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).

Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in chronic thromboembolic pulmonary hypertension patients undergoing pulmonary endarterectomy: A randomized clinical trial.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery. METHODS: The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery. RESULTS: There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups. CONCLUSION: Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Donor heart selection: Evidence-based guidelines for providers.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

Correlation of Echocardiographic and Right Heart Catheterization Estimations of Pulmonary Artery Systolic Pressure.

Background: Pulmonary artery pressure (PAP) is one of the most important and valuable markers in cardiovascular disease, measured by right heart catheterization (RHC) as the gold standard diagnostic modality. However, due to several limitations, such as invasiveness, lack of repeatability, and high health costs, echocardiographic estimation of PAP has been used to substitute RHC for diagnosis and monitoring of this disease. This study aimed to evaluate the correlation of echocardiographic and RHC estimations of systolic PAP. Materials and Methods: In this study, patients, who were referred to Masih Daneshvari Hospital in Tehran, Iran, evaluated by RHC and echocardiography, were selected. The median PAP (mPAP) and systolic PAP (sPAP) for each modality, time interval between the two modalities, sex, and age were extracted from the patients' records. The RHC mPAP data was used for categorization of patients as pulmonary hypertension, while the sPAP data of two modalities was used to assess correlations and define a cut-off point by the ROC analysis. Data analysis was performed using SPSS version 24, and the level of statistical significance was less than 0.05. Results: Seventy-six patients, including 31 males (40.8%) and 45 females (59.2%) with the mean age of 45±14 years, were evaluated in this study. The mean sPAP was 71.98±30.22 mmHg when measured by RHC and 69.75±26.03 mmHg when measured by echocardiography (correlation coefficient=0.805; P<0.001). Agreement between the two measurements was 97%, and the accuracy of echocardiography was 43%. By considering 40 mmHg as the cutoff point, the sensitivity and specificity of echocardiography were estimated at 89.2% and 42.8%, respectively. Based on the ROC analysis, the highest sensitivity (86.7%) and specificity (87.5%) were achieved with an estimated sPAP of 57.5 mmHg. Conclusion: Echocardiography showed a good correlation and agreement with RHC in estimating sPAP; therefore, it is appropriate for screening of patients because of high sensitivity. However, for diagnosis confirmation, monitoring, and follow-up of pulmonary hypertension via echocardiography, high specificity is needed, which can be achieved by considering sPAP of 57.5 mmHg as the cutoff value for pulmonary hypertension.

Investigation of two general venous thromboembolism risk-stratification models in predicting venous thromboembolic events in TB patients.

Background: Tuberculosis (TB) remains an infectious disease with a high prevalence worldwide and represents a major public health concern. It is known that TB causes a hyper-coagulable state due to its infective nature. Thus, patients are prone to higher incidence rates of venous thromboembolism (VTE) in comparison with the general population. Although there are many risk assessment models (RAMs) that estimate the risk of VTE incidence in the general population, none have been proven to show significant prognostic value in early and accurate VTE prediction among TB patients. This study aims to investigate the accuracy of general RAMs in prediction of VTE incidence in the population of TB-positive patients. Methods: The following survey is a retrospective study among patients afflicted with TB, in whom VTE had occurred either during or at the onset of admission. A total number of 865 smear-positive TB cases were recorded in hospital in a 7-year timespan, among which a total sum of 37 patients (67.6% males, age: 56.19 ± 20 years) experienced at least one episode of thromboembolic incidence. We nominated Padua and Geneva RAMs and calculated the scores with regard to their inpatient hospital records. Results: Of 865 adult hospitalized smear-positive TB patients, 37 patients happened to develop VTE in the course of infection, after excluding the unacceptable data. The incidence of VTE was calculated at 4.27%. Of all VTEs, 73% turned out to be deep venous thromboembolism (DVT), 18.9% were pulmonary thromboembolism (PTE), and 8.1% of patients developed both DVT and PTE during the course of disease. Among all cases, 32.4% revealed Geneva score equivalent or >3. It conveys the meaning that these patients were at greater risk for VTE development and were indicated to receive prophylactic medication. Similarly, Padua model was capable of predicting 29.7% cases scoring >4, which is alarming for elevated VTE probability. 21.6% of TB patients, who had developed VTE during the course of their disease eventually passed away. Conclusion: Our statistics show minimal positive predictive value for Padua and Geneva RAMs, which are seemingly in sharp contrast with the excellent validation of these models verified by numerous surveys in general population. This fact could be attributable to failing to consider TB, or in general chronic infections, as independent indicators of VTE incidence. These findings indicate the need for revising the presenting RAMs or establishing a separate RAM for VTE prediction in TB patients, resembling the VTE risk assessment model for cancer patients.

