Changes in liver enzymes and association with prognosis in patients with COVID-19: a retrospective case–control study

ObjectiveCOVID-19 has recently emerged as a serious threat to global health. This study examined the laboratory investigations of patients with COVID-19, with an emphasis on liver enzymes.MethodsThis retrospective, single-center study was performed on patients with COVID-19 who were admitted to Imam Reza Hospital, Iran from March 2020 to February 2021. Laboratory tests included a complete blood cell count, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), and alkaline phosphatase. Patient survival was among the outcome measures investigated in association with laboratory findings.ResultsWe enrolled 77 patients with COVID-19 and 63 healthy controls. In comparison with the control group, patients with COVID-19 showed COVID-19 increased ALT, WBC, neutrophils, NLR, and PLR, and decreased platelet counts and lymphocytes.ConclusionAlthough elevated levels of AST, NLR, PLR, and LMR were found in patients with COVID-19, they were not linked to mortality. Given the presence of AST in other tissues, the influence of SARS-CoV-2 on the liver should be interpreted with caution.     

A Case-Crossover Analysis of Indoor Heat Exposure on Mortality and Hospitalizations among the Elderly in Houston,Texas

Background: Despite the substantial role indoor exposure has played in heat wave–related mortality, few epidemiological studies have examined the health effects of exposure to indoor heat. As a result, knowledge gaps regarding indoor heat–health thresholds, vulnerability, and adaptive capacity persist.Objective: We evaluated the role of indoor heat exposure on mortality and morbidity among the elderly (≥65 years of age) in Houston, Texas.Methods: Mortality and emergency hospital admission data were obtained through the Texas Department of State Health Services. Summer indoor heat exposure was modeled at the U.S. Census block group (CBG) level using building energy models, outdoor weather data, and building characteristic data. Indoor heat–health associations were examined using time-stratified case-crossover models, controlling for temporal trends and meteorology, and matching on CBG of residence, year, month, and weekday of the adverse health event. Separate models were fitted for three indoor exposure metrics, for individual lag days 0–6, and for 3-d moving averages (lag 0–2). Effect measure modification was explored via stratification on individual- and area-level vulnerability factors.Results: We estimated positive associations between short-term changes in indoor heat exposure and cause-specific mortality and morbidity [e.g., circulatory deaths, odds ratio per 5°C increase=1.16 (95% CI: 1.03, 1.30)]. Associations were generally positive for earlier lag periods and weaker across later lag periods. Stratified analyses suggest stronger associations between indoor heat and emergency hospital admissions among African Americans compared with Whites.Discussion: Findings suggest excess mortality among certain elderly populations in Houston who are likely exposed to high indoor heat. We developed a novel methodology to estimate indoor heat exposure that can be adapted to other U.S. locations. In locations with high air conditioning prevalence, simplified modeling approaches may adequately account for indoor heat exposure in vulnerable neighborhoods. Accounting for indoor heat exposure may improve the estimation of the total impact of heat on health. https://doi.org/10.1289/EHP6340     

A Biomechanical Foot-Worn Device Improves Total Knee Arthroplasty Outcomes

Background

Biomechanics after total knee arthroplasty (TKA) often remain abnormal and may lead to prolonged postoperative recovery. The purpose of this study is to assess a biomechanical therapy after TKA.

Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells

Introduction: There is a high expression of receptor tyrosine kinase like orphan receptor-1 (ROR-1), a tyrosine kinase receptor, in various tumor-cell types. ROR-1 is involved in many key processes in cancer including proliferation, survival and metastasis. Hence, ROR-1 is an attractive and promising therapeutic target. There are many therapeutic approaches that target ROR-1 and these include specific monoclonal antibodies (mAbs), modified T cells (CART cell), miRNAs and tyrosine kinase inhibitors (TKI).

Areas covered: This review examines ROR-1 structure and function, immunotherapeutic strategies including specific chimeric antigen receptor (CARs) T cells and miRNAs and other targeted approaches such as the use of tyrosine kinase inhibitors.

Expert opinion: Chimeric antibodies, CARs T cells, bi-specific T cell engagers (BiTEs), miRNAs and TKIs are used to target the ROR-1 marker on cancer cell lines. By selecting the most favorable therapeutic approaches regarding ROR-1 in vivo, anti-ROR-1 antibodies or CAR T cells can be also used for diagnosis of ROR-1⁺ cancer cells in new technologies such as biosensors. Moreover, ROR-1 targeted combination therapy with other cancer biomarkers could be considered a novel therapeutic strategy for cancer treatment.     

