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Introduction: Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality. Methods: We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations. Results: 91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE - Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence. Conclusion: This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes.
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Doenças Cardiovasculares , Nefrite Lúpica , Humanos , Nefrite Lúpica/complicações , Feminino , Masculino , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Prognóstico , BiópsiaRESUMO
PURPOSE: Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS: The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS: Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION: This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.
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Calcitonina , Carcinoma Neuroendócrino , Neoplasia Endócrina Múltipla Tipo 2b , Neoplasias da Glândula Tireoide , Humanos , Calcitonina/sangue , Calcitonina/uso terapêutico , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Feminino , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/sangue , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/genética , Proteínas Proto-Oncogênicas c-ret/genética , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PURPOSE: Acute kidney injury (AKI) is a frequent complication among COVID-19 patients in the intensive care unit, but it is less frequently investigated in general internal medicine wards. We aimed to examine the incidence, the predictors of AKI, and AKI-associated mortality in a prospective cohort of non-ventilated COVID-19 patients. We aimed to describe the natural history of AKI by describing trajectories of urinary markers of hemodynamic, glomerular, and tubular injury. METHODS: 141 COVID-19 patients were enrolled to the study. AKI was defined according to KDIGO guidelines. Urine and renal function parameters were followed twice a week. Multivariate logistic regression was used to determine the predictors of AKI and mortality. Trajectories of urinary markers were described by unadjusted linear mixed models. RESULTS: 19.7% patients developed AKI. According to multiple logistic regression, higher urinary albumin-to-creatinine ratio (OR 1.48, 95% CI 1.04-2.12/1 mg/mmol) and lower serum albumin (OR 0.86, 95% CI 0.77-0.94/1 g/L) were independent predictors of AKI. Mortality was 42.8% in the AKI and 8.8% in the group free from AKI (p < 0.0001). According to multiple logistic regression, older age, lower albumin, and AKI (OR 3.9, 95% CI 1.24-12.21) remained independent predictors of mortality. Urinary protein-to-creatinine trajectories were diverging with decreasing values in those without incident AKI. CONCLUSION: We found high incidence of AKI and mortality among moderately severe, non-ventilated COVID-19 patients. Its development is predicted by higher albuminuria suggesting that the originally damaged renal structure may be more susceptible for virus-associated effects. No clear relationship was found with a prerenal mechanism, and the higher proteinuria during follow-up may point toward tubular damage.
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Injúria Renal Aguda , COVID-19 , Humanos , COVID-19/complicações , Estudos Prospectivos , Creatinina , Albumina Sérica , Injúria Renal Aguda/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Distal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal. Purpose: To describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies. Data Sources: We searched Medline from inception to May 2021. Study Selection: Original data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up. Data Extraction: was completed by diabetes specialists with clinical experience in neuropathy assessment. Data Synthesis: Data was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression. Results: A total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias. Limitations: Not all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous. Conclusions: DSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Polineuropatias , Humanos , Qualidade de Vida , Fatores de RiscoRESUMO
BACKGROUND: It is generally accepted that the metabolic effects of leptin are diminished in the obese due to leptin resistance. Hormone resistance may develop if diurnal (including meal-related) changes in hormone levels are disrupted. We sought to describe leptin changes after a 75 g oral glucose tolerance test (OGTT) in women with a prior diagnosis of gestational diabetes mellitus (a high risk group for the metabolic syndrome) compared to that in healthy controls. METHODS: In 2000 a retrospective cohort study was performed on women who had been diagnosed with gestational diabetes mellitus (WHO criteria 1985, n = 57) between 1996 and 1998 and on a healthy control female group (n = 36) all of whom had had a prior pregnancy without any diagnosis of diabetes. All the women underwent a standard 75 g OGTT. Serum leptin was measured by radioimmunoassay before and 90 min after the OGTT. RESULTS: Using multilevel models of change, fasting leptin levels were shown to be associated with body mass index; 10.1% (95% CI 8.1-12.1%) increase per 1 kg/m(2) increase in body mass index), homeostasis model assessment insulin sensitivity; 0.4% (95% CI 0.2-0.7%) decrease per 1% increase in insulin sensitivity); abnormal glucose tolerance (24% decrease, 95% CI 8-37%); and smoking (31% decrease, 95% CI 16-44%). Postload (90 min) leptin levels decreased significantly in women with normal glucose tolerance by 13% (95% CI 8-18%), while no significant change in postload leptin level was apparent in women with abnormal glucose tolerance (3% increase, 95% CI -4% to 29%). CONCLUSIONS: Disturbed leptin changes were found following an OGTT in women with abnormal glucose tolerance that might be either a cause or a consequence of leptin resistance.
