Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres.

BACKGROUND: Although some male patients with congenital hypogonadotropic hypogonadism (CHH) undergo spontaneous reversal following treatment, predictors of reversal remain elusive. We aimed to assemble the largest cohort of male patients with CHH reversal to date and identify distinct classes of reversal. METHODS: This multicentre cross-sectional study was conducted in six international CHH referral centres in Brazil, Finland, France, Italy, the UK, and the USA. Adult men with CHH (ie, absent or incomplete spontaneous puberty by age 18 years, low serum testosterone concentrations, and no identifiable cause of hypothalamic-pituitary-gonadal [HPG] axis dysfunction) were eligible for inclusion. CHH reversal was defined as spontaneous recovery of HPG axis function off treatment. Centres provided common data elements on patient phenotype, clinical assessment, and genetics using a structured, harmonised data collection form developed by COST Action BM1105. Latent class mixture modelling (LCMM) was applied to establish whether at least two distinct classes of reversal could be identified and differentially predicted, and results were compared with a cohort of patients without CHH reversal to identify potential predictors of reversal. The primary outcome was the presence of at least two distinct classes of reversal. FINDINGS: A total of 87 male patients with CHH reversal and 108 without CHH reversal were included in the analyses. LCMM identified two distinct reversal classes (75 [86%] in class 1 and 12 [14%] in class 2) on the basis of mean testicular volume, micropenis, and serum follicle-stimulating hormone (FSH) concentration. Classification probabilities were robust (0·998 for class 1 and 0·838 for class 2) and modelling uncertainty was low (entropy 0·90). Compared with class 1, patients in class 2 had significantly larger testicular volume (p<0·0001), no micropenis, and higher serum FSH concentrations (p=0·041), consistent with the Pasqualini syndrome (fertile eunuch) subtype of CHH. Patients without CHH reversal were more likely to have anosmia (p=0·016), cryptorchidism (p=0·0012), complete absence of puberty (testicular volume <4 cm³; p=0·0016), and two or more rare genetic variants (ie, oligogenicity; p=0·0001). Among patients who underwent genetic testing, no patients (of 75) with CHH reversal had a rare pathogenic ANOS1 variant compared with ten (11%) of 95 patients without CHH reversal. Individuals with CHH reversal had a significantly higher rate of rare variants in GNRHR than did those without reversal (nine [12%] of 75 vs three [3%] of 95; p=0·025). INTERPRETATION: Applying LCMM to a large cohort of male patients with CHH reversal uncovered two distinct classes of reversal. Genetic investigation combined with careful clinical phenotyping could help surveillance of reversal after withdrawing treatment, representing the first tailored management approach for male patients with this rare endocrine disorder. FUNDING: National Institutes of Health National Center for Advancing Translational Sciences; Ministry of Health, Rome, Italy; Ministry of University, Rome, Italy; National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the Josiah Macy Jr Foundation. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Screening with urine Histoplasma antigen test in asymptomatic patients starting TNF-alpha inhibitor therapy: a cohort study.

Background: Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals. Methods: This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis. Results: From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive. Conclusion: The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.

Using a urine test for fungal infection to screen people without symptoms who are about to start taking immunobiologic medications This study looked at the prevalence of histoplasmosis, a fungal infection, in asymptomatic patients who were about to start treatment with TNF-α inhibitors, which are medications used for autoimmune diseases. The researchers tested urine samples for Histoplasma antigen before the patients started the treatment and followed them for 180 days after starting the medication to see if they developed any symptoms of histoplasmosis. The study included 54 patients in southern Brazil, and they found that 14.8% of the patients tested positive for the Histoplasma antigen before starting the treatment. However, none of the patients, including those who tested positive, developed histoplasmosis during the 6-month follow-up. The researchers concluded that histoplasmosis infection may be more common in these patients than previously thought, but it's still not clear if asymptomatic patients with a positive antigen test will develop the infection when starting TNF-α inhibitor treatment. The study did not find any specific risk factors for developing histoplasmosis in this group of patients, and based on their findings, they did not recommend routine screening or preventive therapy for histoplasmosis before starting TNF-α inhibitor treatment.