Isolated Cleft Mitral Valve with Posterior and Anterior Clefts: a Rare Cause of Congenital Valve Regurgitation

We report a case of isolated cleft mitral valve with two clefts in the posterior and one in the anterior leaflet. Our case adds to the few reports of posterior and multiple mitral valve clefts and to our knowledge is the first using real‐time transoesophageal three‐dimensional echocardiography (3DE) for assessment of isolated cleft mitral valve. (Echocardiography 2010;27:E50‐E52)     

Predictors of venous obstruction following pacemaker or implantable cardioverter-defibrillator implantation: a contrast venographic study on 100 patients admitted for generator change, lead revision, or device upgrade.

AIM: Venous obstruction following transvenous device implantation rarely cause immediate clinical problems. When lead revision or device upgrade is indicated, venous obstruction become a significant challenge. The aim of this study was to determine the predictors of venous obstruction after transvenous device implantation, and to asess likely effects of antiplatelet/anticoagulant drugs in preventing venous thrombosis. METHODS AND RESULTS: Between March 2005 and July 2006, contrast venography was performed in 100 patients who were candidates for generator change, lead revision, or device upgrade. Vessel patency was graded as either completely obstructed, partially obstructed (>70%), or patent. The incidence of venous obstruction was 26%, with 9% of patients having total obstruction and 17% of patients exhibiting partial obstruction. No statistically significant differences between obstructed and non-obstructed patients were seen for age, sex, indication for device implantation, atrial fibrillation, cardiothoracic ratio, insulation material, operative technique, device type, and manufacturer (all Ps > 0.05). In a univariate analysis, multiple leads (P = 0.033), and presence of dilated cardiomyopathy (P = 0.036) were associated with higher risk of venous obstruction, whereas anticoagulant/antiplatelet therapy (P = 0.047) significantly reduced incidence of venous obstruction. Multivariate logistic regression analysis showed that only number of the leads (P = 0.039, OR: 2.22, and 95% CI: 1.03-4.76) and antiplatelet/anticoagulant therapy (P = 0.044, OR: 2.79, and 95% CI: 0.98-7.96) were predictors of venous obstruction. CONCLUSION: Total or partial obstruction of the access veins occurs relatively frequently after pacemaker or ICD implantation. Multiple pacing or ICD leads are associated with an increased risk of venous obstruction, whereas antiplatelet/anticoagulant therapy appears to have a preventive effect on development of access vein thrombosis.     

Electrocardiographic and electrophysiologic characteristics of anteroseptal, midseptal, and posteroseptal accessory pathways.

BACKGROUND: Approximately 30% of all accessory pathways (APs) are located in the septal area, and understanding the electrocardiographic and electrophysiologic of these APs is crucial for safe and effective ablation of these pathways. OBJECTIVE: In this study, the electrocardiographic and electrophysiologic characteristics of anteroseptal, midseptal, and posteroseptal APs were investigated in detail to elucidate unique electrical properties of APs in each location. METHODS: From April 2002 to October 2006, a total of 120 patients with a septal AP-mediated tachycardia were enrolled in the study. A detailed examination including electrocardiographic analysis and electrophysiologic study was performed in all patients. RESULTS: A total of 120 patients, including 98 patients with posteroseptal APs, 14 patients with anteroseptal APs, and 8 patients with midseptal APs, were studied. The anteroseptal APs could be differentiated from the midseptal APs by the 2 or more positive delta waves in inferior leads, whereas there is significant overlap in electrocardiographic features of midseptal and posteroseptal APs. The mean tachycardia cycle length was significantly shorter in patients with midseptal AP compared with those with anteroseptal and posteroseptal APs (284 +/- 49 ms vs 342 +/- 46 ms vs 350 +/- 68 ms, P = .03). The AH interval during tachycardia was also shorter in patients with midseptal APs (149 +/- 16 ms vs 200 +/- 51 ms vs 168 +/- 48 ms, P = .04). The patients with posteroseptal AP had a significantly higher incidence of atrial fibrillation (35%) than those with either midseptal (12%) or anteroseptal (14%) APs (P = .04). The patients with posteroseptal APs also had a significantly shorter antegrade effective refractory period of the AP (276 +/- 54 ms) than those with either midseptal (313 +/- 71 ms) or anteroseptal (325 +/- 61) APs (P = .036). CONCLUSION: Electrocardiographic analysis is a reliable method for differentiation of the anteroseptal from the midseptal APs, whereas the same is not true for the midseptal and posteroseptal APs. Midseptal APs were characterized by faster orthodromic tachycardia, whereas posteroseptal APs had a higher inducibility of atrial fibrillation.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.