Sleep disorder syndromes of post-acute sequelae of SARS-CoV-2 (PASC) / Long Covid.

INTRODUCTION: COVID-19 infection has resulted in a high prevalence of a post-infectious syndrome, known as post-acute sequelae of SARS-CoV-2 (PASC) or "Long COVID". PASC is a heterogeneous disease with a high prevalence of sleep disturbances, varying from an insomnia disorder to excessive daytime sleepiness. METHODS: Patients seen in the Covid Survivorship Program at the Beth Israel Deaconess Medical Center Boston, USA, were screened for sleep disorders as part of a comprehensive multi-system evaluation. Those who screened positive were referred for a comprehensive sleep evaluation in a dedicated COVID-19-Sleep clinic, followed by diagnostic sleep testing and treatment. This report summarizes patients who completed an American Academy of Sleep Medicine (AASM) accredited facility-based diagnostic evaluation. International Classification of Sleep Disorders 3rd Edition-Revised criteria were met for all diagnoses. RESULTS: In 42 patients with PASC, five categories of sleep disorder syndromes were observed following a sleep clinic evaluation, including obstructive sleep apnea, chronic insomnia disorder, primary hypersomnia, REM behavior disorder (RBD), and new onset circadian phase delay. Seven patients met criteria for idiopathic hypersomnia, and two had narcolepsy type 2. RBD patients were infected in three different waves; circadian disturbance patients were all infected in the winter wave of 2020/21, and the primary hypersomnolence group occurred during all waves, predominantly the initial wave of 2020. A peculiar form of insomnia was a persistent loss of sleep regularity. CONCLUSIONS: Specific sleep symptoms/syndromes are reported in this select group of patients with PASC/Long Covid. As new onset sleep complaints are prevalent in PASC, we recommend a complete clinical and investigative sleep evaluation for persistent severe sleep symptoms following COVID-19 infection.

New-onset diabetes after kidney transplantation: Assessing urinary Wilm's tumor-1 protein to predict renal allograft dysfunction.

PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 â€‹mL/min/1.73 â€‹m2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

Statins and new-onset diabetes in primary prevention setting: an updated meta-analysis stratified by baseline diabetes risk.

AIMS: The use of statins has been associated with an increased risk of new-onset diabetes. The characteristics of the population could influence this association. The objective of this study was to determine the risk of new-onset diabetes with the use of statins in patients in primary prevention, with an assessment of the results according to the baseline risk of developing diabetes of the included population. METHODS: We performed an updated meta-analysis including randomized trials of statin therapy in primary prevention settings that report new-onset diabetes. The rate of new cases of diabetes in the control arms was estimated for each study. The studies were classified into two groups (low rate: < 7.5 events per 1000 patients-year; high rate; ≥ 7.5 events per 1000 patients-year). The fixed-effects model was performed. RESULTS: Eight studies (70,453 patients) were included. Globally, statin therapy was associated with an increased risk of new-onset diabetes (OR 1.1; 95% CI 1.0-1.2, I2 35%). When we analyzed the studies according to the baseline diabetes risk in the control groups, the results showed that there was a greater risk only in the studies with a high baseline rate (OR 1.2; 95% CI 1.1-1.3, I2 0%; interaction p value = 0.01). CONCLUSION: Globally, the use of statins in patients in primary prevention was associated with an increased risk of new-onset diabetes. In the stratified analysis, this association was observed only in the group of studies with a high baseline rate of events.

Newly Diagnosed Diabetes Mellitus During COVID-19: The New Pandemic - A Literature Review.

