Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play pro-inflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects.
Born in Portugal and the son of Marranos (Christianized Jews from Spain), Eliahu de Luna Montalto lived during a particularly harsh period for the Jewish people. Throughout Europe, the situation for Jews was unfavorable; laws had been passed forbidding them to live in England for the past 300 years, and for the past 200 years in France. Additionally, in France, while Jews were permitted to study at some universities, the practice of medicine was forbidden to them. It is within this context that Eliahu de Luna Montalto, who had returned to his original faith (Judaism), was recruited to the French court. This paper pays tribute to Montalto’s life and medical practice—so exemplary that the Queen of France would ask Montalto to serve at the court and receive Papal permission for Montalto openly to observe his faith as a Jew, this despite the objections of the King of France.
Epidemiological studies have shown that patients with psoriatic arthritis (PsA) are often affected by numerous comorbidities that carry significant morbidity and mortality. Reported comorbidities include diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, osteoporosis, inflammatory bowel disease, autoimmune eye disease, non-alcoholic fatty liver disease, depression, and fibromyalgia. All health care providers for patients with PsA should recognize and monitor those comorbidities, as well as understand their effect on patient management to ensure an optimal clinical outcome.
Juvenile idiopathic arthritis (JIA) is the most common chronic disease of childhood. Improved understanding of its pathogenesis has led to international cooperation in clinical studies. Multicenter, international collaborations and research facilitate rapid enrollment of enough patients to enable a variety of studies, including those of epidemiology, diagnostic and classification criteria, genetic disease predisposition, pathogenesis, outcomes, and treatment protocols. In the last 20 years, the vision of the Pediatric Rheumatology International Trial Organization (PRINTO) has become a reality of worldwide collaboration in pediatric rheumatology research, including North American and European research groups. Major advances have been made in treating systemic JIA and its main complication, macrophage-activating syndrome (MAS). Single Hub and Access Point to Pediatric Rheumatology in Europe (SHARE) is a project of the European Society of Pediatric Rheumatology with the goal of improving clinical care. Based on evidence in the scientific literature, position papers regarding optimal clinical approaches and care have been published. Formal, validated assessment tools to evaluate response to treatment have been developed. Recommendations have been established to encourage international research collaborations, especially in light of major advances achieved in the genetics of pediatric rheumatologic diseases and the need to share biological samples among different countries and continents. Every participating country has disease information available for patients and families. Additionally, educational programs and updated syllabi for pediatric rheumatology have been written to promote similar, high-level academic training in different countries. These efforts have resulted in significant improvements in treatment and in patient prognosis. However, improved cooperation is needed to enhance research with biological and genetic samples. The Israeli Research Group for Pediatric Rheumatology is very active and has made significant contributions to the field.
Autoinflammatory diseases (AID) are characterized by seemingly unprovoked self-limited attacks of fever and systemic inflammation potentially leading to amyloidosis. Familial Mediterranean fever (FMF) is the most common AID and therefore the most studied. Besides FMF, the other main hereditary AID are tumor necrosis factor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic fever syndrome (CAPS). These hereditary diseases result from a mutant gene that is involved in the regulation of inflammation, resulting in a characteristic clinical phenotype. The differential diagnosis of AID can be challenging due to a wide overlap in clinical manifestations. Moreover, a considerable proportion of patients present with autoinflammatory symptoms but without a pathogenetic variant on genetic analysis. Furthermore, non-hereditary AID, such as the periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome, which is the most common AID in children worldwide, must be excluded in certain circumstances. Herein we shall review the main AID and describe a practical approach to diagnosis in a patient with a clinical suspicion of AID.
Long-standing diabetes leads to structural and functional alterations in both the micro- and the macro-vasculature. Designing therapies to repair these abnormalities present unique and sophisticated challenges. Vascular endothelial cells are the primary cells damaged by hyperglycemia-induced adverse effects. Vascular stem cells that give rise to endothelial progenitor cells and mesenchymal progenitor cells represent an attractive target for cell therapy for diabetic patients. In this review, we shed light on challenges and recent advances surrounding stem cell therapies for diabetes vascular complications and discuss limitations for their clinical adoption.
