This review describes cyclooxygenase (COX), which synthesizes prostanoids that play an important role in living things. The authors conducted a national and international literature review on the subject. The COX enzyme uses arachidonic acid to form prostanoids, which play a role in several physiological and pathological conditions. This enzyme has different isoforms, mainly COX-1 and COX-2. The constitutive isoform is COX-1, while COX-2 is the inducible isoform. Both are expressed in different tissues and at different levels, but they may also coexist within the same tissue. Both isoforms show essentially the same mode of action, but their substrates and inhibitors may differ. The COX-1 isoform, which plays a role in the continuation of physiological events, has an increased expression level in various carcinomas, and the COX-2 isoform, which is increased in inflammatory conditions, is typically expressed at low physiological levels in some tissues such as the brain, kidney, and uterus. In addition to investigating the efficacies of the COX-1 and COX-2 isoforms, the discovery of potential new COX enzymes and their effect continues. This review also looks at the roles of the COX enzyme in certain physiological and pathological conditions.
Objective: Early identification of atherosclerosis using a non-invasive tool like ankle–brachial index (ABI) could help reduce the risk for cardiovascular disease among long-term hemodialysis patients. The study objective was to assess the frequency and impact of abnormal ABI as a marker of subclinical peripheral artery disease (PAD) in chronic hemodialysis patients.
Methods: This was a historic cohort study of kidney failure patients on long-term hemodialysis for at least 6 months. The ABI, measured with two oscillometric blood pressure devices simultaneously, was used to assess subclinical atherosclerosis of low limb extremities. Abnormal ABI was defined as ABI <0.9 or >1.3 (PAD present). Survival was defined as time to death. Independent factors associated with abnormal ABI were assessed using multiple logistic regression analysis. Kaplan–Meier method (log-rank test) was used to compare cumulative survival between the two groups; a P value <0.05 was statistically significant.
Results: Abnormal ABI was noted in 50.6% (n=43) of the 85 kidney failure patients included in the study; 42.4% (n=36) had a low ABI, and 8.2% (n=7) had a high ABI. Factors associated with PAD present were cholesterol (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 1.01–1.04; P=0.019), inflammation (AOR, 9.44; 95% CI, 2.30–18.77; P=0.002), phosphocalcic product (AOR, 6.25; 95% CI, 1.19–12.87; P=0.031), and cardiac arrhythmias (AOR, 3.78; 95% CI, 1.55–7.81, P=0.009). Cumulative survival was worse among patients with PAD present (log-rank; P=0.032).
Conclusion: The presence of PAD was a common finding in the present study, and associated with both traditional and emerging cardiovascular risk factors as well as a worse survival rate than patients without PAD.
Query (Q) fever is a zoonotic bacterial infection caused by Coxiella burnetii. In a minority of patients, chronic disease can occur after acute infection. Endocarditis and infections of aneurysms or vascular prostheses are the most common forms of chronic Q fever in adults. We report a case of an elderly female patient with chronic Q fever vertebral osteomyelitis at the site of her previous cement vertebroplasty, complicated by paravertebral abscess. Patient treatment required prolonged drainage in addition to the long duration of antibiotic treatment by doxycycline and hydroxychloroquine. Osteomyelitis is a rare clinical presentation in adults with chronic Q fever. However, it is important to consider Q fever in the differential diagnosis of culture-negative osteomyelitis, especially in countries where C. burnetii is endemic, such as Israel.
Introduction. A clinical and/or research fellowship abroad has become a prevalent choice among Israeli physicians. However, the influence of fellowship programs on the career path is unclear. We evaluated the role of physicians returning from fellowship in the organizational hierarchy and their professional and academic status.
Methods. This was a retrospective, descriptive, cross-sectional study of physicians who completed a survey after accomplishing a fellowship. The survey included questions about the physicians’ attitudes toward the program, programs’ details, and the physicians’ current academic, professional, and administrative status. Information about scientific publications was also collected.
Results. Of the 106 physicians receiving the questionnaire, 101 responded. The majority completed a two-year fellowship in North America. Forty percent participated in an integrated program (research and clinical), and 40% participated in clinical programs. Subjectively, the physicians attributed a significant value to the fellowship and positively recommend it. Most of the physicians held managerial positions, academic appointments, and had generated significant research.
Discussion. The subjective perspective of all physicians participating in the study was that attending a fellowship program had a positive impact on their careers. Objectively, the accomplishment of a fellowship program empowered the studied physicians to become scholars, senior executives, and opinion leaders in their professional field.
Because of rising antivaccine activism and some key global policy missteps, we risk eroding more than 70 years of global health gains. This is occurring through an enabled and empowered antiscience ecosystem, with anti-Semitism and the targeting of Jewish biomedical scientists at its core.
