with chronic heart failure. Age and female gender were higher in acute heart failure group (p < 0.001) as was the number of comorbidities (4.0 ± 3.0 vs 4.0 ± 2.0, p = 0.044). Hyperuricemia (odds ratio 2.46, confidence interval 95% 1.41 - 4.31, p = 0.002), obesity (odds ratio 2.22, confidence interval 95% 1.31 - 3.76, p = 0.003), atrial fibrillation (odds ratio 1.93, confidence interval 95% 1.31 - 2.87, p = 0.001), peripheral artery disease (odds ratio 2.12, confidence interval 95% 1.01 - 4.42, p = 0.046) and chronic kidney disease (odds ratio 2.47, confidence interval 95% 1.65 - 3.71, p < 0.001) were associated with acute heart failure. Obesity, atrial fibrillation, peripheral artery disease and chronic kidney disease were identified as independent risk factors. Patients with multiple comorbidities had a superior risk of hospitalization due to heart failure: zero comorbidities - odds ratio 0.43, 95% confidence interval 0.28 - 0.67, p < 0.001; one comorbidity - odds ratio 0.69, 95% confidence interval 0.47 - 1.01, p = 0.057; two comorbidities - odds ratio 1.85, 95% confidence interval 1.11 - 3.08, p = 0.019; ≥ three comorbidities - odds ratio 5.81, 95% confidence interval 2.77 - 12.16, p < 0.001. DISCUSSION: This study shows an association between several comorbidities and hospital admission due to acute heart failure. The association seems to strengthen in the presence of multiple comorbidities. CONCLUSION: A comorbidome is a useful tool to identify comorbidities associated with higher risk of acute heart failure. The identification of vulnerable patients may allow multidimensional interventions to minimize future hospital admissions.

Introdução: A insuficiência cardíaca frequentemente coexiste com diversas comorbilidades. O nosso objetivo é avaliar o valor prognóstico de diferentes comorbilidades no risco de desenvolvimento de insuficiência cardíaca aguda. Material e Métodos: As comorbilidades dos doentes com insuficiência cardíaca aguda foram, retrospetivamente, comparadas com um grupo controlo de doentes com insuficiência cardíaca crónica admitidos numa unidade de Medicina Interna no período de dois anos. Modelos de regressão logística foram construídos para determinar as comorbilidades associadas a insuficiência cardíaca aguda e para a construção do comorbidoma. Resultados: Foram identificados 229 doentes com insuficiência cardíaca aguda e 201 com insuficiência cardíaca crónica. A idade e género feminino foram superiores no grupo insuficiência cardíaca aguda (p < 0,001), tal como o número de comorbilidades (4,0 ± 3,0 vs 4,0 ± 2,0, p = 0,044). A hiperuricemia (odds ratio 2,46, intervalo confiança 95% 1,41 ­ 4,31, p = 0,002), a obesidade (odds ratio 2,22, intervalo confiança 95% 1,31 ­ 3,76, p = 0,003), a fibrilação auricular (odds ratio 1,93, intervalo confiança 95% 1,31 ­ 2,87, p = 0,001), a doença arterial periférica (odds ratio 2,12, intervalo confiança 95% 1,01 ­ 4,42, p = 0,046) e a doença renal crónica (odds ratio 2,47, intervalo confiança 95% 1,65 ­ 3,71, p < 0,001) associaram-se com a insuficiência cardíaca aguda. A obesidade, a fibrilação auricular, a doença arterial periférica e a doença renal crónica foram identificadas como fatores de risco independentes. Doentes com múltiplas comorbilidades tiveram um risco superior de hospitalização por insuficiência cardíaca: zero comorbilidades ­ odds ratio 0,43, 95% intervalo confiança 0,28 ­ 0,67, p < 0,001; uma comorbilidade ­ odds ratio 0,69, 95% intervalo confiança 0,47 ­ 1,01, p = 0,057; duas comorbilidades ­ odds ratio 1,85, 95% intervalo confiança 1,11 ­ 3,08, p = 0,019; ≥ três comorbilidades ­ odds ratio 5,81, 95% intervalo confiança 2,77 ­ 12,16, p < 0,001. Discussão: Este estudo mostra uma associação entre várias comorbilidades e a hospitalização por insuficiência cardíaca aguda. A associação parece fortalecer-se na presença de múltiplas comorbilidades. Conclusão: O comorbidoma é uma ferramenta útil para identificar comorbilidades associadas a maior risco de insuficiência cardíaca aguda. A identificação de doentes vulneráveis pode permitir a instituição de intervenções multidimensionais para minimizar hospitalizações futuras.

