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1.
Artigo em Inglês | MEDLINE | ID: mdl-38299563

RESUMO

Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided a framework for understanding the pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow and blood hypercoagulability. In the last years, it has become apparent that immunity plays a central role in thrombosis, interacting with classical prothrombotic mechanisms, oxidative stress and vascular factors. Thrombosis amplifies inflammation, and exaggerated inflammatory processes can trigger thrombosis mainly due to the activation of leukocytes, platelets, and endothelial cells. APE-related endothelium injury is a major trigger for immune system activation. Endothelium is also a key component mediating inflammatory reaction and it is relevant to maintain vascular permeability. Exaggerated right ventricular wall stress and overload, with coexisting systemic hypotension and hypoxemia, result in myocardial injury and necrosis. Hypoxia, tissue factor activation and cytokine storm are engaged in the thrombo-inflammatory processes. Thrombus development is characterized by inflammatory state vascular wall caused mainly by an early extravasation of leukocytes and intense selectins and cytokines production. Nevertheless, immunity of DVT is well described, little is known about potential chemokine and cellular differences between thrombus that develops in the vein and thrombus that detaches and lodges in the pulmonary circulation being a cause of APE. There is a paucity of data considering inflammatory state in the pulmonary artery wall during an acute episode of pulmonary embolism. The main aim of this review is to summarize the knowledge of immunity in acute phase of pulmonary embolism in experimental models.


Assuntos
Hominidae , Embolia Pulmonar , Trombose , Animais , Células Endoteliais , Embolia Pulmonar/complicações , Trombose/complicações , Inflamação , Modelos Animais
2.
Ugeskr Laeger ; 186(3)2024 Jan 15.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38305265

RESUMO

Paediatric patients with ventricular pre-excitation/asymptomatic WPW syndrome have a higher risk of atrial fibrillation degenerating into ventricular fibrillation and sudden cardiac death (SCD). In more than half of these patients this can be the first symptom presenting. Hence, it is important to conduct a risk stratification for SCD in asymptomatic patients with pre-excitation/delta wave in the ECGs. In this review, invasive risk stratification by electrophysiologic testing and ablation is recommended when possible. Catheter ablation is reported to have a high rate of success and low risk of complications.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Síndrome de Wolff-Parkinson-White , Criança , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Ablação por Cateter/efeitos adversos , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia , Risco , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia , Síndrome de Wolff-Parkinson-White/complicações , Síndrome de Wolff-Parkinson-White/diagnóstico
3.
Eur Rev Med Pharmacol Sci ; 28(2): 534-541, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305599

RESUMO

OBJECTIVE: Single-organ cutaneous small-vessel vasculitis (SoCSVV) is an inflammatory skin-limited vascular disease affecting the dermal and/or hypodermal vessel wall. Pathogenetically, idiopathic forms are described, as well as the induction from different triggers, such as infections, drugs, and vaccines. Following the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic outbreak, cases of cutaneous vasculitis induced by both COVID-19 and COVID-19 vaccinations have been reported in literature. The aim of this study is to provide the most recent evidence on new etiological factors, clinical features, and management of the SoCSVV. PATIENTS AND METHODS: We included 42 patients (22 women, 20 men) with SoCSVV and no systemic involvement in the study. The mean age of the patients was 57.3 years. Palpable purpura was the most frequent clinical manifestation (38 cases-90.4%). All patients were diagnosed with leukocytoclastic vasculitis by skin biopsy. RESULTS: The etiological factors were as follows: idiopathic in 9 (21%) patients, drug-related in 19 (45%) patients, COVID-19 infection-related in 5 (12%) patients, post-COVID-19 vaccination in 5 (12%) patients, paraneoplastic in 2 (5%) patients, and drug and infection and sepsis in 1 patient each. Among the drug-related cases, 16 (84%) were antibiotic-related, and most of them were beta-lactam antibiotics. Eosinophilia was present in skin biopsy in the cases related to vaccination and drugs, while intense necrosis and vascular damage in the skin were observed in the cases related to COVID-19 infection, unlike the others. A rapid resolution was observed with the cessation of drugs and short-term steroid treatment for the precipitating factors. CONCLUSIONS: SoCSVV is usually associated with drugs, preceding infections, and vaccines. COVID-19 infection and COVID-19 vaccinations have been reported as new etiological factors. SoCSVV indicates that the disease seems to be a mild, self-limiting illness with a good clinical result.


