Israel Medical Association Journal

Background: Pregnant women with Marfan syndrome (MS) have a high risk of aortic dissection around delivery and their optimal management requires a multi-disciplinary approach, including proper cardio-obstetric care and adequate pain management during labor, which may be difficult due to the high prevalence of dural ectasia (DE) in these patients.

Objectives: To evaluate the multidisciplinary management of MS patients during labor.

Methods: Nineteen pregnant women (31 pregnancies) with MS were followed by a multi-disciplinary team (cardiologist, obstetrician, anesthesiologist) prior to delivery.

Results:^. Two patients had kyphoscoliosis; none had previous spine surgery nor complaints compatible with DE. In eight pregnancies (7 patients), aortic root diameter (ARd) before pregnancy was 40 to 46 mm. In this high-risk group, one patient underwent elective termination, two underwent an urgent cesarean section (CS) under general anesthesia, and five had elective CS; two under general anesthesia (GA), and three under spinal anesthesia. In 23 pregnancies (12 patients), ARd was < 40 mm. In this non-high-risk group three pregnancies (1 patient) were electively terminated. Of the remaining 20 deliveries (11 patients), 14 were vaginal deliveries, 9 with epidural analgesia and 5 without. Six patients had a CS; four under GA and two2 under spinal anesthesia. There were no epidural placement failures and no failed responses. There were 2 cases of aortic dissection, unrelated to the anesthetic management.

Conclusions: The optimal anesthetic strategy during labor in MS patients should be decided by a multi-disciplinary team. Anesthetic complications due to DE were not encountered during neuraxial block

Background: Consent rates for organ donation remain one of the most important factors determining the number of organs available for transplantation. Trauma casualties constitute a substantial part of the deceased organ donor pool and have unique characteristics that distinguish them from the general donor population. However, this group has not been extensively studied.

Objectives: To identify donor factors associated with positive familial consent for solid organ donation among trauma casualties.

Methods: This retrospective study included all trauma casualties who were admitted to the Rabin Medical Center, Beilinson hospital, during the period from January 2008 to December 2017, who were potential organ donors. Data collected included demographic features, the nature of the injury, surgical interventions, and which organs were donated. Data was collected from the Rabin Medical Center Trauma Registry.

Results: During the study period 24,504 trauma patients were admitted and 556 died over their hospital course. Of these 76 were potential donors, of whom 32 became actual donors and donated their organs. Two factors showed a statistically significant correlation to donation, namely female gender (P = 0.018) and Jewish religion of the deceased (P = 0.032).

Conclusions: Only a small group of in hospital trauma deaths were potential solid organ donors (13.7%) and less than half of these became actual donors. Consent rates were higher when the deceased was female or Jewish

Background: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines.

Objectives: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel.

Methods: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result.

Results: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment.

Conclusions: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

Background: Dependence on technology and electronic media devices (EMDs) is a significant phenomenon of modern life with many people experiencing adverse symptoms during abstention. Orthodox Jews abstain from using all forms of EMDs for 25 consecutive hours every week on the Sabbath but do not appear to experience significant adverse reactions during this abstention.

Objectives: To better examine whether Sabbath observant Jews experience fewer and less severe adverse symptoms while abstaining from EMDs on the Sabbath compared to weekdays.

Methods: Ten Sabbath observant Jews abstained from using all forms of EMDs for 25 hours on a Sabbath and again on a weekday. At the end of each 25-hour period participants completed a 12-item Likert-type scale self-assessment of 1–5, once as a report of their condition at 10:00 and again after 25 hours of abstaining. The authors compared the mean results of Sabbath and weekday using Wilcoxon signed ranks test. P ≤ 0.05 was considered significant.

Results: Overall, discomfort on Sabbath was less than on weekdays. A statistically significant decrease on the Sabbath was found at both the 10:00 reporting time and after 25 hours in anxiety, restlessness, thoughts and plans of using devices, and overall difficulty to abstain. Significance was found for feelings of not knowing what to do with time (10:00) and moodiness and irritability, being drawn to devices, and cravings achieved significance (after 25 hours).

Conclusions: Sabbath observant Jews reported statistically significant less adverse reactions while abstaining from EMDs on the Sabbath compared to on a weekday.

Background: Survivors of acute myocardial infarction (AMI) are at increased risk for recurrent cardiac events and tend to use excessive healthcare services, thus resulting in increased costs.

