Israel Medical Association Journal

Familial spastic paraparesis is a non-progressive disorder. However, clinical experience shows that after trauma, disease, surgery, or limb fracture that force a patient's long immobilization, a significant functional deterioration is observed. I describe two patients with Silver syndrome who experienced such functional deterioration after sustaining a simple fracture. A description of Silver syndrome and a biographical sketch of Dr. Silver, who explained the disorder in 1966, are given.

Background: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

Objectives: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest©.

Methods: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two‐dimensional SWE or FibroTest©; APRI and FIB-4 scores.

Results: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6–33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5–100), 13.4 kPa (range 5.5–51) at 6 months, and 11.4 kPa (range 6.1–35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

Conclusions: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis

Background: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable.

Objectives: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005.

Methods: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007.

Results: The INCR’s completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005.

Conclusions: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

Background: Patients with critical limb ischemia (CLI) involving the below-the-knee (BTK) arteries are at increased risk of limb loss. Despite improvement in endovascular modalities, it is still unclear whether an aggressive approach results in improved limb salvage.

Objectives: To assess whether an aggressive approach to BTK arterial disease results in improved limb salvage.

Methods: A comparative study of two groups was conducted. Group 1 included patients treated between 2012 and 2014, primarily with transfemoral angioplasty of the tibial arteries. Group 2 included patients treated between 2015–2019 with a wide array of endovascular modalities (stents, multiple tibial artery and pedal angioplasty, retrograde access). Primary endpoint was freedom from amputation at 4 years.

Results: A total of 529 BTK interventions were performed. Mean age was 71 ± 10.6 years, 382 (79%) were male. Patients in group 1 were less likely to be taking clopidogrel (66% vs. 83%, P < 0.01) and statins (72 % vs. 87%, P < 0.01). Several therapeutic modalities were used more often in group 2 than in group 1, including pedal angioplasty (24 vs. 43 %, P = 0.01), tibial and pedal retrograde access (0 vs. 10%, P = 0.01), and tibial stenting (3% vs. 25%, P = 0.01). Revascularization of two or more tibial arteries was performed at a higher rate in group 2 (54% vs. 50%, P = 0.45). Estimated freedom from amputation at 40 months follow-up was higher in group 2 (53% vs. 63%, P = 0.05).

Conclusions: An aggressive, multimodality approach in treating BTK arteries results in improved limb salvage.

Background: Lung cancer is the most common cause of cancer-related death.

Objectives: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period.

Methods: Primary lung cancers, all types and all stages, diagnosed during 1990–2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence.

Results: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005–2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients.

Conclusions: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.

Background: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is associated with decreased perioperative morbidity and mortality.

Objectives: To report the outcomes of EVAR among patients older than 80 years of age.

Methods: In this retrospective study, we reviewed patients older than 80 years of age who underwent elective EVAR at our institution between 2007 and 2017. The demographics, perioperative morbidity and mortality, and long-term results are reported.

Results: During the study period, 444 patients underwent elective EVAR for AAAs. Among them 128 patients (29%) were > 80 years of age. Mean age was 84 ± 3.4 (range 80–96) years, and 110 patients (86%) were male. The EVAR was technically successful in 127 patients (99%) and there were intraoperative mortalities. Within 30 days of the surgery, nine patients (7%) died. Major and minor adverse events occurred in 26 (20%) and 59 (46%) patients, respectively. Factors associated with increased risk of perioperative morbidity and mortality included chronic kidney disease, peripheral artery disease, and the existence of three or more co-morbidities.

Conclusions: EVAR in the elderly can be performed with a high rate of success; however, it is associated with a substantial rate of morbidity and mortality, particularly when patients present with multiple co-morbidities. When performing EVAR in this population group, the risk of rupture must be considered opposed to the life expectancy of these patients and the risk of perioperative morbidity and mortality.

Background: The number of cancer survivors has been increasing worldwide and is now approximately 32.6 million and growing. Cancer survivors present a challenge to health care providers because of their higher susceptibility to long-term health outcomes related to their primary disease and treatment.

Objective: To report on the number of cancer survivors and incident cancer cases in the period 1960–2009 in Israel, in order to provide data on the scope of the challenge Israel’s health care funds face.