Robotic technology has been used in cardiovascular medicine for over a decade, and over that period its use has been expanded to interventional cardiology and percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted interventions has been demonstrated in multiple studies ranging from simple to complex coronary lesions, and in the treatment of ileofemoral and infrapopliteal disease. These studies have shown a reduction in operator exposure to harmful ionizing radiation, and the use of robotics has the intuitive benefit of alleviating the occupational hazard of operator orthopedic injuries. In addition to the interventional operator benefits, robotically assisted intervention has the potential also to be beneficial for patients by allowing more accurate lesion length measurement, stent placement, and patient radiation exposure; however, more investigation is required to elucidate these benefits fully.
The authors present a systematic review of randomized and observational, retrospective and prospective studies to compare between robotic surgery as opposed to laparoscopic, abdominal, and vaginal surgery for the treatment of both benign and malignant gynecologic indications. The comparison focuses on operative times, surgical outcomes, and surgical complications associated with the various surgical techniques. PubMed was the main search engine utilized in search of study data. The review included studies of various designs that included at least 25 women who had undergone robotic gynecologic surgery. Fifty-five studies (42 comparative and 13 non-comparative) met eligibility criteria. After careful analysis, we found that robotic surgery was consistently connected to shorter post-surgical hospitalization when compared to open surgery, a difference less significant when compared to laparoscopic surgery. Also, it seems that robotic surgery is highly feasible in gynecology. There are quite a few inconsistencies regarding operative times and estimated blood loss between the different approaches, though in the majority of studies estimated blood loss was lower in the robotic surgery group. The high variance in operative times resulted from the difference in surgeon’s experience. The decision whether robotic surgery should become mainstream in gynecological surgery or remain another surgical technique in the gynecological surgeon’s toolbox requires quite a few more randomized controlled clinical trials. In any case, in order to bring robotic surgery down to the front row of surgery, training surgeons is by far the most important goal for the next few years.
Background: It has been reported that a natural cycle (NC) is similar to or even better than hormone replacement therapy (HRT) in patients with regular cycles who undergo frozen embryo transfer (FET). Hundreds of FETs are managed yearly in our clinic. Scheduling these cycles is critical in a busy unit like ours. This is why we have to prove if a NC really shows a better outcome than other endometrium preparation protocols.
Methods: Hence we carried out a prospective study between June 2011 and June 2012, which included 530 patients (570 FET cycles) randomly allocated to two study groups: Group 1 (n=280 cycles), artificial cycle (HRT); or group 2 (n=290 cycles), natural cycle. Natural cycles were later divided into two groups: 169 patients scheduled with human chorionic gonadotropin (hCG) and 121 with endogenous luteinizing hormone (LH) surge. The inclusion criteria were: age <39 years, regular menstrual cycles (26–35 days), and previous IVF cycle with embryo cryopreservation. The exclusion criteria were polycystic ovarian syndrome and endometriosis stage III/IV.
Results: No statistical differences were found in the baseline characteristics among groups, nor between implantation or ongoing pregnancy rates (30.8% HRT group; 32.7% hCG group; 34.5% LH surge group). However, a higher miscarriage rate was observed in the HRT group when compared to hCG or LH surge (21.2 versus 12.9 versus 11.1%, P<0.01). Live birth rates were similar among groups, as were perinatal outcomes, for rates of natural delivery and weight and length of newborns.
Conclusions: We conclude that scheduling FET with HRT at weekends and avoiding work overload at weekends prove efficient and safe in cycle outcome terms. Another reason for the convenience of an HRT protocol is having fewer visits to the clinic compared to natural cycle protocols.
Objective: During July–August 2014,the military operation “Protective Edge” presented Israel with a threat of missile attacks. We aimed to investigate the influence of the “Protective Edge” operation on the rate of pregnancy complications among the population exposed to missile attacks, compared to the population not exposed.
Study Design: This was a retrospective study. Pregnancy outcomes were compared between women who during pregnancy were exposed to the stress of the military operation (exposed group, n=4,673) and gave birth at the Wolfson Medical Center, and women who gave birth in the previous year (unexposed group, n=4,735).
Results: Rates of pregnancy complications did not differ between the groups.
Conclusion: Exposure to environmental stress during pregnancy, for a period of almost two months, was not found to be associated with increased risk for pregnancy complications.
