Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).     

Ulnar artery aneurysm in a patient with Behçet’s disease

Behçet’s disease is a systemic disease characterized by oral aphthosis, genital ulcers, ocular lesions, gastrointestinal, musculoskeletal, neurological and major vessel involvement. Arterial involvement, aneurysms and arterial thrombosis have been reported in 1.5–3% of patients. In this case report, we present a patient with ulnar arterial aneurysm associated with Behçet’s disease.     

Effect of transvenous cardiac resynchronization therapy device implantation on cardiac troponin I release

BACKGROUND: Pacemaker and implantable cardioverter defibrillator (ICD) implantation increases cardiac troponin I (cTnI) levels which indicates myocardial injury. During implantation of a cardiac resynchronization therapy (CRT) device, balloon inflation for coronary sinus (CS) venogram, cannulation of CS side branch, and electrode advancement may interfere with CS drainage and, hence, may decrease the washout of toxic metabolites from the heart. Thus, CRT implantation may further increase cTnI levels. In this study, we investigated the effects of CRT implantation on cTnI release. METHODS: We included 10 patients (mean age = 57 +/- 15 years) in whom a successful transvenous CRT system was implanted (CRT group). Twenty patients (mean age = 65 +/- 10 years) who underwent a transvenous pacemaker or ICD implantation were included as the control group. Blood samples for cTnI were drawn at baseline and at six, 12, 18, and 24 hours thereafter. RESULTS: Baseline median cTnI levels were similar in CRT and control groups (0.03 ng/mL vs 0.02 ng/mL, respectively; P = 0.1). Postoperative cTnI levels during 24 hours were significantly higher in the CRT group (P < 0.05) by two-way repeated measures of analysis of variance. Post hoc analysis revealed that cTnI levels were higher at the 6th, 12th, 18th, and 24th hours compared to baseline levels (P < 0.001, P < 0.001, P < 0.01, and P < 0.01, respectively). There was a significant difference in the area under the curves (AUCs) of cTnI measurements (1.79 hr.ng/mL in the CRT group and 0.78 hr.ng/mL in the control group, P < 0.05). CONCLUSION: Postoperative cTnI levels were higher after CRT implantation than simple pacemaker/ICD implantation. This may be due to CS manipulation during CRT implantation.     

The relationship of chronic angiotensin converting enzyme inhibitor use and coronary collateral vessel development

BACKGROUND: Angiotensin II induces various growth factors such as vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor, and recent studies suggest that the expression of these growth factors promotes collateral growth. We hypothesized that the blockage of angiotensin II production by ACE inhibitors might interfere with collateral development in patients with coronary occlusion. METHODS: The study group consisted of 187 patients (114 males, mean ages, 62 +/- 11 years) who had chronic (> 1 month) coronary occlusion (TIMI flow grade < or = 1) in one of 3 epicardial coronary arteries. Collaterals were graded using the Rentrop classification, and the patients were divided into 2 groups according to having good (grade 2 and 3) or poor (grade 0 and 1) collaterals (n = 127 and 60, respectively). Clinical and angiographic characteristics were compared in the 2 groups. RESULTS: ACE inhibitor use (52% versus 35%, P = 0.04) and the prevalence of diabetes mellitus (DM) (43% versus 27%, P = 0.02) was higher in patients with poor collaterals. Patients with poor collaterals had a higher frequency of circumflex artery (Cx) occlusion, worse wall motion, and lower ejection fraction. In multivariate analysis, ACE inhibitor use (OR: 2.4; 95% CI = 1.23-4.68, P = 0.01) and the occlusion of Cx (OR: 3.3, 95% CI; 1.33-8.12, P = 0.01) were found to be independent predictors for poor collateral development, whereas there was a trend for DM as a predictor for poor collaterals (OR: 1.9, 95% CI = 0.97-3.8, P = 0.06). CONCLUSION: The findings suggest that ACE inhibitor therapy may contribute to poor collateral development in patients with coronary occlusion.     

Factor V Leiden and G20210A prothrombin mutations in patients with recurrent pregnancy loss: data from the southeast of Turkey

Factor V Leiden (FV-Leiden) and prothrombin gene mutations (FII G20210A) are well-established independent risk factors for thrombosis. In the recent years, many studies have suggested that these mutations are associated with an increased risk of recurrent pregnancy loss (RPL). We aimed to investigate the prevalence of these molecular defects in subjects with a history of early RPL. One hundred and fourteen women with three or more consecutive unexplained first-trimester miscarriages were compared to 185 parous women with uncomplicated pregnancies from the same ethnic origin. The presence of FV-Leiden and FII G20210A mutations was assessed by polymerase chain reaction analysis. Overall, 11 out of the 114 women with early RPL (9.6%) had either FV-Leiden or FII G20210A mutation, as compared with 16 out of the 185 women with normal pregnancies (8.6%; p = 0.756). The prevalence of FV-Leiden mutation was 7.9% (9/114) in patient group, compared with 7% (13/185) in control group (p = 0.780). One hundred and two patients were primary and 12 were secondary aborters. All FV-Leiden positive cases were primary aborters (8.8%; 9/102, p = 0.584). Concerning the FII G20210A, two out of 114 (1.7%) were first-trimester RPL (primary aborters) and three out of 185 (1.6%) controls were carriers of the FII G20210A mutation (1.7 vs 1.6%, p = 0.931). The results obtained from patients with first-trimester RPL and the control group have no statistical significant differences in the prevalence of FV-Leiden and FII G20210A mutations. These results suggest that mutations have no role in etiology of first-trimester recurrent abortions.     

Value of tissue Doppler myocardial velocities of tricuspid lateral annulus for the diagnosis of right heart failure in patients with COPD

OBJECTIVE: Aim of this study was to investigate the value of systolic indices of tricuspid valve annular motion measured by tissue Doppler imaging for the diagnosis right ventricular failure in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD with right heart failure symptoms and/or right ventricular dilatation were enrolled for the study. The control group consisted of age and sex matched patients referred to the echocardiography laboratory who had normal echocardiographic examination. Tricuspid valve annulus peak systolic velocity and myocardial acceleration during isovolumic contraction were recorded by tissue Doppler imaging. RESULTS: IVA and Sa wave velocities were found to be significantly decreased in patients with right ventricular failure. For the prediction of right heart failure IVA <3.8 m/sec2 had 91% sensitivity, 80% specificity, 90% positive predictive value (PPV), and 82% negative predictive value (NPV) and Sa wave velocity <9.2 cm/sec had 80% sensitivity, 62% specificity, 75% PPV, and 68% NPV. CONCLUSION: Tricuspid valve annular velocities measured by tissue Doppler imaging especially IVA, offer potential diagnostic value for the diagnosis of right heart failure in patients with COPD.