Acceptability and feasibility of a parent-mediated social-communication therapy for young autistic children in Brazil: A qualitative implementation study of Paediatric Autism Communication Therapy.

LAY ABSTRACT: Parents of autistic children and health professionals who work with autistic children in Brazil had positive views about introducing Paediatric Autism Communication Therapy as a therapy for autistic children in Brazil. The parents and clinicians also mentioned some difficulties about using Paediatric Autism Communication Therapy in Brazil. We made adaptations to Paediatric Autism Communication Therapy to address these difficulties. Paediatric Autism Communication Therapy is a therapy to support the development of social and communication skills for autistic children aged 2-10 years. The therapy is conducted with the autistic child's parent. Paediatric Autism Communication Therapy has not been used in Brazil before. There are few therapy options available for autistic children in Brazil and we believed that Paediatric Autism Communication Therapy may be useful. We asked three groups of people in Brazil about their views of Paediatric Autism Communication Therapy, after explaining how the therapy works. Group 1 included 18 parents of autistic children aged 2-10 years. Group 2 included 20 health professionals such as psychologists who work with autistic children. Group 3 included 15 parents of autistic children aged 2-7 years who received the Paediatric Autism Communication Therapy. We learned that parents and clinicians felt that Paediatric Autism Communication Therapy would be a beneficial therapy for autistic children in Brazil. We also found out about the challenges of using Paediatric Autism Communication Therapy in Brazil. We used these findings to make small cultural adaptations to Paediatric Autism Communication Therapy to make it more suitable for Brazil.

Green chemistry production of biopolymeric film-derived biomaterial prepared using natural alginate and vanillin compounds for application as a biocurative.

The present work presents the results obtained in the production of vanillin-doped alginate biopolymeric film using green chemistry methodology. Alginate dressings are already a therapeutic reality, but they act only by maintaining the appropriate environment for healing. In order to improve their properties, the incorporation of vanillin was proposed due to its antioxidant and antimicrobial potential. Different biopolymeric films were produced employing the experiment planning through response surface analysis, which allowed determining the best region for a medium value of solubility and high degree of swelling. This region refers to values above 0.07 g of CaCl2 and concentrations above 0.024 g of vanillin, triggering solubility between 25 and 30% and a degree of swelling above 100% and with fixed values of alginate (0.85 g). Such data are related to experiments (A), (B), and (C) listed in Table 1. Regarding the optimization of the process, the normal boundary intersection (NBI) method allowed the analysis of concave regions, predicting the optimal points and generating the Pareto chart with equidistant limits. The antimicrobial test allowed observing the antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa microorganisms from the biopolymeric films, as well as a solution of vanillin with calcium chloride and glycerol obtaining a halo of inhibition only in the presence of vanillin, and there was no significant difference between the results obtained in the experiments (A) and (B). The thermal analyses showed that the material has thermal stability in the ideal temperature range (~ 25 °C) for application as a biocurative. We preliminarily concluded that the alginate biopolymeric film doped with vanillin prepared using green chemical methodology presents antimicrobial properties and thermal stability that indicate its potential use as biocurative.

Risk Factors Associated with Ischemic Stroke in the Immediate Postoperative Period of Cardiac Surgery.

