Favipiravir-induced bradycardia: A case report.

Key Clinical Message: The purpose of this case report is to reveal one of the cardiovascular side effects of favipiravir, sinus bradycardia. Abstract: Favipiravir has emerged as a potential treatment for COVID-19, with its antiviral properties showing promise in inhibiting viral replication. However, concerns regarding its safety profile, particularly its cardiac adverse effects, remain a subject of debate. We present the case of a 58-year-old man with a history of diabetes mellitus and chronic obstructive pulmonary disease who developed bradycardia following treatment with favipiravir for COVID-19 pneumonia. Despite being asymptomatic, the patient exhibited sinus bradycardia, which resolved upon discontinuation of favipiravir. Favipiravir has been associated with QT prolongation and sinus bradycardia, though the exact mechanisms remain unclear. Our case adds to the growing body of evidence highlighting the potential cardiac complications of favipiravir therapy in COVID-19 patients. Further research is warranted to clarify the underlying mechanisms and optimize patient management strategies. Clinicians should be cautious for cardiac adverse events when prescribing favipiravir for COVID-19 treatment, especially in patients with preexisting cardiac conditions. Continued research is essential to ensure the safe and effective use of favipiravir in the management of COVID-19.

Pericardial effusion in patients with chronic kidney disease: A two-center study.

BACKGROUND AND AIMS: Pericardial effusion (PE) is a prevalent form of pericardial involvement in chronic kidney disease (CKD). This study aims to investigate the clinical and laboratory features associated with PE severity in patients with CKD. METHODS: In this cross-sectional study, we examined the medical records of patients admitted to tertiary hospitals with International Classification of Diseases 10th Revision (ICD-10) codes associated with CKD and PE. We included 112 CKD patients in stage 4 and 5 non-dialysis (ND) with PE for assessing the clinical and laboratory features of severity. RESULTS: Patients were divided into two categories based on the severity of PE. Seventy-two patients had mild and 40 had moderate and severe PE. Univariate analysis of demographic and laboratory features on the date of admission demonstrated that chest pain, dyspnea, serum albumin, and neutrophil-to-lymphocyte ratio (NLR) are associated with the severity of PE. The univariate analysis on the date of echocardiography showed significantly higher white blood cell count (WBC), neutrophil count (percentage and absolute count), and NLR, along with significantly lower lymphocyte percentage and serum albumin among patients with moderate and severe PE. In the multivariable analysis of laboratory features, on admission hypoalbuminemia (p-value = 0.014, OR = 4.03, CI: 1.32-12.25) and NLR greater than 5.5 (p-value = 0.015, OR = 4.22, CI: 1.32-13.50) were significantly associated with moderate and severe PE. In a parallel matter, at the time of echocardiography hypoalbuminemia (p-value = 0.004, OR = 5.38, CI: 1.74-16.65) and neutrophilia (p-value = 0.005, OR = 7.94, CI: 1.89-33.44) were significantly associated with moderate and severe PE. CONCLUSION: Despite advancements in the diagnosis and treatment of CKD, PE is still a concerning issue in these patients. This study revealed that hypoalbuminemia, neutrophilia, and NLR greater than 5.5 could be predictive factors of moderate and severe PE in CKD patients with PE. Further prospective study with larger sample size is needed to confirm these results.

Investigating the expression level of miR-17-3p, miR-101-3p, miR-335-3p, and miR-296-3p in the peripheral blood of patients with acute myocardial infarction.

