Israel Medical Association Journal

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: 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: 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.

Background: Family physicians and internal medicine specialists play an essential role in treating cancer patients. Modern technological advances in radiotherapy are not widely appreciated by primary care physicians. Bone metastases are a frequent complication of cancer. Palliative radiation therapy, as a component of modern advances in radiation treatments, should not subject normal bodily structures to excessive doses of irradiation. The sacrum is a common destination site for bone metastases, yet its concave shape along with its proximity to the rectum, intestines, and femoral heads creates treatment-planning challenges.

Objectives: To investigated whether the volumetric modulated arc therapy (VMAT) technique is preferable to more conventional radiation strategies.

Methods: The study comprised 22 patients with sacral metastases who were consecutively treated between 2013 and 2014. Two plans were generated for the comparison: three-dimensional (3D) and VMAT.

Results: The planning target volume (PTV) coverage of the sacrum was identical in VMAT and 3D planning. The median values for the rectal dose for 3D and VMAT were 11.34 ± 5.14 Gy and 7.7 ± 2.76 Gy, respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22 cases, while the upper pole of the rectum ended at the level above S3 in just 3 cases.

Conclusions: Radiation therapy continues to be an integral component of the palliative armamentarium against painful metastases. Radiation oncologist, in conjunction with referral physicians, can tailor treatment plans to reflect the needs of a given patient.

Background: A dental appliance for obstructive sleep apnea (OSA) is recommended for patients who cannot adjust to continuous positive airway pressure (CPAP) treatments.



Objectives: To describe patients with extremely severe OSA who were successfully treated with a dental appliance and to compare their characteristics with the relevant literature to identify clinical features associated with a good outcome.



Methods: The clinical, management, and outcome data of three patients with an apnea-hypopnea index (AHI) of > 80 who showed clinical improvement following treatment with a dental appliance were collected retrospectively from sleep laboratory reports in Israel over a period of 3 years. 



Results: The patients included one man and two women, aged 33, 56, and 61 years, respectively. The diagnosis of OSA was based on clinical examination and polysomnography. AHI values at presentation were 83, 81, and 84, respectively. Treatment with a dental appliance (Herbst® or MDSA®) was proposed due to patient noncompliance with CPAP. Follow-up polysomnography with the dental appliance revealed a reduction in the AHI to 1.7, 10.7, and 11, respectively. All patients had supine OSA and a retrognathic mandible, both of which have been found to be associated with a good prognosis for treatment with a dental appliance.



Conclusions: Dental appliances may be considered an appropriate second-choice option to treat severe OSA in patients who are noncompliant with CPAP. This study helps physicians identify patients with extremely severe OSA who are suitable for dental appliance treatment. Well-designed large-scale studies are needed to reach definitive conclusions. 

Background: Williams syndrome (WS) is a neurogenetic syndrome characterized by a variety of medical conditions and cognitive deficits along with distinct psychiatric and behavioral characteristics. To the best of our knowledge, no studies to date have comprehensively reported the prevalence of medical, cognitive deficits, and psychiatric disorders in one cohort of people with WS in one study.

Objectives: To detail the prevalence of the various clinical features of WS in a large nationwide Israeli cohort. To examine potential risk factors for attention deficit hyperactivity disorder (ADHD) in WS.

Methods: We investigated the effects of cardiovascular anomalies, intellectual quotient (IQ), and phonophobia (fear of sounds) on the likelihood of ADHD. The study included 80 participants with WS (mean age 7.76 years). Relevant medical information from medical records was obtained retrospectively. In addition, IQ testing and psychiatric assessments using structured tools were conducted. The association between ADHD and cardiovascular anomalies, IQ, and phonophobia was analyzed using a logistic regression.

Results: Supravalvular aortic stenosis and supravalvular pulmonary stenosis are the prevalent cardiovascular anomaly in WS. Phonophobia and ADHD are the most prevalent psychiatric diagnoses in people with WS. Phonophobia was significantly associated with the risk for ADHD in WS participants.

Conclusions: Our findings regarding the type and prevalence of medical, cognitive, and psychiatric characteristics in WS correspond to results in previous publications. We also showed a potential link between phonophobia and ADHD that merits further research.

Background: Vitamin D deficiency and insufficiency have been reported in fibromyalgia. However, to the best of our knowledge, only one study has evaluated the role of 25-hydroxyvitamin D [25(OH)D] supplementation on fibromyalgia symptoms.

Objectives: To analyze the effects of 3 months of 25(OH)D supplementation on symptoms of fibromyalgia.

Methods: This study included 11 female patient. Demographic and clinical data, tender points, visual analog scale results, and pre- and post-serum levels of 25(OH)D supplementation were analyzed. The levels of 25(OH)D were measured by a radioimmunologic test.