Assuntos
COVID-19 , Dermatopatias Vasculares , Vasculite Leucocitoclástica Cutânea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Pele/patologia , Dermatopatias Vasculares/diagnóstico , Dermatopatias Vasculares/etiologia , Dermatopatias Vasculares/patologia , Vasculite Leucocitoclástica Cutânea/diagnóstico , Vasculite Leucocitoclástica Cutânea/etiologia , Vasculite Leucocitoclástica Cutânea/patologia
4.
A A Pract ; 18(2): e01721, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305709

RESUMO

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disorder characterized by episodes of polymorphic ventricular tachycardia. Clinically, patients who have CPVT present with juvenile sudden death or stress-induced syncope. We present a case of an 18-year-old girl with CPVT resistant to traditional pharmacotherapies. Instead of a typical stellate ganglion block (SGB), the patient underwent bilateral continuous proximal intercostal blocks that successfully inhibited arrhythmogenic events. This therapeutic method may provide an alternative to SGBs and demonstrates proof of concept for an early elective intervention to be included in the diagnostic and therapeutic algorithm for patients with CPVT.


Assuntos
Taquicardia Ventricular , Adolescente , Feminino , Humanos , Síncope/complicações , Síncope/diagnóstico , Taquicardia Ventricular/terapia
5.
BMC Ophthalmol ; 24(1): 52, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308203

RESUMO

BACKGROUND: To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). RESULTS: The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P < 0.05). After pupil dilation, there were no changes in iris blood flow and PD in the T1DM group compared to healthy children, whereas the T2DM group showed a significantly smaller PD compared to healthy adults. Multivariate regression analysis revealed that in the T2DM group, glycated hemoglobin was an independent factor of PD after dilation (ß=-0.490, p = 0.031), with no such factors identified in the T1DM group. CONCLUSION: The insufficiently dilated pupil diameter after drug-induced mydriasis is correlated to the level of glycated hemoglobin among T2DM patients. TRIAL REGISTRATION: The registration number on the clinical trial website was NCT03631108.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Midríase , Adulto , Criança , Humanos , China , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Dilatação Patológica , Hemoglobinas Glicadas , Pressão Intraocular , Iris , Midríase/induzido quimicamente , Pupila/fisiologia , Tomografia de Coerência Óptica , Masculino , Feminino
6.
Alzheimers Res Ther ; 16(1): 25, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308344

RESUMO

BACKGROUND: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial. METHODS: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status. RESULTS: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status. CONCLUSION: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.


Assuntos
Doença de Alzheimer , Transtornos Cerebrovasculares , Disfunção Cognitiva , Substância Branca , Idoso , Feminino , Humanos , Masculino , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/patologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Cognição , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Substância Branca/patologia , Ensaios Clínicos como Assunto
7.
BMC Infect Dis ; 24(1): 160, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308222

RESUMO

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.


Assuntos
Doenças Cardiovasculares , Infecções por HIV , Humanos , Adulto , Terapia Antirretroviral de Alta Atividade , Proteína C-Reativa , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Lipídeos
8.
BMC Pregnancy Childbirth ; 24(1): 104, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308265

RESUMO

BACKGROUND: Excessive gestational weight gain, especially among women with gestational diabetes, is associated with several adverse perinatal outcomes. Our study aimed to analyse the impact of the use of pedometers to supervise physical activity on maternal health and the obstetric outcomes of pregnant women with obesity and early gestational diabetes. METHODS: 124 pregnant patients were enrolled in the presented research. INCLUSION CRITERIA: singleton pregnancy, age > 18 years, gestational diabetes diagnosed in the first half of pregnancy (< 20th week of pregnancy), obesity according to the American Endocrine Society criteria. Each patient was advised to take at least 5000 steps daily. Patients were randomly assigned to pedometers (N = 62), and were recommended to monitor daily the number of steps. The group without pedometers (N = 62) was not observed. Visit (V1) was scheduled between the 28th and 32nd gestational week (GW), and visit (V2) occurred between the 37th and 39th GW. Anthropometric measurements and blood samples were collected from all patients at each appointment. Foetal and maternal outcomes were analysed at the end of the study. RESULTS: In the group supervised by pedometers, there were significantly fewer newborns with macrosomia (p = 0,03). Only 45% of patients satisfied the recommended physical activity guidelines. Patients who walked more than 5000 steps per day had significantly higher body weight at baseline (p = 0,005), but weight gain was significantly lower than in the group that did not exceed 5000 steps per day (p < 0,001). The perinatal outcome in the group of patients performing more than 5000 steps did not demonstrate significant differences with when compared to less active group. ROC curve for weight gain above the guidelines indicated a statistically substantial cut-off point for this group at the level of 4210 steps/day (p = 0.00001). CONCLUSIONS: Monitoring the activity of pregnant patients with gestational diabetes and obesity by pedometers did not have a significantly impact on their metabolic control and weight gain. However, it contributed to less macrosomia. Furthermore, physical activity over 5,000 steps per day positively affects weight loss, as well as contributes to improved obstetric and neonatal outcomes.


