Israel Medical Association Journal

Background: Previously described as a subcategory of obsessive compulsive disorder (OCD), hoarding disorder was added to the fifth Diagnostic and Statistical Manual of Mental Disorders (DSM-V) as a stand-alone diagnosis for the first time. The first formal research in the 1990s surprisingly found no connection between material deprivation early in life and hoarding; however, later studies linked early traumatic life experiences with hoarding. Subsequent familial studies demonstrated a genetic predisposition for hoarding. Emerging evidence suggests a link between a post-traumatic stress disorder (PTSD) and hoarding in Jewish Holocaust survivors.

Objectives: To evaluate the literature on PTSD among Jewish Holocaust survivors for associations between PTSD and hoarding.

Methods: A systematic search of selected databases, including PubMed, Google Scholar, NCBI, Psych Info, and EBSCO Host was conducted from 1 March 2017 to 15 July 2018 using the following search terms: hoarding, hoarding disorder, obsessive compulsive disorder, OCD, compulsive hoarding, Jewish Holocaust survivors, Shoa, post-traumatic stress disorder, and PTSD. Inclusion criteria included peer reviewed research published on adults in English since 1990. Because no publications linking hoarding and PTSD in Jewish Holocaust survivors were found, references in retained papers were also searched for any relevant published work.

Results: Seven articles linking PTSD and hoarding were identified for this review. However, no articles were found linking PTSD and hoarding in Jewish Holocaust survivors.

Conclusions: A relationship between PTSD and hoarding in Jewish Holocaust survivors is conceivable and should be explored to effectively diagnose and care for affected individuals.

Background: Enlarged lymph nodes (ELN) pose a great diagnostic challenge. They may represent the first clinical finding of a hematologic disease or other malignancy and may be an indication of a wide range of infectious and non-infectious diseases. Because many patients undergo percutaneous biopsy, surgical excisional biopsy is not often considered.

Objectives: To analyze indications for a patient's referral for surgical biopsy of ELN and diagnostic steps to follow until referral, and to determine the number of ELN.

Methods: A retrospective study was conducted of prospectively collected data of patients who underwent surgical biopsy of ELN from January 2004 to December 2013.

Results: Of 118 patients who underwent surgical biopsy of ELN, only 52 (44%) had needle biopsy (NB) before referral. Lymphoma was diagnosed by NB in 24 (46%) of the referred patients. In patients with a previous diagnosis of lymphoma, NB of ELN yielded a sensitivity of 67% and specificity of 79%. In patients with lymphadenopathy but with no previous history of malignancy, sensitivity for lymphoma was 68% and specificity was 71%. The investigative time period until final diagnosis was 3 months in patients who had NB but only 1.25 months in patients who were referred directly for surgery (P < 0.0001).

Conclusions: Surgical biopsy of ELN still has a place in the clinical evaluation of patients with ELN. Surgery may significantly reduce the length of investigation and prevent unnecessary diagnostics, especially in patients with suspected lymphoma recurrence.

Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.

Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.

Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.

Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.

Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.

Background: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD.

Objectives: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype.

Methods: The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC.

Results: The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found.

Conclusions: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.

Background: Trabectedin is a marine-derived chemotherapy, which has received U.S. Food and Drug Administration approval for use in anthracycline-resistant advanced soft tissue sarcoma (STS), especially liposarcoma and leiomyosarcoma (L-sarcomas).

Objectives: To describe our 10 year real-life experience with trabectedin regarding safety and efficacy in a cohort of 86 patients.

Methods: In our study cohort, 46.51% were diagnosed with liposarcoma and 43.02% with leiomyosarcoma. A total of 703 cycles of trabectedin were given, with a median of five cycles per patient (range 1–59). Median overall survival was 13.5 months for the whole cohort, 11 months for liposarcoma patients (range 1–63), and 15 months for leiomyosarcoma patients (range 1–35).

Results: There was no statistically significant difference in progression free survival when stratified according to previous treatment lines given. Trabectedin exhibited a favorable safety profile, with only 22% requiring dose reductions. Grade 3 and higher toxicity was noted in 25% of the patients, mostly due to myelosuppression. There were no treatment-related deaths.

Conclusions: Trabectedin is a safe and effective drug for treating advanced STS. Our results reflect real-life data with patients receiving the drug as a third and even fourth line of treatment, or with a suboptimal performance status, yet achieving impressive clinical benefit rates and survival.

Background: Sepsis is a common cause of hospitalization, particularly in intensive care units (ICUs), and is a major cause of morbidity and mortality. Diagnosis is often difficult due to the absence of characteristic clinical signs (e.g., fever and leukocytosis); therefore, additional markers, in addition to C-reactive protein (CRP) and white blood cell (WBC) count, are needed.

Objectives: To prospectively link resting energy expenditure (REE) with CRP, WBC count, and sequential organ failure assessment (SOFA) scores in ICU patients. Such a correlation may suggest REE measurement as an additional parameter for sepsis diagnosis.

Methods: Our study comprised 41 ventilated consecutive patients > 18 years of age. Patient demographic data, height, actual body weight, and SOFA scores were collected at admission. REE was measured by indirect calorimetry. REE, CRP, and WBC measurements were collected at admission, on day three after admission, and 1 week later or as clinically indicated.

Results: Comparison of the REE and CRP changes revealed a significant correlation between REE and CRP changes (r = 0.422, P = 0.007). In addition, CRP changes also correlated with the changes in REE (r = 0.36, P = 0.02). Although no significant correlations in REE, WBC count, and SOFA score were found, a significant trend was observed.

Conclusions: To the best of our knowledge, this is the first study to link REE and CRP levels, indicative of severe infection. Further study is needed to establish these findings.

Background: With advances in myelodysplastic syndromes (MDS), patient cohorts from different time periods might be different.

Objectives: To compare presentation and outcomes between two cohorts.

Methods: Data were collected from George Washington University Medical Center, Washington, DC, USA 1986–1987 (DC), and Tel Aviv Medical Center, Israel 1999–2009 (TA).

Results: The study comprised 227 patients (139 TA, 88 DC). TA patients were older (75.4 ± 9.8 vs. 63.8 ± 14.3 years, P < 0.001) and had more cardiovascular diseases (56.8% vs. 14.8%, P < 0.001), fewer cytopenias (1.67 ± 0.82 vs. 2.0 ± 0.93, P = 0.003), and lower mean corpuscular volume (94.3 ± 9.9 fl vs. 100.5 ± 15.3 fl, P < 0.001). Hemoglobin, leukocyte, neutrophil, and platelet counts were similar. More TA patients had dysplasias. Bone marrow cellularity and cytogenetics were similar, but more TA patients had blasts < 5% (73.4% vs. 50.6%, P = 0.003). More TA patients had early French-American-British (FAB) disease (66.9% vs. 40.9%, P < 0.001) and lower risk disease per International Prognostic Scoring System (81% vs. 50%, P < 0.001). The 5 year survival (5YS) of TA patients was not significantly greater (62% vs. 55%). 5YS by FAB was also slightly greater for TA patients (77% vs. 65% for early FAB; 43% vs. 37% for advanced FAB, P > 0.05).

Conclusions: Although patients diagnosed with MDS at a later period were older and had more cardiovascular co-morbidities, they had fewer cytopenias, tended to have earlier disease, and had minimally greater, but not significant, 5YS.

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

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.