Purpose of Review: Coronavirus disease 2019 (COVID-19) has caused a spike in newly diagnosed diabetes mellitus (NDDM). NDDM and COVID-19 infection are not well established as a cause-and-effect relationship; hence, the present review aims to define the underlying causes and consequences of COVID-19 infection in relation to the condition. Recent Findings: ß-Cells are infiltrated by SARS-CoV-2, causing glycometabolic dysfunction and insulin dysregulation. The disease causes systemic inflammation and pro-inflammatory cytokines, as well as hormonal changes that lead to insulin resistance and hyperglycemia that are difficult to manage. As a result of NDDM, complications related to COVID-19 infection become more severe. Summary: NDDM related to COVID-19 infection complicates hospitalization outcomes and adversely affects quality of life in patients. There are many possible causes and consequences associated with NDDM, but for establishing preventive measures and treatments for NDDM, more evidence regarding its epidemiology, physiopathology, etiology, and nutritional aspects is required.

Predictive value of uric acid/albumin ratio for the prediction of new-onset atrial fibrillation in patients with ST-Elevation myocardial infarction.

Background: There is a lack of studies supporting the association between the uric acid/albumin ratio (UAR) and the development of new-onset atrial fibrillation (NOAF) in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI). Objective: The objective of the study was to assess the efficacy of the UAR for predicting the occurrence of NOAF in STEMI patients undergoing pPCI. Methods: We recruited 1484 consecutive STEMI patients in this retrospective and cross-sectional investigation. The population sample was classified based on the development of NOAF during hospitalization. NOAF was defined as an atrial fibrillation (AF) observed during hospitalization in patients without a history of AF or atrial flutter. The UAR was computed by dividing the serum uric acid (UA) level by serum albumin level. Results: After pPCI, 119 STEMI patients (8%) were diagnosed with NOAF. NOAF patients had higher serum UAR levels than individuals who did not have NOAF. According to the multivariable logistic regression model, the UAR was an independent predictor for NOAF in STEMI patients (OR: 6.951, 95% CI: 2.978-16.28, p < 0.001). The area under curve (AUC) value of the UAR in a receiver operating characteristics (ROC) evaluation was 0.758, which was greater than those of its components (albumin [AUC: 0.633] and UA [AUC: 0.647]) and C-reactive protein (AUC: 0.714). The optimal UAR value in predicting NOAF in STEMI patients was greater than 1.39, with a sensitivity of 69% and a specificity of 74.5%. Conclusion: To the best of our knowledge, this is the first study indicating that the UAR was an independent predictor of NOAF development in STEMI patients.

Predictive Value of Uric Acid/Albumin Ratio for the Prediction of New-Onset Atrial Fibrillation in Patients with ST-Elevation Myocardial Infarction

ABSTRACT Background: There is a lack of studies supporting the association between the uric acid/albumin ratio (UAR) and the development of new-onset atrial fibrillation (NOAF) in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI). Objective: The objective of the study was to assess the efficacy of the UAR for predicting the occurrence of NOAF in STEMI patients undergoing pPCI. Methods: We recruited 1484 consecutive STEMI patients in this retrospective and cross-sectional investigation. The population sample was classified based on the development of NOAF during hospitalization. NOAF was defined as an atrial fibrillation (AF) observed during hospitalization in patients without a history of AF or atrial flutter. The UAR was computed by dividing the serum uric acid (UA) level by serum albumin level. Results: After pPCI, 119 STEMI patients (8%) were diagnosed with NOAF. NOAF patients had higher serum UAR levels than individuals who did not have NOAF. According to the multivariable logistic regression model, the UAR was an independent predictor for NOAF in STEMI patients (OR: 6.951, 95% CI: 2.978-16.28, p < 0.001). The area under curve (AUC) value of the UAR in a receiver operating characteristics (ROC) evaluation was 0.758, which was greater than those of its components (albumin [AUC: 0.633] and UA [AUC: 0.647]) and C-reactive protein (AUC: 0.714). The optimal UAR value in predicting NOAF in STEMI patients was greater than 1.39, with a sensitivity of 69% and a specificity of 74.5%. Conclusion: To the best of our knowledge, this is the first study indicating that the UAR was an independent predictor of NOAF development in STEMI patients.

