Epidemiology, prognosis, and challenges in the management of hyperthyroidism-related atrial fibrillation.

Atrial fibrillation (AF) is a common condition with a global estimated prevalence of 60 million cases, and the most common cardiac complication of hyperthyroidism, occurring in 5-15% of overtly hyperthyroid patients. Additionally, subclinical hyperthyroidism and high-normal free T4 have been associated with an increased risk in the development of AF. Hyperthyroidism-related AF is a reversible cause of AF, and the majority of patients spontaneously revert to sinus rhythm in 4-6 months during or after restoration of euthyroidism. Therefore, restoring thyroid function is an indispensable element in hyperthyroidism-related AF management. Rate control with beta-blockers consists another first-line therapy, reserving rhythm control in cases of persistent hyperthyroidism-related AF. It is still controversial whether hyperthyroidism is an independent risk factor of stroke in nonvalvular AF. As a result, initiating anticoagulation should be guided by the clinical thromboembolic risk score CHA2DS2-VASc score in the same way it is applied in patients with non-hyperthyroidism-related AF. Treatment with the novel direct oral anticoagulants appears to be as beneficial and may be safer than warfarin in patients with hyperthyroidism-related AF. In this review, we address the epidemiology, prognosis, and diagnosis of hyperthyroidism-related AF, and we discuss the management strategies and controversies in patients with hyperthyroidism-related AF.

Current and Emerging Pharmacological Therapies for Cushing's Disease.

Cushing's Disease (CD), hypercortisolism due to pituitary ACTH secreting neuroendocrine neoplasm, is associated with increased morbidity and, if untreated, mortality in about half of the affected individuals. Consequently, the timely initiation of effective treatment is mandatory. Neurosurgery is the first line and the only potentially curative treatment; however, 30% of patients will have persistent disease post-surgery. Furthermore, a small percentage of those initially controlled will develop hypercortisolism during long-term follow- up. Therefore, patients with persistent or recurrent disease, as well as those considered non-eligible for surgery, will need a second-line therapeutic approach, i.e., pharmacotherapy. Radiation therapy is reserved as a third-line therapeutic option due to its slower onset of action and its unfavorable profile regarding complications. During the past few years, the understanding of molecular mechanisms implicated in the physiology of the hypothalamus-pituitary-adrenal axis has evolved, and new therapeutic targets for CD have emerged. In the present review, currently available treatments, compounds currently tested in ongoing clinical trials, and interesting, potentially new targets emerging from unraveling molecular mechanisms involved in the pathophysiology of Cushing's disease are discussed.

The reporting completeness and transparency of systematic reviews of prognostic prediction models for COVID-19 was poor: a methodological overview of systematic reviews.

OBJECTIVES: To conduct a methodological overview of reviews to evaluate the reporting completeness and transparency of systematic reviews (SRs) of prognostic prediction models (PPMs) for COVID-19. STUDY DESIGN AND SETTING: MEDLINE, Scopus, Cochrane Database of Systematic Reviews, and Epistemonikos (epistemonikos.org) were searched for SRs of PPMs for COVID-19 until December 31, 2022. The risk of bias in systematic reviews tool was used to assess the risk of bias. The protocol for this overview was uploaded in the Open Science Framework (https://osf.io/7y94c). RESULTS: Ten SRs were retrieved; none of them synthesized the results in a meta-analysis. For most of the studies, there was absence of a predefined protocol and missing information on study selection, data collection process, and reporting of primary studies and models included, while only one SR had its data publicly available. In addition, for the majority of the SRs, the overall risk of bias was judged as being high. The overall corrected covered area was 6.3% showing a small amount of overlapping among the SRs. CONCLUSION: The reporting completeness and transparency of SRs of PPMs for COVID-19 was poor. Guidance is urgently required, with increased awareness and education of minimum reporting standards and quality criteria. Specific focus is needed in predefined protocol, information on study selection and data collection process, and in the reporting of findings to improve the quality of SRs of PPMs for COVID-19.

The Importance of Out-of-Office Blood Pressure Measurement, as Highlighted by the Correlation with Left Ventricular Hypertrophy in an Untreated Hypertensive Population.