Assuntos
Diabetes Gestacional , Ganho de Peso na Gestação , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Índice de Massa Corporal , Exercício Físico , Macrossomia Fetal/etiologia , Macrossomia Fetal/complicações , Obesidade/complicações , Resultado da Gravidez/epidemiologia , Aumento de Peso
9.
Artigo em Inglês | MEDLINE | ID: mdl-38311379

RESUMO

A significant body of evidence has supported a negative impact of endometriosis on ovarian follicles; however, the origin and relevance of this ovarian impairment in endometriosis is still a matter of debate. The ovarian damage can be caused by endometriosis itself or by surgeries aiming to remove endometriotic lesions. In this review, we summarized the existing knowledge on the mechanisms by which endometriosis can impact the ovarian follicles, from molecular to clinical points of view. From a molecular standpoint, the presence of endometriosis or its consequences can induce oxidative stress, inflammation, aberrant mitochondrial energy metabolism and inappropriate steroid production in granulosa cells, phenomena that may impair the quality of oocytes to variable degrees. These alterations may have clinical relevance on the accelerated exhaustion of the ovarian reserve, on the ovarian response to gonadotrophin stimulation in IVF cycles and on the competence of the oocytes. Critical points to be considered in current clinical practices related to fertility issues in endometriosis are discussed.


Assuntos
Endometriose , Infertilidade , Feminino , Humanos , Endometriose/complicações , Endometriose/patologia , Folículo Ovariano , Ovário , Oócitos
10.
Rinsho Ketsueki ; 65(1): 1-6, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311382

RESUMO

A 66-year-old man was diagnosed with symptomatic IgG-λ multiple myeloma based on the presence of anemia, thrombocytopenia, renal dysfunction, and a tumor on the right sixth rib. Bone marrow aspiration yielded a dry tap and biopsy revealed myelofibrosis grade 2. Partial response was achieved with Bd (bortezomib and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone). The patient received autologous stem cell transplantation, but the myeloma relapsed 3 months later, and liver tumors developed as well. DKd (daratumumab, carfilzomib, and dexamethasone) was administered, but the patient died due to disease progression. Autopsy revealed multiple extramedullary lesions in the liver, spleen, gallbladder, adrenal glands, kidneys, and multiple lymph nodes, as well as ascites.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Mielofibrose Primária , Masculino , Humanos , Idoso , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Bortezomib/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia , Transplante Autólogo
11.
Rinsho Ketsueki ; 65(1): 13-17, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311383

RESUMO

A 24-year-old man was found to have an ileocecal ulcer by colonoscopy. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) with diffuse positive reaction of Epstein-Barr encoding region (EBER) by in situ hybridization was made based on analysis of the specimen. Acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis jirovecii pneumonia was also diagnosed. As no other significant lymphomatous lesions were identified by further examination, a clinical diagnosis of EBV-positive mucocutaneous ulcer (EBVMCU) was made. Rather than performing systemic chemotherapy, the lesion was closely monitored and antiretroviral therapy (ART) for AIDS was started with the hope of treating the lesion through immune reconstitution. The lesion had completely disappeared by day 79 after starting ART, and has not recurred for over 3 years. EBVMCU is known to develop secondary to various immunosuppressive states including AIDS. Here we report a rare case of EBVMCU detected at diagnosis of AIDS that entered complete remission after immune reconstitution by ART.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por Vírus Epstein-Barr , Infecções por HIV , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Adulto Jovem , Adulto , Úlcera/etiologia , Herpesvirus Humano 4 , Remissão Espontânea , Síndrome de Imunodeficiência Adquirida/complicações , Recidiva Local de Neoplasia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico
12.
Nature ; 626(7998): 271-279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326590