New-Onset Ocular Myasthenia after Multisystem Inflammatory Syndrome in Children.

Neurologic complications have been associated with multisystem inflammatory syndrome in children, possibly involving autoimmune mechanisms. Here, we report a 6-year-old girl who developed myasthenia 11 weeks after severe acute respiratory syndrome coronavirus 2 infection and 8 weeks after the onset of severe multisystem inflammatory syndrome in children.

Echocardiographic prognostication of new onset heart failure in a cohort of ischemic heart disease patients / Pronóstico Ecocardiográfico de un nuevo evento de insuficiencia cardíaca en una cohorte de pacientes con Cardiopatía Isquémica

Background: Echocardiographic predictors for new onset heart failure in patients with ischemic heart disease with reduced left ventricular ejection fraction (HFrEF) or with preserved left ventricular ejection fraction (HFpEF) in Ethiopian and Sub-Saharan African is not well-known.Methods: Two hundred twenty-eight patients with ischemic heart disease were retrospectively recruited and followed. Analysis on baseline clinical and echocardiographic characteristics of patients, and risk factors for new onset HFpEF and new onset HFrEF were done. The exclusion criteria were known heart failure at baseline and those who did not have echocardiography data.Results: During the follow up period, heart failure developed in 62.2% (61/98) of ischemic heart disease patients with preserved left ventricular ejection fraction and in 70.1% (92/130) of ischemic heart disease patients with reduced left ventricular ejection fraction. We did not find significant difference between HFrEF and HFpEF in time to new onset heart failure. Systolic blood pressure, diastolic blood pressure, diabetes, left atrium and diastolic left ventricular dimension had significant association with new onset HFrEF on univariate regression analysis. Whereas new onset HFpEF was significantly associated with age, sex, presence of hypertension, Systolic blood pressure and diastolic left ventricular dimension. On cox regression analysis diastolic left ventricular dimension was associated with both new onset HFpEF and HFrEF. Age, diabetes, and dimension of left atrium were also associated with HFrEF.Conclusion: This cohort study in ischemic heart disease patients suggests a key role for the diastolic left ventricular dimension, left atrium size, diabetes, sex and age as predictors of new onset HFrEF and HFpEF. Strategies directed to prevention and early treatment of diabetes, dilatation of left ventricle and left atrium may prevent a considerable proportion of HFrEF or HFpEF.

Antecedentes: Los predictores ecocardiográficos de nuevos eventos de insuficiencia cardiaca en pacientes con cardiopatía isquémica con fracción de eyección ventricular preservada (HFpEF) o con fracción de eyección ventricular reducida (HFrEF) no son bien conocidos en la Africa etíope y subsahariana.Métodos: Doscientos veintiocho pacientes con cardiopatía isquémica fueron reclutados y seguidos retrospectivamente. Se realizaron análisis sobre las características clínicas y ecocardiográficas basales de los pacientes, así como los factores de riesgo para un nuevo evento de HFpEF y un nuevo evento de HFrEF. Los criterios de exclusión fueron insuficiencia cardíaca conocida al inicio del estudio y aquellos que no tenían datos de ecocardiografía.Resultados: Durante el período de seguimiento, la insuficiencia cardíaca se desarrolló en el 62,2% (61/98) de pacientes con cardiopatía isquémica con fracción de eyección ventricular izquierda preservada y en el 70,1% (92/130) de pacientes con cardiopatía isquémica con fracción de eyección ventricular izquierda reducida. No encontramos diferencias significativas entre HFrEF y HFpEF en el tiempo hasta la nueva aparición de insuficiencia cardíaca. La presión arterial sistólica, la presión arterial diastólica, la diabetes y las dimensiones de la aurícula iquierda y del ventrículo izquierdo en diástole tuvieron una asociación significativa con nuevos eventos de HFrEF en el análisis de regresión univariada. Mientras que un nuevo evento de HFpEF se asoció significativamente con la edad, el sexo, la presencia de hipertensión, la presión arterial sistólica y la dimensión ventricular izquierda diastólica. En el análisis de regresión de cox, la dimensión ventricular izquierda diastólica se asoció con HFpEF de nuevo inicio y HFrEF. La edad, la diabetes y la dimensión de la aurícula izquierda también se asociaron con HFrEF. Conclusión: Este estudio de cohorte en pacientes con cardiopatía isquémica sugiere un papel clave para la dimensión ventricular izquierda diastólica, el tamaño de la aurícula izquierda, la diabetes, el sexo y la edad como predictores de un nuevo evento de HFrEF y HFpEF. Las estrategias dirigidas a la prevención y el tratamiento temprano de la diabetes, la dilatación del ventrículo izquierdo y la aurícula izquierda pueden prevenir una proporción considerable de HFrEF o HFpEF.

