Artigos e Materiais de Revistas Científicas - FM/MCM

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
A single session of aerobic exercise reduces systolic blood pressure at rest and in response to stress in women with rheumatoid arthritis and hypertension
(2024) LUNA, Tatiane Almeida de; REZENDE, Diego Augusto Nunes; BRITO, Leandro Campos de; FECCHIO, Rafael Yokoyama; LIMA, Fernanda Rodrigues; PINTO, Ana Lucia de Sa; RIBEIRO, Ana Cristina de Medeiros; BONFIGLIOLI, Karina Rossi; GUALANO, Bruno; ROSCHEL, Hamilton; PECANHA, Tiago
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by increased risk of cardiovascular disease and hypertension (HT). A single session of aerobic exercise may reduce blood pressure (BP) in different clinical groups; however, little is known about the acute effects of exercise on BP in RA patients. This is a randomized controlled crossover study that assessed the effects of a single session of aerobic exercise on resting BP, on BP responses to stressful stimuli, and on 24-h BP in women with RA and HT. Twenty women with RA and HT (53 +/- 10 years) undertook sessions of 30-min treadmill exercise (50% VO2max) or control (no exercise) in a crossover fashion. Before and after the sessions, BP was measured at rest, and in response to the Stroop-Color Word Test (SCWT), the Cold Pressor Test (CPT), and an isometric handgrip test. After the sessions, participants were also fitted with an ambulatory BP monitor for the assessment of 24-h BP. A single session of exercise reduced resting systolic BP (SBP) (-5 +/- 9 mmHg; p < 0.05), and reduced SBP response to the SCWT (-7 +/- 14 mmHg; p < 0.05), and to the CPT (-5 +/- 11 mmHg; p < 0.05). Exercise did not reduce resting diastolic BP (DBP), BP responses to the isometric handgrip test or 24-h BP. In conclusion, a single session of aerobic exercise reduced SBP at rest and in response to stressful stimuli in hypertensive women with RA. These results support the use of exercise as a strategy for controlling HT and, hence, reducing cardiovascular risk in women with RA.
The Prolonged Activation of the p65 Subunit of the NF-Kappa-B Nuclear Factor Sustains the Persistent Effect of Advanced Glycation End Products on Inflammatory Sensitization in Macrophages
(2024) ASSIS, Sayonara Ivana Santos de; AMENDOLA, Leonardo Szalo; OKAMOTO, Maristela Mitiko; FERREIRA, Guilherme da Silva; IBORRA, Rodrigo Tallada; SANTOS, Danielle Ribeiro; SANTANA, Monique de Fatima Mello; SANTANA, Kelly Gomes; CORREA-GIANNELLA, Maria Lucia; BARBEIRO, Denise Frediani; SORIANO, Francisco Garcia; MACHADO, Ubiratan Fabres; PASSARELLI, Marisa
Advanced glycation end products (AGEs) prime macrophages for lipopolysaccharide (LPS)-induced inflammation. We investigated the persistence of cellular AGE-sensitization to LPS, considering the nuclear content of p50 and p65 nuclear factor kappa B (NFKB) subunits and the expression of inflammatory genes. Macrophages treated with control (C) or AGE-albumin were rested for varying intervals in medium alone before being incubated with LPS. Comparisons were made using one-way ANOVA or Student t-test (n = 6). AGE-albumin primed macrophages for increased responsiveness to LPS, resulting in elevated levels of TNF, IL-6, and IL-1beta (1.5%, 9.4%, and 5.6%, respectively), compared to C-albumin. TNF, IL-6, and IL-1 beta secretion persisted for up to 24 h even after the removal of AGE-albumin (area under the curve greater by 1.6, 16, and 5.2 times, respectively). The expressions of Il6 and RelA were higher 8 h after albumin removal, and Il6 and Abca1 were higher 24 h after albumin removal. The nuclear content of p50 remained similar, but p65 showed a sustained increase (2.9 times) for up to 24 h in AGE-albumin-treated cells. The prolonged activation of the p65 subunit of NFKB contributes to the persistent effect of AGEs on macrophage inflammatory priming, which could be targeted for therapies to prevent complications based on the AGE-RAGE-NFKB axis.
Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation
(2024) DIAZ, Ana Claudia Marques Barbosa; WITKIN, Steven Sol; ALMEIDA-NETO, Cesar de; MENDRONE-JUNIOR, Alfredo; ROCHA, Vanderson; COSTA, Silvia Figueiredo; RAMOS, Jessica Fernandes; MENDES-CORREA, Maria Cassia
Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.