INTRODUCTION: Stroke remains a major complication of cardiac surgery. Despite all efforts, the incidence of postoperative stroke remains as high as 6%. We aimed to investigate risk factors for ischemic stroke in a contemporary cohort of patients undergoing cardiac surgery. METHODS: This is a retrospective cohort study of 678 consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass in a tertiary hospital in Brazil between July 1, 2011, and December 31, 2018. The primary outcome was the rate of early (perioperative and seven-day postoperative) stroke, defined as the occurrence of the outcome during the index admission. We developed a predictive model of stroke using the Poisson regression analysis with robust variance. RESULTS: Postoperative stroke occurred in 24 patients (3.5%), 23 (3.3%) were ischemic, and 21 (3.0%) were diagnosed in the first 72 hours after surgical procedure. After multivariate analysis, the following factors were significantly associated with stroke: previous stroke/transient ischemic attack (relative risk [RR]=2.75; 95% confidence interval [CI], 1.11-6.82), carotid artery disease (RR=4.0; 95% CI, 1.43-11.0), previous atrial fibrillation (RR=3.26, 95% CI, 1.31-8.1), and postoperative platelets > 200,000/mm3 (RR=2.26; 95% CI, 1.01-5.1). CONCLUSION: We developed a contemporary model to determine risk predictors for stroke after cardiac surgery. This model may help clinicians to identify patients at risk and could be useful in clinical practice.

Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review.

INTRODUCTION: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota. OBJECTIVE: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma. METHODS: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic. RESULTS: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response. CONCLUSION: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.

SIN3A Defects Associated with Syndromic Congenital Hypogonadotropic Hypogonadism: An Overlap with Witteveen-Kolk Syndrome.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. More than 40 genes have been associated with the pathogenesis of CHH, but most cases still remain without a molecular diagnosis. Mutations involving the same gene (e.g., FGFR1, PROK2/PROKR2, CHD7) were found to cause normosmic CHH and Kallmann syndrome (KS), with and without associated phenotypes, illustrating the coexistence of CHH with signs of other complex syndromes. The Witteveen-Kolk syndrome (WITKOS), caused by defects of the SIN3A gene, is a heterogeneous disorder characterized by distinctive facial features, microcephaly, short stature, delayed cognitive, and motor development. Although micropenis and cryptorchidism have been reported in this syndrome, WITKOS has not been formally associated with CHH so far. PATIENTS AND METHODS: A man with KS associated with mild syndromic features (S1) and a boy with global developmental delay, syndromic short stature, micropenis and cryptorchidism (S2), in whom common genetic defects associated with CHH and short stature had been previously excluded, were studied by either chromosomal microarray analysis or whole exome sequencing. RESULTS: Rare SIN3A pathogenic variants were identified in these 2 unrelated patients with CHH phenotypic features. A 550 kb deletion at 15q24.1, including the whole SIN3A gene, was identified in S1, and a SIN3A nonsense rare variant (p.Arg471*) was detected in S2. CONCLUSION: These findings lead us to propose a link between SIN3A defects and CHH, especially in syndromic cases, based on these 2 patients with overlapping phenotypes of WITKOS and CHH.

Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review / Transplante de microbiota fecal e suas repercussões em pacientes com melanoma refratário à terapia anti-PD-1: revisão de escopo

ABSTRACT Introduction: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota. Objective: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma. Methods: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic. Results: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response. Conclusion: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.

RESUMO Introdução: apesar de extremamente eficaz em alguns casos, até 70% dos pacientes com melanoma não respondem aos anti-PD-1/PD-L1 (resistência primária) e muitos dos respondedores, eventualmente, acabam progredindo (resistência secundária). Extensos esforços estão sendo realizados para superar esta resistência através de novas estratégias, sobretudo, visando a modulação da microbiota intestinal. Objetivo: avaliar se o transplante de microbiota fecal (TMF), associado à imunoterapia, é benéfico no curso clínico do paciente com melanoma refratário. Métodos: trata-se de uma revisão de escopo, baseada em estudos coletados nas plataformas MEDLINE, ScienceDirect, The Cochrane Library, Embase e BMJ Journals; utilizando os descritores: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; e "Microbiota". Foram incluídos ensaios clínicos, na língua inglesa, com dados relevantes sobre a temática e disponíveis integralmente. Não foi determinado um período de corte temporal, devido à quantidade limitada de evidências sobre o tema. Resultados: o cruzamento dos descritores permitiu a identificação de 342 publicações e, após a aplicação dos critérios de elegibilidade, permitiu a seleção de 4 estudos. A partir das análises, observou-se que grande parte dos estudados superaram a resistência aos inibidores do checkpoint imunológico pós-TMF, com melhor resposta ao tratamento, menor crescimento tumoral e aumento da resposta imunológica benéfica. Conclusão: nota-se que o TMF favorece a resposta do melanoma à imunoterapia, traduzido por benefício clínico significativo. Entretanto, novos estudos são necessários para a completa elucidação das bactérias e mecanismos envolvidos, bem como para que haja a translação das novas evidências para a prática assistencial oncológica.

