The genetics of spontaneous coronary artery dissection: a scoping review.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a multifactorial process that involves predisposing factors and precipitating stressors. Genetic abnormality has been implicated to play a mechanistic role in the development of SCAD. This systematic review aims to summarize the current evidence concerning the link between SCAD and genetic abnormalities. METHODS: We reviewed original studies published until May 2023 that reported SCAD patients with a genetic mutation by searching PubMed, Embase Ovid, and Google Scholar. Registries, cohort studies, and case reports were included if a definitive SCAD diagnosis was reported, and the genetic analysis was performed. Exclusion criteria included editorials, reviews, letters or commentaries, animal studies, meeting papers, and studies from which we were unable to extract data. Data were extracted from published reports. RESULTS: A total of 595 studies were screened and 55 studies were identified. Among 116 SCAD patients with genetic abnormalities, 20% had mutations in the COL gene, 13.70% TLN1 gene, and 8.42% TSR1 gene. Mutations affecting the genes encoding COL and TLN1 were most frequently reported (20 and 13.7%, respectively). Interestingly, 15 genes of this collection were also reported in patients with thoracic aortic diseases as well. The genetic commonality between fibromuscular dysplasia (FMD) and SCAD was also included. CONCLUSION: In this review, the inherited conditions and reported genes of undetermined significance from case reports associated with SCAD are collected. A brief description of the encoded protein and the clinical features associated with pathologic genes is provided. Current data suggested that the diagnostic yield of genetic studies for patients with SCAD would be low and routine genetic screening of such patients with no clinical features indicative of associated disorders remains debatable. This review can be used as a guide for clinicians to recognize inherited syndromic and nonsyndromic disorders associated with SCAD.

Association of D-dimer with short-term risk of venous thromboembolism in acutely ill medical patients: A systematic review and meta-analysis.

BACKGROUND: D-dimer, a marker of ongoing procoagulant activity, has been widely used for the diagnosis of venous thromboembolism (VTE). The prognostic significance of D-dimer in stratifying VTE risk for acutely ill medical patients has not been well-established. METHODS: A literature search was performed to collect studies that compared the incidence of short-term VTE between acutely ill medical patients with elevated or nonelevated D-dimer levels. The cutoff of D-dimer was 0.5 µg/mL or otherwise defined by included studies. The study endpoint was any occurrence of VTE (inclusive of deep vein thrombosis [DVT], pulmonary embolism, or VTE-related death) within 90 days of hospital presentation. A meta-analytic approach was employed to estimate the odds ratio (OR) with 95% CI by fitting random-effects models using the generic inverse variance weighted approach. RESULTS: A total of 10 studies representing 31,119 acutely ill medical patients were included. Compared to those with nonelevated D-dimer levels, patients with elevated D-dimer had approximately threefold greater odds for short-term VTE within 90 days (OR, 3.28; 95% CI, 2.44 to 4.40; p < 0.0001). The association of elevated D-dimer with VTE composite (OR, 3.33; 95% CI, 2.20 to 5.02) and with DVT (OR, 3.26; 95% CI, 2.32 to 4.58) was comparable. The association was significant among patients who presented various acute medical illness (OR, 2.68; 95% CI, 2.01 to 3.58) and those who presented with acute stroke (OR, 3.25; 95% CI, 2.31 to 4.58). CONCLUSION: Elevation of D-dimer was predictive of the occurrence of VTE within 90 days among acutely ill medical patients.

Early and late recurrent cardiovascular events among high-risk patients with an acute coronary syndrome: Meta-analysis of phase III studies and implications on trial design.

BACKGROUND: Despite low-density lipoprotein cholesterol-lowering therapies and other standard-of-care therapy, there remains a substantial residual atherosclerotic risk among patients with an acute coronary syndrome (ACS). This study aims to estimate the risk of early and late recurrent major adverse cardiovascular events (MACE) and address its implications on trial design. METHODS: A literature search was performed to collect phase III interventional trials on high-risk ACS patients. Pooled event rates at 90 and 360 days were estimated by fitting random-effects models using the DerSimonian-Laird method. Under the assumption of a total sample size of 10,000 and 1:1 allocation at a one-sided alpha of 0.025 using the log-rank test, the relationship between power and relative risk reduction (RRR) or absolute risk reduction (ARR) was explored for early versus late MACE endpoint. RESULTS: Seven trials representing 82,727 recent ACS patients were analyzed. The pooled rates of recurrent MACE were 4.1% and 8.3% at 90 and 360 days. Approximately 49% of events occurred within the first 90 days. Based on the estimated risks at 90 and 360 days, to attain 90% statistical power, a lower magnitude of RRR is required for late MACE than early MACE (22% vs. 30%), whereas a lower magnitude of ARR is required for early MACE than late MACE (1.2% vs. 1.8%). CONCLUSION: The initial 90-day window after ACS represents a vulnerable period for recurrent events. From a trial design perspective, determining a clinically important benefit by RRR versus ARR may influence the decision between early and late MACE as the study endpoint.

