Israel Medical Association Journal

Background: A patient`s individual chance of being diagnosed with cardiovascular disease can be determined by risk scores.

Objectives: To determine the risk score profiles of patients presenting with a first acute coronary event according to pre-admission risk factors and to evaluate its association with long-term mortality.

Methods: The research was based on a retrospective study of a cohort from the 2010 and 2013 Acute Coronary Syndrome Israeli Surveys (ACSIS). Inclusion criteria included first event and no history of coronary heart disease or cardiovascular disease risk equivalent. The Framingham Risk Score, the European Systematic COronary Risk Evaluation (SCORE), and the American College of Cardiology/American Heart Association/ (ACC/AHA) risk calculator were computed for each patient. The risk profile of each patients was determined by the three scores. The prognostic value of each score for 5 year survival was evaluated.

Results: The study population comprised 1338 patients enrolled in the prospective ACSIS survey. The ACC/AHA score was the most accurate in identifying patients as high risk based on pre-admission risk factors (73% of the subjects). The Framingham algorithm identified 53%, whereas SCORE recognized only 4%. After multivariate adjustment for clinical factors at presentation, we found that no scores were independently associated with 5 year mortality following the first acute coronary event.

Conclusions: Patients with first acute coronary event had a higher pre-admission risk scores according to the ACC/AHA risk algorithm. No risk scores were independently associated with 5 year survival after an event.

Background: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE).

Objectives: To conduct the first nationwide survey focused on BrS patients with documented AE.

Methods: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2).

Results: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13–84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30–53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine.

Conclusions: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

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: Gender-related differences (GRD) exist in the outcome of patients with cardiac resynchronization therapy (CRT).

Objectives: To assess GRD in patients who underwent CRT.

Methods: A retrospective cohort of 178 patients who were implanted with a CRT in a tertiary center 2005–2009 was analyzed. Primary outcome was 1 year mortality. Secondary endpoints were readmission and complication rates.

Results: No statistically significant difference was found in 1 year mortality rates (14.6% males vs. 11.8% females, P = 0.7) or in readmission rate (50.7% vs. 41.2%, P = 0.3). The complication rate was only numerically higher in women (14.7% vs. 5.6%, P = 0.09). Men more often had CRT-defibrillator (CRT-D) implants (63.2% vs. 35.3%, P = 0.003) and had a higher rate of ischemic cardiomyopathy (79.2% vs. 38.2%, P < 0.001). There was a trend to higher incidence of ventricular fibrillation/ventricular tachycardia in men before CRT implantation (29.9% vs. 14.7%, P = 0.07%). A higher proportion of men upgraded from implantable cardioverter defibrillator (ICD) to CRT-D, 20.8% vs. 8.8%, P = 0.047. On multivariate model, chronic renal failure was an independent predictor of 1 year mortality (hazard ratio [HR] 3.6; 95% confidence interval [95%CI] 1.4–9.5), CRT-D had a protective effect compared to CRT-pacemaker (HR 0.3, 95%CI 0.12–0.81).

Conclusions: No GRD was found in 1 year mortality or readmission rates in patients treated with CRT. There was a trend toward a higher complication rate in females. Men were implanted more often with CRT-D and more frequently underwent upgrading of ICD to CRT-D.

Cesarean section has undergone a transformation that has radically changed the prognosis of both the pregnant woman and her unborn child. The attributed mortality rate of Cesarean section during the 19th century was over 50% worldwide. Today, mortality from Cesarean delivery is rare. However, the technique of transversely incising the uterus in its lower uterine segment, although less than a century old, is passed on from instructor to apprentice, often without either of them being aware of its noble history. In this brief review, we discuss the reported history regarding this incision and the significant role played by John Munro Kerr.

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

Background: Accurate pulse oximetry reading at hospital admission is of utmost importance, mainly for patients presenting with hypoxemia. Nevertheless, there is no accepted or evidence-based protocol for such structured measuring.

Objectives: To devise and assess a structured protocol intended to increase the accuracy of pulse oximetry measurement at hospital admission.

