Israel Medical Association Journal

Kidney involvement in systemic sclerosis (SSc) is common with altered kidney function present in approximately half of the patients [1]. Scleroderma renal crisis (SRC), the most severe kidney manifestation, occurs in about 20% of patients with this autoimmune disorder [1]. SRC mainly affects patients with the diffuse cutaneous systemic sclerosis (dcSSc) subtype of the disease, and particularly in those who are seropositive to anti RNA polymerase III antibodies [2]. In recent years, the prevalence of SRC has decreased following the initiation of medication therapy with angiotensin-converting-enzyme inhibitors (ACE-i). Previously, SRC mortality rates were as high as 78%. Contemporary studies in the post-ACE-i era suggest lower rates, with mortality rate ranging from 30% to 36% [3]. Nevertheless, progression to end-stage renal disease (ESRD) is evident and may require renal replacement therapies (RRTs). While renal transplant rates in SSc have increased, they constitute a small proportion of SSc-SRC patients (3–8%) and SSc-ESRD patients (4–17%).

War is a chaotic situation for most of the public sectors in the countries involved. These sectors also include the medical systems, especially medical education, of which medical communication is often neglected or forgotten due to objective and subjective causes on either side of the involved countries. By planning lessons on various aspects of medicine for countries at war and close mentoring and utilization of modern communications technologies, these difficulties can be minimized without jeopardizing the quality of medical studies nor medical communication. In this perspective article, we describe the objective and subjective measures taken by our team to achieve these goals during the Iron Swords war in our region.

Takotsubo syndrome (TTS) often develops following stressors such as cardiac surgery. It may be fatal in rare cases. Our 70-year-old female patient presented with a rare case of tricuspid valve papillary fibroelastoma, which was complicated by fatal TTS after successful resection. The patient had a right atrial mass that was investigated with computed tomography and transesophageal echocardiography (TTE). She was scheduled for surgery. Pathology findings were consistent with papillary fibroelastoma of the tricuspid valve. Three weeks after successful surgery, the patient was admitted due to cardiogenic shock with echocardiographic findings of apical ballooning and left ventricular outflow tract obstruction consistent with TTS. The patient died one hour after her admission despite optimal medical therapy.

Background: Current guidelines for choosing between revascularization modalities may not be appropriate for young patients.

Objectives: To compare outcomes and guide treatment options for patients < 40 years of age, who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2008 and 2018.

Methods: Outcomes were compared for 183 consecutive patients aged < 40 years who underwent PCI or CABG between 2008 and 2018, Outcomes were compared as time to first event and as cumulative events for non-fatal outcomes.

Results: Mean patient age was 36.3 years and 96% were male. Risk factors were similar for both groups. Drug eluting stents were implemented in 71% of PCI patients and total arterial revascularization in 74% of CABG patients. During a median follow-up of 6.5 years, 16 patients (8.6%) died. First cardiovascular events occurred in 35 (38.8%) of the PCI group vs. 29 (31.1%) of the CABG group (log rank P = 0.022), repeat events occurred in 96 vs. 51 (P < 0.01), respectively. After multivariate adjustment, CABG was associated with a significantly reduced risk for first adverse event (hazard ratio [HR] 0.305, P < 0.01) caused by a reduction in repeat revascularization. CABG was also associated with a reduction in overall repeat events (HR 0.293, P < 0.01). There was no difference in overall mortality between CABG and PCI.

Conclusions: Young patients with coronary disease treated by CABG showed a reduction in the risk for non-fatal cardiac events. Mortality was similar with CABG and PCI.

Background: Ga-prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA PET/CT) is part of the initial workup of patients with intermediate and high-risk prostate cancer provided by the Israeli national health services.

Objectives: To assess the incidence of metastatic spread in consecutive patients with newly diagnosed cancer, and the potential added value of Ga-PSMA PET/CT to the staging imaging algorithm.

Methods: Patients with newly diagnosed intermediate- and high-risk prostate cancer were referred for initial staging by Ga-PSMA PET/CT between May 2016 and April 2017. Blood prostate-specific antigen (PSA) levels, clinical history, imaging reports and histopathological reports (including Gleason scores) were obtained. Maximal standardized uptake values (SUVmax) were determined for the primary lesions detected within the prostate.

Results: The study included 137 consecutive patients with intermediate- and high-risk disease who underwent Ga-PSMA PET/CT staging. Of these, 75 had Ga-PSMA uptake in both prostate lobes, 57 had unilateral uptake, and 5 patients had no uptake. SUVmax in the primary tumor correlated significantly with PSA levels. Thirty-five patients had increased uptake compatible with metastatic disease involving lymph nodes, bone, and viscera. Twenty-seven patients had available bone scintigraphy results: 18 (69%) of their 26 bone metastases detected by Ga-PSMA PET/CT were missed on bone scintigraphy.

