Cyclopenta[b]indoles as novel antimicrotubule agents with antileukemia activity.

Acute leukemias present therapeutic challenges despite advances in treatments. Microtubule inhibitors have played a pivotal role in cancer therapy, inspiring exploration into novel compounds like C2E1 from the cyclopenta[b]indole class. In the present study, we investigated C2E1's potential as a therapeutic agent for acute leukemia at molecular, cellular, and genetic levels. C2E1 demonstrated tubulin depolarization activity, significantly reducing leukemia cell viability. Its impact involved multifaceted mechanisms: inducing apoptosis, arrest of cell cycle progression, and inhibition of clonogenicity and migration in leukemia cells. At a molecular level, C2E1 triggered DNA damage, antiproliferative, and apoptosis markers and altered gene expression related to cytoskeletal regulation, disrupting essential cellular processes crucial for leukemia cell survival and proliferation. These findings highlight C2E1's promise as a potential candidate for novel anti-cancer therapies. Notably, its distinct mode of action from conventional microtubule-targeting drugs suggests the potential to bypass common resistance mechanisms encountered with existing treatments. In summary, C2E1 emerges as a compelling compound with diverse effects on leukemia cells, showcasing promising antineoplastic properties. Its ability to disrupt critical cellular functions selective to leukemia cells positions it as a candidate for future therapeutic development.

Intraoperative radiofrequency ablation for unresectable abdominal paraganglioma: a case report.

For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range <0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.

Giant endometrioma in an asymptomatic patient.

Endometriosis is a chronic inflammatory gynecologic disorder characterized by the presence of endometrial-like tissue, including endometrial glands and stroma, outside of the uterine cavity. It is a prevalent condition worldwide, affecting approximately 10% of reproductive-age women and up to 50% of infertile women. Endometriosis manifests in three ways: superficial peritoneal endometriosis, deep infiltrative endometriosis, and ovarian endometriomas, with the possibility of coexistence among them. The disease presents with a range of symptoms, including chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Additionally, patients may experience nongynecological symptoms such as dyschezia, dysuria, hematuria, flank pain, and fatigue, among others. The ovaries are the most affected site in endometriosis, typically with cysts measuring less than 6 cm in diameter. Therefore, even in the presence of a large ovarian cyst or in asymptomatic patients, the consideration of an endometrial cyst should not be overlooked.

The challenges to control epilepsy in an isolated indigenous tribe in Brazil's Amazon: 15 years of follow-up / Os desafios do controle de epilepsia em indígenas de uma tribo isolada da Amazônia: 15 anos de seguimento

Abstract Background Epilepsy is a common neurological disease that affects people all over the world, but it is rarely described in indigenous peoples. Objective To study the epilepsy characteristics and risk factors for seizure control in people from an isolated indigenous population. Methods This is a retrospective and historical cohort study conducted from 2003 to 2018 (15 years), at a neurology outpatient clinic, of 25 Waiwai tribes' indigenous individuals with epilepsy, inhabitants of an isolated forest reserve in the Amazon. Clinical aspects, background, comorbidities, exams, treatment, and response were studied. Factors that impacted seizure control over 24 months were identified using Kaplan-Meier curves and Cox and Weibull regression models. Results The majority of cases started in childhood, with no difference regarding gender. Focal epilepsies were predominant. Most patients had tonic-clonic seizures. A quarter of them had a family history, and 20% had referred febrile seizures. There was intellectual disability in 20% of patients. Neurological examination and psychomotor development were altered in one third of the participants. The treatment controlled 72% of the patients (monotherapy in 64%). Phenobarbital was the most prescribed anti-seizure medication, followed by carbamazepine and valproate. The most relevant factors that impacted seizure control over time were abnormal neurological exam and family history. Conclusion Family history and abnormal neurological exam were predicted risk factors for refractory epilepsy. Even in an isolated indigenous tribe, the partnership between the indigenous people and the multidisciplinary team ensured treatment adherence. The public healthcare system must guarantee modern anti-seizure medications, mainly for this vulnerable population, which has no other source of treatment.