Risk Factors Associated with Ischemic Stroke in the Immediate Postoperative Period of Cardiac Surgery

ABSTRACT Introduction: Stroke remains a major complication of cardiac surgery. Despite all efforts, the incidence of postoperative stroke remains as high as 6%. We aimed to investigate risk factors for ischemic stroke in a contemporary cohort of patients undergoing cardiac surgery. Methods: This is a retrospective cohort study of 678 consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass in a tertiary hospital in Brazil between July 1, 2011, and December 31, 2018. The primary outcome was the rate of early (perioperative and seven-day postoperative) stroke, defined as the occurrence of the outcome during the index admission. We developed a predictive model of stroke using the Poisson regression analysis with robust variance. Results: Postoperative stroke occurred in 24 patients (3.5%), 23 (3.3%) were ischemic, and 21 (3.0%) were diagnosed in the first 72 hours after surgical procedure. After multivariate analysis, the following factors were significantly associated with stroke: previous stroke/transient ischemic attack (relative risk [RR]=2.75; 95% confidence interval [CI], 1.11-6.82), carotid artery disease (RR=4.0; 95% CI, 1.43-11.0), previous atrial fibrillation (RR=3.26, 95% CI, 1.31-8.1), and postoperative platelets > 200,000/mm3 (RR=2.26; 95% CI, 1.01-5.1). Conclusion: We developed a contemporary model to determine risk predictors for stroke after cardiac surgery. This model may help clinicians to identify patients at risk and could be useful in clinical practice.

Grupo comunitário de saúde mental: um olhar dos discentes de Psicologia / Community mental health group: the view of Psychology discents / Grupo comunitario de salud mental: la visión de los discentes de Psicología

O Grupo Comunitário de Saúde Mental visa promover a compreensão da relação entre a pessoa e sua realidade cotidiana buscando a promoção de saúde. A presente pesquisa se direciona para uma atividade de grupo comunitário realizada no processo de formação de Psicólogos em uma Universidade do interior Paulista. Portanto, o objetivo constitui em verificar a importância da realização dos Encontros do Grupo Comunitário de Saúde Mental na perspectiva dos estudantes de Psicologia. A metodologia utilizada foi a pesquisa descritiva-qualitativa, uma pesquisa de campo junto aos universitários que participaram dos encontros do grupo comunitário no período de março a junho de 2018 e 2019. O instrumento para coleta de dados foi um questionário eletrônico via formulário do Google Drive. Por se tratar de pesquisa com humanos o projeto foi submetido ao Comitê de Ética e aprovado, número CAAE: 26948819.4.0000.5495. A análise dos dados foi realizada a partir das repostas dos participantes ao questionário, analisadas na perspectiva de três aspectos que configuram o Grupo Comunitário de Saúde Mental: 1. atenção à realidade e à experiência humana; 2. o grupo como local de encontro e 3. o processo grupal, aprendizagem e saúde mental. Assim, verificou-se com esta pesquisa a importância do grupo comunitário na formação de psicólogos como um espaço para trabalhar aspectos relacionados à saúde mental. Ademais, percebe-se ainda outro aspecto fundamental a respeito da valorização da vida, onde os participantes do grupo começam a olhar para o próximo de forma humanizada, compreendem que em acontecimentos cotidianos estão presentes experiências de vida importantes e a partir dos encontros do grupo comunitário passaram a reconhecê-las.