Background and Objectives: Hypertensive heart disease, especially left ventricular hypertrophy (LVH), is considered to be one of the main types hypertension-mediated organ damage. Hence, the purpose of this study was to examine which method of measuring BP (office BP measurement (OBPM), 24 h ambulatory BP monitoring (ABPM), or home BP monitoring (HBPM)), can be better correlated with echocardiographic LVH in the untreated hypertensive population. Materials and Methods: This study's population consisted of 202 patients 58 ± 15 years old (40.8% males). All patients reported elevated home BP measurements for at least 3 months, but they had never been treated before for hypertension. Office and out-of-office BP measurements, including ABPM on a usual working day and seven-day HBPM, as well as 2D echocardiography, were performed. Results: In the univariate analysis, LVH was associated (p < 0.05) with a mean 24 h systolic BP (OR: 1.93, CI: 1.29-2.91), a mean 24 h diastolic BP (OR: 1.30, CI: 1.16-1.80), ambulatory daytime systolic (OR: 1.11, CI:1.01-1.82) and diastolic BP (OR: 1.13, CI:1.09-1.17), ambulatory nighttime systolic BP (OR: 2.11, CI: 1.04-4.31), and mean home systolic BP (OR: 1.05, CI:1.01-1.12). Pearson's correlation analysis showed a significant correlation between the LV mass index and the mean 24 h systolic BP (r = 0.58, p < 0.05), daytime systolic BP (r = 0.59, p < 0.05), and nighttime systolic BP (r = 0.57, p < 0.05). Most of the population with confirmed LVH presented confirmed hypertension (based on ABPM, 48.1% or HBPM, 40%). The second most dominant phenotype was masked hypertension (ABPM, 32.7% and HBPM, 23.7%). The majority (59.3%) had non-dipping status, 20.4% had a reverse dipping pattern, 13% had a dipping pattern, and only 7.3% had extreme dipping BP. Conclusions: Out-of-office BP measurement devices seemed to be superior compared to in-office. This advantage is highlighted by better correlations in the identification of LVH as well as the diagnosis of masked hypertension, a condition also highly correlated with LVH.

Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVE: To provide a systematic review, critical appraisal, assessment of performance and generalisability of all the reported prognostic models for heart failure (HF) in patients with type 2 diabetes (T2D). METHODS: We performed a literature search in Medline, Embase, Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus (from inception to July 2022) and grey literature to identify any study developing and/or validating models predicting HF applicable to patients with T2D. We extracted data on study characteristics, modelling methods and measures of performance, and we performed a random-effects meta-analysis to pool discrimination in models with multiple validation studies. We also performed a descriptive synthesis of calibration and we assessed the risk of bias and certainty of evidence (high, moderate, low). RESULTS: Fifty-five studies reporting on 58 models were identified: (1) models developed in patients with T2D for HF prediction (n=43), (2) models predicting HF developed in non-diabetic cohorts and externally validated in patients with T2D (n=3), and (3) models originally predicting a different outcome and externally validated for HF (n=12). RECODe (C-statistic=0.75 95% CI (0.72, 0.78), 95% prediction interval (PI) (0.68, 0.81); high certainty), TRS-HFDM (C-statistic=0.75 95% CI (0.69, 0.81), 95% PI (0.58, 0.87); low certainty) and WATCH-DM (C-statistic=0.70 95% CI (0.67, 0.73), 95% PI (0.63, 0.76); moderate certainty) showed the best performance. QDiabetes-HF demonstrated also good discrimination but was externally validated only once and not meta-analysed. CONCLUSIONS: Among the prognostic models identified, four models showed promising performance and, thus, could be implemented in current clinical practice.

The Role of Somatostatin Analogues in the Control of Diarrhea and Flushing as Markers of Carcinoid Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Somatostatin analogues (SSAs) are the cornerstone of treatment for carcinoid syndrome (CS)-related symptoms. The aim of this systematic review and meta-analysis is to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of long-acting SSAs in patients with CS. METHODS: A systematic electronic literature search was conducted in PubMed, Cochrane, and Scopus to identify eligible studies. Any clinical trials reporting data on the efficacy of SSAs to alleviate symptoms in adult patients were considered as potentially eligible. RESULTS: A total of 17 studies reported extractable outcomes (PR/CR) for quantitative synthesis. The pooled percentage of patients with PR/CR for diarrhea was estimated to be 0.67 (95% confidence interval (CI): 0.52-0.79, I2 = 83%). Subgroup analyses of specific drugs provided no evidence of a differential response. With regards to flushing, the pooled percentage of patients with PR/CR was estimated to be 0.68 (95% CI: 0.52-0.81, I2 = 86%). Similarly, no evidence of a significant differential response in flushing control was documented. CONCLUSIONS: We estimate there is a 67-68% overall reduction in symptoms of CS associated with SSA treatment. However, significant heterogeneity was detected, possibly revealing differences in the disease course, in management and in outcome definition.

Study Level Meta-Analysis of Transcatheter Aortic Valve Implantation With the ACURATE neo Self-Expanding Transcatheter Heart Valve.