Evaluation of Cardiac Troponin and Adverse Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Several studies have demonstrated the usefulness of cardiac troponin I (cTn) levels in predicting adverse clinical outcomes of patients with anerusmal subarachnoid hemorrhage (aSAH). However, it remains unclear whether cTn levels can be a useful factor in predicting adverse neurologic and cardiovascular outcomes regarding follow-up duration. The study aimed to evaluate the clinical value of cTn elevation among patients with aSAH. A systematic literature search was performed in PubMed and Cochrane to collect original studies that compared the adverse outcomes in patients with aSAH who had elevated cTn levels and those who did not have elevated cTn levels. Data on patient demographics and outcome measurements (mortality, major disability, delayed cerebral ischemia, cardiac dysfunction, and pulmonary edema) were extracted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed by fitting a random effects model. A total of 4,117 patients with aSAH were included in the meta-analysis. Elevated cTn levels was associated with a higher all-cause mortality (OR 3.64; 95% CI 2.68-4.94; I2 = 22.05%), poor major disability (OR 2.27; 95% CI 1.5-3.37; I2 = 52.07%), delayed cerebral ischemia (OR 2.10; 95% CI 1.46-3.03; I2 = 13.80%), cardiac dysfunction (OR 9.20; 95% CI 4.31-19.60; I2 = 39.89), and pulmonary edema (OR 10.32; 95% CI 5.64-18.90; I2 = 0.00%). Additionally, elevated cTn levels was associated with higher mortality in prospective studies (OR 3.66; 95% CI 2.61-5.14) as well as when compared with studies with short-term and long-term follow-up periods. Patients with aSAH who had elevated cTn levels also tended to experience poor short-term major disability (OR 2.36; 95% CI 1.48-3.76). Among patients with aSAH, elevated cTn levels was associated with higher mortality and adverse neurologic and cardiovascular outcomes. Given its clinical value, cardiac troponin levels may be included in the assessment of patients withs aSAH.

Clinical outcomes of pharmacological thromboprophylaxis among patients with intracerebral hemorrhage: Systematic review and meta-analysis.

OBJECTIVE: Efficacy and safety of pharmacologic thromboprophylaxis after an episode of intracerebral hemorrhage remains unclear. This meta-analysis aimed at comparing the clinical outcomes of intracerebral hemorrhage patients with or without pharmacologic thromboprophylaxis. METHODS: We performed a comprehensive literature review of PubMed to identified relevant studies. The primary and secondary endpoints included venous thromboembolism, deep venous thrombosis, pulmonary emboli, rebleeding, hematoma enlargement (defined as increase in hematoma volume of ≥33%), major disability (defined as modified Rankin score of 3-5), and death. Pooled outcomes were estimated by fitting random effects model with restricted maximum likelihood method. A total of 8 original studies including 3893 patients were analyzed. RESULT: Compared to the control group, pharmacologic thromboprophylaxis was associated with a lower risk of pulmonary embolism (odds ratio [OR]: 0.34, 95% CI: 0.15-0.80, P = 0.01). There was no significant difference in the risk of DVT (OR: 0.75; [95% CI: 0.37-1.53], P = 0.44) and VTE (OR: 0.65; [95% CI: 0.34-1.25], P = 0.20). Finally, anticoagulation was not associated with an increase rate of major disability (OR:1.36; [95% CI: 0.57 - 3.23], P = 0.48), rebleeding (OR: 0.35; [95% CI: 0.10-1.19], P = 0.09), hematoma enlargement (OR:1.34; [95% CI: 0.58-3.12], P = 0.49), or death (OR:0.90; [95% CI: 0.68-1.19], P = 0.46). CONCLUSION: Among patients with intracerebral hemorrhage, pharmacologic thromboprophylaxis was associated with a significant reduction in pulmonary embolism, without an increase in rebleeding or hematoma enlargement. The results of this meta-analysis need to be further validated in large scale clinical trials.

Role of GATA3 in tumor diagnosis: A review.

