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  • Juvenile Idiopathic Arthritis in the Era of International Cooperation

    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.
  • Letter to the Editor: Chikungunya Virus Infection—An Update on Chronic Rheumatism in Latin America

    To the Editor, the article of Krutikov and Manson1 was interesting. However, no comment was made on the impact and related clinical epidemiology of the chikungunya virus (CHIKV) infection during the 2014–2015 epidemics in Latin America, the most recent area affected by CHIKV. Certainly, persistent musculoskeletal manifestations of the disease have been shown to affect a highly variable proportion of infected patients (even >87%). Following the epidemics in La Réunion Island and India,2 and now in Latin America, this disease is having a significant impact. ...
  • Author’s Reply to “A Few Suggestions for Preventing Failure of Ultrasound-Guided Blocks for Below the Shoulder Surgery”

    To the Editor, Dr Nair’s letter to the editor regarding the failed nerve blocks mentioned in our paper, “Comparison of the supraclavicular, infraclavicular and axillary approaches for ultrasound-guided brachial plexus block for surgical anesthesia”,1 raised several points that I believe are worth looking at in more detail. We are grateful for Dr Nair’s comments which have contributed to the furthering of scholarly discourse. In general, Dr Nair’s letter relates to the blocks that our research classified as failed. He then discusses various approaches and suggests the reason for the failures of the axillary approach blocks.
  • Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment

    Objective: The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery. Materials and methods: A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality. Results: The study analyzed the patients who were treated between January 2012 and June 2015. Among 705 patients with carcinoma of the tongue treated primarily with wide local excision and neck dissection, 383 received adjuvant treatment. A total of 215 patients received radiation, and 168 received concurrent radio-chemotherapy. Of 378 patients, 78 developed hypothyroidism during follow-up: 27 patients received concurrent radio-chemotherapy, and the remaining 51 received only radiation. Lower neck received 40–48 Gy in 2 patients, 50 Gy in 74 patients, and 60–70 Gy and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months. Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the oral tongue. The minimum period to develop hypothyroidism was 3 months in this study. Gender and adjuvant treatment were not found to be significant for the incidence of hypothyroidism. Conclusions: A significant number of patients with carcinoma of the tongue who receive adjuvant treatment will develop hypothyroidism, hence frequent monitoring of thyroid function is advised during follow-up.
  • Review of Robotic Surgery in Gynecology—The Future Is Here

    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.
  • Nucleated Red Blood Cells as a Marker of Acute and Chronic Fetal Hypoxia in a Rat Model

    Objective: To examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth. Methods: Pregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis. Results: As the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count. Conclusion: In a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.
  • Impact of Endometrial Preparation Protocols for Frozen Embryo Transfer on Live Birth Rates

    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.
  • Maternal Inflammation, Fetal Brain Implications and Suggested Neuroprotection: A Summary of 10 Years of Research in Animal Models

    A growing body of evidence implicates that maternal inflammation during pregnancy is associated with increased risk of neurodevelopmental disorders in the offspring. The pathophysiological mechanisms by which maternal inflammation evokes fetal brain injury and contribute to long-term adverse neurological outcomes are not completely understood. In this review, we summarize our 10 years’ research experience on maternal inflammation and the implications upon the fetal/offspring brain. We review our findings regarding the underlying mechanisms that connects maternal inflammation and fetal brain injuries (e.g. cytokines, oxidative stress), we discuss our imaging, pathological and behavioral test results which support brain damage following maternal inflammation and finally we describe some of the therapeutic strategies which might prevent the damage.
  • Anovulatory Patients Demonstrate a Sharp Decline in LH Levels upon GnRH Antagonist Administration during IVF Cycles

    To evaluate the decrease in luteinizing hormone (LH) levels following gonadotropin-releasing hormone (GnRH) antagonist administration in in vitro fertilization (IVF) cycles, data were retrospectively collected from 305 consecutive IVF or intracytoplasmic sperm injection (ICSI) cycles of patients who underwent ovarian stimulation with gonadotropins and were treated with GnRH antagonist for the prevention of premature luteinization. We compared the percent change in LH concentration from stimulation start to that observed before ovulation triggering in patients with or without anovulation. Anovulatory patients were younger, with higher body mass index (BMI), and demonstrated higher ovarian reserve parameters as compared to ovulatory patients. The decline in LH concentration was almost two-fold greater in anovulatory versus ovulatory patients. Numbers of oocytes, fertilizations, cleavage stage embryos, and transferred embryos were similar; however, implantation rates were higher in anovulatory versus ovulatory patients. Older patients (age ≥39) showed a smaller decline in LH levels as compared to younger ones (age <39) and exhibited poor IVF outcomes. There is a wide range of pituitary responses to GnRH antagonists. Anovulatory patients are more susceptible to GnRH antagonists and therefore demonstrate over-suppression of the pituitary. Older patients demonstrate a reduced pituitary response to GnRH antagonists than younger ones. Cycle scheduling with estradiol pretreatment did not influence LH decline, nor IVF treatment outcomes.
  • Fear of Vaginal Penetration in the Absence of Pain as a Separate Category of Female Sexual Dysfunction: A Conceptual Overview

    Functional sexual pain disorders in women are a particular challenge to the gynecologist, inasmuch as phobic avoidance and guarding on the part of the patient lead to difficulties in the gynecological examination and diagnosis. In some such cases examination may even be impossible. Vaginismus is the commonly diagnosed etiology of such cases. This article offers an overview of vaginismus and approaches to its treatment but also examines a subset of penetration-avoidant patients who do not appear to have a pain component. We have reviewed this separate category conceptually and clinically, and propose that this case subset be separated from the diagnosis of vaginismus and designated as vaginal penetration phobia (VPP). We further propose that this category be diagnosed as one of several possible presentations of phobic disorder, under the rubric of mental health disorder, and thus be separated from gynecology. The nosological implications are raised.