Methods: The Israel National Cancer Registry (INCR) database was used to identify new cancer cases diagnosed during the period 1960–2009. Lifetable analysis was used to assess changes in cumulative survival and population prevalence of cancer survivors throughout the 50 year study period.

Results: Almost 600,000 invasive cancer cases were diagnosed during the period 1960–2009 (overall absolute survival rate 54%). Within this time period, the number of new patients diagnosed with cancer increased fivefold and that of cancer survivors ninefold. The absolute survival of cancer patients and the prevalence of cancer survivors in the general population significantly increased with time from 34% and 0.5%, respectively (1960–1969), to 62% and 1.9%, respectively (2000–2009). Cumulative absolute survival for 5, 10 and 15 years following diagnosis increased with time as well.

Conclusions: The INCR database is useful to assess progress in the war against cancer. The growing numbers of cancer survivors in Israel present a challenge to the national health and social services system.

Objectives: To describe a single-center experience with fenestrated and branched endografts for the treatment of complex aortic aneurysms.

Methods: We reviewed all cases of complex aortic aneurysms treated with branched or fenestrated devices in our center. Data collected included device specifics, perioperative morbidity and mortality, re-intervention rates and mid-term results.

Results: Between 2007 and 2012 nine patients were treated with branched and fenestrated stent grafts. Mean age was 73 years. Mean aneurysm size was 63 mm. Perioperative mortality was 22% (2/9). During the follow-up, re-interventions were required in 3 patients (33%). Of 34 visceral artery branches 33 remained patent, resulting in a patency rate of 97%. Sac expansion was seen in a single patient due to a large endoleak. No late aneurysm- related deaths occurred.

Conclusions: Branched and fenestrated stent grafts are feasible and relatively safe alternatives for the treatment of complex aortic aneurysms involving the visceral segment. Further research is needed to determine the long-term durability of this new technology. 

Objectives: To assess the results of endovascular revascularization for lower extremity ischemia in dialysis patients.

Methods: We conducted a retrospective review of all dialysis patients who underwent endovascular treatment for critical limb ischemia (CLI) in our institution between 2007 and 2011. Data collected included comorbidities, clinical presentation, anatomic distribution of vascular lesions, amputation and survival rates.

Results: We identified 50 limbs (41 patients). Indications included: gangrene in 22%, non-healing wounds in 45%, rest pain in 31%, and debilitating claudication in 4%. Mean follow-up was 12 months (1–51 months). Nineteen patients required amputations. Freedom from amputation at 5 years was 40%. Factors associated with amputation included non-healing wounds or gangrene (68% and 36% respectively) and diabetes (P < 0.05). The survival rate was 80% after 5 years.

Conclusions:  Despite improvement in endovascular techniques for lower extremity revascularization, the incidence of limb salvage among dialysis patients remains poor, resulting in a high rate of major amputations. 

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 present the feasibility and safety of DSMR in Israel.

Methods: Thirty patients with suspected or known CAD were studied. DSMR images were acquired during short breath-holds in three short axis views and four-, two-, and three-chamber views. Patients were examined at rest and during a standard dobutamine-atropine protocol. Regional wall motion was assessed in a 16-segment model and the image quality was evaluated using a four-point scale for the visibility of the endocardial border.

Results: In 28 patients (93.4%) DSMR was successfully performed and completed within an average of 55 ± 6 minutes. One patient could not be examined because of claustrophobia and another patient, who was on beta-blockers, did not reach the target heart rate. Image quality was excellent and there was no difference between the rest and stress images in short axis (3.91 ± 0.29 vs. 3.88 ± 0.34, P = 0.13, respectively) and long axis (3.83 ± 0.38 vs. 3.70 ± 0.49, P = 0.09, respectively) views. Segmental intra-observer agreement for wall motion contractility at rest and stress cine images was almost perfect (κ = 0.88, 95% confidence interval = 0.93–0.84, and κ = 0.82, 95% CI = 0.88–0.76) respectively. No serious side effects were observed during DSMR.

Conclusion: The present study confirms the feasibility, safety and excellent image quality of DSMR for the diagnosis of coronary artery diseases.

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.