GATA binding protein 3 (GATA3) belongs to a family of transcription factors comprising six members. These proteins identify G-A-T-A containing sequences in the target gene and bind to DNA target via two zinc-finger domains. The aim of this study was to evaluate the role of GATA3 in the diagnosis of tumors and its value as a prognostic marker. To perform this review, a comprehensive search was conducted through PubMed, Embase, Scopus, Cochrane and Google Scholar databases from 1985 to 2020. Articles were considered thoroughly by independent reviewers and data were extracted in predefined forms. Final synthesis was conducted by using appropriate data from included articles in each topic. Studies have shown that GATA3 has a critical role in the development of epithelial structures in both embryonic and adult tissues. The majority of studies regarding GATA3 expression in tumor evaluation focused on breast and urothelial neoplasms, whether primary or metastatic. Its sensitivity in these neoplasms has been reported to be high and made this marker more valuable than other available immunohistochemistry markers. However, GATA3 expression was not restricted to these tumors. Studies have shown that GATA3 immunostaining could be a useful tool in various tumors in kidney, salivary gland, endocrine system, hematopoietic system, and skin. GATA3 can also be used as a useful prognostic tool. Although GATA3 is a multi-specific immunohistochemical stain, it is a valuable marker in the panel for confirming many epithelial or mesenchymal neoplasms as both a diagnostic and prognostic tool.

Effect of azithromycin and hydroxychloroquine in patients hospitalized with COVID-19: Network meta-analysis of randomized controlled trials.

Chloroquine or its derivative hydroxychloroquine (HCQ) combined with or without azithromycin (AZ) have been widely investigated in observational studies as a treatment option for coronavirus 2019 (COVID-19) infection. The network meta-analysis aims to summarize evidence from randomized controlled trials (RCTs) to determine if AZ or HCQ is associated with improved clinical outcomes. PubMed and Embase were searched from inception to March 7, 2021. We included published RCTs that investigated the efficacy of AZ, HCQ, or its combination among hospitalized patients with COVID-19 infection. The outcomes of interest were all-cause mortality and the use of mechanical ventilation. The pooled odds ratio was calculated using a random-effect model. A total of 10 RCTs were analyzed. Participant's mean age ranged from 40.4 to 66.5 years. There was no significant effect on mortality associated with AZ plus HCQ (odds ratio [OR] = 0.562 [95% confidence interval {CI}: 0.168-1.887]), AZ alone (OR = 0.965 [95% CI: 0.865-1.077]), or HCQ alone (OR = 1.122 [95% CI: 0.995-1.266]; p = 0.06). Similarly, based on pooled effect sizes derived from direct and indirect evidence, none of the treatments had a significant benefit in decreasing the use of mechanical ventilation. No heterogeneity was identified (Cochran's Q = 1.68; p = 0.95; τ2 = 0; I2 = 0% [95% CI: 0%-0%]). Evidence from RCTs suggests that AZ with or without HCQ was not associated with a significant effect on the mortality or mechanical ventilation rates in hospitalized patients with COVID-19. More research is needed to explore therapeutics agents that can effectively reduce the mortality or severity of COVID-19.

Current Opinion on the use of Direct Oral Anticoagulants for the Prophylaxis of Venous Thromboembolism among Medical Inpatients.

Venous thromboembolism (VTE) is a known cause of morbidity and mortality, especially among acutely ill medical patients. Although VTE prophylaxis is part of post-discharge clinical care in surgical patients, there is controversy regarding its use in acutely ill medical patients and the current guideline statements suggest against its routine use. Recent clinical trials (APEX, MAGELLAN and MARINER) compared the safety and efficacy of direct oral anticoagulants (including betrixaban and rivaroxaban) with the standard of the care, enoxaparin, to identify the risk-benefit tradeoff. In this review, we summarized the key findings from these trials and substudies and recent updates in society guidelines regarding VTE prevention. In addition, we discussed the potential barriers, cost-effectiveness, and COVID-19 with respect to the implementation of extended-duration or post-discharge usage of direct oral anticoagulants.

COVID-19-associated coagulopathy: a concise review on pathogenesis and clinical implications.

In this review, we summarize the possible mechanisms of COVID-19-associated coagulopathy and compare its features to other similar conditions. The recent COVID-19 pandemic has caused enormous mortality and morbidity worldwide. It is important to note that COVID-19-associated thrombotic events play a huge role in the morbidity of this disease. Interestingly, it has been observed that this complication may occur despite prophylactic anticoagulant therapy. Recent studies on COVID-19-associated coagulopathy revealed that the COVID-19-associated hypercoagulability is more frequently observed among those with a severe course of the disease. Various mechanisms have been suggested as explanations for this condition and possible underlying etiologies.