The Community Mental Health Group aims to promote the understanding of the relationship between the person and their daily reality, seeking health promotion. The present research is directed towards a community group activity conducted in the process of training Psychologists at a University in the interior of São Paulo. Therefore, the objective is to verify the importance of holding the Meetings of the Community Mental Health Group from the perspective of Psychology students. The methodology used was the descriptive-qualitative research, field research with the university students who participated in the community group meetings between March and June 2018 and 2019. The instrument for data collection it was an electronic questionnaire via Google Drive form. As it is research with humans, the project was submitted to the Ethics Committee and approved, CAAE number: 26948819.4.0000.5495. Data analysis was performed based on the participants' responses to the questionnaire, analyzed from the perspective of the three aspects that make up the Community Mental Health Group: 1. attention to reality and human experience; 2. the group as a meeting place and 3. the group process, learning and mental health. Thus, it was verified with this research the importance of the community group in the formation of psychologists as a space to work aspects related to mental health. In addition, there is yet another fundamental aspect regarding the valorization of life, where the group members begin to look at others in a humanized way, understand that in everyday events important life experiences are present and from the meetings of the community mental health group they started to recognize them.

El Grupo Comunitario de Salud Mental tiene como objetivo promover la comprensión de la relación entre la persona y su realidad diaria, buscando la promoción de la salud. La presente investigación se dirige hacia una actividad grupal que se realiza en el proceso de formación de Psicólogos en una Universidad del Interior Paulista. Por tanto, el objetivo es verificar la importancia de la realización de los Encuentros del Grupo Comunitario de Salud Mental desde la perspectiva de los estudiantes de Psicología. La metodología utilizada fue la investigación descriptiva-cualitativa, una investigación de campo con los estudiantes universitarios que participaron en las reuniones grupales de marzo a junio de 2018 y 2019. El instrumento para La recopilación de datos fue un cuestionario electrónico a través del formulario de Google Drive. Por tratarse de una investigación con humanos, el proyecto fue presentado al Comité de Ética y aprobado, número CAAE: 26948819.4.0000.5495. El análisis de los datos se realizó a partir de las respuestas de los participantes al cuestionario, analizadas desde la perspectiva de los tres aspectos que conforman el Grupo Comunitario de Salud Mental: 1. atención a la realidad y experiencia humana; 2. el grupo como lugar de encuentro y 3. el proceso grupal, aprendizaje y salud mental. Así, se comprobó con esta investigación la importancia del desarrollo del grupo en la formación de psicólogos como espacio para trabajar aspectos relacionados con la salud mental. Además, hay otro aspecto fundamental en cuanto a la valoración de la vida, donde los participantes del grupo comienzan a mirar a los demás de Artigo

Social communication therapy for children at risk for neurodevelopmental difficulties: Protocol for a clinical trial.

Exposure to adverse environments are risk factors for neurodevelopmental problems in childhood. Children exposed to such environments may benefit from interventions that target social communication abilities, since these are protective factors for healthy neurodevelopment. This randomized controlled trial will test the efficacy of Paediatric Autism Communication Therapy (PACT) in improving social communication development in young children at risk for neurodevelopmental difficulties living in poverty in Brazil. Participants will be 160 children aged 2-4 years with lower-than-average social communication abilities and their primary caregivers. Child-caregiver dyads will be recruited from public childhood education centers in impoverished urban regions of the city of São Paulo, Brazil. Lower-than-average social communication abilities will be defined by standard scores (≤84) on the socialization and/or communication domains of the Vineland Adaptive Behavior Scales. Child-caregiver dyads will be randomized to receive 12 sessions of the PACT intervention (n = 80) or 5 months of community support as usual plus psychoeducation (n = 80). The primary outcome (parent-child interaction) and secondary outcomes (parent-reported social communication abilities and neurophysiological activity during a live social interaction) will be measured pre- and postintervention. This study may lead to new interventions for vulnerable young children in Brazil and better understanding of the neural mechanisms of PACT.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.

