Heterogeneity and high prevalence of bone manifestations, and bone mineral density in congenital generalized lipodystrophy subtypes 1 and 2.

Introduction: Congenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease caused by mutations in genes responsible for the formation and development of adipocytes. Bone abnormalities are described. However, there is a scarcity of data. Objective: To describe bone characteristics in a large CGL1 and 2 case series. Methods: Cross-sectional study that assessed bone radiological features of CGL patients of a reference hospital in Fortaleza (CE), Brazil. Patients underwent clinical and bone mineral metabolism evaluation, radiographs of the axial and appendicular skeleton and bone mineral density (BMD) assessment by DEXA (dual energy X-ray absorptiometry). Results: Nineteen patients were included, fourteen were CGL1 and 5, CGL2. Median age was 20 years (8-42) and 58% were women. Median BMI and percentage of body fat were, respectively, 21 Kg/m² (16-24), and 10.5% (7.6-15). The median leptin concentration was 1 ng/mL (0.1-3.3). Diabetes mellitus and dyslipidemia were present in 79% and 63% of patients, respectively. Median calcium and phosphate were normal in almost all patients (95%). Median parathyroid hormone and 25-OH-vitamin D were 23 pg/mL (7-75) and 28 ng/mL (18-43). Osteolytic lesions, osteosclerosis and pseudo-osteopoikylosis, were present in 74%, 42% and 32% of patients, respectively. Lytic lesions were found predominantly in the extremities of long bones, bilaterally and symmetrically, spine was spared. Osteosclerosis was present in axial and appendicular skeleton. Pseudo-osteopoikilosis was found symmetrically in epiphyses of femur and humerus, in addition to the pelvis. BMD Z-score greater than +2.5 SD was observed in 13 patients (68.4%). BMD was higher in CGL1 compared to CGL2 in lumbar spine and total body in adults. No associations were found between high BMD and HOMA-IR (p=0.686), DM (p=0.750), osteosclerosis (p=0.127) or pseudo-osteopoikilosis (p=0.342), and, between pain and bone lesions. Fractures were found in 3 patients. Conclusion: Bone manifestations are prevalent, heterogeneous, and silent in CGL1 and CGL2. Osteolytic lesions are the most common, followed by osteosclerosis and pseudo-osteopoikilosis. Bone mass is high in most cases. There was no pain complaint related to bone lesions. Thus, systematic assessment of bone manifestations in CGL is essential. Studies are needed to better understand its pathogenesis and clinical consequences.

Perception of Medical Students Regarding Implementing Telemedicine Practice Activities at a University Center in Brazil / Percepção de Estudantes de Medicina sobre a Implementação de Vivências em Telemedicina em um Centro Universitário do Brasil

Objective: evaluate medical students' perceptions regarding implementing Telemedicine teaching during their undergraduate studies. Methods: this is a cross-sectional qualitative study with 30 medical students. Three focus group sessions were conducted, and the data were analyzed using a content analysis approach. Results/Discussion: the students recognized the importance of digital health strategies and digital information and communication technologies (ICTs) for the healthcare ecosystem. However, some students pointed out that this area is still challenging for some doctors who oppose Telemedicine. They reported a need for training professionals and students, emphasizing the need to improve skills and competencies for teleconsultation and other Telemedicine modalities. They stated that these experiences helped them enhance their empathy skills for establishing a good doctor-patient relationship. When referring to the negative aspects of the experiences, they mentioned the dependence on reliable internet connection and digital tools. Another limitation mentioned was the difficulty in conducting specific physical examination components. Conclusions: the students experienced Telemedicine activities in a safe healthcare environment, learning about the bioethical principles for responsible teleconsultations, understanding the limiting factors of the method, and having the opportunity to improve skills and competencies for their future professional practice.