Resumo Antecedentes A epilepsia é uma doença neurológica que afeta povos do mundo todo, mas raramente é descrita em povos indígenas. Objetivos Estudar as características da epilepsia e os fatores de risco para o controle das crises em pessoas de uma população indígena isolada. Métodos Este é um estudo de coorte retrospectivo e histórico, conduzido de 2003 a 2018 (15 anos) no ambulatório de neurologia, de 25 indígenas Waiwai com epilepsia, habitantes de uma reserva florestal na Amazônia. Aspectos clínicos, antecedentes, comorbidades, exames, tratamento e resposta foram estudados. Identificou-se os fatores que afetaram o controle das crises ao longo de 24 meses usando curvas de Kaplan-Meier e modelos de regressão de Cox e Weibull. Resultados A maioria dos casos teve início na infância, sem diferença quanto ao gênero. Predominavam as epilepsias focais. A maioria dos pacientes apresentava crises tônico-clônicas. Um quarto deles tinha história familiar e 20% referiram convulsões febris. Vinte por cento dos pacientes apresentava deficiência intelectual. Um terço tinha exame neurológico e desenvolvimento psicomotor alterados. O tratamento controlou 72% dos pacientes (monoterapia em 64%). Fenobarbital foi o medicamento mais prescrito, seguido por carbamazepina e valproate, e os fatores que mais impactaram o controle das crises ao longo do tempo foram exame neurológico anormal e história familiar. Conclusão História familiar e exame neurológico anormal foram fatores de risco preditores para epilepsia refratária. Mesmo em uma tribo indígena isolada, a parceria entre os indígenas e a equipe multidisciplinar garantiu a adesão ao tratamento. O sistema público de saúde deve garantir medicamentos modernos anticrise, principalmente para essa população vulnerável, que não tem outra fonte de tratamento.

Discovery of indolizine lactones as anticancer agents and their optimization through late-stage functionalization.

Indolizines fused with a seven-member lactone ring were identified as a promising scaffold in the search for new anticancer agents. Through a modular synthetic sequence, a library of cis and trans indolizines lactones had their antiproliferative activity evaluated against hormone-refractory prostate DU-145 and triple-negative breast MDA-MB-231 cancer cell lines. A methoxylated analogue was identified as an initial hit against MDA-MB-231 and late-stage functionalization of the indolizine core led to analogues within potencies up to twenty times higher than the parent precursor.

The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders / O eixo microbiota-intestino-cérebro no tratamento de desordens neurológicas e psiquiátricas

Abstract The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

Resumo A microbiota intestinal humana é um ecossistema complexo feito de trilhões de microrganismos, cuja composição pode ser afetada pela dieta, pelo metabolismo, pela idade, geografia, pelo estresse, pelas estações do ano, pela temperatura, pelo sono e por medicamentos. A crescente evidência sobre a existência de uma correlação estreita e bidirecional entre a microbiota intestinal e o cérebro indica que o desequilíbrio intestinal pode desempenhar um papel vital no desenvolvimento, na função e nos distúrbios do sistema nervoso central. Os mecanismos de interação entre a microbiota intestinal e a atividade neuronal são amplamente discutidos. Várias vias potenciais estão envolvidas com o eixo microbiota-intestino-cérebro, incluindo o nervo vago e as vias endócrinas, imunes e bioquímicas. A disbiose intestinal tem sido associada a distúrbios neurológicos de diferentes maneiras que envolvem a ativação do eixo hipotálamo-hipófise-adrenal, o desequilíbrio na liberação de neurotransmissores, a inflamação sistêmica e o aumento da permeabilidade das barreiras intestinal e hematoencefálica. As doenças mentais e neurológicas tornaram-se mais prevalentes durante a pandemia de coronavirus disease 2019 e são uma questão global essencial na saúde pública. Compreender a importância de diagnosticar, prevenir e tratar a disbiose é fundamental porque o desequilíbrio microbiano intestinal é um fator de risco significativo para esses distúrbios. Esta revisão resume as evidências que demonstram a influência da disbiose intestinal em distúrbios mentais e neurológicos.

Quality assessment of prostate MRI by PI-QUAL score: Inter-reader agreement and impact on prostate cancer local staging at 3 Tesla.