Identification of environmental and genetic factors that influence warfarin time in therapeutic range.

Warfarin is an oral anticoagulant prescribed to prevent and treat thromboembolic disorders. It has a narrow therapeutic window and must have its effect controlled. Prothrombin test, expressed in INR value, is used for dose management. Time in therapeutic range (TTR) is an important outcome of quality control of anticoagulation therapy and is influenced by several factors. The aim of this study was to identify genetic, demographic, and clinical factors that can potentially influence TTR. In total,422 patients using warfarin were investigated. Glibenclamide co-medication and presence of CYP2C9*2 and/or *3 alleles were associated with higher TTR, while amiodarone, acetaminophen and verapamil co-medication were associated with lower TTR. Our data suggest that TTR is influenced by co-medication and genetic factors. Thus, individuals in use of glibenclamide may need a more careful monitoring and genetic testing (CYP2C9*2 and/or *3 alleles) may improve the anticoagulation management. In addition, in order to reach and maintain the INR in the target for a longer period, it is better to discuss dose adjustment in office instead of by telephone assessment. Other studies are needed to confirm these results and to find more variables that could contribute to this important parameter.

Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real-life study in Brazil.

INTRODUCTION: The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre-specified timepoints after ART onset. However, data from real-life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil. METHODS: Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir-boosted atazanavir (regimen 3)). RESULTS AND DISCUSSION: We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12-month cumulative viraemia. The model predicted a 45-unit increase in log10 copy-days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70-unit increase in log10 copy-days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir-lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders. CONCLUSIONS: Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.

Comparative effectiveness of first-line antiretroviral therapy: results from a large real-world cohort after the implementation of dolutegravir.

OBJECTIVE: We aimed to assess the effectiveness of first-line antiretroviral therapy (ART) regimens in achieving viral suppression at 12 months, from 2014 to 2017 in Brazil. DESIGN: A retrospective cohort study utilizing programmatic data from the Brazilian HIV Program. METHODS: Adults (aged 15-80 years) who started ART from January 2014 to July 2017 and had a viral load 365 (±90) days after treatment initiation were included. Associations with achieving viral suppression (<50 copies/ml) at 365 (±90) days were assessed using logistic regression. Our main study variable was ART regimen, and covariates included year of ART initiation, sex/exposure group, age, education, race, region, baseline CD4 and viral load counts, and adherence measured by pharmacy refill data. We performed both intent-to-treat and per-protocol analogous analyses. RESULTS: Out of 107 647 ART-naive patients, 71.5% initiated with tenofovir/lamivudine/efavirenz (TLE) and 10.5% with tenofovir/lamivudine/dolutegravir (TLD). Median age and CD4 cell counts were 34 [interquartile range (IQR) 26-46] and 379 cells/µl (IQR 190-568), respectively; 68.0% were men. Viral suppression by 12 months was 84.0% [95% confidence interval (95% CI) 83.7-84.2] with TLE and 90.5% (95% CI 90.0-91.0) with TLD, and below 80% for protease-inhibitor-based regimens. In the multivariable intent-to-treat-analogous analysis, controlling for cofactors related to viral suppression including adherence, the adjusted odds ratio (aOR) for TLD's viral suppression relative to TLE was 1.56 (95% CI 1.40-1.75). Findings were robust to secondary per-protocol analogous and sensitivity analysis. CONCLUSION: Our results showed the superiority of dolutegravir- over efavirenz- and protease-inhibitor-based regimens in suppressing viral replication in a real-word cohort of HIV-positive adults. This superiority was not driven by higher levels of adherence with dolutegravir-based regimens.

A new in silico approach to investigate molecular aspects of factor IX missense causative mutations and their impact on the hemophilia B severity.

Factor IX (encoded by F9) is a protein in the coagulation process, where its lack or deficiency leads to hemophilia B. This condition has been much less studied than hemophilia A, especially in Latin America. We analyzed the structural and functional impact of 54 missense mutations (18 reported by us previously, and 36 other mutations from the Factor IX database) through molecular modeling approaches. To accomplish this task, we examine the electrostatic patterns, hydrophobicity/hydrophilicity, disulfide, and H-bond differences of the Factor IX structures harboring the missense mutations found, correlating them with their clinical effects. The 54 mutated sequences were modeled and their physicochemical features were determined and used as input in clusterization tools. The electrostatic pattern seems to influence in disease severity, especially for mutations investigated in epidermal growth factors 1 and 2 (EGF1/2) domains. The combined use of all physicochemical information improved the clustering of structures associated to similar phenotypes, especially for mutations from GLA and EGF1-2 domains. The effect of mutations in the disease phenotype severity seems to be a complex interplay of molecular features, each one contributing to different impacts. This highlights that previous studies and tools analyzing individually single features for single mutations are missing elements that fulfill the whole picture.