The ACURATE neo transcatheter aortic valve is a self-expanding device. Several studies have investigated safety and efficacy, but meta-analysis and pooled data are lacking. We aimed to provide a comprehensive systematic review and meta-analysis on the clinical outcomes of transcatheter aortic valve implantation with the ACURATE neo valve. A systematic literature search for eligible records was conducted. The primary endpoint was device success as designated by Valve Academic Research Consortium-2 criteria. The secondary endpoints (time frame: 30 days) were all-cause mortality, stroke, myocardial infarction, need for new permanent pacemaker, major vascular complications, major bleeding, acute kidney injury stage II or III, and paravalvular regurgitation grade moderate or severe (II or III). Our search yielded a total of 355 records, 20 of those (n = 5858 ACURATE neo receivers) were included in our meta-analysis. Device success was achieved in 94.5% (95% confidence interval [CI], 91.4-96.5%) of the patients. The 30-day all-cause mortality incidence proportion was 1.8% (95% CI, 1.3-2.4%). New pacemaker implantation was required in 7.7% (95% CI, 6.4-9.2%) of the patients, stroke occurred in 1.9% (95% CI, 1.6-2.3%), myocardial infarction in 0.5% (95% CI, 0.3-0.7%), major bleeding in 5.0% (95% CI, 3.9-6.5%), major vascular complication in 5.6% (95% CI, 4.0-7.8%), acute kidney injury stage ≥2 in 2.5% (95% CI, 1.8-3.4%), and paravalvular leak grade ≥moderate was observed in 4.3% (95% CI, 3.0-6.2%). Balloon predilatation and postdilatation incidence was 93.9% (95% CI, 87.0-97.3%) and 43.2% (95% CI, 37.9-48.6%), respectively. ACURATE neo appears to be safe and effective in our analysis with high device success incidence, low mortality, and low new pacemaker implantations.

Hobnail Papillary Thyroid Carcinoma, A Systematic Review and Meta-Analysis.

Although papillary thyroid carcinoma (PTC) is considered to have an excellent prognosis, some recently identified more aggressive variants show reduced overall survival rates. Hobnail PTC (HPTC) was newly recognized as one of these aggressive forms, affecting recurrence, metastasis, and overall survival rates. Herein, we performed a systematic review and meta-analysis of studies including cases or case series with patients with HPTC. Furthermore, we included our individual case series consisting of six patients. The pooled mortality rate in the cohort, consisting of 290 patients, was 3.57 (95% CI 1.67−7.65) per 100 person/years. No sex differences could be observed concerning mortality (p = 0.62), but older age and tumor size significantly affected mortality (p = 0.004 and p = 0.02, respectively). The percentage of hobnail cells did not affect mortality (p = 0.97), neither did the presence of BRAF mutations. Classical characteristics such as the presence of extrathyroidal extension (p = 0.001), distant metastases (p < 0.001), and lymph node metastases (p < 0.001) all had a significant impact on mortality. Thus, HPTC appears to correlate with worse overall survival, and all PTC cases should be carefully assessed for this variant.

Reproducibility of masked hypertension and office-based hypertension: a systematic review and meta-analysis.

Blood pressure (BP) phenotypes have a prognostic significance for target organ damage in long-term studies. However, it remains uncertain whether a single baseline phenotype classification is reproducible over time and represents accurately the patients' BP status. The aim of this study was to systematically investigate the reproducibility of masked hypertension and office-based hypertension either with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM). PubMed, Cochrane Library and Web of Science were searched to identify studies with paired baseline office BP and ABPM or HBPM measurements at two timepoints. The outcome of the analysis was the individual phenotype reproducibility between the baseline and follow-up timepoints. The used effect measure was Cohen's kappa coefficient. We found 15 studies eligible for the meta-analysis enrolling a total of 5729 patients. The reproducibility of masked hypertension was better with ABPM, kappa reliability test: 0.41 [95% confidence interval (CI): 0.32-0.49], than with HBPM, kappa reliability test: 0.26 (95% CI: 0.10-0.40). The reproducibility of office-based hypertension with both methods was low, indicating slight agreement. Kappa reliability test was slightly better with ABPM (κ: 0.27, 95% CI: 0.12-0.41) than with HBPM (κ: 0.18, 95% CI: 0.08-0.27). This systematic review and meta-analysis show a slight to fair reproducibility of masked hypertension and office-based hypertension assessed through ABPM and HBPM. Considering that poor reproducibility may be a result of office BP measurements, an ABPM/HBPM-based strategy should be established for the evaluation and treatment of patients with masked hypertension or office-based hypertension.