RESUMO

Mitochondria retain bacterial traits due to their endosymbiotic origin, but host cells do not recognize them as foreign because the organelles are sequestered. However, the regulated release of mitochondrial factors into the cytosol can trigger cell death, innate immunity and inflammation. This selective breakdown in the 2-billion-year-old endosymbiotic relationship enables mitochondria to act as intracellular signalling hubs. Mitochondrial signals include proteins, nucleic acids, phospholipids, metabolites and reactive oxygen species, which have many modes of release from mitochondria, and of decoding in the cytosol and nucleus. Because these mitochondrial signals probably contribute to the homeostatic role of inflammation, dysregulation of these processes may lead to autoimmune and inflammatory diseases. A potential reason for the increased incidence of these diseases may be changes in mitochondrial function and signalling in response to such recent phenomena as obesity, dietary changes and other environmental factors. Focusing on the mixed heritage of mitochondria therefore leads to predictions for future insights, research paths and therapeutic opportunities. Thus, whereas mitochondria can be considered 'the enemy within' the cell, evolution has used this strained relationship in intriguing ways, with increasing evidence pointing to the recent failure of endosymbiosis being critical for the pathogenesis of inflammatory diseases.


Assuntos
Inflamação , Mitocôndrias , Modelos Biológicos , Simbiose , Humanos , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Dieta/efeitos adversos , Homeostase , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/fisiologia , Proteínas Mitocondriais/metabolismo , Ácidos Nucleicos/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Fosfolipídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Simbiose/fisiologia , Animais
13.
BMC Med Inform Decis Mak ; 24(1): 39, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321399

RESUMO

INTRODUCTION: Incarceration occurred in approximately 5% to 15% of inguinal hernia patients, with around 15% of incarcerated cases progressing to intestinal necrosis, necessitating bowel resection surgery. Patients with intestinal necrosis had significantly higher mortality and complication rates compared to those without necrosis.The primary objective of this study was to design and validate a diagnostic model capable of predicting intestinal necrosis in patients with incarcerated groin hernias. METHODS: We screened the clinical records of patients who underwent emergency surgery for incarcerated inguinal hernia between January 1, 2015, and December 31, 2022. To ensure balanced representation, the enrolled patients were randomly divided into a training set (n = 180) and a validation set (n = 76) using a 2:1 ratio. Logistic regression analysis was conducted using the rms package in R software, incorporating selected features from the LASSO regression model, to construct a predictive model. RESULTS: Based on the results of the LASSO regression analysis, a multivariate logistic regression model was developed to establish the predictive model. The predictors included in the model were Abdominal effusion, Hernia Sac Effusion, and Procalcitonin. The area under the receiver operating characteristic (ROC) curve for the nomogram graph in the training set was 0.977 (95% CI = 0.957-0.992). In the validation set, the AUC for the nomogram graph was 0.970. Calibration curve and decision curve analysis (DCA) verified the accuracy and practicability of the nomogram graph in our study. CONCLUSION: Bowel necrosis in patients with incarcerated inguinal hernia was influenced by multiple factors. The nomogram predictive model constructed in this study could be utilized to predict and differentiate whether incarcerated inguinal hernia patients were at risk of developing bowel necrosis.


Assuntos
Hérnia Inguinal , Humanos , Hérnia Inguinal/complicações , Hérnia Inguinal/cirurgia , Modelos Logísticos , Necrose/complicações , Estudos Retrospectivos
14.
Crit Care ; 28(1): 41, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321529

RESUMO

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.


Assuntos
Sepse , Choque Séptico , Deficiência de Tiamina , Humanos , Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/complicações , Choque Séptico/tratamento farmacológico , Tiamina/uso terapêutico , Deficiência de Tiamina/complicações , Deficiência de Tiamina/tratamento farmacológico
15.
Clin Exp Pharmacol Physiol ; 51(3): e13843, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302075

RESUMO

This study explores the potential mechanisms of obstructive sleep apnoea (OSA) complicates type 2 diabetes mellitus (T2DM) by which chronic intermittent hypoxia (CIH) induces insulin resistance and cell apoptosis in the pancreas through oxidative stress. Four- and eight-week CIH rat models were established, and Tempol (100 mg/kg/d), was used as an oxidative stress inhibitor. This study included five groups: 4-week CIH, 4-week CIH-Tempol, 8-week CIH, 8-week CIH-Tempol and normal control (NC) groups. Fasting blood glucose and insulin levels were measured in the serum. The expression levels of 8-hidroxy-2-deoxyguanosine (8-OHdG), tribbles homologue 3 (TRB3), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), insulin receptor substrate-1 (IRS-1), phosphorylated IRS-1 (Ser307) (p-IRS-1ser307 ), protein kinase B (AKT), phosphorylated AKT (Ser473) (p-AKTser473 ), B cell lymphoma protein-2 (Bcl-2), cleaved-caspase-3 (Cl-caspase-3), and the islet cell apoptosis were detected in the pancreas. CIH induced oxidative stress in the pancreas. Compared with that in the NC group and CIH-Tempol groups individually, the homeostasis model assessment of insulin resistance (HOMA-IR) and apoptosis of islet cells was increased in the CIH groups. CIH-induced oxidative stress increased the expression of p-IRS-1Ser307 and decreased the expression of p-AKTSer473 . The expression levels of TRB3 and p-JNK were higher in the CIH groups than in both the CIH-Tempol and NC groups. Meanwhile, the expressions of Cl-caspase-3 and Bcl-2 were upregulated and downregulated, respectively, in the CIH groups. Hence, the present study demonstrated that CIH-induced oxidative stress might not only induce insulin resistance but also islet cell apoptosis in the pancreas through TRB3 and p-JNK.