Determinants of survival of people living with HIV/AIDS on antiretroviral therapy in Brazil 2006-2015.

BACKGROUND: We compared AIDS-related mortality rates in people living with HIV (PLHIV) starting antiretroviral therapy (ART) in Brazil during 2006-2015 and examined associated risk factors . METHODS: Data on ART use in PLHIV and AIDS mortality in Brazil was analysed with piecewise constant exponential models. Mortality rates and hazard ratios were estimated for 0-6, 6-12, 13-24, 25-36 and > 36 months of ART use and adjusted for region, age, sex, baseline CD4 cell count and calendar year of ART initiation. An additional analysis restricted to those with data on risk group was also performed. RESULTS: 269,076 individuals were included in the analysis, 165,643 (62%) males and 103,433 (38%) females, with 1,783,305 person-years of follow-up time. 21,749 AIDS deaths were reported and 8898 deaths occurred in the first year of ART. The risk of death in the first six months decreased with early ART initiation; those starting treatment early with CD4 > 500 cells per µL had a hazard ratio of 0.06 (95% CI 0.05-0.07) compared with CD4 < 200 cells per µL. Older age, male sex, intravenous drug use and starting treatment in earlier calendar years were associated with higher mortality rates. People living in the North, Northeast and South of Brazil experienced significantly higher AIDS mortality rates than those in the Southeast (HR 1.44, [95% CI 1.35-1.54], 1.10 [1.05-1.16] and 1.22 [1.17-1.28] respectively). CONCLUSIONS: Early treatment is likely to have contributed to the improved survival in PLHIV on ART, with the greatest benefits observed in women, younger age-groups and those living in the North.

Estimating HIV incidence from surveillance data indicates a second wave of infections in Brazil.

Emerging evidence suggests that HIV incidence rates in Brazil, particularly among men, may be rising. Here we use Brazil's integrated health systems data to develop a mathematical model, reproducing the complex surveillance systems and providing estimates of HIV incidence, number of people living with HIV (PLHIV), reporting rates and ART initiation rates. An age-structured deterministic model with a flexible spline was used to describe the natural history of HIV along with reporting and treatment rates. Individual-level surveillance data for 1,077,295 cases (HIV/AIDS diagnoses, ART dispensations, CD4 counts and HIV/AIDS-related deaths) were used to calibrate the model using Bayesian inference. The results showed a second wave of infections occurring after 2001 and 56,000 (95% Credible Interval 43,000-71,000) new infections in 2015, 37,000 (95% CrI 28,000-54,000) infections in men and 16,000 (95% CrI 10,000-23,000) in women. The estimated number of PLHIV by end-2015 was 838,000 (95% CrI 675,000-1,083,000), with 80% (95% CrI 62-98%) of those individuals reported to the Ministry of Health. Women were more likely to be diagnosed and reported than men; 86.8% of infected women had been reported compared with 75.7% of men. Likewise, ART initiation rates for women were higher than those for men. The second wave contradicts previous estimates of HIV incidence trends in Brazil and there were persistent differences in the rates of accessing care between men and women. Nevertheless, the Brazilian HIV program has achieved high rates of detection and treatment, making considerable progress over the past ten years.

Age-adjusted Charlson Comorbidity Index Does Not Predict Outcomes in Patients Submitted to Noninvasive Ventilation / El índice de comorbilidad de Charlson ajustado por edad no predice los resultados de pacientes sometidos a ventilación no invasiva