The role of inflammation has been proven in acute myocardial infarction (AMI) pathogenesis. Due to the effect of NLRP3 gene expression in the inflammation process of MI, we aimed to explore the expression changes and diagnostic power of four inflammation-related miRNAs including miR-17-3p, miR-101-3p, miR-335-3p, miR-296-3p and their potential target, NLRP3, in ST-segment elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) patients as two major classes of AMI. The expression level of these genes were evaluated in 300 participants equally divided into three groups of STEMI, NSTEMI, and control using quantitative real-time PCR. The expression level of NLRP3 was upregulated in STEMI and NSTEMI patients compared to control subjects. Besides, the expression levels of miR-17-3p, miR-101-3p, and miR-296-3p were significantly downregulated in STEMI and NSTEMI patients compared to controls. The increased expression of NLRP3 had a very strong inverse correlation with miR-17-3p in patients with STEMI and with miR-101-3p in the STEMI and NSTEMI patients. ROC curve analysis showed that the expression level of miR-17-3p had the highest diagnostic power for discrimination between STEMI patients and controls. Remarkably, the combination of all markers resulted in a higher AUC. In summary, there is a significant association between the expression levels of miR-17-3p, miR-101-3p, miR-335-3p, miR-296-3p, and NLRP3 and the incidence of AMI. Although the miR-17-3p expression level has the highest diagnostic power to distinguish between STEMI patients and control subjects, the combination of these miRNAs and NLRP3 could serve as a novel potential diagnostic biomarker of STEMI.

Associations between short-term exposure to fine particulate matter and acute myocardial infarction: A case-crossover study.

BACKGROUND: Previous studies evaluated the impact of particle matters (PM) on the risk of acute myocardial infarction (AMI) based on local registries. HYPOTHESIS: This study aimed to evaluate possible short term effect of air pollutants on occurrence of AMI based on a specific case report sheet that was designed for this purpose. METHODS: AMI was documented among 982 patients who referred to the emergency departments in Tehran, Iran, between July 2017 to March 2019. For each patient, case period was defined as 24 hour period preceding the time of emergency admission and referent periods were defined as the corresponding time in 1, 2, and 3 weeks before the admission. The associations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2 .5 ) and particulate matter with an aerodynamic diameter ≤10 µm (PM10 ) with AMI were analyzed using conditional logistic regression in a case-crossover design. RESULT: Increase in PM2.5 and PM10 was significantly associated with the occurrence of AMI with and without adjustment for the temperature and humidity. In the adjusted model each 10 µg/m3 increase of PM10 and PM2.5 in case periods was significantly associated with increase myocardial infarction events (95% CI = 1.041-1.099, OR = 1.069 and 95% CI = 1.073-1.196, and OR = 1.133, respectively). Subgroup analysis showed that increase in PM10 did not increase AMI events in diabetic subgroup, but in all other subgroups PM10 and PM2 .5 concentration showed positive associations with increased AMI events. CONCLUSION: Acute exposure to ambient air pollution was associated with increased risk of AMI irrespective of temperature and humidity.

Vascular and Neural Invasion in Oral Squamous Cell Carcinoma: A Study in an Iranian Population.

Background: Among various parameters used to predict the outcome of malignancy, nerve invasion has been widely considered as a sign of aggressive behavior in oral cancers. According to the importance of neural invasion in predicting the outcome of oral squamous cell carcinoma (OSCC), this study aimed to evaluate the prevalence of neural and vascular invasion in OSCC. Materials and Methods: In this descriptive, analytical, and cross-sectional study, paraffin-embedded tissues of 62 OSCC in the health center of surgery and pathology were evaluated (2013-2015). Patients' archives were evaluated and recorded in terms of their age and gender. Hematoxylin and eosin (H&E) slides were then examined by two oral pathologists and scrutinized for the presence of nerve involvement, tumor differentiation, vascular and lymph node invasion, and depth of invasion. Data were analyzed using SPSS version 23, t-test, and one-way ANOVA (P < 0.05). Results: Of 62 tumors, 12 patients showed only nerve invasion, 17 cases had only vascular invasion, and seven patients had both neural and vascular invasion, simultaneously, known as a neurovascular invasion. Furthermore, there was no vascular and neural invasion in 26 cases. There was a statistically significant correlation between vascular and neural invasion and the tumor site (P = 0.045). The highest frequency of neural invasion, as well as vascular invasion, was related to tongue tumors. Conclusion: The relation between neural and vascular invasion in OSCC with tumor's location was statistically significant. Lip and tongue carcinoma had shown more neurovascular invasion without relation to gender, age, and cell differentiation.

