Israel Medical Association Journal

Background: The recreational use of nitrous oxide (N₂O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy.

Objectives: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel.

Methods: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments.

Results: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections.

Conclusions: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.

Background: Obliterative vaginal procedures may offer lower perioperative morbidity and equal success rates as reconstructive procedures for frail and elderly women who no longer desire future coital function. The combination of vaginal hysterectomy with either reconstructive or obliterative vaginal procedures has not yet been investigated.

Objectives: To compare peri- and postoperative outcomes of vaginal hysterectomy with pelvic floor reconstruction (VHR) vs. vaginal hysterectomy with colpocleisis (VHC).

Methods: We conducted a retrospective study comparing medical and surgical data of patients undergoing either VHR or VHC between 2006 and 2015. Data were obtained from inpatient and outpatient medical records including peri- and postoperative course, as well as long-term (24 months) follow-up data.

Results: We identified 172 patients who underwent VHR and 44 who underwent VHC. Patients in the VHC group were significantly older (71.3 ± 4.5 vs. 68.6 ± 6.5 years, P = 0.01), and more likely to have medical co-morbidities (P = 0.001 and P = 0.029, respectively). Patients in the VHC group experienced shorter operative time (2.3 ± 0.58 vs. 2.7 ± 1.02 hours, P = 0.007), lower perioperative blood loss (P < 0.0001), shorter hospital stay (P < 0.0001), and lower rates of postoperative urinary retention. Long-term pelvic organ prolapse (POP) recurrence rates were significantly higher among the VHR group. Postoperative resolution of both stress urinary incontinence and overactive bladder were common in both groups.

Conclusions: VHC is associated with lower perioperative blood loss, shorter operative time, shorter hospital stay, shorter time with an indwelling catheter, and lower long-term objective POP recurrence rates.

Background: Vaginal hysterectomy (VH) and colpocleisis are both used for the treatment of advanced pelvic organ prolapse (POP).

Objective: To compare short- and long-term outcomes of vaginal hysterectomy vs. colpocleisis for advanced POP.

Methods: Hospital and outpatient charts of patients who underwent VH or colpocleisis at our institution between January 2006 and December 2015 were reviewed. Clinical data were obtained and analyzed.

Results: In this study, 188 patients underwent VH and 32 patients underwent colpocleisis. The colpocleisis group was significantly older than the VH group (79.5 ± 4.5 vs. 69 ± 6.1 years respectively, P < 0.0001) and presented with significantly higher co-morbidity rates and a higher degree of POP. Perioperative blood loss was significantly lower (250 ± 7.6 ml vs. 300 ± 115 ml, P < 0.0001) and postoperative hospitalization was significantly shorter (2 ± 2.7 vs. 3 ± 2.2 days, P = 0.015) among the colpocleisis group. None of the patients from the colpocleisis group required an indwelling urethral catheter after discharge, compared to 27.5% of the patients from the VH group (P = 0.001). Total postoperative complication rate was significantly lower among the colpocleisis group (25% vs. 31% P < 0.0001). Objective recurrence of POP was significantly more common among the VH group (7% vs. 0% and 21% vs. 0% for the anterior and posterior compartments, respectively, P = 0.04).

Conclusions: Colpocleisis is associated with faster recovery, lower perioperative morbidity, and higher success rates than VH and should be considered for frail and elderly patients.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06–5.6, P = .036) for patients with moderate to severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: The most common complication after tonsillectomy is bleeding. We investigated whether performing the procedure during the summer or the winter affects the bleeding rate.

Objectives: To investigate whether there is an association between meteorological conditions and the occurrence of post-tonsillectomy hemorrhage (PTH) in the southern Israel Negev region.

Methods: All patients who underwent tonsillectomy from 2001–2013 at the Soroka Medical Center were included. We collected patient demographic data and indications for surgery. Meteorological data were obtained from a weather station operated by the Israel Ministry of Environmental Protection.

Results: Of 4438 patients who underwent tonsillectomy, with or without adenoidectomy, 432 (9.73%) experienced hemorrhage. Patients who suffered from PTH were significantly older: median age 9.61 years vs.4.7 years, P < 0.0001. When comparing patients without PTH to those who bled within 0–3 days after surgery, there was a higher risk for bleeding during the warmer seasons: relative risk (RR) 1.38, 95% confidence interval ([95%CI] 1.07–1.77), RR 1.45 (95%CI 1.17–1.80), and 1.62 (95%CI 1.27–2.06) comparing the winter to spring, summer, and fall, respectively. A statistically significant positive association was also found with the average temperature on the day of surgery. Bleeding more than 3 days after surgery was less likely in summer: RR 0.82, 95%CI 0.69–0.97. We found no association with temperature on the day of surgery and PTH after postoperative day 3.

Conclusions: Seasonality, and to an extent temperature, seem to play only a minor role in PTH.

Background: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.

Objectives: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.

Methods: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.

Results: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958–2.682, respectively) with ESBL colonization.