How Do You Treat Spinal Stenosis in the Geriatric Population in Your Practice?
(2023) GARCIA, Yolanda Maria; CASAGRANDE, Amanda Victoria; SANTOS, Gabriela Rodrigues dos; PAULA, Tais Pinto de
Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic
(2021) SANTOMAURO, Damian F.; HERRERA, Ana M. Mantilla; SHADID, Jamileh; ZHENG, Peng; ASHBAUGH, Charlie; PIGOTT, David M.; ABBAFATI, Cristiana; ADOLPH, Christopher; AMLAG, Joanne O.; ARAVKIN, Aleksandr Y.; BANG-JENSEN, Bree L.; BERTOLACCI, Gregory J.; BLOOM, Sabina S.; CASTELLANO, Rachel; CASTRO, Emma; CHAKRABARTI, Suman; CHATTOPADHYAY, Jhilik; COGEN, Rebecca M.; COLLINS, James K.; DAI, Xiaochen; DANGEL, William James; DAPPER, Carolyn; DEEN, Amanda; ERICKSON, Megan; EWALD, Samuel B.; FLAXMAN, Abraham D.; FROSTAD, Joseph Jon; FULLMAN, Nancy; GILES, John R.; GIREF, Ababi Zergaw; GUO, Gaorui; HE, Jiawei; HELAK, Monika; HULLAND, Erin N.; IDRISOV, Bulat; LINDSTROM, Akiaja; LINEBARGER, Emily; LOTUFO, Paulo A.; LOZANO, Rafael; MAGISTRO, Beatrice; MALTA, Deborah Carvalho; MANSSON, Johan C.; MARINHO, Fatima; MONASTA, Ali H. Mokdad Lorenzo; NAIK, Paulami; NOMURA, Shuhei; O'HALLORAN, James Kevin; OSTROFF, Samuel M.; PASOVIC, Maja; PENBERTHY, Louise; REINER JR., Robert C.; REINKE, Grace; RIBEIRO, Antonio Luiz P.; SHOLOKHOV, Aleksei; SORENSEN, Reed J. D.; VARAVIKOVA, Elena; VO, Anh Truc; WALCOTT, Rebecca; WATSON, Stefanie; WIYSONGE, Charles Shey; ZIGLER, Bethany; HAY, Simon I.; VOS, Theo; MURRAY, Christopher J. L.; WHITEFORD, Harvey A.; FERRARI, Alize J.
Background Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020. Methods We conducted a systematic review of data reporting the prevalence of major depressive disorder and anxiety disorders during the COVID-19 pandemic and published between Jan 1, 2020, and Jan 29, 2021. We searched PubMed, Google Scholar, preprint servers, grey literature sources, and consulted experts. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population during the COVID-19 pandemic and had a pre-pandemic baseline. We used the assembled data in a meta-regression to estimate change in the prevalence of major depressive disorder and anxiety disorders between pre-pandemic and mid-pandemic (using periods as defined by each study) via COVID-19 impact indicators (human mobility, daily SARS-CoV-2 infection rate, and daily excess mortality rate). We then used this model to estimate the change from pre-pandemic prevalence (estimated using Disease Modelling Meta-Regression version 2.1 [known as DisMod-MR 2.1]) by age, sex, and location. We used final prevalence estimates and disability weights to estimate years lived with disability and disability-adjusted life-years (DALYs) for major depressive disorder and anxiety disorders. Findings We identified 5683 unique data sources, of which 48 met inclusion criteria (46 studies met criteria for major depressive disorder and 27 for anxiety disorders). Two COVID-19 impact indicators, specifically daily SARS-CoV-2 infection rates and reductions in human mobility, were associated with increased prevalence of major depressive disorder (regression coefficient [B] 0.9 [95% uncertainty interval 0.1 to 1.8; p=0.029] for human mobility, 18.1 [7.9 to 28.3; p=0.0005] for daily SARS-CoV-2 infection) and anxiety disorders (0.9 [0.1 to 1.7; p=0.022] and 13.8 [10.7 to 17.0; p<0.0001]. Females were affected more by the pandemic than males (B 0.1 [0.1 to 0.2; p=0.0001] for major depressive disorder, 0.1 [0.1 to 0.2; p=0.0001] for anxiety disorders) and younger age groups were more affected than older age groups (-0.007 [-0.009 to -0.006; p=0.0001] for major depressive disorder, -0.003 [-0.005 to -0.002; p=0.0001] for anxiety disorders). We estimated that the locations hit hardest by the pandemic in 2020, as measured with decreased human mobility and daily SARS-CoV-2 infection rate, had the greatest increases in prevalence of major depressive disorder and anxiety disorders. We estimated an additional 53.2 million (44.8 to 62.9) cases of major depressive disorder globally (an increase of 27.6% [25.1 to 30.3]) due to the COVID-19 pandemic, such that the total prevalence was 3152.9 cases (2722.5 to 3654.5) per 100 000 population. We also estimated an additional 76.2 million (64.3 to 90.6) cases of anxiety disorders globally (an increase of 25.6% [23.2 to 28.0]), such that the total prevalence was 4802.4 cases (4108.2 to 5588.6) per 100 000 population. Altogether, major depressive disorder caused 49.4 million (33.6 to 68.7) DALYs and anxiety disorders caused 44.5 million (30.2 to 62.5) DALYs globally in 2020. Interpretation This pandemic has created an increased urgency to strengthen mental health systems in most countries. Mitigation strategies could incorporate ways to promote mental wellbeing and target determinants of poor mental health and interventions to treat those with a mental disorder. Taking no action to address the burden of major depressive disorder and anxiety disorders should not be an option.