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.

COVID-19 and Vaccine-Induced Thrombosis.

Coronavirus disease 2019 (COVID-19), a highly contagious infectious disease, has had a catastrophic effect on the world's demographics resulting in more than 2.9 million deaths worldwide till January 2021. It can lead to systemic multi-organ complications; in particular, venous and arterial thromboembolism risk is significantly increased. Venous thromboembolism (VTE) occurs in 22.7% of patients with COVID-19 in the ICU and 8% in non-ICU hospitalized patients. Studies evaluating thromboprophylaxis strategies in patients with COVID-19 are needed to improve the prevention of VTE. VTE is the most commonly reported thrombotic complication, with higher incidence rates among critically ill patients. Several vaccines have been licensed and are currently used to combat the COVID-19 pandemic. Also, several cases of vaccine-induced thrombosis have been reported. Vaccination remains the most critical measure to curb the COVID-19 pandemic. There is a broad consensus that the benefits of vaccination greatly outweigh the potential risks of rare vaccine side effects, such as vaccine-induced immune thrombotic thrombocytopenia (VITT). Therefore, the importance of vaccination should be emphasized. This statement aims to focus on VITT.

Hemoptysis Resolution with Rituximab in Behçet's Disease: A Case Report.

Behçet's disease (BD) is a multisystem, progressive, and inflammatory disorder of unknown etiology. Vasculitis is believed to underlie various clinical manifestations of BD and is known to be one of the main causes of death due to BD, in cases of large vessel involvement. The current study is done in order to examine the effects of rituximab on the patient's debilitating clinical manifestations, as a result of not responding to the standard treatment regimens. The present case is a 28-year-old female patient with BD associated vasculitis. She was referred to the respiratory referral center, chiefly complaining of intermittent episodes of massive hemoptysis. She had also recurrent oral and genital ulcers, and difficulty in walking, despite considering the common treatment approaches for BD. Our patient received two courses of rituximab in combination with intravenous methylprednisolone. Over six months follow-up period from the date of treatment initiation with rituximab, symptoms of BD such as recurrent hemoptysis and aphthous ulcers were reduced in both frequency and severity. Lower limb weakness and difficulty in walking were improved as well. To summarize, rituximab appears to be an effective alternative for treatment-resistant vasculitis in BD patients.

Remdesivir associated sinus bradycardia in patients with COVID-19: A prospective longitudinal study.

