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CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.
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Síndrome de Cushing , Humanos , Síndrome de Cushing/diagnóstico , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Diagnóstico Diferencial , Hormônio Liberador da Corticotropina/metabolismo , Dexametasona , Desamino Arginina VasopressinaRESUMO
Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI.
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Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Atorvastatina/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do TratamentoRESUMO
The bacille Calmette-Guérin (BCG) vaccine is administered in many countries as part of their vaccination schedules. Epidemiologic studies have suggested a possible benefit of this vaccine in the context of the COVID-19 pandemic and other respiratory infections. We aimed to assess the safety of this intervention in BCG-primed adults. Adult health care workers (n = 451) received a single intradermal application of the BCG vaccine (Tokyo 172 strain) in the deltoid region of the right arm. Follow-up (30 days) calls and clinical inspections were guided using a standardized data sheet to assess local and systemic reactions. Early local reactions were common at 24 h and 7 days, such as erythema (74.9%, 69.2%), induration (55.7%, 59%), a papule (53.4%, 47.7%), and edema (48.3%, 38.1). Local symptoms (pruritus 44.8%, heat 16.2%, and pain 34.8%) were less frequent at day 7. Late expected reactions (14 and 30 days) included the formation of crusts (39.6% and 63.9%), a pustule (36.6% and 17%), or ulcers (28.8% and 17.7%). Severe reactions were limited to subcutaneous abscesses (2%) and lymphadenitis (<1%).
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COVID-19 , Exantema , Adulto , Humanos , Imunização Secundária , COVID-19/prevenção & controle , Vacina BCG , Pandemias/prevenção & controleRESUMO
Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.
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Retinopatia Diabética , Hipoglicemia , Insulinas , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Densidade Microvascular , Vasos Retinianos/diagnóstico por imagem , Angiofluoresceinografia/métodos , Retinopatia Diabética/diagnóstico , Perfusão , Hipoglicemia/induzido quimicamenteRESUMO
Background: Randomized Clinical Trials (RCTs) are important tools to establish the effects of a given intervention. Investigators should focus on outcomes that patients perceive: patient-important outcomes (PIOs), clinical endpoints that patients value directly and reflect how they feel, function, or survive. However, it is easier to consider surrogated outcomes to reduce costs and achieve better-looking results. The problem with these outcomes is that they indirectly measure PIOs, which might not correlate linearly or translate reliably into a positive PIO. Methods: We systematically searched MEDLINE for atopic disease RCTs rated among the top 10 allergic diseases and general internal medicine journals from the last 10 years. Two independent reviewers worked in duplicate and independently to collect data from all eligible articles. We gathered information regarding the type of study, title, author information, journal, intervention type, atopic disease, and primary and secondary outcomes. We assessed the outcomes investigators used in RCTs of atopic diseases and asthma. Results: This quantitative analysis included n = 135 randomized clinical trials. The most studied atopic disease during the period selected was asthma (n = 69), followed by allergic rhinitis (n = 51). When divided by atopic disease, primary outcomes in RCTs valuing allergic rhinitis had the most significant proportion of PIOs (76.7), asthma surrogated outcomes (38), and asthma/allergic rhinitis laboratory outcomes (42.9). PIOs in allergic rhinitis trials had the most significant proportion of PIOs favoring the intervention (81.4), asthma had the greatest proportion of surrogated outcomes (33.3), and asthma/allergic rhinitis laboratory outcomes (40). When divided by atopic disease, trials studying atopic dermatitis and urticaria had the same proportion of PIOs (64.7) as their secondary outcomes. Asthma had the highest (37.5) surrogate outcomes. Journals of general/internal medicine had a greater proportion of PIOs, and a post hoc analysis showed a significant difference in the proportion and secondary outcomes that favored the intervention between PIOs and laboratory outcomes. Conclusion: Approximately 7.5 out of 10 primary outcomes in RCTs published in general/internal medicine are PIOs compared to 5 out of 10 primary outcomes in atopic disease journals. Investigators should focus on selecting patient-important outcomes in their clinical trials to establish clinical guidelines with better-quality recommendations that impact patients' life and values. Registration: International Prospective Register of Systematic Reviews (PROSPERO, NIHR) ID: CRD42021259256.