Objetivo: avaliar a percepção dos estudantes de Medicina quanto à implementação do ensino da Telemedicina durante a graduação. Métodos: trata-se de um estudo qualitativo transversal com 30 alunos do curso de Medicina. Foram realizadas três sessões de grupos focais e os dados foram analisados através de uma abordagem de análise de conteúdo. Resultados/Discussão: os estudantes reconheceram a importância das estratégias de Saúde Digital e das Tecnologias Digitais de Informação e Comunicação (TIC) para o ecossistema de saúde. Contudo, alguns estudantes apontaram que esta área ainda é um desafio para alguns médicos que se opõem à prática da Telemedicina. Relataram a necessidade de capacitação de profissionais e estudantes, enfatizando a necessidade de aprimoramento de habilidades e competências para teleconsultas e outras modalidades de Telemedicina. Afirmaram que as vivências os ajudaram a melhorar as suas capacidades de empatia para estabelecer uma boa relação médico-paciente. Ao se referirem aos aspectos negativos das atividades, mencionaram a dependência de conexão confiável à internet e de ferramentas digitais. Outra limitação citada foi a dificuldade na realização de etapas específicas do exame físico. Conclusões: os estudantes vivenciaram as atividades de Telemedicina em um ambiente de saúde seguro, conhecendo os princípios bioéticos para a prática de teleconsultas responsáveis, compreendendo os fatores limitantes do método e tendo a oportunidade de aprimorar habilidades e competências para a sua futura prática profissional.

Reduced gut microbiota diversity in patients with congenital generalized lipodystrophy.

BACKGROUND: Previous studies suggest intestinal dysbiosis is associated with metabolic diseases. However, the causal relationship between them is not fully elucidated. Gut microbiota evaluation of patients with congenital generalized lipodystrophy (CGL), a disease characterized by the absence of subcutaneous adipose tissue, insulin resistance, and diabetes since the first years of life, could provide insights into these relationships. METHODS: A cross-sectional study was conducted with patients with CGL (n = 17) and healthy individuals (n = 17). The gut microbiome study was performed by sequencing the 16S rRNA gene through High-Throughput Sequencing (BiomeHub Biotechnologies, Brazil). RESULTS: The median age was 20.0 years old, and 64.7% were female. There was no difference between groups in pubertal stage, BMI, ethnicity, origin (rural or urban), delivery, breastfeeding, caloric intake, macronutrient, or fiber consumption. Lipodystrophic patients presented a lower alpha diversity (Richness index: 54.0 versus 67.5; p = 0.008). No differences were observed in the diversity parameters when analyzing the presence of diabetes, its complications, or the CGL subtype. CONCLUSION: In this study, we demonstrate for the first time a reduced gut microbiota diversity in individuals with CGL. Dysbiosis was present despite dietary treatment and was also observed in young patients. Our findings allow us to speculate that the loss of intestinal microbiota diversity may be due to metabolic abnormalities present since the first years of life in CGL. Longitudinal studies are needed to confirm these findings, clarifying the possible causal link between dysbiosis and insulin resistance in humans.

Glycemic control in non-critically hospitalized patients in tertiary hospitals in northeast Brazil / Controle glicêmico intra-hospitalar em pacientes não-criticamente enfermos internados em hospitais terciários no nordeste do Brasil

Objective: Inpatient glycemic control is considered an important component of hospital care and patient safety. Nevertheless, its importance in the hospital setting is often underestimated. We aimed to evaluate glycemic control in non-critically hospitalized patients in the state of Ceará, in Northeast Brazil. Methods: A cross-sectional study was conducted in three tertiary hospitals in the state of Ceará. We evaluated non-critically ill inpatients, aged 18 years or older, who had hyperglycemia during hospitalization (random plasma glucose > 140 mg/dL or self-reported diabetes mellitus [DM]). Results: We evaluated 136 patients (66.2% male, mean age 57.9 ± 16.6 years), 64% of whom had a prior DM diagnosis. Specific nutritional support for DM or hyperglycemia was prescribed for 59.6% of patients. In total, 69.9% of the patients were using insulin. Among them, 47.4% used sliding-scale regular insulin, 18.9% basal-bolus (neutral protamine Hagedorn [NPH] insulin), 28.4% basal-plus (NPH) and 3.1% basal insulin (NPH). The prescriptions given were considered adequate for 26.4% of patients. Of the patients, 69.9% presented blood glucose levels > 180 mg/dL and 29.4% presented levels > 300 mg/dL. Hypoglycemia was observed in 25.7% of patients; protocols for hypoglycemia management were prescribed for 76.5% of them. Education on diabetes during hospitalization was reported by 30.1%. Conclusion: The glycemic control regime followed neither national nor international guidelines. These data suggest a need for teams of diabetes specialists in public hospitals in Ceará, working to improve care and following protocols to guide the safety of hospitalized patients.