Autosomal dominant pseudohypoparathyroidism type 1B due to STX16 deletion: a case presentation and literature review.

INTRODUCTION: Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare, genetically related, endocrine disorders, characterized by end-organ resistance to parathyroid hormone (PTH) action and other G protein-coupled receptors (GPCRs) related hormones. The clinical variants of PHP are classified according to the presence of features of Albright's Hereditary Osteodystrophy (AHO) and in vivo response to exogenous PTH. Autosomal dominant PHP1b is often caused by a deletion in the Syntaxin-16 (STX16) gene, leading to a loss of methylation in the A/B exon of the guanine nucleotide-binding protein a-stimulating polypeptide (GNAS) complex. Herein, we present a case of a 41-year-old man with familiar PHP1b due to a maternal inherited 3-kb STX16 deletion, who was referred to us for consultation by artificial reproductive technology specialists. EVIDENCE ACQUISITION: A bibliographic search was performed in electronic databases (PubMed and Cochrane Library) to identify similar cases. EVIDENCE SYNTHESIS: Twenty studies (case-series or reports) were eligible. These studies included collectively 120 patients; 46 patients (38.3%) presented with symptoms of hypocalcemia; 38 were asymptomatic (31.7%); data for 36 patients (30%) were unavailable. Thyroid-Stimulating hormone (TSH) resistance was documented in 25 occasions (21%); growth hormone deficiency in 2 (1.7%); 3 patients shared features of the AHO (2.5%); 6 had abnormal bone mineral density test (5%). Notable is the development of tertiary hyperparathyroidism in 3 individuals (2.5%). CONCLUSIONS: The present review confirms the heterogeneity in the clinical spectrum of familiar PHP1b. Future research should focus on the molecular characterization of the GNAS disorders, leading to a facile diagnosis and appropriate genetic counseling.

The links between sleep duration, obesity and type 2 diabetes mellitus.

Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and ß-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.

Incident atrial fibrillation in patients with differentiated thyroid cancer: a meta-analysis.

Differentiated thyroid cancer (DTC) represents the most common form of thyroid neoplasms and is becoming increasingly prevalent. Evidence suggests a possible relationship between DTC diagnosis and subsequent atrial fibrillation (AF). If confirmed, this may present an alarming health risk (AF) in an otherwise condition with a relatively good prognosis (DTC). The aim of this systematic review and meta-analysis is to provide for the first time a pooled estimate of AF incidence in DTC patients in comparison to healthy controls. A detailed search in electronic databases, clinical trial registries and grey literature was performed to identify studies reporting the incidence of AF in DTC patients. Newcastle-Ottawa quality assessment scale was used to assess study quality. We used a random effects (RE) generalized linear mixed model (GLMM) in pooling of individual studies and also calculated a prediction interval for the estimate of a new study. Six observational studies met the eligibility criteria, which included totally 187,754 patients with DTC and 199,770 healthy controls. The median follow-up period was 4.3 to 18.8 years; the incidence rate of AF was 4.86 (95% CI, 3.29 to 7.17, I2 = 96%) cases per 1000 person-years, while the incidence rate ratio was 1.54 (95% CI, 1.44 to 1.65, I2 = 0%, 95% PI, 1.33 to 1.78).This is the first meta-analysis to confirm that patients with DTC are at a high risk for developing AF, which may be attributed to a state of iatrogenic hyperthyroidism due to long-term thyrotropin suppression therapy.

Risk Models and Scores of Cardiovascular Disease in Patients with Diabetes Mellitus.

Diabetes mellitus (DM) is an established risk factor for atherosclerotic cardiovascular disease (CVD), and patients with DM are at a two to four-fold higher cardiovascular risk, including myocardial infraction, unstable angina, stroke, and heart failure. All of the above have arisen interest in CVD preventive strategies by the use of non-invasive methods, such as risk scores. The most common approach is to consider DM as a CVD equivalent and, therefore, to treat patients with DM in a similar way to those who required secondary CVD prevention. However, this approach has been disputed as all patients with DM do not have the same risk for CVD, and since other potentially important factors within the context of DM, such as DM duration, presence of albuminuria, and comorbidities, should be taken into consideration. Thus, the second and third approach is the application of risk models that were either developed initially for the general population or designed specifically for patients with DM, respectively. This review summarizes the evidence and implications for clinical practice regarding these scores. Up to date, several models that can be applied to the diabetic population have been proposed. However, only a few meet the minimum requirement of adequate external validation. In addition, moderate discrimination and poor calibration, which might lead to inaccurate risk estimations in populations with different characteristics, have been reported. Therefore, future research is needed before recommending a specific risk model for universal clinical practice in the management of diabetes.