Introduction: Comorbidities are thought to have prognostic impact on outcomes of patients submitted to noninvasive ventilation (NIV). Our goal was to determine if age-adjusted Charlson comorbidity index (ACCI) could predict outcomes in patients undergoing NIV due to acute respiratory failure. Methods:Patients in respiratory failure submitted to NIV were prospective evaluated comparing patien's characteristics and outcomes according to ACCI ≤ median vs. ACCI > median. Each comorbidity composing the index was tested as predictor of NIV failure and readmission/mortality risk at 30 and 90 days, using logistic regression analysis. NIV failure was defined as need for invasive mechanical ventilation and/or death. Results: 177 patients were enrolled. Median ACCI score was 5 points. Comparing patients with ACCI > 5 with ACCI ≤ 5, the former group was older but APACHE II was similar. Time to first NIV disconnection was inferior for ACCI > 5 patients (OR 0.46, 95% CI 0.23-0.89, p = 0.021), after gender and age adjustment. No differences were found in length of stay, time on NIV, NIV complications or failure, and 30 and 90-day hospital readmission or death, before and after adjustment. None of the single comorbidities was predictive of NIV failure and readmission risk, when adjusted to sex and age. Conclusion: ACCI is not a good predictor for short and medium-term outcomes in patients submitted to NIV

Introducción: Las comorbilidades parecen tener un impacto en el pronóstico de los resultados de pacientes sometidos a ventilación no invasiva (VNI). Nuestro objetivo fue determinar si el ajuste por edad del índice de comorbilidad de Charlson (ICC) podía predecir los resultados de aquellos pacientes sometidos a VNI por insuficiencia respiratoria aguda. Métodos: Se evaluaron de forma prospectiva pacientes con insuficiencia respiratoria sometidos a VNI, comparando las características de los pacientes y sus resultados valorados como ICCmediana. Mediante un análisis de regresión logística, cada comorbilidad incluida en el índice se evaluó como predictor de fracaso de VNI y de riesgo de reingreso/mortalidad a los 30 y 90 días. Se definió fracaso de VNI como la necesidad de ventilación mecánica asistida y/o muerte. Resultados: Se incluyeron 177 pacientes. La mediana del valor del ICC fue de 5 puntos. En la comparación de pacientes con ICC>5 frente a pacientes con ICC≤5, el primer grupo resultó ser el de mayor edad, aunque la clasificación por APACHE II fue similar. El tiempo hasta la primera desconexión de VNI fue inferior en pacientes con ICC>5 (OR: 0,46; IC 95%: 0,23-0,89; p=0,021), tras el ajuste por género y edad. No se encontraron diferencias en la duración de la hospitalización, el tiempo con VNI, complicaciones o fracaso de la VNI y el reingreso hospitalario o la muerte a los 30 y 90 días, antes y después del ajuste. Ninguna de las comorbilidades analizadas era predictora de fracaso de la VNI o del riesgo de reingreso cuando se ajustaron por sexo edad. Conclusión: El ICC no es un buen predictor de los resultados a corto y medio plazo de pacientes sometidos a VNI

Sociodemographic determinants of attrition in the HIV continuum of care in Brazil, in 2016.

The aim of this study was to identify sociodemographic factors associated with attrition in the 3 steps of the HIV continuum of care related to the 90-90-90 targets - access to diagnosis, treatment initiation, and virologic suppression, in Brazilian adults (15 years or older), in 2016.Programmatic data were obtained from 2 information systems from the Brazilian Ministry of Health, which register all antiretroviral therapy (ART) dispensations and all CD4 and viral load counts (VL) performed within the country's public health system. The 3 attrition indicators were late presentation to care, defined as a first CD4 count <350 cells/mm among ART-naive individuals who performed a first CD4 count in 2016; not being on ART, defined as having no recorded dispensation within the last 100 days of the year, among those who were linked to care in 2016; and not being virologically suppressed, defined as having the last recorded VL >200 copies/mL in 2016, among those with a recorded VL count who were on treatment for at least 6 months. Association of sociodemographic factors with these indicators was analyzed by unconditional logistic regression analysis.Lower educational level and black/brown/indigenous race/color were associated with worse outcomes in the 3 indicators. Environmental indicators, namely the region, size, and social vulnerability index of the municipality of residence, also played an important role in the models. Younger age was strongly associated with not being on ART and not showing virological suppression.Our findings help identify the barriers in the different stages of the HIV continuum of care, which need to be addressed in order to progress toward the achievement of the 90-90-90 targets.

Age-adjusted Charlson Comorbidity Index Does Not Predict Outcomes in Patients Submitted to Noninvasive Ventilation.