Diabetes y COVID-19, una relación de ida y vuelta / Diabetes and COVID-19, one relation to go and comeback

Diabetic patients are at risk of developing unfavorably from SARS-COV19 disease, especially when they have poor glycemic control. On the other hand, in the case of diabetic patients with severe COVID, they evolve with severe hyperglycemia, often difficult to manage. Marked hyperglycemia has also been described in people without a known history of previous diabetes, even there have been reported cases of insulin-dependent diabetes debut in days after the disease. The aim of this review is to analyze possible mechanisms involved in the relationship between COVID-19 and DIABETES.

Circulating PCSK9 levels are not associated with the conversion to type 2 diabetes.

BACKGROUND AND AIMS: PCSK9 is an endogenous inhibitor of the LDL receptor pathway. Recently, Mendelian randomization studies have raised a doubt about the diabetogenic risk of PCSK9 inhibitors. Here, we assessed the relationship between plasma PCSK9 levels and the risk of new onset diabetes (NOD). METHODS: Fasting plasma PCSK9 levels were measured at baseline by ELISA in subjects without lipid lowering treatment in IT-DIAB (n = 233 patients with prediabetes, follow-up 5 years) and ELSA-Brasil (n = 1751; 27.5% with prediabetes, follow-up 4 years) prospective cohorts. The primary outcome in both studies was the incidence of NOD. The association of NOD with plasma PCSK9 levels was studied using multivariable Cox models. RESULTS: Plasma PCSK9 levels were not significantly associated with NOD in IT-DIAB (HR (+1SD) 0.96, CI95% [0.76; 1.21]) and ELSA-Brasil (OR (+1SD) 1.13 [0.89; 1.42]). In ELSA-Brasil, a significant positive association between PCSK9 and worsening of glucose homeostasis, including the progression from normoglycemia to prediabetes, was found (OR (+1SD) 1.17 [1.04; 1.30], p = 0.0074). Plasma PCSK9 concentration was also positively associated with the change in fasting plasma glucose between the first and second visit in ELSA-Brasil (ß = 0.053, CI95% [0.006; 0.10], p = 0.026). Plasma PCSK9 levels positively correlated with total cholesterol in IT-DIAB and ELSA-Brasil, but not with glucose homeostasis parameters, except for a positive correlation with HOMA-IR in ELSA-Brasil. CONCLUSIONS: Plasma PCSK9 levels were not significantly associated with NOD risk in longitudinal analyses. These data suggest that inhibition of the PCSK9 extra-cellular pathway should not be deleterious for glucose homeostasis.