Genomic landscapes of ovarian clear cell carcinoma from latin countries reveal aberrations linked to survival and progression
(2023) BATISTA, Mariana de Paiva; ROFFE, Martin; ROMERO, Ignacio; LOPEZ-GUERRERO, Jose Antonio; ILLUECA, Carmen; LOPEZ, Raquel; COSTA, Alexandre Andre Balieiro Anastacio da; BROT, Louise De; MOLINA, Juan Pablo; BARBOZA, Laura; PERIA, Fernanda Maris; CHAUD, Fernando; YAMADA, Ana Silvia Gouvea; POVEDA, Andres; REGO, Eduardo Magalhaes
BackgroundOvarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries.MethodsHere, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations.ResultsThe median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes.ConclusionsOur results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs.
Measurement of uncertainty tolerance revisited
(2023) POCO, Paula Cristina Eiras; COLLARES, Carlos Fernando; HAYDAR, Ahmed; OLIVEIRA, Victor Braga de; MARTINS, Milton de Arruda; TEMPSKI, Patricia Zen
IntroductionUncertainty tolerance (UT) is attracting increasing attention in medical education due to the numerous challenges associated with uncertainty in professional life. Inconsistencies in analysing the relationship between UT and moderators may arise from inadequate measurement methods. Most instruments were formulated before the most widely accepted framework was published. Our aim was to investigate the validity of an UT scale using an actual framework to corroborate with better and accurate instruments. MethodsA total of 1052 students were invited. Various psychometric methods were used to explore validity of the TAMSAD scale in light of actual framework. Classic exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed. Secondly, content item classification was triangulated with exploratory graph analysis (EGA), and the new EFA, CFA, and cognitive diagnostic modelling (CDM) analysis were conducted. The reliability was calculated using Cronbach's alpha and McDonald's omega. ResultsA total of 694 students (65.9%) responded to the questionnaire. The reliability of the TAMSAD scale was 0.782. The initial EFA revealed no clear interpretable dimensions. The TAMSAD scale items can be classified into sources of uncertainty. The EGA has three dimensions, and the new EFA led to a 17-item TAMSAD scale with the following three dimensions: ambiguity, complexity, and probability. These dimensions lead to better adjustment fit indices in the new CFA and CDM analyses. ConclusionWe found evidence that the TAMSAD scale can be considered a multidimensional scale, organised in terms of sources of uncertainty.
Global Burden of Cardiovascular Diseases and Risks, 1990-2022
(2023) MENSAH, George A.; FUSTER, Valentin; MURRAY, Christopher J. L.; ROTH, Gregory A.
Soluble MICA in endometriosis pathophysiology: Impairs NK cell degranulation and effector functions
(2024) MARIN, Maria Lucia Carnevale; RACHED, Marici Rached; MONTEIRO, Sandra Maria; KALIL, Jorge; ABRAO, Mauricio Simoes; COELHO, Veronica
Problem: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain-related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell-deficient activity in endometriosis. Methods of study: sMICA levels (serum and peritoneal fluid-PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN-gamma and IL-10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. Results: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56(dim)CD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN-gamma expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA-blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. Conclusions: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN-gamma response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.
Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis
(2023) RHEAULT, Michelle N.; ALPERS, Charles E.; BARRATT, Jonathan; BIELER, Stewart; CANETTA, Pietro; CHAE, Dong-Wan; COPPOCK, Gaia; DIVA, Ulysses; GESUALDO, Loreto; HEERSPINK, Hiddo J. L.; INRIG, Jula K.; KIRSZTAJN, Gianna M.; KOHAN, Donald; KOMERS, Radko; KOOIENGA, Laura A.; LIEBERMAN, Kenneth; MERCER, Alex; NORONHA, Irene L.; PERKOVIC, Vlado; RADHAKRISHNAN, Jai; ROTE, William; ROVIN, Brad; TESAR, Vladimir; TRIMARCHI, Hernan; TUMLIN, James; WONG, Muh Geot; TRACHTMAN, Howard
BackgroundAn unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin-angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown.MethodsIn this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of <= 1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated.ResultsA total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P=0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 m(2) of body-surface area per year (95% confidence interval [CI], -1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 m(2) per year (95% CI, -1.3 to 3.0). The mean change in eGFR from baseline to week 112 was -10.4 ml per minute per 1.73 m(2) with sparsentan and -12.1 ml per minute per 1.73 m(2) with irbesartan (difference, 1.8 ml per minute per 1.73 m2; 95% CI, -1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups.ConclusionsAmong patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.)
Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty
(2023) DUCKETT, Katie; WILLIAMSON, Alice; KINCAID, John W. R.; RAINBOW, Kara; CORBIN, Laura J.; MARTIN, Hilary C.; EBERHARDT, Ruth Y.; HUANG, Qin Qin; HURLES, Matthew E.; HE, Wen; BRAUNER, Raja; DELANEY, Angela; DUNKEL, Leo; GRINSPON, Romina P.; HALL, Janet E.; HIRSCHHORN, Joel N.; HOWARD, Sasha R.; LATRONICO, Ana C.; JORGE, Alexander A. L.; MCELREAVEY, Ken; MERICQ, Veronica; MERINO, Paulina M.; PALMERT, Mark R.; PLUMMER, Lacey; REY, Rodolfo A.; REZENDE, Raissa C.; SEMINARA, Stephanie B.; SALNIKOV, Kathryn; BANERJEE, Indraneel; LAM, Brian Y. H.; PERRY, John R. B.; TIMPSON, Nicholas J.; CLAYTON, Peter; CHAN, Yee-Ming; ONG, Ken K.; O'RAHILLY, Stephen
Context The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown. Objective This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Methods We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort. Results MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged & GE;16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07). Conclusion We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype.
Trans-ethnic genomic informed risk assessment for Alzheimer's disease: An International Hundred K plus Cohorts Consortium study
(2023) SLEIMAN, Patrick M.; QU, Hui-Qi; CONNOLLY, John J.; MENTCH, Frank; PEREIRA, Alexandre; LOTUFO, Paulo A.; TOLLMAN, Stephen; CHOUDHURY, Ananyo; RAMSAY, Michele; KATO, Norihiro; OZAKI, Kouichi; MITSUMORI, Risa; JEON, Jae-Pil; HONG, Chang Hyung; SON, Sang Joon; ROH, Hyun Woong; LEE, Dong-gi; MUKADAM, Naaheed; FOOTE, Isabelle F.; MARSHALL, Charles R.; BUTTERWORTH, Adam; PRINS, Bram P.; GLESSNER, Joseph T.; HAKONARSON, Hakon
BackgroundAs a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD). MethodsThe GIRA model was created to include polygenic risk score calculated from the AD genome-wide association study loci, the apolipoprotein E haplotypes, and non-genetic covariates including age, sex, and the first three principal components of population substructure. ResultsWe validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD. ConclusionsAs the initial effort by the IHCC to leverage existing large-scale datasets in a collaborative setting with DAC, we developed a trans-ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications.