PURPOSE: To evaluate whether the Prostate Imaging Quality (PI-QUAL) score impacts prostate cancer (PCa) staging on MRI. The secondary goal was to test inter-reader agreement among radiologists experienced in prostate imaging. METHOD: A retrospective, single-center study with patients who underwent 3 Tesla prostate MRI scans and were submitted to radical prostatectomy (RP) between January 2018 and November 2021 and were eligible for our study. Extraprostatic extension (EPE) data were collected from original MR reports (EPEm) and pathological reports of RP specimens (EPEp). Three expert prostate radiologists (ESUR/ESUI criteria R1, R2, R3) independently evaluated all MRI exams according to PI-QUAL score for image quality (1 to 5; 1: poor, 5: excellent), blinded to original imaging reports and clinical data. We studied the diagnostic performance of MRI using pooled data from PI-QUAL scores (≤3 vs. ≥4). We also performed univariate and multivariate analyses to assess the PI-QUAL score impact on local PCa staging. Cohen's K and Tau-b Kendall tests were used to assess the inter-reader agreement for PI-QUAL score, T2WI, DWI, and DCE. RESULTS: Our final cohort included 146 patients, of which 27.4% presented EPE on pathology. We observed no impact of imaging quality on accuracy for EPE prediction: AUC of 0.750 (95% CI 0.26-1) for PI-QUAL ≤ 3 and 0.705 (95% CI 0.618-0.793) for PI-QUAL ≥ 4. The multivariate analysis demonstrated a correlation of EPEm (OR 3.25, p 0.001) and ISUP grade group (OR 1.89, p 0.012) to predict EPEp. The inter-reader agreement was moderate to substantial (0.539 for R1-R2, 0.522 for R2-R3, and 0.694 for R1-R3). CONCLUSION: Our clinical impact evaluation showed no direct correlation between MRI quality by PI-QUAL score and accuracy in detecting EPE in patients undergoing RP. Additionally, we had moderate to a substantial inter-reader agreement for the PI-QUAL score.

Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.

CONTEXT: Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula. OBJECTIVE: Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs. METHODS: Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint. RESULTS: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin. CONCLUSION: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

Neurological symptoms and comorbidity profile of hospitalized patients with COVID-19 / Sintomas neurológicos e perfil de comorbidades de pacientes hospitalizados com COVID-19

Abstract Background The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. Objective To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. Methods Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. Results The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). Conclusion A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia.

Resumo Antecedentes As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. Objetivo Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. Métodos Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. Resultados A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91 % dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). Conclusão Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia.

Sleep disorders in multiple sclerosis: a case-control study using the São Paulo Epidemiologic sleep study (Episono) database / Alterações de sono em esclerose múltipla: um estudo caso-controle utilizando o banco de dados do São Paulo Epidemiologic Sleep Study (Episono)

Abstract Background Sleep disorders such as obstructive sleep apnea and restless legs syndrome are prevalent in the general population and patients with chronic diseases such as multiple sclerosis (MS). Objectives This study compared the prevalence of sleep disorders complaints, fatigue, depression, and chronotype of adult patients with multiple sclerosis (PwMS) to a representative sample of São Paulo city residents. Methods A comparative study was made between PwMS and volunteers from the São Paulo Epidemiologic Sleep Study (Episono) study. We compared the scores of sleep questionnaires using the multivariate analysis of variance (MANOVA) test to evaluate the effects and analysis of variance (ANOVA) as a follow-up test. Covariates were age, sex, and physical activity. The Pearson correlation test was performed to measure the correlation between Expanded Disability Status Scale (EDSS) and the scores of the sleep questionnaires. Finally, we applied propensity score matching to reduce bias in estimating differences between the two groups. Analyses were performed using Stata 14 (StataCorp, College Station, TX, USA) and IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, NY, USA). Results The Episono group had worse sleep quality, and more excessive daytime sleepiness than PwMS. Obstructive sleep apnea and restless legs syndrome were more frequent in the Episono group. There was no difference in chronotype between the two groups, with morning and intermediate preference. There was no correlation between EDSS and sleep complaints. Fatigue was intensively present among PwMS. Conclusions Disease Modifying Drug (DMD)-treated PwMS had a lower frequency of sleep complaints, no difference in chronotype, and a higher prevalence of fatigue than a sample of São Paulo city residents. The immunomodulatory drugs commonly used to treat MS may have contributed to these findings.