BACKGROUND: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS: Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION: Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.

The effect of mobile health focused on diet and lifestyle on blood pressure: a systematic review and meta-analysis.

To determine the effect of mobile health (mHealth) focused on diet and lifestyle on blood pressure (BP). We performed a systematic review with meta-analysis using the mean difference (MD) of change from baseline as an effect measure. MEDLINE via PubMed, Cochrane Central, and EMBASE were reviewed until 6 May 2020. We included randomized controlled trials of adults who participated in mHealth focused on diet and lifestyle. Interventions were grouped according to the presence of health professional intervention (PI) (PI + mHealth or mHealth only). Eligible controls did not participate in mHealth and were classified as active comparator (PI) or no intervention (NI). Subgroup analyses were performed according to the presence of prior cardiovascular disease and hypertension status. We included 44 trials involving 24 692 participants. Mobile health interventions were superior to NI in reducing SBP in both situations: alone [MD = -1.8 mmHg; 95% confidence interval (CI): -3.6; 0.0] or with PI (MD = -5.3 mmHg; 95% CI: -7.5; -3.1), with a greater effect size in the latter group (P = 0.016). This benefit was not observed when the control was PI. DBP and SBP had consistent results. There was a marked effect of PI + mHealth vs. NI on the BP reduction among hypertensive participants. Current evidence shows that mHealth focused on diet and lifestyle can reduce BP, especially when implemented in hypertensive participants, and PI may provide additional benefit. PROSPERO ID CRD42019141475.

Accuracy of Doppler assessment of the uterine arteries in healthy girls for the diagnosis of pubertal onset.

PURPOSE: To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls. METHODS: Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis. RESULTS: We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a significantly higher mean PI (6.70 ± 2.15) than girls in initial puberty (4.14 ± 1.55) and in late puberty (2.81 ± 1.05) (P < 0.001 for all comparisons), which reflects a progressive increase in blood flow to the uterus with the progression of puberty. ROC curve analysis showed that the PI was able to identify the onset of puberty with a mean area under the curve of 0.838 ± 0.04 (P < 0.001), and the PI cutoff point of 5.05 had a sensitivity of 77%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 79%. The combination of PI < 5.05 plus uterine volume >3.75 cm³ had a sensitivity of 73%, specificity of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty. CONCLUSIONS: We found a significant reduction in the PI during pubertal development, which can possibly be a valuable noninvasive tool in the evaluation of pubertal disorders, alone or in combination with uterine and ovarian volumes.

Hemodynamic effects of increased intra-abdominal pressure in critically ill children

Abstract Objective: To evaluate the influence of intra-abdominal pressure on the cardiac index (CI) at different intra-abdominal hypertension grades achieved when performing an abdominal compression maneuver (ACM). Evaluating the effectiveness of the ACM in distending the left internal jugular vein (LIJV). Methods: Prospective observational study conducted in the PICU of a quaternary care teaching hospital. Participants underwent the ACM and the IAP was measured with an indwelling urinary catheter. At each IAH grade reached during the ACM, the CI was measured by transthoracic echocardiography and the LIJV cross-sectional area (CSA) was determined by ultrasonography. Results: Twenty-four children were included (median age and weight of 3.5 months and 6.37 kg, respectively). The median CI observed at baseline and during IAH grades I, II, III, and IV were 3.65 L/min/m2 (IQR 3.12−4.03), 3.38 L/min/m2 (IQR 3.04−3.73), 3.16 L/min/m2 (IQR 2.70−3.53), 2.89 L/min/m2 (IQR 2.38−3.22), and 2.42 L/min/m2 (IQR 1.91−2.79), respectively. A 25% increase in the LIJV CSA area was achieved in 14 participants (58%) during the ACM. Conclusion: The ACM significantly increases IAP, causing severe reversible impairment in the cardiovascular system and is effective in distending the LIJV in just over half of the subjects. Even low levels of HIA can result in significant cardiac dysfunction in children. Therefore, health professionals should be aware of the negative hemodynamic repercussions caused by the increased IAP.