Objetivo: O controle glicêmico é considerado um componente importante do cuidado hospitalar e da segurança do paciente. Entretanto, sua relevância no contexto hospitalar muitas vezes é subestimada. Nesse estudo, buscamos avaliar o controle glicêmico em pacientes não-críticos internados no estado do Ceará, no Nordeste do Brasil. Métodos: Trata-se de um estudo transversal realizado em três hospitais terciários do estado do Ceará. Foram avaliados os pacientes internados nas unidades de enfermaria, com idade acima de 18 anos, que apresentaram hiperglicemia (definida por medida de glicemia plasmática aleatória acima de 140 mg/dL) ou diagnóstico prévio (autorrelato) de diabetes mellitus (DM). Resultados: Foram avaliados 136 pacientes (66.2% do sexo masculino, idade média 57.9 ± 16.6 anos), dos quais 64% tinham um diagnóstico prévio de DM. O acompanhamento nutricional específico para DM ou hiperglicemia foi prescrito em 59.6% dos pacientes. No total, 69.9% dos pacientes estavam em uso de insulina. Dentre eles, 47.4% utilizavam insulina regular sob demanda (sliding-scale), 18.9% basal-bolus (insulina NPH), 28.4% basal-plus e 3.1% insulina basal (NPH). As prescrições foram consideradas adequadas para 26.4% dos pacientes. Entre os pacientes analisados, 69.9% apresentaram glicemia capilar > 180 mg/dL e 29.4% apresentaram níveis > 300 mg/dL. Hipoglicemia foi observada em 25.7% dos pacientes e protocolo para hipoglicemia foi prescrito em 76.5% deles. Educação sobre diabetes durante a internação foi realizada em 30.1%. Conclusão: O manejo do controle glicêmico não seguiu diretrizes nacionais ou internacionais. Esses dados sugerem a necessidade de uma equipe de especialistas em diabetes em hospitais públicos do Ceará, visando melhorar o cuidado e seguir os protocolos que proporcionam segurança ao paciente internado.

Leu124Serfs*26, a novel AGPAT2 mutation in congenital generalized lipodystrophy with early cardiovascular complications.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the near-total loss of subcutaneous adipose tissue soon after birth, resulting in ectopic fat deposition and severe metabolic disturbances. Most cases are caused by AGPAT2 or BSCL2 gene mutations. We aimed to report two unrelated CGL patients with a novel frameshift mutation in AGPAT2 (p.Leu124Serfs*26). METHODS: Clinical features and laboratory were obtained by medical interview and medical records review. DNA was extracted, amplified and sequenced. Mutation Taster was used to estimate the potential biological impact of the AGPAT2 mutations on the protein function. RESULTS: Patient 1: a 30-year-old woman with lipodystrophy phenotype at birth and diagnosis of diabetes at age 13 presented with severe hypertriglyceridemia and pancreatitis at age 17, hypertension and albuminuria at age 18, proliferative diabetic retinopathy with visual loss at age 25, and an acute myocardial infarction due to multivessel coronary disease during a hospitalization for forefoot amputation at age 29. At this time, she required hemodialysis due to end-stage renal disease. Patient 2: a 12-year-old girl with lipodystrophy phenotype and hypertriglyceridemia detected in the first year of life and abnormalities in the global longitudinal strain, evaluated by speckle-tracking echocardiography last year. Molecular analysis identified a c.369_372delGCTC (p.Leu124Serfs*26) AGPAT2 mutation in both unrelated patients, a compound heterozygous mutation in Patient 1, and homozygous mutation in Patient 2. CONCLUSION: We describe two unrelated patients with type 1 CGL due to Leu124Serfs*26, a novel AGPAT2 frameshift mutation, presenting as early cardiovascular disease. These findings suggest an association between Leu124Serfs*26 and a more aggressive phenotype.

Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in young patients with congenital generalized lipodystrophy.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by the absence of subcutaneous adipose tissue, severe insulin resistance, diabetes mellitus, and cardiovascular complications, including cardiac autonomic neuropathy (CAN), left ventricular hypertrophy (LVH), and atherosclerosis. The present study aimed to access the association between CAN parameters and cardiovascular abnormalities in CGL patients. METHODS: A cross-sectional study was conducted with 10 CGL patients and 20 healthy controls matched for age, sex, BMI, and pubertal stage. We evaluated clinical, laboratory, and cardiovascular parameters-left ventricular mass index (LVMI), interventricular septum thickness (IVS), systolic and diastolic function determined by two-dimensional transthoracic echocardiography; carotid intimal media thickness (cIMT); and cQT interval. Heart rate variability (HRV) was evaluated by spectral analysis components-high frequency (HF), low frequency (LF), very low frequency (VLF), LF/HF ratio, and total amplitude spectrum (TAS)-and cardiovascular reflexes tests (postural hypotension test, respiratory, orthostatic and Valsalva coefficients). RESULTS: In CGL group, four patients (40%) had LVH and diastolic dysfunction. HF component (parasympathetic control) was lower in LVH patients. CGL patients presented higher values of cIMT and cQT interval than heathy subjects. Inverse association between LVMI and LF (p = 0.011), IVS and LF (p = 0.007), and cIMT and leptin (p < 0.001) were observed, even after adjustments by HOMA-IR, A1c, and blood pressure. In CGL group, there were associations between LMVI and HF component (IC95%: - 1.000; - 00.553), LVMI and TAS (IC95%: - 1.000; - 0.012), and IVS and HF component (IC95%: - 1.000; - 0.371). CONCLUSION: The association between increased LV mass and parameters of HRV provides possible speculations about the involvement of CAN in the pathophysiology of the cardiac complications, including LVH, in patients with CGL.

Early commitment of cardiovascular autonomic modulation in Brazilian patients with congenital generalized lipodystrophy.

BACKGROUND: Metabolic abnormalities in congenital generalized lipodystrophy (CGL) are associated with microvascular complications. However, the evaluation of different types of neuropathy in these patients, including the commitment of cardiovascular autonomic modulation, is scarce. The objective of the present study was to determine the prevalence of cardiovascular autonomic neuropathy (CAN) in patients with CGL compared with individuals with type 1 diabetes and healthy subjects. METHODS: Ten patients with CGL, 20 patients with type 1 diabetes and 20 healthy subjects were included in the study. Controls were paired 1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was analyzed using cardiovascular autonomic reflex tests, including postural hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15) coefficients, and spectral analysis of the HRV, determining very low (VLF), low (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as the presence of at least two altered tests. RESULTS: CAN was detected in 40% of the CGL patients, 5% in type 1 diabetes patients and was absent in healthy individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels of 30/15 and VAL in CGL vs. healthy individuals. A significant positive correlation was observed between leptin and 30/15 coefficient (r = 0.396; p = 0.036) after adjusting for insulin resistance and triglycerides. Autonomic cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and albumin/creatinine ratio in CGL cases. CONCLUSIONS: We observed a high prevalence of CAN in young patients with CGL, suggesting that insulin resistance, hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN development. Additional studies are needed to evaluate the role of leptinemia in the physiopathogenesis of the condition.