Resumo Antecedentes Os distúrbios do sono são prevalentes na população em geral e em pacientes com doenças crônicas, como a esclerose múltipla (EM). Objetivos No presente estudo, comparamos a prevalência de queixas de distúrbios do sono, fadiga, depressão e cronotipo de pacientes adultos com EM com uma amostra representativa dos moradores da cidade de São Paulo. Métodos Estudo comparativo entre pacientes com EM e voluntários saudáveis do estudo São Paulo Epidemiologic Sleep Study Episono. Comparamos as pontuações dos questionários de sono usando o teste de análise de variância multivariada (MANOVA, na sigla em inglês) para avaliar os efeitos e o teste de análise de variância (ANOVA, na sigla em inglês) como um teste de acompanhamento. As covariáveis usadas foram idade, gênero e atividade física. O teste de correlação de Pearson foi aplicado para medir a correlação entre o Expanded Disability Status Scale (EDSS) e os escores dos questionários de sono. Por fim, aplicamos o Propensity Score Matching para reduzir o viés na estimativa das diferenças entre os dois grupos. Resultados O grupo Episono apresentou pior qualidade do sono e mais sonolência excessiva diurna do que os pacientes com EM. A apneia obstrutiva do sono e a síndrome das pernas inquietas foram mais frequentes no grupo Episono. Não houve diferença no cronotipo entre os dois grupos, com predomínio matutino e intermediário. Os pacientes com EM apresentaram mais fadiga do que o grupo controle. Conclusões Pacientes com EM tratados apresentaram menor frequência de queixas de sono, sem diferença no cronotipo, com maior prevalência de fadiga do que uma amostra de moradores da cidade de São Paulo. Os medicamentos imunomoduladores comumente usados para tratar EM podem ter contribuído para estes achados.

Princípio bioético da autonomia na atenção à saúde indígena / The bioethical principle of autonomy in caring for the health of Indigenous peoples / Principio bioético de la autonomía en la atención a la salud indígena

Resumo Neste artigo busca-se caracterizar o respeito ao princípio da autonomia no atendimento a populações indígenas em território brasileiro, tendo por base relatos de experiência e uma revisão bibliográfica. Concluiu-se que esse princípio deve ser especialmente consolidado nas ações práticas de cuidado à saúde desenvolvidas com as populações de culturas diferenciadas, como é o caso das comunidades indígenas.

Abstract This article seeks to characterize the respect to the principle of autonomy in the care to indigenous peoples in the Brazilian territory, based on reports on experiences and a bibliographic review. It concluded that this principle must be specially consolidated in the practical actions of health care developed alongside peoples of different cultures, as is the case of indigenous communities.

Resumen Este artículo busca caracterizar el respeto en el principio de autonomía en la atención a las poblaciones indígenas en territorio brasileño a partir de informes de experiencia y revisión de la literatura. Se concluyó que este principio debe consolidarse especialmente en las acciones prácticas de asistencia sanitaria dirigidas a las poblaciones de diferentes culturas, como las comunidades indígenas.

Sleep disorders in Down syndrome: a systematic review / Distúrbios do sono na síndrome de Down: revisão sistemática

ABSTRACT Background: Sleep disorders are commonly observed in children with Down syndrome (DS) and can lead to significant behavioral and cognitive morbidities in these individuals. Objective: To perform a systematic review evaluating sleep disorders in individuals with DS. Methods: Search strategies were based on combinations of keywords: "Down syndrome"; "trisomy 21"; "sleep disorders"; "dyssomnias"; "sleep apnea"; "obstructive"; "sleeplessness"; "insomnia"; "parasomnias"; and "excessive daytime sleepiness". PubMed and Science Direct were used. Only original studies and retrospective reviews in English published between January 2011 and March 2021 were included. Results: 52 articles were included, most of them involving children and adolescents under 18 years of age. The main sleep disorder associated with DS was obstructive sleep apnea (OSA). Some studies reported the presence of cognitive dysfunction in patients with DS and sleep-disordered breathing, and few have been found about parasomnia, insomnia, and daytime sleepiness in these patients. Movement disorders and unusual postures during sleep may be related to disordered sleep breathing in DS. The main treatment options for OSA are continuous positive airway pressure therapy (CPAP), surgery, and weight control. Computational modeling associated with MRI has been used to plan surgical interventions in these patients. Conclusions: Individuals with DS are at high risk of developing sleep-related breathing disorders. The main sleep disorder associated with DS was OSA. The presence of sleep-disordered breathing contributes to a worsening of cognitive function in patients with DS.