Background: Remdesivir is effective against SARS-Cov-2 with little evidence of its adverse effect on the cardiac system. The aim of the present study is investigating the incidence of bradycardia in COVID-19 patients treated with Remdesivir. Methods: This prospective longitudinal study was conducted in a tertiary center on COVID-19 patients for Remdesivir therapy. The objectives were to investigate the incidence of sinus bradycardia, and also the association between their demographics, underlying diseases, and the disease severity with developing bradycardia in COVID-19 patients treated with Remdesivir. Results: Of 177 patients, 44% were male. The mean (±standard deviation) age of patients was 49.79 ± 15.16 years old. Also, 33% were hospitalized due to more severe symptoms. Oxygen support was required for all hospitalized subjects. A total of 40% of the patients had comorbidities, with the most common comorbidity being hypertension. The overall incidence of bradycardia (heart rate<60 bpm) in patients receiving Remdesivir was 27%, of whom 70% had extreme bradycardia (heart rate <50 bpm). There was also a statistically significant reduction in heart rate after five doses of Remdesivir compared to the baseline heart rates. In the multivariable model, none of the covariates including age above 60 years, female sex, CRP>50 mg/L, O2 saturation<90%, underlying cardiovascular disease, hypertension and diabetes mellitus, and beta-blockers were associated with Remdesivir-induced bradycardia. No association was found between the COVID-19 severity indicators and bradycardia. Conclusion: As sinus bradycardia is a prevalent adverse cardiac effect of Remdesivir, it is recommended that all COVID-19 patients receiving Remdesivir, be evaluated for heart rate based on examination; and in the case of bradyarrhythmia, cardiac monitoring should be performed during administration to prevent adverse drug reactions.

Coronavirus disease 2019 outcomes in heart transplant recipients: a single-center case series.

BACKGROUND: With the rapidly expanding pandemic of severe acute respiratory syndrome coronavirus-2, a chronic immunosuppressed state in solid organ transplant recipients is a concern. We reported coronavirus disease 2019 in heart transplant recipients and described the patients' course from diagnosis to either hospital admission or improvement in symptoms. CASE PRESENTATION: This study retrospectively identified 13 white (Iranian) heart transplant patients with coronavirus disease 2019 between December 2019 and October 2020. The mean age of patients was 43.7 years (19-65 years); seven (70%) were men. Laboratory and treatment data were collected for those admitted or managed as outpatients. Outcomes were also recorded for all patients. This report demonstrates a range of symptoms, clinical severity, and disease course in heart transplant recipients with coronavirus disease 2019, including ten hospitalized patients and three patients, managed entirely in the outpatient setting. One patient passed away, and none of them experienced an episode of clinically overt rejection. CONCLUSIONS: We would like to emphasize the importance of being alert in these patients to consider testing in a broad range of clinical presentations and gathering more data for better management.

Comparison of Scores for Child-Pugh Criteria and Standard and Modified Models for End-Stage Liver Disease to Assess Cardiac Hepatopathy in Heart Transplant Recipients.

OBJECTIVES: Congestive hepatopathy as a result of advanced heart failure correlates with poor outcomes. Thus, risk-scoring systems have been established to assess the risks for cardiac surgery and hearttransplant, although these systems were originally designed to measure mortality risk in patients with end-stage liver disease. We compared the scores for the Child-Pugh criteria andstandardandmodifiedModels for End-Stage LiverDisease to evaluate the effect of preoperative liver dysfunction on postoperative outcomes inpatients with heart failure who underwent heart transplant. MATERIALS AND METHODS: Data of 60 consecutive patients who underwent orthotopic heart transplant were analyzed from a historical cohort study from January 1, 2015, to December 31, 2018. We calculated the scores for Child-Pugh criteria and the standard and modified Models for End-Stage Liver Disease. RESULTS: Of the 60 total patients, 48 were male patients, with a median age of 43 years (range, 13-69 years). Twenty patients died before the end of the study. The causes of death were cardiac, liver, and renal diseases. The mortality risk increased 25% (interquartile range, 0.05-0.51) for the patients with 1 point higher score compared with the patients with 1 point lower score based on a modified Model for End-Stage Liver Disease (P = .01). CONCLUSIONS: Preoperative liver dysfunction has a significant effect on patient survival. The modified Modelfor End-Stage LiverDisease scoring system could be an effective predictor of perioperative risk stratification for patients with congestive hepatopathy who are undergoing cardiac transplant.

Angioembolization in massive hemoptysis for a patient with acute coronary syndrome and history of hydatid cyst.