Assuntos
Óxidos N-Cíclicos , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Marcadores de Spin , Animais , Ratos , Apoptose , Caspase 3/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hipóxia/complicações , Estresse Oxidativo , Pâncreas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo
16.
Sci Rep ; 14(1): 2741, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302529

RESUMO

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer's Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.


Assuntos
Doença de Alzheimer , Doenças de Pequenos Vasos Cerebrais , Transtornos Cognitivos , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Doenças Vasculares , Feminino , Humanos , Idoso , Masculino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Cognição , Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Transtornos Cognitivos/patologia , Amiloide/metabolismo , Imageamento por Ressonância Magnética , Doenças Vasculares/patologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Encéfalo/metabolismo
17.
BMC Infect Dis ; 24(1): 156, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302888

RESUMO

BACKGROUND: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. METHODS: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. RESULTS: Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. CONCLUSIONS: Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.


Assuntos
Antimaláricos , Infecções por HIV , Malária , Vacinas , Criança , Gravidez , Feminino , Humanos , Lactente , Antimaláricos/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Quênia/epidemiologia , Infecções por HIV/complicações , Malária/tratamento farmacológico , Malária/complicações , Anticorpos , Citocinas , Vacinas/uso terapêutico
18.
BMC Med ; 22(1): 50, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302923

RESUMO

BACKGROUND: This study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D. METHODS: This study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including ß-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated. RESULTS: During a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for ß-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for ß-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy). CONCLUSIONS: This study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of ß-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.


Assuntos
Diabetes Mellitus Tipo 2 , Lipodistrofia , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Estudos Prospectivos , Bancos de Espécimes Biológicos , Fatores de Risco , Inflamação/complicações , Fumar , Lipodistrofia/complicações
19.
Sci Rep ; 14(1): 2778, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307927

RESUMO

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.


Assuntos
Fibrilação Atrial , Fragilidade , Ataque Isquêmico Transitório , Piridinas , Acidente Vascular Cerebral , Tiazóis , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Inibidores do Fator Xa , Fragilidade/complicações , Ataque Isquêmico Transitório/complicações , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações
20.
Am J Case Rep ; 25: e942938, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308432

RESUMO

BACKGROUND Obesity is a global epidemic often managed through surgical interventions, such as intragastric balloons. Despite the minimally invasive appeal of intragastric balloons, severe complications, such as gastric outlet obstruction, can occur with their use. The most recent guidelines recommend metabolic and bariatric surgery for specific body mass index categories but rarely discuss the potential complications and required postoperative monitoring. Guidelines encourage metabolic and bariatric surgery for patients with a body mass index of 30-34.9 kg/m² and presence of metabolic disease, or body mass index ≥35 kg/m², regardless of co-morbidities. CASE REPORT We report a case of a 35-year-old woman with severe nausea, vomiting, electrolyte imbalance, and chest pain, leading to ICU admission just 2 weeks after intragastric balloon placement in Mexico. Testing and diagnostics were concerning for metabolic imbalance and heart rhythm changes. Imaging and endoscopic investigations confirmed gastric outlet obstruction, necessitating emergent endoscopic balloon deflation and removal. Following the procedure, her symptoms resolved, and she was discharged with appropriate medication and scheduled follow-up. CONCLUSIONS Given the increasing prevalence of obesity and a corresponding surge in surgical interventions, this case serves as a cautionary tale. Selection of a type of metabolic and bariatric surgery should be patient specific, with the patient involved in the decision making. Rigorous preoperative assessments and sustained postoperative monitoring are imperative. This study aims to guide future research toward enhanced patient selection and prevention of severe complications, thus influencing practice and policy in obesity management.


Assuntos
Cirurgia Bariátrica , Balão Gástrico , Obstrução da Saída Gástrica , Manejo da Obesidade , Obesidade Mórbida , Feminino , Humanos , Adulto , Obesidade/complicações , Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia
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