Dynapenia and sarcopenia: association with the diagnosis, duration and complication of type 2 diabetes mellitus in ELSA-Brasil
(2024) SANTOS, Debora Noara Duarte dos; COELHO, Carolina Gomes; DINIZ, Maria de Fatima Haueisen Sander; DUNCAN, Bruce Bartholow; SCHMIDT, Maria Ines; BENSENOR, Isabela Judith Martins; SZLEJF, Claudia; TELLES, Rosa Weiss; BARRETO, Sandhi Maria
Sarcopenia (the loss of muscle mass, strength and skeletal muscle function) increases mortality and the risk of hospitalization in the older population. Although it is known that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of dynapenia and sarcopenia, few studies have investigated these conditions in middle-aged populations. The objective of this study was to investigate whether T2DM, its duration, the presence of albuminuria, and glycemic control are associated with sarcopenia and its components in adults. The cross-sectional analysis was based on data from visit 2 of the Brazilian Longitudinal Study of Adult Health (2012-2014 ). The 2018 European Working Group on Sarcopenia in Older People criteria were used to define dynapenia, low appendicular muscle mass (LAMM), and sarcopenia (absent/ probable/confirmed). The explanatory variables were: T2DM; duration of T2DM; T2DM according to the presence of albuminuria; and glycemic control (HbA1C < 7%) among people with T2DM. A total of 12,132 participants (mean age = 55.5, SD: 8.9 years) were included. The odds ratio for LAMM was greater among those with T2DM, T2DM duration from 5 to 10 years, and T2DM without albuminuria. Chances of dynapenia were higher among those with T2DM, T2DM duration > 10 years, and T2DM with and without albuminuria. The variables T2DM, T2DM >= 10 years, and T2DM with albuminuria increased the odds of probable sarcopenia, and T2DM duration from 5 to 10 years increased the odds of confirmed sarcopenia. The results support the importance of frequently monitoring the musculoskeletal mass and strength of individuals with T2DM to prevent sarcopenia and related outcomes.
Management of cardiovascular risk in SLE
(2020) UROWITZ, Murray; BONFA, Eloisa; PONS-ESTEL, Bernardo
Life Satisfaction and Ideal Cardiovascular Health Score: A Cross-Sectional Study From ELSA-Brasil
(2024) SANTOS, Aline E.; CAMELO, Lidyane V.; SANTOS, Itamar S.; GRIEP, Rosane H.; BENSENOR, Isabela J.; BARRETO, Sandhi M.; GIATTI, Luana
Objectives: To investigate whether higher levels of life satisfaction are associated with a higher ideal cardiovascular health (CVH) score in middle-aged and older populations in the Brazilian context. Method: Cross-sectional analysis of 12,936 participants of the Brazilian Longitudinal Study of Adult Health, Visit 2 (2012-2014), aged 38-79 years. The response variables were the global, lifestyle, and biological ideal CVH scores, as defined by the American Heart Association Life's Simple 7. The scores were categorized as low, intermediate, and optimal. Life satisfaction was measured by the Satisfaction with the Life Scale. Multinomial logistic regression was used to estimate the magnitude with adjustment for potential confounding factors. Low scores were the categories of reference for the analyses. Results: Only 10.5% of the participants had an optimal (>= 5) global ideal CVH score. After total adjustment, 1 SD increment in the life satisfaction score was associated with an odds ratio (OR) of 1.05 (95% confidence interval [CI: 1.01-1.09]) and 1.15 (95% CI [1.07-1.23]) for intermediate and optimal global ideal CVH scores, respectively. Regarding the lifestyle ideal CVH score, the increment of 1 SD in the life satisfaction scale determined an OR of 1.11 (95% CI [1.06-1.15]) and 1.22 (95% CI [1.14-1.31]) for intermediate and optimal lifestyle ideal CVH score, respectively. Life satisfaction was not associated with the biological ideal CVH score. Conclusion: The results suggested that the higher the life satisfaction, the higher the CVH. The findings add to the knowledge of assets to promote CVH. Public Significance Statement There is a growing interest in the health-protective effect of life satisfaction. These findings based on middle-aged and older Brazilians indicated that higher life satisfaction was related to better global cardiovascular health (CVH). The results also suggest that life satisfaction is more related to healthy lifestyle behaviors than subclinical CVH.