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial.

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508).

The association between QTc, QTd, TPE, and fragmented QRS before and after PPCI with hospital mortality in STEMI patients.

INTRODUCTION: ST-elevation myocardial infarction (STEMI) is known to be associated with significant arrhythmia and consequent mortality. QT prolongation is a risk factor for arrhythmia in STEMI patients who underwent primary percutaneous coronary intervention (PPCI). The aim of this investigation was to evaluate the association of corrected QT interval (QTc), QT dispersion (QTd), T-wave peak to end (TPE), and fragmented QRS with mortality in these patients. METHODS: Eligible patients with the characteristic symptoms of STEMI who underwent PPCI were included. QTc, QTd, TPE, and fragmented QRS were measured before and after the PPCI. These predictors were compared between patients who died during hospitalization and discharged patients. RESULTS: After coronary angiography, 10 patients (4%) died during the hospitalization after PPCI. Comparing the non-survivers and discharged patients in terms of arrhythmia predictors showed that the mean QT dispersion and TPE before intervention were significantly higher in the non-survivors. Also, the number of patients who experienced fragmented QRS both before and after the intervention was significantly higher in the non-survivors. CONCLUSION: These data suggested that evaluating such arrhythmia predictors, especially before PPCI, could be used as a predictor of mortality in STEMI patients who underwent PPCI.

The Association Between Hematologic Indices With TIMI Flow In STEMI Patients Who Undergo primary percutaneous coronary intervention.

BACKGROUND: The Primary Percutaneous Coronary Intervention (PPCI) is the preferred therapeutic strategy for patients who experienced ST-Elevation Myocardial Infarction (STEMI). OBJECTIVE: We aimed to evaluate the association of hematological indices, including hemoglobin level, platelets, White Blood Cells (WBCs) count, and MPV before PPCI with the TIMI grade flow after PPCI. METHODS: STEMI patients who experienced PPCI were included in the present retrospective crosssectional study. Then participants were divided into three groups based on their post-procedural TIMI flow grades. Demographic data and hematologic indices of patients before PPCI were collected and their association with the TIMI grade flow after PPCI was evaluated. To compare the quantitative and qualitative variables, chi-square and t-tests were performed, respectively. RESULTS: We found that elevated levels of hemoglobin and decreased levels of MPV had a significant association with an advanced grade of TIMI flow. Interestingly, in the normal range, there was a significant association between higher platelet count and TIMI-flow grade 1. Besides, TIMI flow grades 2 and 3 had a significant association with low and moderate platelets count, respectively. CONCLUSION: In conclusion, evaluating MPV, platelets, and hemoglobin levels before PPCI as easy and accessible parameters may be able to identify high-risk STEMI patients undergoing PPCI.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Early prediction of ventricular functional recovery after myocardial infarction by longitudinal strain study.

BACKGROUND: There are some suggestions that global myocardial strain (GLS) early after ST-elevation myocardial infarction (STEMI) is a predictor of improvement in left ventricular ejection fraction (LVEF). The goal of this study was to evaluate LV recovery after STEMI intervention based on GLS values. METHODS: The study population consists of 43 patients with acute STEMI and no history of prior coronary intervention treated with primary percutaneous coronary intervention. LVEF and myocardial strain indices were measured 48 hours and two months after STEMI by transthoracic echocardiography and speckle tracking method. More than 5% improvement in LVEF was considered significant. RESULTS: GLS values were significantly higher in patients with >5% improvement in LVEF 2 months after the STEMI (GLS=15.76% in patients with >5% improvement vs. 11.54% in the other group, P<0.05). ROC analysis suggested GLS values more than 13.5 to be a predictor of significant LVEF improvement 2 months after STEMI. Higher GLS was observed in patients with inferior, posterior and inferoseptal STEMI versus anterior, extensive or anteroseptal STEMI and in patients with right coronary occlusion versus occlusion of the left anterior descending or circumflex arteries. CONCLUSION: We have observed that early longitudinal LV strain after STEMI is a predictor of recovery after STEMI. This is a useful method to predict early LV recovery after STEMI. GLS values of more than 13.5% are a significant predictor of significant LVEF improvement.