Cystic echinococcosis (CE) or hydatid disease is a zoonosis caused by ingestion of the eggs of the tapeworm Echinococcus granulosus. Larger cysts can cause symptoms by compressing surrounding tissues. Large cysts can also rupture and cause sudden onset of cough, fever, hypersensitivity reactions, and massive hemoptysis. We report a case of hydatid cyst, which caused massive hemoptysis after an urgent percutaneous coronary intervention and was successfully controlled with bronchial artery embolization. .

Evaluation of cardiomyopathy diagnosis in heart transplant recipients: comparison of echocardiographic and pathologic classification.

BACKGROUND: Definite diagnosis of cardiomyopathy types can be challenging in end-stage disease process. New growing data have suggested that there is inconsistency between echocardiography and pathology in defining type of cardiomyopathy before and after heart transplantation. The aim of the present study was to compare the pre-heart transplant echocardiographic diagnosis of cardiomyopathy with the results of post-transplant pathologic diagnosis. RESULTS: In this retrospective cross-sectional clinicopathological study, 100 consecutive patients have undergone heart transplantation in Masih-Daneshvari hospital, Tehran, Iran, between 2010 and 2019. The mean age of patients was 40 ± 13 years and 79% of patients were male. The frequency of different types of cardiomyopathy was significantly different between two diagnostic tools (echocardiography versus pathology, P < 0.001). On the other hand, in 24 patients, the results of echocardiography as regard to the type of cardiomyopathy were inconsistent with pathologic findings. CONCLUSION: Based on the findings of the present study, it could be concluded that there is a significant difference between echocardiographic and pathologic diagnosis of cardiomyopathy; therefore, it is necessary to use additional tools for definite diagnosis of cardiomyopathy like advanced cardiac imaging or even endomyocardial biopsy before heart transplantation to reach an appropriate treatment strategy.

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.

Bronchial Angioembolization for Management of Hemoptysis Due to Pulmonary Tuberculosis.

BACKGROUND: The study aimed to evaluate the effectiveness and safety of BAE in TB patient with massive hemoptysis and evaluate the recurrence rate of hemoptysis after BAE. MATERIALS AND METHODS: In this prospective study, 68 patients with moderate and severe hemoptysis due to active or old tuberculosis who underwent bronchial arteriography were included. CXR and CT scan were performed in all patients. Selective and nonselective bronchial artery angiography was performed in all patient and 62 patients underwent embolization. RESULTS: Thirty-two patients (47.1%) had active TB and 36 patients (52.9%) had inactive TB (post-tuberculosis sequelae). Abnormality was detected in a single vessel in 30 (44.1%) patients, in two vessels in 23 (33.8%) and in more than two vessels in 13 (19.1%) patients. Embolization was performed in 62 patients and overall 95 abnormal arteries were embolized. Hemoptysis control rate was 82.3% at one month, 73.5% at three months, 69.1 % at 6 months, 63.2% at one year and 60.3% after two years. CONCLUSION: No major complication occurred as a result of BAE procedures. BAE is a safe and effective method for the management of hemoptysis in patient with tuberculosis. Only 20.6% of the patients need to repeat BAE during 2 years of follow up.

Superior vena cava obstruction and pulmonary artery involvement as rare findings of immunoglobulin G4-related disease.

We describe a case of immunoglobulin G4-related lung disease presenting as chronic pulmonary hypertension with involvement of right pulmonary artery and superior vena cava. Immunoglobulin G4- related disease is a rare systemic sclerosing disease with autoimmune entity that causes fibrotic, often mass-like manifestations that variably affect different organ systems and can be mistaken with other disorders. Timely diagnosis requires awareness on the part of clinicians and pathologists as well as radiologists to the variable manifestations of this newly recognized disorder. .

Curable Syncope in Primary Pulmonary Hypertension with Novel Atrial Flow Regulator.

