Israel Medical Association Journal

Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.

Recurrent pericarditis is a state of repetitive inflammation of the pericardium with intervals of remission. The etiology of recurrent pericarditis is still largely unknown, yet most causes are presumed to be immune mediated. Genetic factors, including human leukocyte antigen (HLA) haplotypes, can be involved in dysregulation of the immune system and as a predisposition to several autoimmune conditions, including recurrent pericarditis. Several diseases are frequently associated with such manifestations. They include systemic lupus erythematosus, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome. However, idiopathic recurrent pericarditis remains the most frequently observed clinical condition and the conundrum of this disease still needs to be solved.

Background: The sentinel lymph node (SLN) biopsy procedure is a well-known method for identifying solid tumors such as breast cancer, vulvar cancer, and melanoma. In endometrial and cervical cancer, SLN has recently gained acceptance.

Objectives: To evaluate the detection rate of SLN with an indocyanine green and near-infrared fluorescent imaging (ICG/NIR) integrated laparoscopic system in clinically uterine-confined endometrial or cervical cancer.

Methods: Patients with clinically early-stage endometrial or cervical cancer were included in this retrospective study. ICG was injected into the uterine cervix and an ICG/NIR integrated laparoscopic system was used during the surgeries. The National Comprehensive Cancer Network (NCCN) protocol was followed. SLN and/or suspicious lymph nodes were resected. Side-specific lymphadenectomy was performed when mapping was unsuccessful. Systematic lymphadenectomy was completed in patients with high-grade histology or deep myometrial invasion. Enhanced pathology using ultra-staging and immunohistochemistry were performed in all cases.

Results: We analyzed 46 eligible patients: 39 endometrial and 7 cervical cancers. Of these, 44 had at least one SLN (93.6%). In 41 patients (89%) we detected bilateral SLN, in 3 (7%) only unilateral, and in 2 (4%) none were detected. Seven patients presented with lymph node metastasis. All were detected by NCCN/SLN protocol. Of these cases, two were detected with only pathological ultra-staging.

Conclusions: SLN mapping in endometrial and cervical cancer can easily be performed with a high detection rate by integrating ICG/NIR into a conventional laparoscopic system. Precision medicine in patients evaluated by SLN biopsy changes the way patients with endometrial or cervical cancer are managed.

Background: Cannabinoid hyperemesis syndrome (CHS) is under-recognized by clinicians. It is characterized by nausea, severe abdominal pain, and cyclical vomiting in the context of chronic cannabis use. Oral benzodiazepine is a proposed treatment for CHS. It decreases activation of Cannabinoid Type 1 Receptor (CB1) in the frontal cortex, has a sedative and hypnotic effect and reduces the anticipation of nausea and vomiting. These effects on the central nervous system (CNS) might explain its beneficial antiemetic effect for this syndrome.

Objectives: To increase the index of suspicion for CHS, a unique syndrome that requires a unique treatment with benzodiazepines and not antiemetics.

Methods: We describe a series of four patients with documented cannabis use, who were admitted to an internal medicine department of Meir Medical Center due to symptoms consistent with abdominal pain, nausea, and vomiting. They were initially treated with conventional antiemetics and proton pump inhibitors without response. Intensive investigations were conducted to exclude common and sometimes urgent gastrointestinal or CNS syndromes.

Results: After excluding urgent gastrointestinal and CNS origins for the vomiting, we suspected CHS. All four patients experienced similar symptoms and failure of conventional treatment with antiemetics and proton pump inhibitors. They experienced relief after administration of benzodiazepines.

Conclusions: A high index of suspicion for CHS allows for rapid, appropriate treatment with benzodiazepines, which in turn may lead to cessation of the debilitating symptoms caused by this syndrome.

Background: Israel's population is diverse, with people of different religions, many of whom seek spiritual guidance during ethical dilemmas. It is paramount for healthcare providers to be familiar with different religious approaches.

Objectives: To describe the attitudes of the three major monotheistic religions when encountering four complex neonatal situations.

Methods: A questionnaire related to four simulated cases was presented to each participant: a non-viable extremely premature infant (case 1), a severely asphyxiated term infant with extensive brain damage (case 2), a small preterm infant with severe brain hemorrhage and likely extensive brain damage (case 3), and a term infant with trisomy 21 syndrome and a severe cardiac malformation (case 4).

Results: Major differences among the three religious opinions were found in the definition of viability and in the approach towards quality of life.

Conclusions: Neonatologists must be sensitive to culture and religion when dealing with major ethical issues in the neonatal intensive care unit.

Background: Pericardial biopsies are rarely performed during the diagnosis and management of pericardial diseases. The circumstances and clinical profile of patients undergoing pericardial biopsies are largely uncharacterized.



Objectives: To examine the circumstances in which pericardial biopsies are obtained and to evaluate their diagnostic yield.



Methods: We studied a total of 100 cases (71% males, mean age 60.8 years, range 8.1–84.5 years) of surgically resected pericardium specimens obtained from 2000 to 2015 at Sheba Medical Center, the largest medical center in Israel. Patients were classified into groups according to four major histological etiologies: idiopathic pericarditis, constrictive pericarditis, malignant pericarditis, and post-cardiac injury syndrome (PCIS). The clinical history and course, laboratory, echocardiography, and histological results were reviewed retrospectively.