RESUMO Antecedentes: Os distúrbios do sono são comumente observados em crianças com síndrome de Down (SD) e podem levar a morbidades comportamentais e cognitivas significativas nesses indivíduos. Objetivo: Realizar uma revisão sistemática para avaliar os distúrbios do sono em indivíduos com SD. Métodos: As estratégias de busca foram baseadas em combinações de palavras-chave: "Síndrome de Down"; "trissomia 21"; "distúrbios do sono"; "dissonias"; "apneia do sono"; "obstrutivo"; "insônia"; "insônia"; "parassonias" e "sonolência diurna excessiva". PubMed e Science Direct foram usados. Apenas estudos originais e revisão retrospectiva de prontuários escritos em inglês e publicados de janeiro de 2011 a março de 2021 foram incluídos. Resultados: Foram selecionados 52 artigos, a maioria com crianças e adolescentes menores de 18 anos. O principal distúrbio do sono associado à SD foi a apneia obstrutiva do sono (AOS). Alguns estudos relatam a presença de disfunção cognitiva em pacientes com SD e distúrbios respiratórios do sono, e poucos foram encontrados sobre parassonia, insônia e sonolência diurna nesses pacientes. Distúrbios do movimento e posturas incomuns durante o sono podem estar relacionados ao distúrbio respiratório do sono na SD. As principais opções de tratamento para AOS são pressão positiva contínua nas vias aéreas (CPAP), abordagem cirúrgica e controle de peso. A modelagem computacional associada à ressonância magnética tem sido usada para planejar intervenções cirúrgicas nesses pacientes. Conclusões: Indivíduos com SD apresentam alto risco de desenvolver distúrbios respiratórios relacionados ao sono. O principal distúrbio do sono associado à SD foi a AOS. A presença de distúrbios respiratórios do sono contribui para a piora das funções cognitivas em pacientes com SD.

Sleep disorders in Down syndrome: a systematic review.

BACKGROUND: Sleep disorders are commonly observed in children with Down syndrome (DS) and can lead to significant behavioral and cognitive morbidities in these individuals. OBJECTIVE: To perform a systematic review evaluating sleep disorders in individuals with DS. METHODS: Search strategies were based on combinations of keywords: "Down syndrome"; "trisomy 21"; "sleep disorders"; "dyssomnias"; "sleep apnea"; "obstructive"; "sleeplessness"; "insomnia"; "parasomnias"; and "excessive daytime sleepiness". PubMed and Science Direct were used. Only original studies and retrospective reviews in English published between January 2011 and March 2021 were included. RESULTS: 52 articles were included, most of them involving children and adolescents under 18 years of age. The main sleep disorder associated with DS was obstructive sleep apnea (OSA). Some studies reported the presence of cognitive dysfunction in patients with DS and sleep-disordered breathing, and few have been found about parasomnia, insomnia, and daytime sleepiness in these patients. Movement disorders and unusual postures during sleep may be related to disordered sleep breathing in DS. The main treatment options for OSA are continuous positive airway pressure therapy (CPAP), surgery, and weight control. Computational modeling associated with MRI has been used to plan surgical interventions in these patients. CONCLUSIONS: Individuals with DS are at high risk of developing sleep-related breathing disorders. The main sleep disorder associated with DS was OSA. The presence of sleep-disordered breathing contributes to a worsening of cognitive function in patients with DS.

The association between sleep disturbances and tooth loss among post-stroke patients / Prevalência de edentulismo e distúrbios de sono após acidente vascular cerebral

ABSTRACT Background: Loss of teeth has been associated with neurological and sleep disorders. It is considered to be a predictor of stroke and leads to modifications of airway patency and predisposition to obstructive sleep apnea. Objective: To investigate sleep quality, risk of obstructive sleep apnea and excessive sleepiness among post-stroke patients with tooth loss attending the Neurovascular Clinic of the Federal University of São Paulo. Methods: The prevalence rates of different types of stroke were assessed among 130 patients with different degrees of tooth loss, along with the presence of sleep disturbances, risk of obstructive sleep apnea and excessive daytime sleepiness. Results: The prevalence of ischemic stroke was 94.6%, with either no significant disability or slight disability. Our sample had poor sleep quality, and a high risk of obstructive sleep apnea, but without excessive daytime sleepiness. Half of our sample had lost between 9 and 31 teeth, and more than 25% had edentulism. The majority used full removable dental prostheses, and more than half of these individuals slept without removing the prosthesis. Conclusions: We found high prevalence of poor sleep quality and high risk of obstructive sleep apnea among post-stroke patients with tooth loss. This indicates the need for further studies on treating and preventing sleep disturbances in stroke patients with tooth loss.