Methods: The authors performed a prospective comparison of protocol-based pulse-oximetry measurement with non-protocol based readings in consecutive patients at hospital admission. They also calculated the relative percentage of improvement for each patient (before and after protocol implementation) as a fraction of the change in peripheral capillary oxygen saturation (SpO₂) from 100%.

Results: A total of 460 patients were recruited during a 6 month period. Implementation of a structured measurement protocol significantly changed saturation values. The SpO₂ values of 24.7% of all study participants increased after protocol implementation (ranging from 1% to 21% increase in SpO₂ values). Among hypoxemic patients (initial SpO₂ < 90%), protocol implementation had a greater impact on final SpO₂ measurements, increasing their median SpO₂ readings by 4% (3–8% interquartile range; P < 0.05). Among this study population, 50% of the cohort improved by 17% of their overall potential and 25% improved by 50% of their overall improvement potential. As for patients presenting with hypoxemia, the median improvement was 31% of their overall SpO₂ potential.

Conclusions: Structured, protocol based pulse-oximetry may improve measurement accuracy and reliability. The authors suggest that implementation of such protocols may improve the management of hypoxemic patients.

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.

Background: The distribution of pathology and clinical characteristics of lacrimal gland diseases are different in different areas of the world.

Objectives: To evaluate the incidence rate, patient characteristics, and indications for surgical intervention of lacrimal gland lesions in a tertiary care center in Israel.

Methods: All biopsied or surgically removed lacrimal gland lesions at the Goldschleger Eye Institute from 2009 to 2015 were identified. The following data were collected: age, gender, indications for surgical intervention, diagnosis, treatment, and prognosis.

Results: We evaluated 28 lacrimal gland biopsies from 26 patients (11 men, 15 women). Mean age at biopsy was 47.5 years old. The most common presenting symptoms were: eyelid swollenness (57.14%), ptosis (32.14%), and proptosis (10.71%). All patients underwent computed tomography and magnetic resonance imaging. In 28 cases, infiltrations of the lacrimal gland were found. In nine cases infiltration of muscles or orbital extension were found. The most common pathologies were non-specified inflammation (44.82%), lymphoma (20.68%), and immunoglobulin G4-related disease (10.34%). The treatment was diverse according to the patient diagnosis. Prognosis of lacrimal gland disease was good; however, in five patients the systemic disease progressed.

Conclusions: Lesions of the lacrimal gland comprise a wide variety of pathological findings that require different treatment strategies. Lacrimal gland biopsies enable physicians to precisely recognize the pathology; therefore, it is important to consider this surgical method in any patient with lesions in the lacrimal gland.

Background: Multiform fascicular tachycardia (FT) was recently described as a ventricular tachycardia (VT) that has a reentrant mechanism using multiple fascicular branches and produces alternate fascicular VT forms. Ablating the respective fascicle may cause a change in the reentrant circuit resulting in a change in morphology. Ablation of the septal fascicle is crucial for successful treatment.

Objectives: To describe four cases of FT in which ablation induced a change in QRS morphologies and aggravated clinical course.

Methods: Four out of 57 consecutive FT cases at three institutions were retrospectively analyzed and found to involve multiform FT. These cases underwent electrophysiological study, fascicular potential mapping, and electroanatomical mapping. All patients initially had FT with right bundle branch block (RBBB) and superior axis morphology.

Results: Radiofrequency catheter ablation (RFCA) targeting the distal left posterior fascicle (LPF) resulted in a second VT with an RBBB-inferior axis morphology that sometimes became faster and/or incessant and/or verapamil-refractory in characteristics. RFCA in the upper septum abolished the second VT with no complications and uneventful long-term follow-up.

Conclusions: The change in FT morphology during ablation may be associated with a change in clinical course when shifting from one route to another and may aggravate symptoms. Targeting of the proximal conduction system (such as bifurcation, LPF, left anterior fascicle, high septal/auxiliary pathway) may serve to solve this problem.

Background: Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used “gold standard” tests.

Objectives: To validate the accuracy of intraoperative measurements of parathyroid hormone levels in parathyroid adenomas.