Risk factors for new-onset diabetes mellitus after kidney transplantation (NODAT): a Brazilian single center study

ABSTRACT Objectives: This study aims to verify the new-onset diabetes after kidney transplant (NODAT) incidence in recipients within 1 year after kidney transplantation from a single center in Southern Brazil and to assess the associated conditions. Subjects and methods: A retrospective study of 258 post-renal transplant patients was performed. Demographic (gender, age, ethnic background) and clinical (origin of graft, associated infections, body mass index (BMI) at transplant time and 6 and 12 months after, causes of renal failure, and comorbidities) data were analyzed. All patients were on tacrolimus, mycophenolate mofetil, and prednisone treatment. Patients with and without NODAT were compared. Results: A NODAT incidence of 31.2% was noted 1 year post transplantation. In the univariate analysis, patients with NODAT were older (p = 0.001), mostly had African-American ethnic background (p = 0.02), and had renal failure secondary to high blood pressure (HBP) (p = 0.001). The group of patients with NODAT also had more incidence of post-transplant HBP (p = 0.01), heart failure (p = 0.02), and dyslipidemia (p = 0.001). Logistic regression showed that African-American ethnic background, post-transplant HBP, and dyslipidemia were independently associated with NODAT. Conclusion: This study shows a NODAT incidence that is greater in patients with African-American ethnic background and that is associated with HBP and dyslipidemia.

Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network.

BACKGROUND: MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm (controls). METHODS AND RESULTS: Plasma of acute new-onset AF patients (n = 5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm. Samples from well-controlled AF (n = 16) and control (n =  15) patients were collected during medical appointments following an ECG. Expression of miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499 was analyzed by real-time PCR. Ingenuity Pathway Analysis and the TargetScan database identified the top 30 mRNA targets of these miRNA, seeking the miRNA-mRNA interactions in cardiovascular process. Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in patients with acute new-onset AF, compared with well-controlled AF and control patients. Decreased expression of miR-21 was seen in patients with well-controlled AF compared to those with acute new-onset AF and controls (0.6-fold). The miRNA-mRNA interaction demonstrated that SMAD7 and FASLG genes were the targets of miR-21, miR-133b, and miR-499 and were directly related to AF, being involved in apoptosis and fibrosis. CONCLUSION: The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events.

Sustained Posttransplantation Diabetes Is Associated With Long-Term Major Cardiovascular Events Following Liver Transplantation.

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Clinical features and in-hospital mortality associated with different types of atrial fibrillation in patients with acute coronary syndrome with and without ST elevation.

BACKGROUND: In patients with an acute coronary syndrome (ACS), no conclusive agreement has been reached to date regarding the association between the different types of atrial fibrillation (AF) and the in-hospital mortality risk. We conducted a retrospective cohort study in patients with ACS to determine the prognostic implications of the different types of AF. METHODS: We analyzed 6705 consecutive patients with ACS admitted to a coronary care unit (CCU), including 3094 with ST segment elevation myocardial infarction (STEMI) and 3611 with non-ST-elevation acute coronary syndrome (NSTE-ACS). We identified the patients with pre-existing AF, new-onset AF at admission, and new-onset AF at the CCU. RESULTS: The overall incidence of AF was documented in 360 (5.4%) of the patients (STEMI, 5%; NSTE-ACS, 5.6%), 140 (2.1%) of whom had pre-existing AF, and 220 (3.2%) of whom had new-onset AF (AF at admission, 1.3%; AF at the CCU, 1.9%). The patients with AF had high-risk clinical characteristics and developed major adverse events more frequently than did the patients without AF. The unadjusted in-hospital mortality risk was significantly higher in the patients with pre-existing AF (STEMI, 3.79-fold; NSTE-ACS, 3.4-fold) and AF at the CCU (STEMI, 2.02-fold; NSTE-ACS, 8.09-fold). After adjusting for the multivariate analysis, only the AF at the CCU in the NSTE-ACS group was associated with a 4.40-fold increase in the in-hospital mortality risk (odds ratio 4.40, CI 1.82-10.60, p=0.001). In the STEMI group, the presence of any type of AF was not associated with an increased risk of mortality. CONCLUSION: Among the different types of AF in patients with ACS, only the new-onset AF that developed during the CCU stay in patients with NSTE-ACS was associated with a 4.40-fold increase in the in-hospital mortality risk.