Distúrbios metabólicos em doenças infecciosas emergentes e negligenciadas / Metabolic disorders in emerging and neglected infectious diseases

A substituição gradual e progressiva das doenças infecciosas e parasitárias pelas doenças crônico-degenerativas como causas de morbidade e mortalidade, caracterizando o processo de transição epidemiológica, não tem sido observada em várias populações, em especial em países subdesenvolvidos ou em desenvolvimento, verificando-se, na realidade, uma sobre-posição desses perfis (transição incompleta). Além do aumento da prevalência de distúrbios metabólicos, várias doenças infecciosas permanecem endêmicas em diversas regiões, como é o caso da hanseníase, da tuberculose, da leishmaniose, das hepatites virais, entre outras, assim como condições emergentes nas últimas décadas, como a infecção pelo HIV/Aids. Nesse contexto, nos últimos anos tem sido dada uma maior atenção para a ocorrência de distúrbios metabólicos, principalmente a partir da observação de elevada incidência dessas anormalidades associadas à infecção pelo HIV/Aids e à sua terapia com as drogas antirretrovirais. Nesta revisão são abordados aspectos clínico-epidemiológicos dos distúrbios metabólicos reportados em algumas enfermidades infectoparasitárias de relevância mundial e local (no Brasil), assim como possíveis mecanismos e fatores envolvidos nessas associações.

The gradual and progressive replacement of infectious and parasitic by chronic diseases as causes of morbidity and mortality, characterizing the process of epidemiological transition hasn't been observed in various populations, especially in underdeveloped or developing countries characterizing a superposition of these profiles (incomplete transition). Besides the increased prevalence of metabolic disorders, various infectious diseases remain endemic in several regions, such as leprosy, tuberculosis, leishmaniasis, viral hepatitis, among others, as well as emerging diseases in recent decades, as HIV infection/Aids. In this context, more attention has been given to the occurrence of metabolic disturbances in the recent years, mainly from the observation of a high incidence of metabolic disorders associated with HIV infection/Aids, and its therapy with antiretroviral drugs. This review addresses clinical and epidemiological aspects of metabolic disturbances reported in some infectious and parasitic diseases with worldwide and local (Brazil) relevance, as well as possible mechanisms and factors involved in these associations.

[Metabolic disorders in emerging and neglected infectious diseases]. / Distúrbios metabólicos em doenças infecciosas emergentes e negligenciadas.

The gradual and progressive replacement of infectious and parasitic by chronic diseases as causes of morbidity and mortality, characterizing the process of epidemiological transition hasn't been observed in various populations, especially in underdeveloped or developing countries characterizing a superposition of these profiles (incomplete transition). Besides the increased prevalence of metabolic disorders, various infectious diseases remain endemic in several regions, such as leprosy, tuberculosis, leishmaniasis, viral hepatitis, among others, as well as emerging diseases in recent decades, as HIV infection/Aids. In this context, more attention has been given to the occurrence of metabolic disturbances in the recent years, mainly from the observation of a high incidence of metabolic disorders associated with HIV infection/Aids, and its therapy with antiretroviral drugs. This review addresses clinical and epidemiological aspects of metabolic disturbances reported in some infectious and parasitic diseases with worldwide and local (Brazil) relevance, as well as possible mechanisms and factors involved in these associations.

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids: [revisão] / Gonadotrophic axis dysfunction in men with HIV-infection/Aids: [review]

A disfunção do eixo gonadotrófico é frequentemente observada em pacientes infectados pelo HIV. A patogênese é multifatorial e está relacionada à duração da infecção pelo HIV, aos efeitos citopáticos diretos do vírus, ao uso de drogas gonadotóxicas, às infecções oportunistas, às neoplasias, à desnutrição, entre outros fatores. Em homens, a redução dos níveis de testosterona está associada à perda de massa e de força muscular, à redução da densidade mineral óssea, à lipodistrofia, à depressão, à astenia, à fadiga e à disfunção sexual. Em pacientes infectados pelo HIV com hipogonadismo, inúmeros estudos têm comprovado os efeitos benéficos da reposição de testosterona sobre o perfil metabólico e a distribuição da gordura corporal, com aumento da massa corporal magra, além de promover melhora da qualidade de vida, reduzir a perda de massa óssea e reduzir os índices de depressão. Assim, esta revisão teve como objetivo trazer uma breve atualização sobre o presente tema, abordando dados epidemiológicos, mecanismos fisiopatológicos e estratégias terapêuticas para as principais anormalidades do eixo gonadotrófico masculino associadas à infecção pelo HIV e ao seu tratamento.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

[Gonadotrophic axis dysfunction in men with HIV-infection/aids]. / Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.