Safety of the Methotrexate-leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (BiobadaBrasil).

OBJECTIVE: To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi). METHODS: Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons. RESULTS: In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76-1.31, P = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36-0.88, P = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25-0.94, P = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16-0.65, P = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. CONCLUSION: In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.

Diagnosis and management of precocious sexual maturation: an updated review.

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.

Respiratory synchrony comparison between preterm and full-term neonates using inertial sensors.

INTRODUCTION: Due to inefficient respiratory control, newborns become prone to asynchronous thoracoabdominal (TA) movements. The present study quantitatively estimated the synchrony of TA in preterm and full-term newborns through an inertial and magnetic measurement units (IMMUs) system. METHODS: This cross-sectional study was conducted with 20 newborns divided into Preterm Group (PTG, n = 10) and Full-Term Group (FTG, n = 10). Each neonate had IMMUs placed on the sternum and near the umbilicus, thus the TA motion was estimated through the resultant inclination angles calculated using a sensor fusion filter. The respiratory incursions were also manually counted and video-recorded for two minutes, then used to validate a Matlab custom-written routine for their automatic identification. The respiratory cycles were used to calculate the phase change angle (φ) between the thoracic and abdominal compartments. Association between the manual and automatic methods were verified by Pearson's correlation and root mean squared errors (RMSE), and the comparison between the groups was performed through the Student's t test with α = .05. RESULTS: The values of respiratory incursions measured by both methods showed a high association and low measurement error (r = .96, RMSE = 9.8, p < .001). The FTG presented a higher occurrence of TA synchrony (p = .049) while the PTG group presented a higher occurrence of TA asynchrony (p = .036). No difference was found between the groups regarding the paradoxical classification (p = .071). CONCLUSION: The proposed method was valid to quantitatively assess the TA synchrony of hospitalized neonates. Preterm infants had a higher occurrence of the asynchronous respiratory pattern in comparison to full-term infants.

Hemodynamic effects of increased intra-abdominal pressure in critically ill children.

OBJECTIVE: To evaluate the influence of intra-abdominal pressure on the cardiac index (CI) at different intra-abdominal hypertension grades achieved when performing an abdominal compression maneuver (ACM). Evaluating the effectiveness of the ACM in distending the left internal jugular vein (LIJV). METHODS: Prospective observational study conducted in the PICU of a quaternary care teaching hospital. Participants underwent the ACM and the IAP was measured with an indwelling urinary catheter. At each IAH grade reached during the ACM, the CI was measured by transthoracic echocardiography and the LIJV cross-sectional area (CSA) was determined by ultrasonography. RESULTS: Twenty-four children were included (median age and weight of 3.5 months and 6.37kg, respectively). The median CI observed at baseline and during IAH grades I, II, III, and IV were 3.65L/min/m2 (IQR 3.12-4.03), 3.38L/min/m2 (IQR 3.04-3.73), 3.16L/min/m2 (IQR 2.70-3.53), 2.89L/min/m2 (IQR 2.38-3.22), and 2.42L/min/m2 (IQR 1.91-2.79), respectively. A 25% increase in the LIJV CSA area was achieved in 14 participants (58%) during the ACM. CONCLUSION: The ACM significantly increases IAP, causing severe reversible impairment in the cardiovascular system and is effective in distending the LIJV in just over half of the subjects. Even low levels of HIA can result in significant cardiac dysfunction in children. Therefore, health professionals should be aware of the negative hemodynamic repercussions caused by the increased IAP.