Conclusions: Ga-PSMA PET/CT shows promise as a sole whole-body imaging modality for assessing the presence of soft tissue and bone metastases in the setting of prostate cancer.

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFβ2[1]-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD™ as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus®) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet.

Results: The Modulen-treated children showed a significant decrease in PCDAI[2] from 34.3 to 15.7 (P < 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P = 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P = 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group.

Conclusions: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI[3], suggesting an additional advantage of nutritional therapy in children with this disease.

Contamination of food with streptococci could present with unusual outbreaks that may be difficult to recognize in the early stages. This is demonstrated in a large food-borne outbreak of streptococcal pharyngitis that occurred in 2003 in a factory in Israel. The outbreak was reported to the public health services on July 2 and an epidemiologic investigation was initiated. Cases and controls were interviewed and throat swabs taken. An estimated 212 cases occurred within the first 4 days, the peak occurring on the second day. There was a wave of secondary cases during an additional 11 days. The early signs were of a respiratory illness including sore throat, weakness and fever, with high absenteeism rates suggesting a respiratory illness. As part of a case-control study, cases and controls were interviewed and throat swabs taken. Illness was significantly associated with consumption of egg-mayonnaise salad (odds ratio 4.2, 95% confidence interval 1.4–12.6), suggesting an incubation period of 12–96 hours. The initial respiratory signs of food-borne streptococcal pharyngitis outbreaks could delay the identification of the vehicle of transmission. This could be particularly problematic in the event of deliberate contamination.

Background: Multiple sclerosis is a chronic demyelinating disease of the central nervous system that presents with variable signs and symptoms. This variability in the clinical presentation may result in misdiagnosis, unnecessary referrals and misleading information to the patients.

Objectives: To identify the types of misdiagnoses made on the presentation of MS.

Methods: Fifty consecutive MS patients were questioned on their early symptoms, their mental status, the disease course until the diagnosis was confirmed, and the different diagnoses they received.

Results: The patients had been referred to 2.2 ± 1.3 specialists before seeing a neurologist, and learned about their disease 3.5 years after the onset of symptoms. Twenty-nine patients (58%) were initially given 41 wrong diagnoses. While the majority of women were misdiagnosed mentally, orthopedic work-up was offered to the men. Misdiagnosis of MS occurred most often in patients who presented with non-specific sensory symptoms that did not conform to a specific neurologic syndrome. The patients emphasized the fact that not knowing worsened their anxiety, whereas receiving the diagnosis enabled them to begin coping with their disease.

Conclusions: MS is often overlooked when patients present with non-specific sensory complaints. The difference in type of misdiagnosis between men and women may reflect a gender-dependent bias in the way physicians interpret sensory complaints.

Background: Between 1970 and 1979, there was an increase in the incidence of viral hepatitis in Israel with a shift of peak incidence to an older age in the Jewish population, followed by a declining trend during the early 1980s. In July 1999 universal immunization of infants against hepatitis A was introduced.

Objective: To evaluate the chan-ges in the epidemiology of viral hepatitis A in Israel during the past decade.

Methods: Viral hepatitis is a notifiable disease in Israel and cases are reported to the regional health offices, which in turn provide summary reports to the Ministry of Health's Department of Epidemiology. The data in this study were derived from the summary reports and from results of seroprevalence studies.

Results: Following the increase in the incidence of reported viral hepatitis (mainly due to type A) between 1970 and 1979, the rates then stabilized and around 1984 began to decline until 1992. Since then there has been a slight increase. Whereas until 1987 the rates were consistently higher in the Jewish population. since then they are higher in the Arab population. The shift in the peak age-specific incidence from the 1-4 to the 5-9 year age group observed in the Jewish population around 1970 occurred 20 years later in the Arab population. The previously described seasonality is no longer evident. Recent seroprevalence studies indicate that by age 18 years only about 30-40% of the Jewish population have anti-hepatitis A antibodies.

Conclusions: The decline in the incidence of hepatitis probably reflects the changing socioeconomic condition occurring at different times in the two major population groups. Since hepatitis A accounts for almost all the acute viral hepatitis in Israel, the universal vaccination of infants introduced in 1999 should substantially lower the morbidity within the next few years.

Background: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.

Objectives: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.

Methods: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera.  Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.

Results: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18±0.19 optical density for controls, and 1.65±1.14 for patients with celiac disease (P<0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.

Conclusions: A tissue transglutaminase-based ELISA test is both sensitive and specific for  detection of celiac disease.

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AEA = anti-endomysial antibody