Objectives: To evaluate the disparities in healthcare resource utilization and costs throughout a decade following a non-fatal AMI according to sex and ethnicity groups in Israel.

Methods: A retrospective study included AMI patients hospitalized at Soroka University Medical Center during 2002–2012. Data were obtained from electronic medical records. Post-AMI annual length of hospital stay (LOS); number of visits to the emergency department (ED), primary care facilities, and outpatient consulting clinics; and costs were evaluated and compared according sex and ethnicity groups.

Results: A total of 7685 patients (mean age 65.3 ± 13.6 years) were analyzed: 56.8% Jewish males (JM), 26.6% Jewish females (JF), 12.4% Bedouin males (BM), and 4.2% Bedouin females (BF). During the up-to 10-years follow-up (median 5.8 years), adjusted odds ratios [AdjOR] for utilizations of hospital-associated services were highest among BF (1.628 for LOS; 1.629 for ED visits), whereas AdjOR for utilization of community services was lowest in BF (0.722 for primary clinic, 0.782 for ambulatory, and 0.827 for consultant visits), compared with JM. The total cost of BF was highest among the study groups (AdjOR = 1.589, P < 0.01).

Conclusions: Long-term use of hospital-associated healthcare services and total costs were higher among Bedouins (especially BF), whereas utilization of ambulatory services was lower in these groups. Culturally and economically sensitive programs optimizing healthcare resources utilization and costs is warranted.

Background: Asthma is a common respiratory disease, which is linked to air pollution. However, little is known about the effect of specific air pollution sources on asthma occurrence.

Objective: To assess individual asthma risk in three urban areas in Israel characterized by different primary sources of air pollution: predominantly traffic-related air pollution (Tel Aviv) or predominantly industrial air pollution (Haifa bay area and Hadera). 

Methods: The medical records of 13,875, 16- 19-year-old males, who lived in the affected urban areas prior to their army recruitment and who underwent standard pre-military health examinations during 2012–2014, were examined. Nonparametric tests were applied to compare asthma prevalence, and binary logistic regressions were used to assess the asthma risk attributed to the residential locations of the subjects, controlling for confounders, such as socio-demographic status, body mass index, cognitive abilities, and education.

Results: The asthma rate among young males residing in Tel Aviv was 8.76%, compared to 6.96% in the Haifa bay area and 6.09% in Hadera. However, no statistically significant differences in asthma risk among the three urban areas was found in controlled logistic regressions (P > 0.20). This finding indicates that exposure to both industrial- and traffic-related air pollution is associated with asthma prevalence.

Conclusions: Both industrial- and traffic-related air pollution have a negative effect on asthma risk in young males. Studies evaluating the association between asthma risk and specific air pollutants (e.g., sulfur dioxide, particulate matter, and nitrogen dioxide) are needed to ascertain the effects of individual air pollutants on asthma occurrence. 

 

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: 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: The salutary effects of statin therapy in patients with cardiovascular disease (CVD) are well established. Although generally considered safe, statin therapy has been reported to contribute to induction of diabetes mellitus (DM).

Objectives: To assess the risk-benefit of statin therapy, prescribed for the prevention of CVD, in the development of DM.

Methods: In a population-based real-life study, the incidence of DM and CVD were assessed retrospectively among 265,414 subjects aged 40–70 years, 17.9% of whom were treated with statins. Outcomes were evaluated according to retrospectively determined baseline 10 year cardiovascular (CV) mortality risks as defined by the European Systematic COronary Risk Evaluation, statin dose-intensity regimen, and level of drug adherence.

Results: From 2010 to 2014, 5157 (1.9%) new cases of CVD and 11,637 (4.4%) of DM were observed. Low-intensity statin therapy with over 50% adherence was associated with increased DM incidence in patients at low or intermediate baseline CV risk, but not in patients at high CV risk. In patients at low CV risk, no CV protective benefit was obtained. The number needed to harm (NNH; incident DM) for low-intensity dose regimens with above 50% adherence was 40. In patients at intermediate and high CV risk, the number needed to treat was 125 and 29; NNH was 50 and 200, respectively.

Conclusions: Prescribing low-dose statins for primary prevention of CVD is beneficial in patients at high risk and may be detrimental in patients at low CV risk. In patients with intermediate CV risk, our data support current recommendations of individualizing treatment decisions.

