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.
Background: Adequate lymphadenectomy is an important factor affecting survival in gastric cancer patients. Retrieval and examination of at least 15 lymph nodes is recommended in order to properly stage gastric malignancies. The objectives of this study were to evaluate the proportion of patients undergoing inadequate lymphadenectomies and possible risk factors for inadequate surgery.
Methods: This was a retrospective study that included patients, 18 years and older, who underwent gastrectomies with oncologic intent in the Hillel Yaffe Medical Center. We analyzed the association of demographic, clinical, and pathological variables with adequate number of lymph nodes.
Results: The retrieval of less than 15 lymph nodes was reported in 51% (53/104) patients undergoing gastrectomies with oncologic intent. The extent of surgery was the only variable associated with inadequate lymphadenectomy on univariate analysis: subtotal/proximal versus total gastrectomy (P=0.047). Differ¬ences observed for previous surgery (P=0.193), T stage (P=0.053), N stage (P=0.051), and lymphovascular invasion (P=0.14) did not reach significance. Subtotal/proximal gastrectomy resulted in inadequate resec¬tion of lymph nodes in 56% of the patients, while this occurred in only 30% of the patients undergoing total gastrectomy (relative risk 1.865; 95% CI 0.93, 3.741). Logistic regression confirmed that only subtotal/prox¬imal versus total gastrectomy was associated with inadequate number of lymph nodes resected (P=0.043).
Discussion and Conclusion: In this study we analyzed the association of patient, tumor, and surgery-related factors on adequate lymphadenectomy in patients undergoing gastrectomies for possible gastric cancer. Larger extent of the surgery (total, rather than subtotal/proximal gastrectomy) was revealed to be the only indicator positively associated with adequate lymphadenectomy.
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.
Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.
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.
Giant cell arteritis (GCA) is the most prevalent subtype of vasculitis in adults. In recent years, there has been substantial improvement in the diagnosis and treatment of GCA, mainly attributed to the introduction of highly sensitive diagnostic tools, incorporation of modern imaging modalities for diagnosis and monitoring of large-vessel vasculitis, and introduction of highly effective novel biological therapies that have revolutionized the field of GCA. This article reviews state-of-the-art approaches for the diagnosis, monitoring, and treatment options of GCA.
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.
Objective: The aim of our study was to explore the incidence of cardiac involvement in children with dengue infection admitted in a tertiary care hospital and to evaluate the features of cardiac involvement with the severity of dengue fever.
Methods: This was a cross-sectional study conducted from September 2014 to August 2016. A total of 130 patients with confirmed dengue NS1 antigen or IgM antibody positivity between the ages of 1 month and 18 years were evaluated. On the third day of admission, blood samples for cardiac markers were collected, and electrocardiograms (ECG), and echocardiograms were performed for each patient.
Results: Of the 130 dengue patients in the study, 60 (46.2%) were males and 70 (53.8%) were females (male to female ratio, 1:1.16). Cardiac involvement was present in 60 (46.2%) children and was more prominent in children with severe dengue (72.7%), followed by dengue with warning symptoms (53.8%) and dengue fever (28.6%). There was no significant correlation between cardiac involvement and primary/secondary dengue. Both ECG and echocardiography changes were significantly correlated with dengue severity, as opposed to cardiac markers.
Conclusions: Cardiac involvement was present in children with dengue. Evaluation with ECG, echocardiography, and cardiac markers such as CPK-MB are required for the management of cardiac complications in children with dengue. Our study showed an association between cardiac involvement and the severity of dengue. Further studies should be framed, and follow-up of dengue patients with cardiac involvement is necessary for therapeutic management.