Conclusions: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Mechanical thrombectomy with stent retrievers is now the reference therapy for acute ischemic stroke (AIS) in the anterior circulation in association with thrombolysis. We conducted an extensive systematic review and meta-analysis to evaluate the clinical and angiographic outcomes of stent-retriever thrombectomy in patients with acute anterior circulation stroke. Available literature published to date on observational studies and three randomized trials (MR CLEAN, ESCAPE, and EXTEND-IA) involving the stent-retriever device were reviewed. Successful recanalization and favorable clinical outcome were defined by a TICI ≥ 2b and modified Rankin Scale score of ≤ 2 at 90 days following AIS, respectively. A total of 2067 patients harboring an anterior circulation stroke were treated with a stent retriever: 433 patients from 3 randomized trials involving the device and 1634 patients from observational studies. Mean NIH Stroke Scale score on admission was 16.6, and mean time from onset to recanalization was 300 minutes. Successful recanalization was achieved in 82% (95%CI 77–86, 31 studies). The 90 day favorable outcome was achieved in 47% (95%CI 42–5.2, 34 studies) with an overall mortality rate of 17% (95%CI 13–20, 31 studies). Symptomatic intracerebral hemorrhage was identified in 6% (95%CI 4–8, 32 studies). In patients with AIS caused by a proximal intracranial occlusion of the anterior circulation, stent-retriever thrombectomy is safe and restores brain reperfusion in four of five treated patients, allowing favorable clinical outcome in one of two AIS patients with large vessel occlusion. 

Background: Children dependent on gastrostomy tube feeding and those with extremely selective eating comprise the most challenging groups of early childhood eating disorders. We established, for the first time in Israel, a 3 week intensive weaning and treatment program for these patients based on the "Graz model."

Objectives: To investigate the Graz model for tube weaning and for treating severe selective eating disorders in one center in Israel. 

Methods: Pre-program assessment of patients’ suitability to participate was performed 3 months prior to the study, and a treatment goal was set for each patient. The program included a multidisciplinary outpatient or inpatient 3 week treatment course. The major outcome measures were achievement of the target goal of complete or partial tube weaning for those with tube dependency, and expansion of the child's nutritional diversity for those with selective eating. 

Results: Thirty-four children, 28 with tube dependency and 6 with selective eating, participated in four programs conducted over 24 months. Their mean age was 4.3 ± 0.37 years. Of all patients, 29 (85%) achieved the target goal (24 who were tube-dependent and 5 selective eaters). One patient was excluded due to aspiration pneumonia. After 6 months follow-up, 24 of 26 available patients (92%) maintained their target or improved. 

Conclusions: This intensive 3 week program was highly effective in weaning children with gastrostomy tube dependency and ameliorating severe selective eating. Preliminary evaluation of the family is necessary for completion of the program and achieving the child’s personal goal, as are an experienced multidisciplinary team and the appropriate hospital setup, i.e., inpatient or outpatient. 

 

Objectives: To describe the phenotypic and genotypic features in five Bulgarian Jewish patients, from different families, with autosomal dominant OPMD.

Methods: We performed clinical follow-up, electrodiagnostic tests and mutation detection. Blood samples were obtained after informed consent and DNA was extracted; measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD mutations were performed according to standard techniques.

Results: We identified five patients (four females), aged 58 to 71 years, with bilateral ptosis, dysphagia, dysphonia (n=3) and myopathic motor units by electromyography. In all patients we noticed proximal weakness of the upper limbs with winging scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.

Conclusions: OPMD among Bulgarian Jews is produced by a (GCG)13 expansion, identical to the mutation in Uzbek Jews and French Canadians. In addition to the classical neurological and neuro-ophthalmological features, early shoulder girdle weakness is common in Bulgarian Jewish patients; this is an unusual feature during the early stages of OPMD produced by the same mutation in other populations. We suggest that besides the disease-producing GCG expansion, additional ethnicity-related genetic factors may influence the OPMD phenotype. OPMD is a rare disease, and the identification of five affected families in the rather small Bulgarian Jewish community in Israel probably represents a new cluster; future haplotype studies may elucidate whether a founder effect occurred. 

Background: Type 1 diabetes in humans is an autoimmune disease in which T cells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulin-producing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potential vanilloid receptor-1 (TRPV1) gene.

Objectives: To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes.

Methods: We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M315I), rs224534 (T469I) and rs8065080 (I585V) variants of the TRPV1 gene.

Results: There was a significant increase in the rs222747 (M315I) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M315I) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type1 diabetes was significantly associated with rs222747 (M315I), such that having diabetes increased the odds of rs222747 homozygosity (M315I) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08–2.57, P < 0.02. No difference was found in the rs224534 (T469I) and rs8065080 (I585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases.

Conclusions: Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.

Objectives: To assess the ability of perfusion-weighted imaging to differentiate between high grade gliomas and brain metastases.

Methods: During 5 months, 21 patients (age 40–85, median age 61, 16 males and 5 females) with either glioblastoma multiforme (GBM) or metastasis (pathology proven), underwent MRI for assessment of the tumor prior to surgery. Most of the scans were done at 3 Tesla. The scans included perfusion-weighted imaging sequences. Perfusion in the tumor, in the peritumoral edema and in normal tissue were assessed using Functool® software. The ratios of tumor perfusion and peritumoral edema perfusion to normal tissue perfusion were calculated and compared.

Results: Bleeding artifact precluded perfusion assessment in four patients. There was no statistically significant difference between the tumor perfusion ratios of high grade gliomas and those of metastases. The edema perfusion ratios were higher in GBM than in metastases (P = 0.007).

Conclusions: Perfusion-weighted imaging of peritumoral edema can help to differentiate between GBM and metastases.

Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid.

Objectives: To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel.

Methods: We evaluated eight patients clinically and genetically during the years 2006 to 2011.

Results: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation.

Conclusions: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.  
 

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.