RESUMO Antecedentes: A perda de dentes tem sido associada a distúrbios neurológicos e do sono. É considerada um preditor de acidente vascular cerebral (AVC), com modificações na permeabilidade das vias aéreas e predisposição à apneia obstrutiva do sono. Objetivo: Investigar a qualidade do sono, o risco de apneia obstrutiva do sono e a sonolência excessiva em pacientes pós-AVC com perda dentária, atendidos na Clínica Neurovascular da Universidade Federal de São Paulo. Métodos: O estudo avaliou a prevalência de diferentes tipos de AVC em 130 pacientes com diferentes graus de perda dentária e a presença de distúrbios do sono, risco de apneia obstrutiva do sono e sonolência excessiva. Resultados: A prevalência de AVC isquêmico foi de 94,6%, sem deficiência significativa ou deficiência leve. Nossa amostra tinha má qualidade de sono e alto risco de apneia obstrutiva do sono, sem sonolência diurna excessiva. Metade de nossa amostra perdeu entre nove e 31 dentes, e mais de 25% tiveram edentulismo. A maioria usava próteses dentárias totalmente removíveis e, desses pacientes, mais da metade dormia com elas. Conclusões: Encontramos alta prevalência de má qualidade do sono e alto risco de apneia obstrutiva do sono em pacientes pós-AVC com perda dentária. Isso indica a necessidade de mais estudos sobre o tratamento e a prevenção de distúrbios do sono em pacientes com AVC e perda dentária.

Acute organ failure and risk of admission to intensive medical care in cancer patients: a single center prospective cohort study. / Falência aguda de órgão e risco de admissão em unidade de terapia intensiva nos pacientes oncológicos: estudo de coorte prospectivo unicêntrico.

OBJECTIVE: To ascertain the cumulative incidence of acute organ failure and intensive care unit admission in cancer patients. METHODS: This was a single-center prospective cohort study of adult cancer patients admitted for unscheduled inpatient care while on systemic cancer treatment. RESULTS: Between August 2018 and February 2019, 10,392 patients were on systemic treatment, 358 had unscheduled inpatient care and were eligible for inclusion, and 285 were included. The mean age was 60.9 years, 50.9% were male, and 17.9% of patients had hematologic cancers. The cumulative risk of acute organ failure was 39.6% (95%CI: 35 - 44), and that of intensive care unit admission among patients with acute organ failure was 15.0% (95%CI: 12 - 18). On admission, 62.1% of patients were considered not eligible for artificial organ replacement therapy. The median follow-up time was 9.5 months. Inpatient mortality was 17.5%, with an intensive care unit mortality rate of 58.8% and a median cohort survival of 134 days (95%CI: 106 - 162). In multivariate analysis, acute organ failure was associated with 6-month postdischarge mortality (HR 1.6; 95%CI: 1.2 - 2.2). CONCLUSION: The risk of acute organ failure in cancer patients admitted for unscheduled inpatient care while on systemic treatment was 39.6%, and the risk of intensive care unit admission was 15.0%. Acute organ failure in cancer patients was an independent poor prognostic factor for inpatient hospital mortality and 6-month survival.

OBJETIVO: Determinar a incidência cumulativa de falência aguda de órgão e internamento em unidade de terapia intensiva em pacientes oncológicos. MÉTODOS: Estudo de coorte prospectivo de pacientes oncológicos adultos em tratamento sistêmico antineoplásico, internados de forma não programada. RESULTADOS: Entre agosto de 2018 e fevereiro de 2019, 10.392 pacientes foram submetidos a tratamento sistêmico antineoplásico, sendo que 358 necessitaram de internamento hospitalar não programado e foram elegíveis para inclusão; por fim, 258 desses pacientes foram incluídos. A média de idade foi de 60,9 anos, e 50,9% eram do sexo masculino; 17,9% dos pacientes tinham câncer hematológico. O risco acumulado de falência de órgãos foi de 39,6% (IC95% 35 - 44) e o risco de internamento na unidade de terapia intensiva em pacientes com falência aguda de órgão foi de 15,0% (IC95% 12 - 18). À admissão em internamento, 62,1% dos pacientes foram considerados não elegíveis para terapia de substituição artificial de órgãos. O tempo mediano de seguimento foi de 9,5 meses. A mortalidade hospitalar foi de 17,5%, na unidade de terapia intensiva de 58,8%. A mediana de sobrevivência da coorte foi de 134 dias (IC95% 106 - 162). Na análise multivariada, a falência aguda de órgão se associou com a mortalidade aos 6 meses após a alta (hazard ratio: 1,6; IC95% 1,2 - 2,2). CONCLUSÃO: O risco de falência aguda de órgão em pacientes oncológicos admitidos para tratamento hospitalar não programado durante o tratamento sistémico foi de 39,6% e o risco de internamento em unidade de terapia intensiva foi de 15,0%. A falência aguda de órgão em pacientes oncológicos foi um fator de prognóstico independente para maior mortalidade intra-hospitalar e menor sobrevivência aos 6 meses após a alta.