INTRODUCTION: Comorbidities are thought to have prognostic impact on outcomes of patients submitted to noninvasive ventilation (NIV). Our goal was to determine if age-adjusted Charlson comorbidity index (ACCI) could predict outcomes in patients undergoing NIV due to acute respiratory failure. METHODS: Patients in respiratory failure submitted to NIV were prospective evaluated comparing patient's characteristics and outcomes according to ACCI≤median vs. ACCI>median. Each comorbidity composing the index was tested as predictor of NIV failure and readmission/mortality risk at 30 and 90 days, using logistic regression analysis. NIV failure was defined as need for invasive mechanical ventilation and/or death. RESULTS: 177 patients were enrolled. Median ACCI score was 5 points. Comparing patients with ACCI>5 with ACCI≤5, the former group was older but APACHE II was similar. Time to first NIV disconnection was inferior for ACCI>5 patients (OR 0.46, 95% CI 0.23-0.89, p=0.021), after gender and age adjustment. No differences were found in length of stay, time on NIV, NIV complications or failure, and 30 and 90-day hospital readmission or death, before and after adjustment. None of the single comorbidities was predictive of NIV failure and readmission risk, when adjusted to sex and age. CONCLUSION: ACCI is not a good predictor for short and medium-term outcomes in patients submitted to NIV.

Factors Associated With Early Virological Response in HIV-Infected Individuals Starting Antiretroviral Therapy in Brazil (2014-2015): Results From a Large HIV Surveillance Cohort.

OBJECTIVE: To identify clinical, sociodemographic, and treatment-related factors associated with early virological response in HIV-infected adults starting antiretroviral treatment (ART) in Brazil in 2014-2015. METHODS: Data from 4 information systems from the Brazilian AIDS Program were combined to create a historical cohort. Unconditional logistic regression models were used to assess the likelihood of not achieving viral load suppression (VLS), defined as having either a viral load (VL) count >200 copies per milliliter or an aids-related death recorded within 180 ± 90 days after treatment initiation. RESULTS: Among 76,950 individuals, 64.8% were men; median age, CD4, and VL counts were 34 years, 378 cells per micro liter, and 38,131 copies per milliliter, respectively, and 85.2% achieved VLS. In the multivariate analysis, some factors which increased the odds of non-VLS were as follows: lower CD4 and higher VL counts, younger age, heterosexual or injection drug use groups (relative to men who have sex with men), lower educational level, black/brown race, higher pill burden, and higher dosing frequency. Regimens containing boosted protease inhibitors were similar to those containing nonnucleoside reverse transcriptase inhibitors and superior to those containing unboosted protease inhibitors (all P values <0.001). No difference was observed between patients with CD4 counts 350-499 and 500+ cells per micro liter. CONCLUSIONS: Our findings support the decision made in Brazil in 2013 to recommend immediate initiation of ART regardless of clinical stage or CD4. Several factors were found to be associated with poorer virologic outcomes and should be addressed to maximize ART adherence and success rates.

Fatores de risco cardiovascular em mulheres climatéricas com doença arterial coronariana / Cardiovascular risk factors in climacteric women with coronary artery disease

Fundamentos: O aumento da incidência de doenças cardiovasculares em mulheres ocorre durante o período do climatério, especialmente após a menopausa. Objetivo: O objetivo deste estudo foi identificar fatores de risco cardiovasculares entre as mulheres climatéricas com e sem doença arterial coronariana (DAC). Métodos: Trata-se de estudo transversal realizado no Serviço de Hemodinâmica do Hospital Universitário da Universidade Federal do Maranhão, no período de março de 2012 a julho de 2013. Foram incluídas 31 mulheres climatéricas que compareceram ao setor para realização do cateterismo cardíaco, separadas em grupos após resultados do cateterismo, Grupo I (com DAC) e Grupo II (sem DAC). Análise estatística: as variáveis categóricas foram descritas por meio de frequências e porcentagem, as numéricas por meio de média ± desvio padrão ou mediana (Quartil.3 ­ Quartil.1); o teste Shapiro-Wilk para verificar a normalidade dos dados quantitativos, o teste Exato de Fisher para comparações de dados categóricos; para dados contínuos o Test-T para amostras não pareadas ou o Mann-Whitney; foi considerado estatisticamente significativo o valor de p < 0,05. Resultados: Avaliaram-se grupos com DAC (n = 13) e sem DAC (n = 18), os resultados apontaram média de idade entre os grupos de 57,92 ± 5,15 e 51,72 ± 4,63 anos, respectivamente; dentre os fatores de risco cardiovasculares, os mais prevalentes entre as mulheres com DAC foram: a menopausa (84,62%), a hipertensão arterial sistêmica (HAS) (69,23%) e o sedentarismo (69,23). Conclusão: Concluiu-se que, além da menopausa propriamente dita, a HAS e o sedentarismo foram os fatores de risco cardiovasculares mais prevalentes entre as mulheres com DAC