Hispanic ethnicity and in-hospital morbidity and mortality outcomes in Alzheimer's Disease: A U.S. National Study 2005-2015.

BACKGROUND: Hispanics are one of the largest and fastest-growing population in the United States. Having been reported as one of the high-risk ethnicities to develop Alzheimer's Disease (AD) makes elder Hispanics one of the significant groups of AD in the country, indicating a need to study the disparities in Hispanics vs. non-Hispanics patients. We aimed to determine the prevalence, morbidity, and mortality outcomes of AD in Hispanics. METHODS: We surveyed Healthcare Cost and Utilization Project (HCUP) from 2005 to 2015 to identify patients older than 50 years who were admitted for any reason and had AD diagnosis. Prevalence, demographics, age brackets, in-hospital deaths, disease severity, and hospital length of stay (LOS) were compared between the Hispanics and Non-Hispanics. RESULTS: Among 14,135,560 Hispanic discharges, 2.76% had AD, compared with 207,515,260 discharges in Non-Hispanic with 2.61% AD, p < 0.001. Hispanics had significantly more AD in all age brackets, especially over 90 years of age, p < 0.001. A significantly higher prevalence of AD in both Hispanic Females (3.27% vs. 3.10%) and Males (2.17% vs. 2.04%) was noticed, p < 0.001. In northeast and south regions of the country and urban hospitals, AD was more among Hispanics (p < 0.001). Hispanic patients were younger (81.8 ± 7.77 vs. 82.6 ± 7.50, p < 0.001), had longer LOS (6.41 ± 7.72 vs. 6.08 ± 7.05, p < 0.001), had higher hospital charges ($45,989 vs. $37,688, p < 0.001). Hispanic AD patients had higher disease severity and mortality risk (p < 0.001). However, the inpatient mortality was not different between the Hispanic and non-Hispanics. Multivariate analysis showed that Hispanics had the highest AD prevalence in the inpatient setting (OR, 1.38; 95% CI, 1.37-1.39, p < 0.001). CONCLUSION: The prevalence of AD was significantly higher in inpatient Hispanics than non-Hispanics. Hispanic AD patients had a younger age compared with non-Hispanic AD. Disease severity and mortality risks were higher in Hispanics with AD than non-Hispanics with AD. However, no difference was seen in mortality rate during admission in Hispanics vs. non-Hispanics.

Are women more susceptible to ischemic heart disease compared to men? A literature overview.

Ischemic heart disease (IHD) is known as the leading cause of death in both genders. Moreover, significant sex differences were found in cardiac structure, function, pathophysiology, presentation, treatment, and outcome of IHD. The presence of unique risk factors such as exposure to menarche and pregnancy, more anemia, hypertension, and autoimmune disorders in women have recently received attention. Ischemic symptoms are more indefinite and vague in women compared to men as well as a delay in diagnosis, treatment, and worse outcomes compared to men. Women usually receive less evidence-based treatment and intervention, with less concern on preventive health care. Clinical trials primarily recruit male patients and women are underrepresented. Without any correct diagnosis, treatment, and prevention, these problems are accumulated and continue up to older age. Accordingly, with the belief of longer life in women and the increased prevalence of IHD with aging, it will become an important public health problem and concern in the future. This narrative review aimed to provide an overview of some of the differences between the two genders in terms of IHD with paying more attention to practical points.

Definite SUDEP population in Bexar County, Texas: A 36-year data registry.