Venous Thromboembolism among Hospitalized Patients with COVID-19 Undergoing Thromboprophylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among COVID-19 patients. This study aimed to offer benchmark data on the incidence of VTE and to examine the difference in D-dimer levels among anticoagulated COVID-19 patients with and without VTE incident. METHODS: A comprehensive literature review of PubMed from inception to May 2020 was performed for original studies that reported the frequency of VTE and death among COVID-19 patients who received thromboprophylaxis on hospitalization. The endpoints included VTE (a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT)), PE, DVT, and mortality. RESULTS: A total of 11 cohort studies were included. Among hospitalized COVID-19 patients, 23.9% (95% confidence interval (CI), 16.2% to 33.7%; I2 = 93%) developed VTE despite anticoagulation. PE and DVT were detected in 11.6% (95% CI, 7.5% to 17.5%; I2 = 92%) and 11.9% (95% CI, 6.3% to 21.3%; I2 = 93%) of patients, respectively. Patients in the intensive care unit (ICU) had a higher risk for VTE (30.4% )95% CI, 19.6% to 43.9%)) than those in the ward (13.0% (95% CI, 5.9% to 26.3%)). The mortality was estimated at 21.3% (95% CI, 17.0% to 26.4%; I2 = 53%). COVID-19 patients who developed VTE had higher D-dimer levels than those who did not develop VTE (mean difference, 2.05 µg/mL; 95% CI, 0.30 to 3.80 µg/mL; P = 0.02). CONCLUSIONS: The heightened and heterogeneous risk of VTE in COVID-19 despite prophylactic anticoagulation calls into research on the pathogenesis of thromboembolic complications and strategy of thromboprophylaxis and risk stratification. Prominent elevation of D-dimer may be associated with VTE development and can be used to identify high-risk subsets.

Effect of Vitamins and Dietary Supplements on Cardiovascular Health.

Cardiovascular disease marks the leading cause of mortality and morbidity in the United States. Pharmacological therapies have been developed to reduce the burden of cardiovascular diseases in the setting of large-scale randomized controlled trials. In contrast, vitamins and minerals have not undergone an equal level of scrutiny, and the evidence of cardiovascular benefit remains elusive. Multivitamins are the most popular over-the-counter supplements in the United States, despite the lack of clear benefit as a means of primary or secondary cardiovascular prevention. Recent studies indicate a potential role of multivitamins in secondary prevention when concomitantly administered with chelation therapy. Additionally, preclinical and observational studies have shown preliminary evidence of cardiovascular protection with dietary supplements such as carnitine, arginine, and coenzyme Q10. This review summarizes the currently available data about the effect of vitamins and other dietary supplements on the cardiovascular system.

General and abdominal obesity in relation to the prevalence of irritable bowel syndrome.

BACKGROUND: Earlier studies on the obesity-IBS association have mostly been reported from Western nations, and limited data are available in this regard from developing countries. This study was performed to examine the association of general and abdominal obesity with Irritable bowel syndrome (IBS) in a Middle Eastern population. METHODS: In this cross-sectional study, 4763 Iranian adults participated. Data on self-reported anthropometric measurements were collected, and BMI was calculated. Overweight and obesity were defined as 25 ≤ BMI < 30 and BMI ≥ 30 kg/m2 , respectively. Also, we used WC measurements to define the three categories of normal (<94 cm in men <80 cm in women), abdominal overweight (94 ≤ WC < 102 in men and 80 ≤ WC < 88 in women), and abdominal obesity (WC ≥ 102 cm in men and WC ≥ 88 cm in women). Assessment of different GI symptoms including those related to IBS was done using a validated Persian version of the Rome III questionnaire. IBS was defined as the presence of recurrent abdominal pain or discomfort at least sometimes in the last 3 months associated with 2 or more of the following features: improvement with defecation, pain onset associated with a change in frequency of stool, and pain onset associated with a change in form (appearance) of stool. KEY RESULTS: Irritable bowel syndrome was more prevalent among individuals with abdominal obesity compared with normal subjects (23.8% vs 19%). Neither in crude nor in adjusted models, we found any significant association between overweight and obesity and IBS [for overweight: OR: 0.95, 95% CI: 0.66-1.36 and for obesity: OR: 1.06, 95% CI: 0.85-1.31]. We observed a significant positive association between abdominally overweight and IBS in crude model (OR: 1.31, 95% CI: 1.09-1.60); however, this association became non-significant after adjustment for potential confounders (OR: 1.09, 95% CI: 0.82-1.44). Across BMI categories, neither in crude nor in adjusted models, we did not find any significant association between overweight (OR: 0.89, 95% CI: 0.62-1.27), obesity (OR: 1.05, 95% CI: 0.58-1.87), and abdominal pain severity. Abdominal overweight (OR: 0.96, 95% CI: 0.65-1.40) and obesity (OR: 1.61, 95% CI: 0.67-1.63) were not associated with abdominal pain severity. CONCLUSIONS AND INFERENCES: It is concluded that general or abdominal obesity was not associated with odds of IBS. Future longitudinal studies are needed to clarify the association between obesity and IBS.