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PURPOSE: This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D). METHODS: A comprehensive search was conducted in six databases, from inception to January 27, 2022. Clinical trials that compared fibrate therapy with other lipid-lowering interventions or placebo were included. Outcomes of interest comprised cardiovascular (CV) events, complications of T2D, metabolic profile, and adverse events. Random-effects meta-analyses were performed to estimate mean differences (MD) and risk ratios (RR), alongside 95% confidence intervals (CI). RESULTS: A total of 25 studies were included, six comparing fibrates against statins, 11 against placebo, and eight evaluating the combination of fibrates with statins. Overall risk of bias was rated as moderate, and most outcomes rendered low confidence per GRADE approach. Fibrates showed reduction of serum triglycerides (TGs) (MD -17.81, CI -33.92 to -1.69) and a marginal increase of high-density lipoprotein cholesterol (HDL-c) (MD: 1.60, CI 0.29 to 2.90) in adults with T2D, but no differences were found in CV events when compared to statin therapy (RR 0.99, CI 0.76 to 1.09). When used in combination with statins, no major differences were exhibited regarding lipid profile and CV outcomes. Adverse events were comparable between fibrate and statin monotherapies (e.g., RR of 1.03 for rhabdomyolysis, and 0.90 for gastrointestinal events). CONCLUSIONS: Fibrate therapy in patients with T2D results in a marginal improvement of TGs and HDL-c but without reducing the risk of CV events and mortality. Their use should be reserved for very specific scenarios after a deliberative dialogue between patients and clinicians regarding their benefits and harms.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Adulto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Ácidos Fíbricos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , HDL-Colesterol , Triglicerídeos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controleRESUMO
Background: The short cosyntropin test is widely used for adrenal insufficiency screening and diagnosis. Lower cosyntropin doses may have greater sensitivity vs. the standard dose in detecting adrenal dysfunction. Obesity and overweight are increasing, impacting the clinical presentation of some diseases. Currently more than 50% of the subjects diagnosed with autoimmune adrenal insufficiency have a BMI greater than 25, and hence individuals living with overweight and obesity are more frequently requiring evaluation of the adrenal cortical function. Fixed-dose cosyntropin stimulation may not be appropriate for individuals with obesity. Objective: The primary objective was to compare cortisol response to a weight-adapted cosyntropin dose vs. a fixed low dose (1 µg) and a more physiologically fixed dose (10 µg). Methods: Twenty individuals with obesity and 20 age-matched healthy controls underwent in a randomized sequence at least one-week apart, to the The short cosyntropin test with three different doses, 0.2 µg/kg of body weight, 1 or 10 µg fixed dose stimuli. The assessment and data analysis were blinded to the individual and the investigator. Results: Cortisol response was reduced in the group with obesity with the 1 µg fixed dose stimuli at 30 minutes (median, IQR) 649.6 µg, 567.3-738.4 µg for the control group vs. 568.6 µg, 528.4-623.13 µg, p=0.04; there was a lower cortisol peak at 60' in all the three evaluated doses, with a dose-dependent trend. A weight-adapted cosyntropin dose of 0.2 µg in obesity produces a similar response to the one observed in individuals without obesity. The 1 µg ACTH test falls short on stimulating the cortisol adrenal response in individuals with obesity.
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INTRODUCTION: There exists clinical interest in the following question: Is there an association between HOMA-IR and the risk of developing metabolic diseases? AIMS: Assessing the association between high values of HOMA-IR with the incidence of T2DM, MACE, essential hypertension, dyslipidemia, NASH, and cancer in healthy participants and participants with a component of metabolic syndrome. METHODS: Databases were searched by an experienced librarian to find eligible studies. Observational cohort studies enrolling healthy adults and adults with metabolic syndrome components that evaluated HOMA as a marker of IR were considered for inclusion. Eligibility assessment, data extraction and risk of bias assessment were performed independently and in duplicate. Baseline characteristics of patients, cutoff values of HOMA-IR to predict metabolic events were extracted independently and in duplicate. RESULTS: 38 studies (215,878 participants) proved eligible. A higher HOMA-IR value had a significant effect on the risk of developing T2DM (HR 1.87; CI 1.40-2.49), presenting non-fatal MACE (HR 1.46; CI 1.08-1.97) and hypertension (HR 1.35; CI 1.15-1.59). No association was found regarding cancer mortality and fatal MACE with higher HOMA-IR values, there was not enough information to carry out a meta-analysis to establish an association between higher values of HOMA with cancer incidence, dyslipidemia, and NASH. CONCLUSIONS: High values of HOMA were associated with an increased risk of diabetes, hypertension, and non-fatal MACE; yet, not for cardiovascular or cancer mortality. More research is needed to determine the value of the HOMA index in metabolic and cardiovascular outcomes. PROSPERO REGISTRATION NUMBER: CRD42020187645.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipertensão , Resistência à Insulina , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/complicações , Avaliação de Resultados em Cuidados de SaúdeRESUMO
OBJECTIVE: To describe the humoral response in a cohort with mild and asymptomatic SARS-CoV-2 infection previ-ously identified in a community-based serological survey. MATERIALS AND METHODS: This study was an observational follow up of 193 subjects previously identified with positive anti-SARS-CoV-2 antibodies invited for a second test 112 days after the first sampling. All completed a standardized electronic questionnaire. IgM/IgG antibodies were determined using a qualitative IgM/IgG chemiluminescent immunoassay. RESULTS: Among the 193 eligible subjects, a total of 174 (90%) attended the follow-up visit, and their serum samples were tested. Of the samples, 171 (98.3%) were still positive, and 3 (1.7%) were negative. Also, the cut-off index (COI) value of the immunoassay significantly increased from the first to the second test (P <0.001). CONCLUSIONS: Our findings support a sustained humoral response in individuals with mild and asymptomatic SARS-CoV-2 infection up to 112 days after a positive serologic baseline test, accompanied by increasing antibody titers.