Pulmonary artery hypertension (PAH) occurs when mean pulmonary artery pressure (PAP) is higher than 25 mmHg in rest or 30 mmHg during activity. Idiopathic pulmonary artery hypertension (IPAH) is defined as PAH without a definite reason. The IPAH is a rare disease with a high mortality rate if left untreated. To date, there has been no definite cure for this entity, and most treatments are for symptom relief or improvement in the quality of life. For many years, decompressing the right heart through a hole in the interatrial septum has been advised to alleviate some of their symptoms, specifically syncope. Atrial flow regulator (AFR) is a device to make an iatrogenic interatrial hole and finally a unidirectional shunt. It has been used for some PAH patients for symptom relief. Herein, we report a 36-year-old female case with diagnosed IPAH for 6 years. In the last 3 years, the case had frequent syncope with shortening intervals. The AFR was implanted for her without any complications. Then, within 6 months of follow-up, she had only one syncope episode. A significant change was observed in her 6-minute walk and PAP.

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.

BACKGROUND: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. METHODS: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. CONCLUSIONS: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.

Preemptive non-selective bronchial artery angioembolization to reduce recurrence rate of hemoptysis.

BACKGROUND: Massive hemoptysis which is presented in advanced lung diseases is a life-threatening condition. Bronchial artery embolization as a minimally invasive procedure is the treatment of choice either in first or recurrent hemoptysis. This study aimed to assess the early and late efficacy of bronchial angioembolization (BAE) without microcatheter. METHODS: In this prospective cohort study, all patients with hemoptysis who had undergone BAE from August 2018 to March 2019 were included. Angiographic patterns including bleeding sources, number of involved vessels, the underlying etiology, and recurrence rate were evaluated in a one-year follow up. RESULTS: 153 patients were included with mean age of 55 ±16 years. 68% of them were male and 58% had life-threatening massive hemoptysis. Three distinct angiographic patterns were recognized. The culprit bleeding vessel was bronchial in 126 (92%), intercostal in 4 (3%), and both vessels in 7 (5%) of cases (p<0.05). One vessel involvement was seen in 56 patients; however it was observed in 69% of non-cystic fibrosis lobar bronchiectasis patients. In 1, 3 and 12 months follow up, recurrent hemoptysis was reported in 15 (11%), 4 (2.5%), and 24 (15.5%), respectively. In 52% of cases, no abnormal vessels were observed during aorta injection, but culprit bronchial or intercostal arteries were found in selective investigational angiography. CONCLUSION: BAE was successful in the control of hemoptysis and resulted in a low rate of recurrence in different types of lung diseases. This could be due to the embolization of all pathological arteries found during angiography which might have prevented recurrent bleeding.

Future Balloon-Expandable Stents: High or Low-Strength Materials?

PURPOSE: Recent progress in material science allows researchers to use novel materials with enhanced capabilities like optimum biodegradability, higher strength, and flexibility in the design of coronary stents. Considering the wide range of mechanical properties of existing and newfangled materials, finding the influence of variations in mechanical properties of stent materials is critical for developing a practical design. METHODS: The sensitivity of stent functional characteristics to variations in its material plastic properties is obtained through FEM modeling. Balloon-expandable coronary stent designs: Absorb BVS, and Xience are examined for artificial and commercial polymeric, and metallic materials, respectively. Standard tests including (1) the crimping process followed by stent implantation in an atherosclerotic artery and (2) the three-point bending test, have been simulated according to ASTM standards. RESULTS: In Absorb BVS, materials with higher yield stress than PLLA have similar residual deflection and maximum bending force to PLLA, which is not the case for Xience stent and Co-Cr. Moreover, elevated yield stress significantly reduces stent flexibility only in Xience stent. For both stents, with different degree of influence, an increase in yield or ultimate stress improves stent radial strength and stiffness and reduces arterial stress and plastic strain of stent, which consequently enhances the stent mechanical performance. Contrarily, yield or ultimate stress elevation increases stent recoil which adversely affects stent performance. CONCLUSION: Using high-strength materials has a double-edged sword effect on the stent performance and existing uncertainty in the precise estimate of stent mechanical properties adversely affects the reliability of numerical models' predictions.