OBJECTIVE: Sudden unexplained death in epilepsy (SUDEP) is one of the leading causes of mortality in epilepsy. In this study, cases of definite SUDEP are reported for Bexar County from a 36-year period. METHODS: Death reports by Bexar County Medical Examiner (BCME) from 1983 to 2018 were reviewed to identify cases with definite SUDEP. The findings were based upon investigators' reports, which included medical history, medication list, sleep position, time of death, and pathology reports. In addition to these potential risk factors, body mass indices (BMI), as well as heart, lung, and brain weights were compared between SUDEP victims with therapeutic vs subtherapeutic anti-seizure medication (ASM) levels. RESULTS: Definite SUDEP was identified in 286 cases. The incidence of definite SUDEP was 0.51 ±â€¯0.26/1000 person-years among PWE and 0.56 ±â€¯0.29 per 100,000 person-years among the general population in Bexar County. The median age was 37 years old (interquartile range 27-48), and the majority were male (65%). While 171 (60%) people were prescribed at least one ASM, ASM levels were subtherapeutic in 239 cases (83.6%). Risk factors for SUDEP did not differ between SUDEP victims with therapeutic vs subtherapeutic ASM levels. While BMIs were only slightly increased in adherent vs nonadherent SUDEP victims, they were significantly associated with subtherapeutic ASM levels. Abnormal lung, heart, and brain weights were reported in 48 (16.8%), 67 (23.4%), and 43 (15.0%) SUDEP cases, respectively. SIGNIFICANCE: This study is one of the largest autopsy-based registries of definite SUDEP. Subtherapeutic ASM levels measured in post-mortem blood samples suggest that nonadherence to ASM therapy was a leading risk factor for SUDEP. As BMI was elevated in this cohort, and obesity was significantly associated with subtherapeutic ASM levels, it may also be a risk factor for SUDEP. Case-controlled studies are needed to validate the specific role of obesity and related comorbidities in this population.

Primary payer status in patients with seizures: A nationwide study during 1997-2014 in the United States.

OBJECTIVE: In countries where health coverage is not universal, there is ample evidence of disparities in healthcare, often associated with insurance. People with seizures, similar to those living with any complicated chronic medical comorbidity, need further health-related attention to improve their quality-of-life outcomes. METHODS: We conducted a retrospective cohort study of the National Inpatient Sample (NIS) component of the Healthcare Cost and Utilization Project (HCUP) national database between 1997-2014. The analysis focused on the mortality rate, and patients with a principal admission diagnosis of seizure at the time of discharge were identified. Primary Payer Status (PPS) included Medicare, Medicaid, private, and uninsured. Multivariate linear regression modeling was conducted to examine the contribution of the predictive variables to in-hospital mortality. RESULTS: Between 1997-2014, 4,594,213 seizure-related discharges was recorded. The overall mean patient age was 41.69 ± 0.98 years, and 58.1 % were female. The average age during this period decreased significantly in Medicare, increased substantially in uninsured, without significant change in Medicaid and private. Patients in Medicare had the highest length of stay (LOS) (4.49 ± 0.29 days), and uninsured (2.79 ± 0.15) had the least. Over time, there was a significant increase in the number of seizure discharges in Medicare, Medicaid, and private insurance. However, there was a significant decrease in in-hospital mortality in Medicare, Medicaid, and private, with the most prominent decline in Medicare. Risk-adjusted for age, gender, LOS, illness severity, and time, regression results showed Medicare has a significantly higher association with less in-hospital mortality compared with other insurances. CONCLUSIONS: Our study showed a significant increase in the number of seizure diagnoses at discharge in Medicare, Medicaid, and private in the United States between 1997-2014; however, there was a decrease in the in-hospital mortality rate across all insurance payers. Uninsured patients had the highest mortality rate after Medicare without risk justification. Risk-stratified models confirmed Medicare was significantly associated with a less in-hospital mortality rate.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Retinal changes in patients with angina pectoris and anginal equivalents: a study of patients with normal coronary angiography.

