Israel Medical Association Journal

Background: There is a lack of information regarding acute pancreatitis in Israel. However, the most prevalent worldwide etiologic causes of acute pancreatitis are biliary stones and alcohol abuse.

Objectives: To delineate the prevalence, main causes, rate of recurrence, mortality, and complications of acute pancreatitis in southern Israel.

Methods: In this retrospective study medical files of all hospitalized patients diagnosed with acute pancreatitis during a 13-year period were reviewed.

Results: The study comprised 602 patients with acute pancreatitis (120/100,000 patients or 1.2/1000 admissions). The main causes were: biliary stones (41.5%), alcohol (8.8%), and drugs (8.3%). Disothiazide was the most common drug associated with acute pancreatitis followed by sitagliptin, angiotensin converting enzyme (ACE) inhibitors, and simvastatin. Undetermined etiology made up 33.6% of the cases. Recurrence rate was 33.8% (alcohol 3.7%, hypertriglyceridemia 1.8%). This finding had no implications on mortality rate, which was stable at 4.3%. Bilateral pleural effusion, advanced computed tomography severity index (CTSI) grading, older age, and being single were found to be poor prognostic predictive factors.

Conclusions: Biliary pancreatitis is the main cause of acute pancreatitis in southern Israel, similar to the rest of the world, and constitutes a much more common etiology than alcohol. Furthermore, drug-induced pancreatitis is a common etiology, with disothiazide being the most common drug associated with pancreatitis followed by ACE-Inhibitors, sitagliptin, and simvastatin. Recurrence of pancreatitis is common in this geographic area, and older age, advanced CTSI grading, bilateral pleural effusion, and being single are all poor prognostic predictive factors.

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs.

Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type.

Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration.

Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route.

Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

Background: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

Objectives: To review the experience with MBC of a single center in Israel over a period of 22 years.

Methods: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993–2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

Results: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A–2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2–178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

Conclusions: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.

Background: The number of investigative esophagogastroduodenoscopies (EGD) in children has increased over several decades, despite their unclear diagnostic yields.

Objectives: To evaluate the indications for performing EGD, their diagnostic yields, and consequences on pediatric patient management.

Methods: A retrospective chart review was performed of consecutive pediatric patients aged 0–18 years, who underwent EGD between January and August 2014.

Results: During the study period, 547 EGD were performed on 478 children. The most frequent indications were suspected celiac disease, chronic non-specific abdominal pain, persistent Helicobacter pylori infection, and gastrointestinal hemorrhage. The yield of the diagnostic EGD was 59.2%, and the most common new diagnoses were celiac disease (28%), Helicobacter pylori-positive gastritis (16.5%), and Crohn’s disease (5.4%). Of the patients with documented follow-up, 74.1% reported improved symptoms. Procedures performed for chronic unexplained abdominal pain had significantly lower yields (26.2%) and only 39.3% improved at follow-up.

Conclusions: Our findings suggest a general high diagnostic yield for EGD in pediatric patients, stemming mainly from patients in whom a specific condition was suspected a priori. However, the role of the procedure in the diagnosis and management of non-specific gastrointestinal complaints was minor suggesting that EGD may be superfluous for some of these patients.

Background: Post-pericardiotomy syndrome (PPS) is a major cause of pericarditis, yet data on the risk of recurrence are limited, and the impact of steroids and colchicine in this context is unknown.

Objectives: To examine the effect of prednisone and colchicine on the rate of recurrence of PPS.

Methods: Medical files of patients diagnosed with PPS were reviewed to extract demographic, echocardiographic, X-ray imaging, and follow-up data.

Results: The study comprised 132 patients (57% men), aged 27–86 years. Medical treatment included prednisone in 80 patients, non-steroidal anti-inflammatory agents in 41 patients, colchicine monotherapy in 2 patients, and no anti-inflammatory therapy in 9 patients. Fifty-nine patients were given colchicine for prevention of recurrence. The patients were followed for 5–110 months (median 64 months). Recurrent episodes occurred in 15 patients (11.4%), 10 patients had a single episode, 4 patients had two episodes, and one patient had three episodes. The rate of recurrence was lower in patients receiving colchicine compared to patients who did not (8.5% vs. 13.7%), and in patients not receiving vs. receiving prednisone (7.7% vs. 13.8%) but the differences were non-significant. Twenty-three patients died and there were no recurrence-related deaths.