Methods: A prospective study included 22 patients diagnosed with primary hyperparathyroidism who underwent parathyroidectomy due to an adenoma or hyperplasia. Aspirations of tissues extracted from three adjacent areas (the pathological parathyroid, thyroid, and muscle tissues) were sent for rapid parathyroid hormone analysis. The assay values of these tissue aspirates were compared to the results of the pathology report based on frozen section analysis and the final pathology report.

Results: All assay results were significantly higher for parathyroid tissue 16,800 to 1,097,986 pmol/L (median 26,600), than for either thyroid 1.7 to 415 pmol/L (median 6.5), P < 0.001, or muscle tissue 1.1 to 1230 pmol/L, (median 11.3), P < 0.001. All tissues showing high parathyroid assay values were also verified by pathology examinations: 7 had adenomas and 15 had a differential diagnosis of adenoma or hyperplasia. The frozen section identified all but one (false negative). Rapid intraoperative parathyroid levels > 1500 predicted parathyroid tissue with a 99% level of confidence, while levels between 1000 and 1500 predicted it with 95% confidence. The intraoperative parathyroid hormone assay showed > 70% decrease in 15/21 cases.

Conclusions: Rapid intraoperative parathyroid hormone analysis is a reliable and precise technique, equally accurate for frozen section analysis in predicting with high certainty intraoperative parathyroid tissue.

Background: In 2006, the Israeli Ministry of Health distributed guidelines for improving cardiopulmonary resuscitation (CPR) knowledge among hospital staff. The impact of these guidelines on survival after in-hospital cardiac arrest (IHCA) is unclear.

Objectives: To compare rates of incidence and survival to discharge after IHCA, preceding and subsequent to issuance of the guidelines: 1995–2005 and 2006–2015.

Methods: Data were retrieved from the computerized records of patients who had an IHCA and underwent CPR. In addition, we retrieved data available from the hospital's resuscitation committee that included number, type, methods of training in CPR refresher courses, type and number of audits carried out during the past 10 years, and type of CPR quality assessments.

Results: From 1995 to 2015, IHCA incidence increased from 0.7 to 1.7 per 1000 admissions (P < 0.001), while survival rate did not increase (P = 0.37). Survival for shockable rhythms increased from 15.4 to 30.2% (P = 0.05) between the two time periods. The ratio of non-shockable to shockable rhythms increased from 2.4 to 4.6 (P = 0.01) between the two time periods.

Conclusions: Overall IHCA survival did not improve following the issuance of guidelines requiring CPR refresher courses, although survival improved for patients with initial shockable dysrhythmia. A decrease of events with initial shockable dysrhythmia, an increase with acute renal failure, and a decrease occurring in intensive care units contributed to understanding the findings. We found that CPR refresher courses were helpful, although an objective measure of their effectiveness is lacking.

Background: Enthesopathy may lead to calcification of the stylohyoid ligament and can cause elongation of the styloid process (SP).

Objectives: To evaluate whether SP elongation is associated with two common enthesitis-related diseases: ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).

Methods: Cervical spine computed tomography (CT) examinations of patients with DISH (n=64, Resnick criteria), AS (n=24, New York criteria) and a controls (no radiological signs of DISH or AS, n=54) were retrospectively evaluated. The DISH group was further divided into patients with and without cervical DISH. The length of right and left SP was measured independently by two readers on coronal and sagittal curved reformats. The average right and left styloid length and average length per person were compared among the groups.

Results: Demographic characteristics were similar between the DISH and control groups (average age 68.2 ± 15.7, 69.2 ± 12.7 years, male:female ratio 48:16 and 35:19, respectively, P > 0.05), whereas age was significantly lower (average age: 53 ± 15 years, P < 0.0001) in the AS group, which was also composed mainly of men. The AS and DISH groups had significantly longer SP compared to controls (AS 37.9 ± 9.6 mm, DISH 34.4 ± 9 mm, control 30.3 ± 10.1 mm, P < 0.05). There was no correlation between age and SP length. Inter-reader reliability of SP measurements was excellent in all groups (ICC = 0.998, P < 0.0001).

Conclusions: SP elongation is associated with both AS and DISH substantiating the enthesopathy-related pathophysiology of this finding.