Does [18F]F-FDG-PET/MRI add metabolic information to magnetic resonance image in childhood-onset Takayasu's arteritis patients? A multicenter case series

Abstract Background: The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods: A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results: Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28-59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusions: Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

Prostate imaging features on magnetic resonance imaging of young patients

ABSTRACT Objective To identify magnetic resonance imaging findings of the prostate in young adults, including symptomatic and asymptomatic patients. The aim of this study is to evaluate the main aspects of prostate imaging in young patients. Methods A total of 102 patients under 40 years of age, who underwent prostate magnetic resonance imaging between January 2016 and January 2019, were included in this study. The patients were divided into two groups: symptomatic for prostatitis (Group 1) and asymptomatic (Group 2). Magnetic resonance imaging scans were anonymized and interpreted by a radiologist blinded for clinical information. The study evaluated peripheral zone signal in T2-weighted sequences, diffusion and apparent diffusion coefficient map; peripheral zone enhancement pattern; seminal vesicles and periprostatic fat. Results All evaluated criteria did not present statistically significant differences between the two groups. The most common pattern was heterogeneous hyposignal on T2 (57.9% in Group 1 and 57.8% in Group 2; p=0.506), mild diffuse / wedge-shaped areas of hypointensity on apparent diffusion coefficient map (61.4% in Group 1 and 64.4% in Group 2; p=0.931) and early post-contrast enhancement (73.7% in Group 1 and 68.9% in Group 2, p=0719). Conclusion The magnetic resonance imaging aspect of young patients showed no differences between symptomatic and asymptomatic patients.

Falência aguda de órgão e risco de admissão em unidade de terapia intensiva nos pacientes oncológicos: estudo de coorte prospectivo unicêntrico / Acute organ failure and risk of admission to intensive medical care in cancer patients: a single center prospective cohort study

RESUMO Objetivo: Determinar a incidência cumulativa de falência aguda de órgão e internamento em unidade de terapia intensiva em pacientes oncológicos. Métodos: Estudo de coorte prospectivo de pacientes oncológicos adultos em tratamento sistêmico antineoplásico, internados de forma não programada. Resultados: Entre agosto de 2018 e fevereiro de 2019, 10.392 pacientes foram submetidos a tratamento sistêmico antineoplásico, sendo que 358 necessitaram de internamento hospitalar não programado e foram elegíveis para inclusão; por fim, 258 desses pacientes foram incluídos. A média de idade foi de 60,9 anos, e 50,9% eram do sexo masculino; 17,9% dos pacientes tinham câncer hematológico. O risco acumulado de falência de órgãos foi de 39,6% (IC95% 35 - 44) e o risco de internamento na unidade de terapia intensiva em pacientes com falência aguda de órgão foi de 15,0% (IC95% 12 - 18). À admissão em internamento, 62,1% dos pacientes foram considerados não elegíveis para terapia de substituição artificial de órgãos. O tempo mediano de seguimento foi de 9,5 meses. A mortalidade hospitalar foi de 17,5%, na unidade de terapia intensiva de 58,8%. A mediana de sobrevivência da coorte foi de 134 dias (IC95% 106 - 162). Na análise multivariada, a falência aguda de órgão se associou com a mortalidade aos 6 meses após a alta (hazard ratio: 1,6; IC95% 1,2 - 2,2). Conclusão: O risco de falência aguda de órgão em pacientes oncológicos admitidos para tratamento hospitalar não programado durante o tratamento sistémico foi de 39,6% e o risco de internamento em unidade de terapia intensiva foi de 15,0%. A falência aguda de órgão em pacientes oncológicos foi um fator de prognóstico independente para maior mortalidade intra-hospitalar e menor sobrevivência aos 6 meses após a alta.