Background and aims. Approximately 10-30% of the patients with typical symptoms of angina pectoris have normal angiography showing normal macrovasculature. In these patients, however, the microvascular problems should be monitored. Hence, the main aim of this study is to evaluate retinal changes in normal angiographic patients.Methods. In this descriptive cross-sectional study, 60 normal angiographic patients with typical chest pain or anginal equivalents visiting Modarres Hospital Cardiology Research Center between 2018 and 2019 were enrolled and retinal changes were determined in Labbafinejad Hospital by Optical Coherence Tomography Angiography using Foveal Avascular Zone (FAZ), Superficial Vascular Density (SVD), and Deep Vascular Density (DVD).Results. The results of this study demonstrated that FAZ was normal in all subjects, but SVD and DVD were abnormal in 45% and 8.3%, respectively. Totally, 18.5% and 66.7% showed abnormal SVD among stable angina (SA) and unstable angina (UA) cases, respectively (P < 0.001). There was no statistically significant difference between abnormal DVD in SA and UA cases (P = 0.058). Abnormal SVD was significantly more common among diabetic patients (P < 0.001), while DVD was not related to diabetes presence in the study population (P > 0.05). Moreover, abnormal SVD was more common among patients with chest pain (P = 0.036), while there was no significant difference for DVD (P = 0.371). Interestingly, abnormal ECG was associated with both abnormal DVD and SVD.Conclusions. The results of this study showed that nearly half of the patients with angina pectoris or anginal equivalents who revealed normal angiographic findings may suffer from retinal changes. Thus, retinal assessment is needed in these patients to evaluate microvascular changes.

Prognostic value of inflammatory biomarkers for predicting the extent of lung involvement and final clinical outcome in patients with COVID-19.

BACKGROUND: Inflammation plays a major role in coronavirus disease (COVID-19). Factors that convey information about the status of inflammation could predict disease severity and help identify patients prone to clinical deterioration. Here, we aimed to evaluate the predictive value of inflammatory markers on the extent of lung involvement and survival of patients with COVID-19. MATERIALS AND METHODS: Eighty patients with confirmed COVID-19 were enrolled. Demographic, clinical, and laboratory data were collected at admission. All patients underwent chest computed tomography (CT); the extent of lung involvement was assessed by a scoring system. Patients were followed up until death or discharge occurred. Logistic regression analysis was performed to evaluate the association of investigated variables with COVID-19-related death. The association between different variables and CT score was assessed using linear regression model. Receiver operator characteristic curve analysis was applied to identify the predictive value of inflammatory markers and CT score on survival. RESULTS: The mean age of patients was 54.2 ± 15.2 years; 65% were male. Increased neutrophil-to-lymphocyte ratio (ß =0.69, odds ratio [OR] =1.50), platelet-to-lymphocyte ratio (ß =0.019, OR = 1.01), and decreased lymphocyte to C-reactive protein ratio (LCR) (ß = -0.35, OR = 0.62) were significantly associated with a higher CT score and increased odds of death (P < 0.05). Lactate dehydrogenase level was also positively related with extensive lung involvement and death (ß =1.15, OR = 1.52, P < 0.05). The LCR threshold for identifying survivors from nonsurvivors was 0.53 (area under curve [AUC] =0.82, 78% sensitivity and 74% specificity). Lung involvement ≥50% on chest CT was an excellent predictor of death (AUC = 0.83, 81% sensitivity and 79% specificity). CONCLUSION: Daily-performed laboratory tests that represent inflammation have great value for predicting the amount of disease burden and risk of mortality. Moreover, their cost-effectiveness and feasibility turn them into ideal prognostic markers.

Management of ST-segment-elevation myocardial infarction during the coronavirus disease 2019 (COVID-19) outbreak: Iranian"247" National Committee's position paper on primary percutaneous coronary intervention.