Background: The increased incidence of cardiovascular disease in women occurs during the climacteric period, especially after menopause. Objective: The aim of this study was to identify risk factors among climacteric women with and without coronary artery disease (CAD). Method: This cross-sectional study was performed in the Catheterization Laboratory at the Federal University Hospital of Maranhão, in the Northeast region of Brazil, between March 2012 and July 2013. We included 31 climacteric women who went to the care center for cardiac catheterization. They were divided into groups after catheterization results: Group I (with DAC) and Group II (without CAD). Statistical analysis: Categorical variables were described by means of frequencies and percentages, numerical variables by mean ± standard deviation or median (Quartile.3 - Quartile.1); the Shapiro-Wilk test was used to verify the normality of quantitative data. Fisher's exact test was used for categorical data comparisons. For continuous data, we used Student's test or the Mann-Whitney for unpaired samples; statistical significance was set at p < 0.05. Results: We evaluated groups with CAD (n = 13) and without CAD (n = 18). The results showed a mean age between the groups of 57.92 ± 5.15 and 51.72 ± 4.63 years, respectively. Among the cardiovascular risk factors, the most prevalent among women with CAD were menopause (84.62%), systemic arterial hypertension (SAH) (69.23%) and sedentary life style (69.23%). Conclusion: We concluded that, in addition to menopause itself, SAH and sedentary lifestyle were the most prevalent cardiovascular risk factors among women with CAD

Association Between Left Ventricle Diastolic Dysfunction and Unfavorable Prognostic Markers in Patients with Aortic Insufficiency.

INTRODUCTION: The presence of symptoms, systolic dysfunction and Left Ventricle (LV) dilation are considered unfavourable prognostic markers in Aortic Valve Insufficiency (AVI). The role of diastolic dysfunction, which is considered unfavourable outcome marker in cardiac pathologies, is not well established in AVI. AIM: To evaluate if the presence of diastolic dysfunction may be associated with unfavourable prognostic markers in AVI patients. MATERIALS AND METHODS: A cross-sectional prospective study was performed on 22 patients with moderate or severe AVI. They underwent clinical evaluation and transthoracic echocardiography. Associations between clinical, epidemiological and echocardiographic were evaluated by Student t-test for normally distributed variables or Mann-Whitney test for non-normal distribution. Comparison between proportions was performed by Chi-square test. RESULTS: There was an association between increased LV filling pressure, assessed by E' and E/E' of Mitral Tissue Doppler, and impaired LV systolic function, respectively: R = 0.563, R2 = 0.281; p = 0.008 and R = 0.639, R2 = 0.378; p = 0.002. The LV indexed mass also was inversely associated with the LV ejection fraction (R = 0.62, R2 = 0.35 and p = 0.003). CONCLUSION: There was an association of LV diastolic dysfunction and ventricular hypertrophy with impaired left ventricle systolic function. Increased LV filling pressure and LV indexed mass should be considered in the management of AVI patients.

Dacryocystectomy as a treatment of chronic dacryocystitis in the elderly.

To evaluate the dacryocystectomy (DCT) outcomes for chronic dacryocystitis in an elderly population over 70 years old. A retrospective chart review was performed for patients over 70 years old who were diagnosed with chronic dacryocystitis and underwent DCT at the Botucatu School of Medicine, UNESP, Brazil, from 2007 to July 2014. Data were collected about patient demographics, age, gender, previous nasal, or ophthalmic diseases, symptoms related to the lacrimal drainage system preoperatively and postoperatively, signs of enlargement of the lacrimal sac (regurgitation of secretion), and histopathologic evaluation. The study sample was comprised of 17 patients with an average age of 76.5 ± 8.5 years. The major complaint for all patients was tearing and 17.6% patients had an additional complaint of discharge. Regurgitation of secretion with lacrimal sac expression was present in 76.5% of patients. Postoperatively, 76.5% of the patients reported improvement of the initial complaint, likely due to the total excision of the lacrimal sac which removed the focal site of chronic infection. Epiphora persisted in 23.5% of patients, of whom 11.7% underwent successful lacrimal stent intubation. DCT for chronic dacryocystitis should be considered a primary procedure in individuals over 70 years old. This procedure has a much lower risk to these patients who often have associated comorbidities.