Conclusions: The rate of recurrence after PPS is low and multiple recurrences are rare. The survival of patients with recurrent PPS is excellent. Prednisone pre-treatment was associated with a numerically higher rate of recurrence and colchicine treatment with a numerically lower rate, but the differences were non-significant.

Background: Heart failure centers with specialized nurse-supervised management programs have been proposed to improve prognosis. The Heart Failure Center in Beit Shemesh, Israel, is located within a large primary care facility. The specialist team supervised the managememt of patients both within the frame of the center and while they were hospitalized.

Objectives: To evaluate the health services utilization by heart failure patients treated at a heart failure center and their clinical outcome.

Methods: In this retrospective study, we compared the clinical outcome of patients treated at a heart failure center to patients who received the standard care in 2013–2014. The clinical outcome included primary care visits, emergency room visits, hospitalizations, and death.

Results: The study comprised 430 heart failure patients; 82 were treated at the heart failure center and 348 under standard care. At baseline, no significant differences were seen in clinical parameters between the groups. Healthcare utilization was higher among the study group. No significant changes in healthcare utilization were found. During follow-up, patients treated in a heart failure center were more likely to get recommended heart failure medications. Mortality was significantly lower in patients treated in the heart failure center compared with those receiving standard care 3.6% vs. 24%, respectively (P = 0.001), hazard ratio 0.19, 95% confidence interval 0.06–0.62, P = 0.005.

Conclusions: Joint management of heart failure by primary clinics and a specialized community heart failure center reduced mortality. There was no decrease in healthcare utilizations among heart failure center patients, despite the reduction in mortality.

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

Falling from a height accounts for 14.1% of all hospital admissions for traumatic injury. In 5% of cases, the injury is severe or critical, and in 1.5%, it is fatal. The dangers of falling have been recognized since time immemorial. Indeed, the Bible instructs us to build a parapet around the roof of our home so that, “…you may not bring the guilt of bloodshed on your house if someone falls from it” (Deuteronomy 22:8). This commandment highlights the relatively simple and practical means by which we can prevent falls. It is also one of a series of ethical laws that are presented to help us understand and obey the larger Biblical precepts of loving one’s neighbor and guarding the sanctity of life. The concept teaches us that it is the responsibility of all individuals to be cognizant of others and to avoid harming people through negligence or carelessness. The aim of this article is to explain the commandment to build a parapet in the context of the risk of falling from a height and to expand on its wider implications. The present work was prompted in part by the alarming increase in fatal and near-fatal accidents in Israel in two particular populations.

Background: Anastomotic leakage (AL) is a major complication following colorectal surgery, with many risk factors established to date. The incidence of AL varies in the medical literature and is dependent on research inclusion criteria and diagnostic criteria.

Objectives: To determine the incidence of and the potential risk factors for AL following colorectal surgery at a single academic medical center.

Methods: We retrospectively reviewed all operative reports of colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center during 2012. AL was defined according to the 1991 United Kingdom Surgical Infection Study Group criteria. Data were assessed for leak incidence within 30 days. In addition, 17 possible risk factors for leakage were analyzed. A literature review was conducted.

Results: This cohort study comprised 260 patients, and included 261 procedures performed during the study period. The overall leak rate was 8.4%. In a univariate analysis, male sex (odds ratio [OR] 3.37, 95% confidence interval [95%CI] 1.21–9.43), pulmonary disease (OR 3.99, 95%CI 1.49–10.73), current or past smoking (OR 2.93, 95%CI 1.21–7.10), and American Society of Anesthesiologist score ≥ 3 (OR 3.08, 95%CI 1.16–8.13) were associated with an increased risk for anastomotic leakage. In a multivariate analysis, male gender (OR 3.62, 95%CI 1.27–10.33) and pulmonary disease (OR 4.37, 95%CI 1.58–12.10) were associated with a greater risk.

Conclusions: The incidence of AL in the present study is similar to that found in comparable series. Respiratory co-morbidity and male sex were found to be the most significant risk factors.