World Health Organization has designated coronavirus disease 2019 (COVID-19) as a pandemic. During the past several weeks, a considerable burden has been imposed on the Iranian's healthcare system. The present document reviewed the latest evidence and expert opinion regarding the management of ST-segment-elevation myocardial infarction during the outbreak of COVID-19 and outlines a practical algorithm for it.

The Association of CT-measured Cardiac Indices with Lung Involvement and Clinical Outcome in Patients with COVID-19.

RATIONALE AND OBJECTIVES: Cardiac indices can predict disease severity and survival in a multitude of respiratory and cardiovascular diseases. Herein, we hypothesized that CT-measured cardiac indices are correlated with severity of lung involvement and can predict survival in patients with COVID-19. MATERIALS AND METHODS: Eighty-seven patients with confirmed COVID-19 who underwent chest CT were enrolled. Cardiac indices including pulmonary artery-to-aorta ratio (PA/A), cardiothoracic ratio (CTR), epicardial adipose tissue (EAT) thickness and EAT density, inferior vena cava diameter, and transverse-to-anteroposterior trachea ratio were measured by non-enhanced CT. Logistic regression and Cox-regression analyses evaluated the association of cardiac indices with patients' outcome (death vs discharge). Linear regression analysis was used to assess the relationship between the extent of lung involvement (based on CT score) and cardiac indices. RESULTS: Mean (±SD) age of patients was 54.55 (±15.3) years old; 65.5% were male. Increased CTR (>0.49) was seen in 52.9% of patients and was significantly associated with increased odds and hazard of death (odds ratio [OR] = 12.5, p = 0.005; hazard ratio = 11.4, p = 0.006). PA/A >1 was present in 20.7% of patients and displayed a nonsignificant increase in odds of death (OR = 1.9, p = 0.36). Furthermore, extensive lung involvement was positively associated with elevated CTR and increased PA/A (p = 0.001). CONCLUSION: CT-measured cardiac indices might have predictive value regarding survival and extent of lung involvement in hospitalized patients with COVID-19 and could possibly be used for the risk stratification of these patients and for guiding therapy decision-making. In particular, increased CTR is prevalent in patients with COVID-19 and is a powerful predictor of mortality.

Epicardial adipose tissue, inflammatory biomarkers and COVID-19: Is there a possible relationship?

BACKGROUND & AIMS: Adipose tissue is a biologically active organ with pro-immunogenic properties. We aimed to evaluate the prognostic value of epicardial adipose tissue (EAT) in COVID-19 and its correlation with other inflammatory biomarkers. MATERIAL AND METHODS: One-hundred patients with COVID-19 were enrolled. C-reactive protein (CRP), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-CRP ratio (LCR), and platelet-to-lymphocyte ratio (PLR) were evaluated on admission. EAT volume and density were measured by computed tomography. Patients were followed until death or discharge. Univariate and multivariate analysis was performed and ROC curve analysis was used to assess the ability of inflammatory markers in predicting survival. The relationship between EAT and other inflammatory markers was also investigated. RESULTS: The mean ± SD age of patients was 55.5 ± 15.2 years old; 68% were male. Univariate analysis revealed that increased lung involvement, blood urea nitrogen, LDH and NLR, and decreased platelet count were significantly associated with death. After adjustment, LDH was independently predictive of death (OR = 1.013, p-value = 0.03). Among inflammatory markers, LCR had the best ability for predicting survival with 79.7% sensitivity and 64.3% specificity at an optimal cut-off value of 20.8 (AUC = 0.744, 95% CI = 0.612-0.876, p-value = 0.004). EAT volume demonstrated positive correlation with NLR and PLR (p = 0.001 and 0.01), and a negative correlation with LCR (p = 0.02). EAT density was significantly different between decedents and survivors (p = 0.008). CONCLUSION: Routine laboratory tests that represent status of inflammation can be used as cost-effective prognostic markers of COVID-19. Also, the significant association between EAT volume and other inflammatory biomarkers might explain the more severe disease in obese patients.