Israel Medical Association Journal

Background: The lack of organs for liver transplantation has prompted transplant professionals to study potential solutions, such as the use of livers from donors older than 70 years. This strategy is not widely accepted because potential risks of vascular and biliary complications and recurrence of hepatitis C.

Objectives: To examine the efficacy and safety of liver grafts from older donors for transplantation.

Methods: A retrospective analysis of data on 310 adults who underwent deceased donor liver transplantation between 2005 and 2015 was conducted. We compared graft and recipient survival, as well as major complications, of transplants performed with grafts from donors younger than 70 years (n=265, control group) and those older than 70 years (n=45, older-donor group), followed by multivariate analysis, to identify risk factors.

Results: There was no significant difference between the control and older-donor group at 1, 5, and 10 years of recipient survival (79.5% vs. 73.3%, 68.3% vs. 73.3%, 59.2% vs. 66.7%, respectively) or graft survival (74.0% vs. 71.0%, 62.7% vs. 71.0%, 54.8% vs. 64.5%, respectively). The rate of biliary and vascular complications was similar in both groups. Significant risk factors for graft failure were hepatitis C (hazard ratio [HR] = 1.92, 95% confidence interval [95%CI] 1.16–2.63), older donor age (HR = 1.02, 95%CI 1.007–1.031), and male gender of the recipient (HR = 1.65, 95%CI 1.06–2.55).

Conclusion: Donor age affects liver graft survival. However, grafts from donors older than 70 years may be equally safe if cold ischemia is maintained for less than 8 hours.

Background: Leukoplakia of the vocal cords may represent a pre-cancerous lesion of the larynx. The management of cases of recurrent leukoplakia with pathologically proven dysplasia is still controversial.

Objectives: To present a series of patients with recurrent vocal cord leukoplakia and to examine their malignant transformation rate in relation to the clinical characteristics, risk factors, and histological findings.

Methods: A retrospective cohort study was conducted between 1999 and 2017. The study comprised 52 patients with recurrent leukoplakia of the vocal cords who required ≥ 2 direct laryngeal procedures within a minimum of 3 months between each procedure. Malignant transformation rate over follow-up period, risk factors for malignant transformation, and interval to develop laryngeal squamous cell carcinoma were investigated.

Results: All patients presented with hoarseness. An average of three procedures per patient was performed (range 2–13). Ten male patients (19.2%) developed squamous cell carcinoma. Of these, four with severe dysplasia developed SCC within 19 months of the first direct laryngoscopy. In the six other patients, SCC developed within an average of 3.7 years. The follow-up period ranged from 9–253 months (mean 109 months). Heavy smoking and severe dysplasia in the first biopsy were found to be significant risk factors for developing squamous cell carcinoma, as was male gender.

Conclusions: We showed an increased malignant transformation rate in recurrent leukoplakia cases among heavy smokers and male patients. In addition, severe dysplasia at initial diagnosis was a risk factor for SCC development. Close follow-up of patients with recurrent leukoplakia is warranted.

Background: Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often advised prior to radical orchiectomy. However, whether affected testes contribute to fertility is unclear.

Objectives: To determine whether maximal tumor diameter (MTD) is correlated with ipsilateral fertility (IF) in patients treated for GCT.

Methods: We reviewed medical charts for demographic and clinical data of patients with GCT who had undergone orchiectomy at our institution between 1999 and 2015. The extent of spermatogenesis was categorized into three groups: full spermatogenesis, hypospermatogenesis, and absence of spermatogenesis. The presence of mature spermatozoa in the epididymis tail was also assessed. We defined IF as the combination of full spermatogenesis in more than 100 tubules and the presence of mature spermatozoa in the epididymis tail. Mann–Whitney was applied to determine the correlation between MTD and IF.

Results: Of 57 patients, IF was present in 28 (49%). Mean patient age was 32.8 years in patients with positive IF and 33.4 years those with negative IF. Seminoma was diagnosed in 46.4% of patients with positive IF and in 65.5% of patients with negative IF. Full spermatogenesis was observed in 33 patients (57.8%). In 48 (82.7%), mature epididymal spermatozoa were found. No correlation was found between MTD and IF.

Conclusions: IF is present in almost half of the patients undergoing radical orchiectomy. Because IF cannot be predicted by MTD, routine pre-orchiectomy sperm banking is suggested.

Background: Pacemaker pocket early post-implantation inflammation (EPII) is defined as clinical signs of local erythema without any systemic signs of infection occurring early after implantation. Data on the best treatment regimen for apparent superficial EPII is scarce. 

Objectives: To investigate the prognostic value of medical treatment, rather than extraction surgery, in patients with EPII. 

Methods: Data from 6013 consecutive patients who underwent cardiac implantable electronic device (CIED) implantation or replacement from 2007–2015 were retrospectively analyzed; 40 (0.7%) presented with EPII. Our goal was the absence of major complications and to avoidance of extraction. 

Results: Patients with EPII were initially treated medically. Nineteen (47%) (group A) recovered with antibiotic treatment only. In the other 21 patients (53%) (group B), CIED extraction was performed. Group B had more major complications compared to group A (15 [71%] vs. 0 [0%], P < 0.001). The only significant difference in baseline characteristics was history of non-initial procedure. While 86% of group B patients had a previous non-initial procedure, only 53% of group A patients underwent previous replacement (P < 0.05). In multivariate analysis, previous non-initial procedure was the only predictor for need of extraction at 1 year, hazard ratio 3.5, 95% confidence interval 1.001–11.73, P < 0.05.