Results: Patients with fibromyalgia diagnosis and 25(OH)D values ≤ 30 ng/ml were recruited to receive 50,000 IU of oral vitamin D once every week for 3 months. The disease was diagnosed based on the American College of Rheumatology criteria. The median age of all patients was 48.5 (28–67) years and 63.4% were Caucasian. Disease duration varied from 1–10 years. The 25(OH)D levels increased significantly after 3 months, 18.4 (15.5–25.8) ng/ml vs. 33.8 (28–58) ng/ml, P = 0.01. Interestingly, an improvement of visual analog scale scores was observed at 3 months, 90 (0–100) vs. 30 (0–80), P = 0.002. Eight patients (72.2%) responded that they experienced a very significant improvement in symptoms. In addition, a trend for reduction of the number of tender points was observed after 3 months, 17 (11–18) vs. 10 (0–18), P = 0.07.

Conclusions: The 25(OH)D levels and disease symptoms in patients with fibromyalgia and vitamin D deficiency/insufficiency seem to improve with vitamin D supplementation.

Background: The recommendation of the U.S. Centers for Disease Control and Prevention regarding universal screening for Group B Streptococcus (GBS) at 35–37 weeks gestational age in pregnancy is not accepted in Israel. The National Council for Obstetrics, Neonatology and Genetics recommends intrapartum prophylaxis, mainly based on risk factors, to prevent early neonatal GBS infection. This policy is based on past studies demonstrating low colonization rates of the bacteria in Israeli pregnant women and very low neonatal sepsis rates.

Objectives: To determine the applicability of the high-risk group prophylaxis policy for Arab Israeli pregnant women.

Methods: Vaginorectal swabs from Arab Israeli pregnant women who attended the labor ward between October 2015 and February 2016, were obtained before any pelvic examination for GBS identification using Quidel’s AmpliVue® GBS assay. Women who tested positive received intrapartum antibiotic prophylaxis to prevent neonatal infection. Obstetric data were collected from each woman from a standardized questionnaire. Data regarding the delivery and neonates were collected as well.

Results: The study comprised 188 Arab pregnant women who met the inclusion criteria and signed a consent form to participate in the study. Of these, 59 had positive tests, and a carriage rate of 31%. No neonatal colonization of GBS was found.

Conclusions: The carrier rate in Arab pregnant women in northern Israel is higher than the national average, at least partially due to the more sensitive method of GBS detection used in the present study.

Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules.

Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology.

Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere.

Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group.

Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

Background: Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients.

Objectives: To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL.

Methods: The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1–8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes.

Results: Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant.

Conclusions: Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL. 

 

Background: Management of patients with hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is evolving worldwide. Evaluating the Israeli experience may provide valuable insights.

Objectives: To compare demographics and icatibant treatment patterns and outcomes in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey (IOS) in Israel with those in other countries.

Methods: The IOS is an ongoing observational study that prospectively monitors real-world icatibant safety/tolerability and treatment outcomes.

Results: By July 2016, 58 patients from Israel and 594 patients from other countries were enrolled. Median age at diagnosis (16.7 vs. 21.3 years, P = 0.036) and median delay between symptom onset and diagnosis (0.8 vs. 6.6 years, P = 0.025) were lower in Israel compared with other countries, respectively. Differences in attack severity were not significant (P = 0.156); however, during follow-up, Israeli patients were less likely to miss > 7 days of work/school due to C1-INH-HAE-related complications (P = 0.007). A trend was also shown in Israel for earlier time to treatment (median 0.5 vs. 1.3 hours, P = 0.076), attack duration was shorter (median 5.0 vs. 9.0 hours, P = 0.026), and patients more often self-administered icatibant (97.2% vs. 87.5%, P = 0.003), respectively. However, Israeli patients were less likely to treat attacks (P = 0.036). Whereas patients in Israel reported exclusive use of danazol for long-term prophylaxis, those in other countries used various agents, including C1-INH.

Conclusions: Recognition of C1-INH-HAE and timeliness of icatibant treatment appear more favorable, and attack duration shorter, in Israel compared with other countries.

Background: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate.

Objectives: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC.

Methods: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel. HPV DNA typing and immunohistochemistry for p16INK4A antibodies were conducted to evaluate their incidence in OSCC tissues. Statistical analysis regarding its expression in the different sub-populations (Jews, Arabs, Druze) was conducted using chi-square and Fisher’s exact tests.

Results: The study included 82 patients: 53 men and 29 woman; median age 62.1 years; 54 Jews, 25 Arabs, and 3 Druze. The overall incidence of HPV expression was 45% (n=37). The median age of HPV-positive patients was 53 years vs. 65.8 in the negative group (P < 0.001). The 5 year overall survival of HPV-positive patients was not significantly higher than HPV-negative patients. A significant association was found between P16 expression and overall survival (log-rank P = 0.001).

Conclusions: HPV infection in OSCC was not found to be significant in this study; however, P16 expression in the tumor tissue was found to be a positive prognostic factor for better survival.