Background: Avoiding rectal thermometry is recommended in patients with neutropenic fever. Permeability of the anal mucosa may result in a higher risk of bacteremia in these patients. Still, this recommendation is based on only a few studies.
Methods: This retrospective study included all individuals admitted to our emergency department during 2014–2017 with afebrile (body temperature <38.3°C) neutropenia (neutrophil count <500 cells/microL) who were over the age of 18. Patients were stratified by the presence or absence of a rectal temperature measurement. The primary outcome was bacteremia during the first five days of index hospitalization; the secondary outcome was in-hospital mortality.
Results: The study included 40 patients with rectal temperature measurements and 407 patients whose temperatures were only measured orally. Among patients with oral temperature measurements, 10.6% had bacteremia, compared to 5.1% among patients who had rectal temperature measurements. Rectal temperature measurement was not associated with bacteremia, neither in non-matched (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.07–1.77) nor in matched cohort analyses (OR 0.37, 95% CI 0.04–3.29). In-hospital mortality was also similar between the groups.
Conclusions: Patients with neutropenia who had their temperature taken using a rectal thermometer did not experience a higher frequency of events of documented bacteremia or increased in-hospital mortality.
The coronavirus 2019 (COVID-19COVID) pandemic has highlighted the ways in which municipal, state, and Federal agencies in the USA have failed to address the inequities of present-day health systems. As alternative organizing centers outside these agencies, local communities are potentially situated to redress the inequities of present-day health systems in a collaborative manner that demonstrates solidarity by supplementing a purely scientific model of medicine and healthcare. In the mid-twentieth century, the Black Panthers, a revolutionary African American nationalist organization that focused on socialism and self-defense, introduced highly influential free clinics, which sought to bring expertise to the Black community on their own terms. This required bringing the benefits of biomedicine to those who customarily had not seen them. By extension, their approach raises questions regarding community- and expertise-centered approaches for the Jewish community: how is it engaged in healthcare for itself (in its diverse subcategories) and for others? Moreover, understanding how the Jewish community has been ill-served by present-day health-care systems might spur Jewish institutions to reimagine how healthcare should work.
Treatment with biological agents has become standard of care in treatment of immune-mediated diseases (IMD), including rheumatoid arthritis and psoriatic arthritis. Yet, a significant proportion of patients experience loss of response to biologics, need treatment escalation, or develop side effects. During the past decade, new biologic agents with different targeted molecular pathways have been approved for treatment of IMD, introducing the possibility of concomitant dual biologic therapy. The role of dual biologic therapy targeting different inflammatory pathways has become an area of great interest in the field of IMD, addressing the unmet clinical need of patients with refractory diseases and treatment of comorbidities, such as osteoporosis, asthma, atopic dermatitis, and urticaria. Despite the increasing use of biologics as a dual therapy across different indications, there is a paucity of data concerning the safety of the simultaneous use of more than one biological agents. The purpose of this review is to summarize the current literature on the use of dual biologics in patients with rheumatoid arthritis and psoriatic arthritis, addressing the potential adverse effects associated with combination therapy, and highlighting future directions in the use of this novel therapeutic modality.
Idiopathic inflammatory myopathies (IIM) are a rare group of disorders that feature progressive immune-mediated skeletal muscle destruction along with skin, lung, and joint involvement. Management of IIMs necessitates glucocorticoid therapy followed by conventional steroid-sparing agents to control disease activity. In the settings of refractory myositis or life-threatening manifestations, e.g. lung involvement or oropharyngeal dysphagia, second-line therapies are needed to minimize disease burden, avoid end-organ damage and steroid toxicity, and decrease mortality. These therapies may include biological disease-modifying antirheumatic drugs (bDMARDs), and to a lesser extent, targeted synthetic disease-modifying antirheumatic drugs (TSD). This article reviews the current use of bDMARDs, e.g. intravenous immunoglobulin and rituximab, and a TSD—Janus kinase inhibitors (JAKI)—along with their indications, efficacy, and safety in managing IIM.
Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells through CCR3 receptor binding. Higher levels of CCL24 and CCR3 were found in the skin and sera of patients with SSc compared with healthy controls; elevated levels of CCL24 and CCR3 were associated with fibrosis and predictive of greater lung function deterioration. Growing evidence supports the potency of a CCL24-blocking antibody as an anti-inflammatory and anti-fibrotic modulating agent in multiple preclinical models that involve liver, skin, and lung inflammation and fibrosis. This review highlights the role of CCL24 in orchestrating immune, vascular, and fibrotic pathways, and the potential of CCL24 inhibition as a novel treatment for SSc.