Background: Previous studies have demonstrated the utility of exercise hemodynamics during right heart catheterization (RHC) in the diagnosis of diastolic dysfunction (DD). Little data exists regarding exercise hemodynamics during RHC in symptomatic systemic sclerosis (SSc) patients. 

Objectives: To assess the added diagnostic value of using exercise hemodynamics during RHC in assessment of patients with symptomatic SSc.

Methods: We performed 22 RHCs in 17 SSc patients with dyspnea and/or pulmonary arterial hypertension (PAH). Exercise was performed in 15 RHCs using isotonic arm exercises while holding a 1 kg weight in each hand. Measurements of pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), and cardiac output (CO) were taken at rest and during peak exercise. 

Results: Normal resting RHC (PAP 22 ± 3 mmHg, PAWP 11 ± 3 mmHg) was found in seven cases. Of these, exercise induced elevation in PAP was found in three (38 ± 7 mmHg), and exercise induced elevation in PAWP was found in four (24 ± 6 mmHg). Elevated resting PAP was found in 15 (41 ± 11 mmHg) with minor changes in exercise. Of the 22 RHCs, elevation of the PAWP was found in 11 (50%), half of which were in response to exercise. 

Conclusions: In symptomatic SSc patients, exercise hemodynamics provides important information on diastolic dysfunction that is not available with non-invasive testing. Findings on exercise RHC can explain patient symptoms in up to 50% of cases. Earlier and more accurate diagnosis of patient symptoms can aid in tailoring the correct therapy for each.

A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren’s syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed. The pattern of beat-to-beat blood pressure associated with performance of the Valsalva maneuver, and a low plasma norepinephrine level that did not increase in response to standing, established that the orthostatic hypotension was neurogenic. Treatment with an alpha-adrenoceptor agonist and fludrocortisone yielded partial improvement. After systemic diseases involving autonomic failure were excluded, cardiac sympathetic neuroimaging was performed by ¹²³I-metaliodobenzylguanidine (MIBG) scanning. The normal uptake seen in the heart indicated intact post ganglionic sympathetic innervation. There were no signs of central neurodegeneration or peripheral neuropathy. Because of symptoms and signs of both parasympathetic and sympathetic failure without denervation, an autonomic ganglionopathy was considered. A high titer of antibody to the neuronal nicotinic receptor, which mediates ganglionic neurotransmission, was obtained. The diagnosis of autoimmune autonomic ganglionopathy (AAG) was made, and the management strategy shifted to first lowering the antibody burden by plasma exchanges and then instituting chronic anti-autoimmune treatment with rituximab and a low dose of cortiosteroid. The patient showed remarkable improvement.

Background: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs).

Objectives: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. 

Methods: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded.

Results: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6–12 months follow-up. 

Conclusions: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.

 

Background: Trauma is the leading cause of childhood morbidity and mortality. Abdominal bleeding is one of the common causes of mortality due to trauma. Angiography and embolization are well recognized as the primary treatments in certain cases of acute traumatic hemorrhage in adults; however, evidence is lacking in the pediatric population. 

Objectives: To assess the safety and efficacy of transcatheter arterial embolization (TAE) for blunt and penetrating abdominal and pelvic trauma in the pediatric age group.

Methods: Three children with blunt abdominal trauma and one child with iatrogenic renal injury (age 4–13 years) were managed with TAE for lacerated liver (one patient), pelvic fractures (one patient) and renal injuries (two patients). The first two patients, victims of road accidents, had multisystem injuries and were treated by emergency embolization after fluid resuscitation in the Emergency Department (ED). The other two patients had renal injuries: a 4 year old boy with blunt abdominal trauma was diagnosed on initial computed tomography with an unexpected Wilms tumor and was treated with embolization 1 day after admission due to hemodynamic deterioration caused by active arterial tumor bleeding. The following day he underwent successful nephrectomy. The other patient was 13 year old boy with nephrotic syndrome who underwent renal biopsy and developed hemodynamic instability. After fluid resuscitation, he underwent an initial negative angiography, but second-look angiography the following day revealed active bleeding from an aberrant renal artery, which was then successfully embolized.

Results: In all four patients, TAE was diagnostic as well as therapeutic, and no child required surgical intervention for control of bleeding.

Conclusions: We propose that emergency transcatheter angiography and arterial embolization be considered following resuscitation in the ED as initial treatment in children with ongoing bleeding after blunt abdominal trauma or iatrogenic renal injury. Implementation of this policy demands availability and cooperation of the interventional radiology services.