ABSTRACT Objective: To ascertain the cumulative incidence of acute organ failure and intensive care unit admission in cancer patients. Methods: This was a single-center prospective cohort study of adult cancer patients admitted for unscheduled inpatient care while on systemic cancer treatment. Results: Between August 2018 and February 2019, 10,392 patients were on systemic treatment, 358 had unscheduled inpatient care and were eligible for inclusion, and 285 were included. The mean age was 60.9 years, 50.9% were male, and 17.9% of patients had hematologic cancers. The cumulative risk of acute organ failure was 39.6% (95%CI: 35 - 44), and that of intensive care unit admission among patients with acute organ failure was 15.0% (95%CI: 12 - 18). On admission, 62.1% of patients were considered not eligible for artificial organ replacement therapy. The median follow-up time was 9.5 months. Inpatient mortality was 17.5%, with an intensive care unit mortality rate of 58.8% and a median cohort survival of 134 days (95%CI: 106 - 162). In multivariate analysis, acute organ failure was associated with 6-month postdischarge mortality (HR 1.6; 95%CI: 1.2 - 2.2). Conclusion: The risk of acute organ failure in cancer patients admitted for unscheduled inpatient care while on systemic treatment was 39.6%, and the risk of intensive care unit admission was 15.0%. Acute organ failure in cancer patients was an independent poor prognostic factor for inpatient hospital mortality and 6-month survival.

Development and validation of the sleep assessment instrument for older adults with pain / Desenvolvimento e validação do instrumento de avaliação de sono para idosos com dor

Abstract Background: The co-occurrence of chronic pain and sleep disturbance contribute to a significant functional and social impact in older adults. However, there are no validated instruments to measure sleep disturbance and pain in this population that could be used to screen or diagnose individuals or monitor treatment effectiveness. Objective: Our aim was to develop and validate a brief, practical, and comprehensive tool to assess the impact of co-occurring pain and sleep disturbance in older adults. Methods: Development and validation of a measurement tool for assessing pain and sleep in older adults consisting of seven items. Results: We applied the "Sleep Assessment Instrument for Pain in older adults" (SAIOAP) in a sample of 100 older individuals. A Cronbach's alpha of 0.602 indicated a moderate level of reliability, and item-total correlations of ≥0.4 for all items indicated good homogeneity. There were statistically significant correlations between the SAIOAP and sleep quality (PSQI, r=61.5), pain intensity (VNS, r=30.5), the multidimensional impacts of pain (GPM, r=40.5), depression (GEAP, r=45.5), comorbidity (r=27.9), and medication use (r=30.4). A ROC curve indicated a sensitivity of 73.2% and a specificity of 79.1% in relation to the prediction of sleep disturbances associated with pain in older adults. Conclusions: The SAIOAP presented adequate metric properties and was demonstrated to be a simple and practical tool for the assessment of the impact of pain on sleep in older adults.

RESUMO Introdução: A co-ocorrência de dor crônica e de distúrbios do sono contribuem para um impacto funcional e social negativo em idosos. Porém, o binômio dor-sono não foi explorado em relação a questionários para idosos, a fim de auxiliar na triagem, no diagnóstico ou no monitoramento da eficácia do tratamento médico. Objetivo: Desenvolver e validar um instrumento breve, prático e abrangente para avaliar a concorrência de condições álgicas crônicas e distúrbios de sono em idosos. Métodos: Estudo descritivo e qualitativo de metodologia de desenvolvimento e validação de instrumento de medida para avaliação de dor e sono em idosos, composto por sete itens. Após a fundamentação teórica, desenvolveram-se os itens do instrumento, seguidos de um estudo quantitativo (validação), em que testamos pacientes idosos com dor crônica. Resultados: Aplicou-se o Instrumento de Avaliação de Sono para Dor em Idosos (IASID) a uma amostra de 100 idosos. Alcançou-se o alfa de Cronbach (0,602) de boa homogeneidade por correlação item-total (≥0,4). Encontramos correlações estatisticamente significativas entre o IASID e a qualidade do sono (PSQI, r=61,5%); a intensidade da dor (NVS, r=30,5%); seus impactos (GPM, r=40,5); depressão (GEAP, r=45,5%); comorbidades (r=27,9) e uso de medicamentos (r=30,4). A curva ROC apontou sensibilidade de 73,2% e especificidade de 79,1% para predição de distúrbios do sono associados à dor crônica em idosos. Conclusões: O IASID apresentou propriedades métricas adequadas e demonstrou ser uma ferramenta simples e prática para a avaliação do impacto da dor no sono em idosos.