Results: Causes of pericarditis according to histological definitions included idiopathic pericarditis (29%), constrictive pericarditis (29%), PCIS (9%), and malignant pericarditis (26%). Overall sensitivity of the pericardial biopsy in patients with malignancy was 57.7%. During the study period, we found a trend toward an increased number of biopsies due to constrictive pericarditis and PCIS, along with a decrease in the number of biopsies performed in patients with malignant or idiopathic pericarditis. The diagnosis following biopsy did not change for any of the patients.



Conclusions: Our findings suggest a low diagnostic yield from pericardial biopsies, especially in malignant pericarditis. This conclusion, along with novel therapies, resulted in the infrequent use of pericardial biopsy in recent years.

Background: Pulmonary embolism (PE) is the third most frequently occurring cardiovascular disease. However, the clinical presentation in patients with PE is variable.

Objectives: To evaluate the prevalence of radiological findings detected in contrast-enhanced computed tomography angiography (CTA) and their significance in patients with PE; and to assess whether the CTA findings differed in patients receiving tissue plasminogen activator (tPA) therapy from those who did not.

Methods: We retrospectively reviewed CTA scans of 186 patients diagnosed with acute PE. Incidental findings on CTA scan were assessed, including mediastinal and parenchymal lymph nodes, pleural effusion, space-occupying lesions, consolidations, emphysema, and pericardial effusion.

Results: Patients receiving tPA (19.9%) were less likely to have pleural effusion (29.7% vs. 50.3%, P = 0.024). Other CTA findings did not differ between the tPA and non-tPA groups, including lung infiltrates (40.5% vs. 38.9, P = 0.857), space-occupying lesions (5.4% vs. 6.7%, P = 1), pericardial effusion (8.1% vs. 8.7%, P = 1), emphysema (21.6% vs. 17.4%, P = 0.557), lung (18.9% vs. 24.2%, P = 0.498), and mediastinal ( 24.3% vs. 25.5%, P = 0.883) lymph nodes, respectively.

Conclusion: The prevalence of pleural effusion (unilateral or bilateral) was higher in patients not treated with tPA. Therefore, in patients with a borderline condition, the presence of pleural effusion could support the decision not to give tPA treatment.

Background: The currently accepted treatment for idiopathic sudden sensorineural hearing loss (ISSHL) is systemic steroids as first-line and intratympanic steroids as salvage therapy. Intratympanic (IT) treatment is applied worldwide in many different ways with no universally accepted protocol.

Objectives: To present the current disparity in ISSHL management and to discuss the necessity for establishing a common national protocol.

Methods: In 2014 we conducted a national survey by sending questionnaires on ISSHL management to otologists in every otolaryngology department in the country.

Results: The majority of otolaryngology departments (56%) admit patients with sudden sensorineural hearing. Almost two-thirds (61%) of departments recommend supplementary initial treatment in addition to systemic steroids. None of the medical centers offer intratympanic steroid treatment as primary therapy, but 94% offer this treatment as a salvage therapy. Fewer than half the medical centers (44%) consider the maximal period for intratympanic therapy to be 4 weeks since hearing loss appears. Almost half (48%) the departments use intratympanic steroids once every 5–7 days, usually in an ambulatory setting. Almost half (44%) the medical centers tend to use not more than four courses of IT steroids. In 44% of departments an audiogram is performed at the beginning and at the end of the intratympanic course.

Conclusions: Our results demonstrate a variability among Israeli medical centers in many aspects of intratympanic treatment. We believe this reinforces the need for a comparative international study in order to establish a standard protocol.

Background: The epidemiology of human brucellosis (HB) continues to evolve.

Objectives: To describe the current epidemiology of HB in Israel in general and in the population at risk.

Methods: We calculated the incidence of HB in Israel for the period 2009–2015, overall and for the Arab population. Data are based on mandatory reporting of HB in Israel, defined clinically with either laboratory confirmation or epidemiological linkage to a laboratory-confirmed case. We mapped the geographic distribution of HB throughout the study period according to localities. We specified localities with high incidence (≥ 10 per 100,000 population) and mapped the distribution of dense localities with time.

Results: The incidence of HB in the general population in Israel increased sharply from 1.9 per 100,000 in 2009 to a peak of 7.3 per 100,000 in 2014. Each year, 95–100% of cases occurred among Arabs, thus the incidence in the Arab population increased from 10 per 100,000 in 2009 to 33.5 per 100,000 in 2014. Throughout this period 133 different localities reported at least one case of HB, and of these 20 were high-incidence localities during one year at least. During the period 2009–2013 the number of affected localities ranged from 35 to 44 per year and the disease was local, while in 2014 there were 82 localities distributed across the country.

Conclusions: We demonstrate the importance of analyzing incidence in the population at risk for a disease. HB is an urgent public health issue in the Arab population in Israel, mandating an immediate and long-term eradication and control program.