Prospective study of consecutive patch testing in patients with contact dermatitis using an adapted Latin American baseline series
(2023) BELLUCO, Paulo Eduardo Silva; GIAVINA-BIANCHI, Pedro; BELLUCO, Rosana Zabulon Feijo; NOVAES, Maria Rita Carvalho garbi; REIS, Carmelia Matos Santiago
Background. Contact dermatitis is characterized by pruritic skin lesions with high prevalence rates. Our objective is to describe the clinical and epidemiological characteristics of a population with suspected contact dermatitis who underwent to a patch testing using an adapted Latin American baseline series. Methods. Observational, descriptive, analytical clinical study with prospective data collection was performed. 208 participants who underwent patch testing using an adapted Latin American baseline series containing 40 allergens were analyzed. The prevalence of contact allergies was compared with data from the literature. Pearson's chi-square test was used for qualitative variables. Quantitative variables were compared using the Mann-Whitney U test. The significance of the regression parameters was tested using the Wald statistical test. Results. A total of 69.7% had one or more positive tests. Among those, 82.8% were women (OR 1.371; p = 0.398). The hands were the most commonly affected site at 43%. An occupational history was detected in 19.2%. The most common allergens were nickel sulfate (32.2%), sodium tetrachloropalladate (19.7%), fragrance mix I (15.4%), and methylisothiazolinone (13.5%). In multivariate logistic regression models, nickel was significantly related to female sex, as well as palladium. Fragrance mix I was related to a family history of allergy (p < 0.05). Methylisothiazolinone was statistically significantly related to face and hand lesions. Conclusions. This study demonstrated a detailed profile of a population with suspected allergic contact dermatitis. Our patch test results, using an adapted Latin American baseline series, represent a significant update of this important diagnostic tool.
Acute promyelocytic leukaemia in lowincome and middle income countries: a Brazilian experience
(2024) PEREIRA-MARTINS, Diego A.; WEINHAEUSER, Isabel; COELHO-SILVA, Juan L.; AMMATUNA, Emanuele; HULS, Geruin; SCHURINGA, Jan Jacob; REGO, Eduardo M.; LUCENA-ARAUJO, Antonio R.
Professional values at the beginning of medical school: a quasi-experimental study
(2024) VILAGRA, Sandra; VILAGRA, Marlon; GIAXA, Renata; MIGUEL, Alice; VILAGRA, Lahis W.; KEHL, Mariana; MARTINS, Milton A.; TEMPSKI, Patricia
BackgroundTeaching professionalism in medical schools is central to medical education and society. We evaluated how medical students view the values of the medical profession on their first day of medical school and the influence of a conference about the competences of this profession on these students' levels of reflection.MethodsWe studied two groups of medical students who wrote narratives about the values of the medical profession and the influence of the COVID-19 pandemic on these values. The first group wrote the narratives after a conference about the competences of the medical profession (intervention group), and the second group wrote the same narratives after a biochemistry conference (control group). We also compared the levels of reflection of these two groups of students.ResultsAmong the 175 medical students entering in the 2022 academic year, 159 agreed to participate in the study (response rate = 90.8%). There were more references to positive than negative models of doctor-patient relationships experienced by the students (58.5% and 41.5% of responses, respectively). The intervention group referred to a more significant number of values than the control group did. The most cited values were empathy, humility, and ethics; the main competences were technical competence, communication/active listening, and resilience. The students' perspectives of the values of their future profession were strongly and positively influenced by the pandemic experience. The students realized the need for constant updating, basing medical practice on scientific evidence, and employing skills/attitudes such as resilience, flexibility, and collaboration for teamwork. Analysis of the levels of reflection in the narratives showed a predominance of reflections with a higher level in the intervention group and of those with a lower level in the control group.ConclusionsOur study showed that medical students, upon entering medical school, already have a view of medical professionalism, although they still need to present a deeper level of self-reflection. A single, planned intervention in medical professionalism can promote self-reflection. The vision of medical professional identity was strongly influenced by the COVID-19 pandemic, positively impacting the formation of a professional identity among the students who decided to enter medical school.
Assessment of Bone Microarchitecture in Patients with Systemic Mastocytosis and its Association with Clinical and Biochemical Parameters of the Disease
(2023) FRANCO, Andre S.; MURAI, Igor H.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; MARCHI, Luan L.; VELLOSO, Elvira D. R. P.; PEREIRA, Rosa M. R.
Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (rho, 0.46; P = 0.036) and tibia (rho, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (rho, -0.46; P = 0.035) and tibia (rho, -0.52; P = 0.016). Strong and positive associations between F.load (rho, 0.75; P < 0.001) and stiffness (rho, 0.70; P < 0.001) at the radius, and between F.load at the tibia (rho, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength.

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