Conclusions: Conservative treatment in patients with EPII after non-initial procedure can lead to serious adverse events resulting in the need for extraction. Close follow-up and aggressive treatment should be considered early in the therapeutic course.

Background: Mortality and decrease in function after hip fracture are significantly related to patient factors including age, gender, co-morbidities, and mental status. Several studies demonstrated ethnic disparities in incidence, mortality, and functional outcome after hip fractures in the United States.

Objectives: To assess the relationship between ethnicity and hip fracture incidence and outcomes of mortality, functional change, and perioperative complications in the Israeli population.

Methods: We reviewed our institutional hip fracture registry for all patients from 2014–2015. Patients with incomplete data, < 60 years of age, or pathologic and periprosthetic fractures were excluded. Our study comprised 693 patients. Ethnicity was based on country of birth. Specifically, for those born in Israel, the nationality of either Jewish or Arab was further dichotomized. Perioperative complications, mortality, and mobility status at 1 year follow-up were recorded. The ethnicities of 27,130 patients admitted to the medicine and surgical wards during the same time interval served as a control group for the hip fracture cohort.

Results: Immigrants from Europe and America had the highest incidence of hip fractures. Fracture types varied in incidence in groups with 70% of extracapsular hip fractures occurring in Arabs and immigrants from Eastern countries, compared to 60% in immigrants from Western countries and the former Soviet Union. Mortality, perioperative complications, and mobility at 1 year were similar in all ethnic groups.

Conclusion: Our study demonstrated significant differences in incidence and fracture characteristic among ethnicities, but no difference in patient outcome. These findings differed from the available North American studies.

Background: Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. Its occurrence in the general population is 1/100,000, and 20/100,000 among overweight women of childbearing age. Familial occurrence is reportedly uncommon and not well-characterized.

Objectives: To describe a familial association with IIH.

Methods: We conducted a retrospective chart review of all familial cases of IIH examined in the neuro-ophthalmology clinic of our medical center between January 2006 and June 2013.

Results: Of a total of 520 patients with IIH, 15 had other family members with IIH (from seven different families). The family relation was a mother and daughter in two families, a brother and sister in four families, and an aunt and two first-degree cousins in the seventh family. Symptoms, course of disease, and risk factors were similar among the relatives of all seven families, except for the age at diagnosis, which was different in one family. All of the adult patients of six families were obese (body mass index 25–35 kg/m²), and all of the members of the other family were morbidly obese. There was no association between other systemic risk factors and IIH.

Conclusions: IIH occurrence within a family is more common than previously believed, and its incidence in families is more common than in the general population. The clinical course appears to be similar in family members. Our findings suggest a genetic predisposition. Further investigation of familial cases may yield useful information on the pathogenesis and genetic nature of this condition.

Background: Correct diagnosis of cardiac masses is a challenge in clinical practice. Accurate identification and differentiation between cardiac thrombi and tumors is crucial because prognosis and appropriate clinical management vary substantially.

Objectives: To evaluate the diagnostic performances of cardiac magnetic resonance imaging (CMR) in differentiating between cardiac thrombi and tumors.

Methods: A retrospective review of a prospectively maintained database of all CMR scans was performed to distinguish between cardiac thrombi and tumors during a 10 year period in a single academic referral center (2004–2013). Cases with an available standard of reference for a definite diagnosis were included. Correlation of CMR differentiation between thrombi and tumors with an available standard of reference was performed. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were reported.

Results: In this study, 101 consecutive patients underwent CMR for suspicious cardiac masses documented on transthoracic or transesophageal echocardiography. CMR did not detect any cardiac pathology in 17% (17/101), including detection of anatomical variants and benign findings in 18% (15/84). Of the remaining 69 patients, CMR diagnosis was correlated with histopathologic result in 74% (51/69), imaging follow-up in 22% (15/69), and a definite CMR diagnosis (lipoma) in 4% (3/69). For tumors, diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 96.6%, 98%, 86.6%, 96.2%, and 96.6%, respectively. For thrombi, the results were 93.6%, 86.7%, 98.04%, 92.9%, and 97%, respectively.

Conclusions: CMR is highly accurate in differentiating cardiac thrombi from tumors and should be included in the routine evaluation of cardiac masses.

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: Nail-patella syndrome (NPS) is characterized by changes in the nails, knees, and elbows, as well as the presence of iliac horns detected by X-ray of the pelvis. A higher occurrence of psychiatric disorders has also been suggested in NPS. Heterozygous mutations in the gene encoding the LIM-homeodomain transcription factor (LMX1B) are identified in most patients with typical clinical findings of NPS.

Objective: To report on the association between NPS and schizophrenia.

Methods: Genomic DNA were isolated from a patient's venous blood and collected on ethylenediaminetetraacetic 5% with the Gentra Puregene Blood Kit. All exons and flanking regions of the LMX1B gene (LMX1B: NM_001174146.1) were amplified by standard polymerase chain reaction and analyzed by direct DNA sequencing with BigDye Terminators on an ABI 3100 sequencer. Sequence chromatograms were analyzed using SeqScape software version 1.1. Mutation analysis and characterization of variants was performed with the Alamut Software Version 2.1.

Results: We report a patient presenting to the psychiatry department with schizophrenia. Clinical examination revealed characteristic findings consistent with NPS. Since NPS was suspected, based on clinical findings, sequencing of all coding exons of LMX1B gene was completed. Results revealed a novel heterozygous mutation in the proband: c.546_547insACCG(het); p.Glu183Thrfs*11.

Conclusions: Based on LMX1B expression in brain regions that are implicated in neuropsychiatric illness, and especially in the development of dopaminergic neurons, we hypothesize that schizophrenia may be part of the clinical spectrum of NPS.