CD4+CD25+Foxp3+ regulatory T cells (Treg) are critical to the maintenance of immune tolerance. Treg are known to utilize a number of molecular pathways to control immune responses and maintain immune homeostasis. Fibrinogen-like protein 2 (FGL2) has been identified by a number of investigators as an important immunosuppressive effector of Treg, which exerts its immunoregulatory activity by binding to inhibitory FcγRIIB receptors expressed on antigen-presenting cells including dendritic cells, endothelial cells, and B cells. More recently, it has been suggested that FGL2 accounts for the immunosuppressive activity of a highly suppressive subset of Treg that express T cell immunoreceptor with Ig and ITIM domains (TIGIT). Here we discuss the important role of Treg and FGL2 in preventing alloimmune and autoimmune disease. The FGL2–FcγRIIB pathway is also known to be utilized by viruses and tumor cells to evade immune surveillance. Moving forward, therapies based on modulation of the FGL2–FcγRIIB pathway hold promise for the treatment of a wide variety of conditions ranging from autoimmunity to cancer.
I appreciate Dr Walsh’s feedback regarding my recent article, “Teaching and Assessing Profession-alism in Medical Learners and Practicing Physicians.” I agree with Dr Walsh that quality improvement is a topic of importance within the professionalism domain. ...
Rambam Maimonides Medical Journal was once a new and unknown publication. Today we have more than 17,000 subscribers from 146 nations and territories. We published 39 scientific medical papers in 2017 out of 61 submitted manuscripts.
We are now indexed by PubMed and Thompson Reuters Emerging Sources Citation Index, to name a few. Next year, the Journal is scheduled to receive an official impact factor from Thompson Reuters.
We are not so unknown anymore.
As a new Journal, most of the papers submitted were naturally reviews. However, the most important aspect for the promotion and advancement of medicine is publication of original research. To promote such efforts the editors of Rambam Maimonides Medical Journal established in 2017 the Maimonides Best Published Original Research Prize. This annual prize of $1,000 is to be awarded to the first author of the best original research paper published in the journal over the previous year.
I am pleased to announce that the winner of the 2018 Maimonides Best Published Original Research Prize is Dr. Louise Kezerle, the first author of the paper entitled, “A Population-based Study of Peripartum Cardiomyopathy in Southern Israel: Are Bedouin Women a New High-risk Group?” with co-authors Iftach M. Sagy, Leah Shalev, Offer Erez, and Leonid Barski.
Idiopathic hypereosinophilic syndrome (HES) is a rare, heterogeneous disorder characterized by a strikingly high eosinophil count (>1,500 cells/µL), over a long period of time (>6 months), with end organ damage. We present a 60-year-old patient with idiopathic HES with isolated liver involvement, a rare systemic dis¬ease and a rare solid organ involvement. The patient had a thorough investigational work up until HES was established, including liver biopsy. He needed intensive immunosuppressive treatment at first with steroids, then with azathioprine in conjunction with a low dose of steroids. After 16 years of follow-up, the patient showed no evidence of liver dysfunction. To the best of our knowledge, this is the longest follow-up for a patient with HES-associated chronic hepatitis. Our observation suggests that, with appropriate treatment, liver involvement in HES may be well controlled without deterioration to advanced liver failure.
Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma) has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF)-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC) is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP) upon binding of nitric oxide (NO) to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs) are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK) inhibitor which targets multiple TKs, in SSc.
For the purpose of reducing maternal and neonatal morbidity, elective single transfer (eSET) in in vitro fertilization (IVF) was first proposed in 1999. The purpose of this review is to summarize recent oral debate between a proponent and an opponent of expanded eSET utilization in an attempt to determine whether a blanket eSET policy, as is increasingly considered, is defensible. While eSET is preferable when possible, and agreed upon by provider and patient, selective double embryo transfer (DET) must be seriously entertained if deemed more appropriate or is desired by the patient. Patient autonomy, let alone prolonged infertility and advancing age, demand nothing less. Importantly, IVF-generated twins represent only 15.7% of the national twin birth rate in the United States. Non-IVF fertility treatments have been identified as the main cause of all multiple births for quite some time. However, educational and regulatory efforts over the last decade, paradoxically, have exclusively only been directed at the practice of IVF, although IVF patient populations are rapidly aging. It is difficult to understand why non-IVF fertility treatments, usually applied to younger women, have so far escaped attention. This debate on eSET utilization in association with IVF may contribute to a redirection of priorities.
Final oocyte maturation is a crucial step in in vitro fertilization, traditionally achieved with a single bolus of human chorionic gonadotropin (hCG) given 36 hours before oocyte retrieval. This bolus exposes the patient to the risks of ovarian hyperstimulation syndrome (OHSS), particularly in the face of ovarian hyper-response to gonadotropins. Although multiple measures were developed to prevent OHSS, gonadotropin-releasing hormone (GnRH) agonist triggering is now globally recognized as the best approach to achieve this goal. The first report on the use of GnRH agonist as ovulation trigger in the context of OHSS prevention came from the Rambam Health Care Campus, Haifa, Israel and appeared in 1988. This review details the events that culminated in worldwide acceptance of this measure and describes its benefit in the field of assisted reproductive technology.
Obstetric anal sphincter injuries (OASIs) following vaginal deliveries are the main reason for subsequent development of anal incontinence in women. The diagnosis of such tears is crucial for treating and preventing such a grave sequela. The reported rate of OASIs in Israel was between 0.1% and 0.6%, out of all vaginal births, which is 10-fold lower than that reported in Europe and the United States. Structured hands-on training in repair of OASIs in seven medical centers in Israel significantly increased the detection rate of third-degree perineal tears. The implementation of such programs is crucial for increasing awareness and detection rates of OASIs following vaginal deliveries.
Objective: Data on the prevalence of patent processus vaginalis (PPV) and hernia in patients with cryptorchidism are controversial. While some pediatric surgeons do not dissect the processus vaginalis (PV), most prefer to do so to prevent hernia formation and to achieve an effective orchiopexy outcome. This study was performed to evaluate the importance of dissection and high ligation of the PV during treatment of undescended testis (UT).
Methods: The clinical findings and surgical procedures of 55 patients with UT were retrospectively investigated.
Results: The mean patient age was 2.5 (range 1.0–12.0) years. Non-palpable testis (NPT) was located on the right and left side in 39 and 16 patients, respectively. Ultrasonography revealed no testis in 10 patients and an atrophic testis in 7 patients. Seven patients had a parent with an inguinal hernia, and the silk sign or a PPV was detected during inguinoscrotal examination in 22 patients. Undescended testis repair was performed by an inguinal approach in all patients. The inguinal canal was opened in all patients; 42 patients had a wider-than-normal internal ring (>2.5 cm), and the posterior wall of the inguinal canal was consequently weakened. Two-stage orchiopexy was performed in 2 patients, and 15 underwent the Prentiss maneuver. In the remaining patients, the dissection was easily done, and the orchiopexy was performed without any difficulty. Scrotal edema and wound infection occurred in five and two patients, respectively. One patient presented with an atrophic testis, and three had recurrent UT. Inguinal hernia was not observed in any of the patients during the study period, and all procedures were performed on an outpatient basis.
Conclusion: High ligation of the PV is an effective method for successful orchiopexy and prevention of inguinal hernia in patients with NPT and UT.