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Diabetes Gestacional/fisiopatologia , Intolerância à Glucose/fisiopatologia , Leptina/sangue , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Seguimentos , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Modelos Estatísticos , Gravidez , Estudos Retrospectivos , Fumar , Fatores de TempoRESUMO
OBJECTIVE: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients. PATIENTS AND METHODS: 353 patients with diabetes (DM) were recruited (age: 60.2±7.4 years; female: 57.2%; BMI: 29.3±2.1 kg/m2; DM duration: 15.6±9.9 years; HbA1c: 7.8±1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test. RESULTS: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (y=0.004, p=0.563), 30/15 ratio (y=0.282, p=0.357), Valsalva ratio (y=-0.058, p=0.436) and orthostatic hypotension (y=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006). CONCLUSION: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM-associated complications by initiating early treatment.
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Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea , Sistema Cardiovascular/inervação , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Força da Mão , Hipertensão/fisiopatologia , Exame Neurológico/métodos , Idoso , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/diagnóstico , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Valor Preditivo dos Testes , Reflexo , Reprodutibilidade dos Testes , Mecânica Respiratória , Manobra de ValsalvaRESUMO
BACKGROUND: Cardiovascular autonomic neuropathy (CAN) has been thought to underlie the loss of normal nocturnal blood pressure dipping, which is associated with a higher risk for nephropathy in Type 1 diabetes. Previous analyses also suggest however that nephropathy is a major predictor of subsequent CAN. OBJECTIVE: To investigate links between non-dipping phenomenon (NDP) and complications, particularly CAN and nephropathy. METHODS: 24-h ambulatory blood pressure monitoring was performed on 61 consecutively recruited subjects (mean age: 38.5+/-8.1, mean duration: 29.5+/-8.2 years) from the Pittsburgh Epidemiology of Diabetes Complications cohort (658 subjects with childhood onset Type 1 diabetes diagnosed between 1950 and 80). NDP was diagnosed if nocturnal fall of both systolic and diastolic blood pressure was <10% of the average daytime blood pressure. CAN was detected by abnormal (
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Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Adulto , Feminino , Humanos , Masculino , Proteinúria/fisiopatologiaRESUMO
AIMS: The aim of the present study was to determine the prevalence of abnormal glucose tolerance and the metabolic syndrome in a cohort of previously gestational diabetic (GDM) women 4 years after delivery. METHODS: Sixty-eight prior GDM and a control group of 39 women with normal glucose tolerance during pregnancy were invited to participate in a follow-up study. RESULTS: The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose (IFG) was 21%, 16%, and 6% among prior GDM women and 0%, 15%, and 0% among controls respectively (P=0.0039). Independently of the metabolic syndrome criteria used this status was found more frequently among women with prior GDM (all P<0.05). The prevalence of the metabolic syndrome showed a dose-response relationship with the level of weight categories (P<0.005) as well as with the level of glucose intolerance (P=0.024). CONCLUSION: According to our results a disturbed carbohydrate metabolism and a clustering of cardiovascular risk factors might be observed in previous GDM women 4 years after delivery.