Background: The frequency of increased high-sensitivity C-reactive protein (hs-CRP) and the time course of evolution of their levels in patients with acute idiopathic pericarditis (AIP) are not well established.

Objective: To assess the time course of evolution of hs-CRP levels and the possible clinical significance of maximal hs-CRP levels in patients with AIP

Methods: We retrospectively reviewed the medical files of 241 patients admitted to the hospital with a diagnosis of AIP between March 2006 and March 2017. Data on demographics, time of symptom onset, laboratory and imaging findings, and outcome were collected.

Results: Data on serum hs-CRP levels were available for 225 patients (age 18–89 years, 181 men). Fever, pleural effusion, and age were independently associated with hs-CRP levels. Major cardiac complications (MCC) (death, cardiac tamponade, cardiogenic shock, large pericardial effusion, ventricular tachycardia, pericardiocentesis, or pericardiectomy) were more common in patients with hs-CRP levels above the median compared to those below (21.2% vs. 4.5%, respectively, P < 0.001). Hs-CRP levels were independently associated with MCC (odds ratio [OR] 1.071, 95% confidence interval [95%CI] 1.016–1.130, P = 0.011). Hs-CRP levels were elevated in 76.0%, 92.3% and 96.0% of the patients tested <6 hours, 7-12 hours, and >12 hours of symptom onset, respectively (P = 0.003). The frequency of elevated hs-CRP among patients tested > 24 hours was 98.1%.

Conclusions: Hs-CRP levels rise rapidly among patients with AIP. Maximal hs-CRP levels are associated with MCC. A normal hs-CRP level is rare among patients tested > 24 hours of symptom onset.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated.

Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL.

Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment.

Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4–22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001).

Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Background: Cryptosporidium is a major threat to water supplies worldwide. Various biases and obstacles in case identification are recognized. In Israel, Cryptosporidiosis was included among notifiable diseases in 2001 in order to determine the burden of parasite-inflicted morbidity and to justify budgeting a central drinking water filtration plant.

Objective: To summarize the epidemiologic features of 14 years of Cryptosporidium surveillance and to assess the effects of advanced water purification treatment on the burden of disease.

Methods: From 2001 to 2014, a passive surveillance system was used. Cases were identified based on microscopic detection in stool samples. Confirmed cases were reported electronically to the Israeli Ministry of Health. Overall rates as well as age, gender, ethnicity and specific annual incidence were calculated per 100,000 population in five age groups: 0–4, 5–14, 15–44, 45–64, > 65 years.

Results: A total of 522 Cryptosporidium cases were reported in all six public health districts. More cases were detected among Jews and among males, and mainly in young children, with a seasonal peak during summer. The Haifa sub-district reported 69% of the cases. Most were linked to an outbreak from the summer of 2008, which was attributed to recreational swimming pool activity. Cases decreased after installation of a central filtration plant in 2007.

Conclusions: As drinking water in Israel is treated to maximal international standards, the rationale for further inclusion of Cryptosporidium among mandatory notifiable diseases should be reconsidered. Future surveillance efforts should focus on timely detection of outbreaks using molecular high-throughput testing.

Background: Congenital factor VII deficiency is a rare recessive autosomal bleeding disorder with a wide spectrum of clinical manifestations.

Objectives: To compare the clinical and laboratory findings in Jewish and Bedouin patients with factor VII deficiency.

Methods: The clinical and laboratory findings of patients with factor VII deficiency treated at Soroka Medical Center, a tertiary hospital in Israel, from 2005 to 2015 were analyzed regarding blood factor levels, illness severity, treatment administration, and disease outcome.

Results: Seventy-eight patients were enrolled (1:13,000 of the population in southern Israel) of whom 26 were diagnosed with severe factor VII deficiency (1:40,000). Sixty (76.9%) patients were Jewish and 18 (23.1%) were Bedouin. In univariable analysis, Bedouin patients exhibited a more severe illness, with significantly higher complication and fatality rates, and required more preventive treatment than the Jewish patients.

Conclusions: The prevalence of congenital factor VII deficiency (including severe deficiency) in the Jewish and Bedouin populations of southern Israel is higher than previously reported. The clinical spectrum of the disease was found to be more severe in the Bedouin population.