Israel Medical Association Journal

Background: Since the implementation of a hepatitis A virus (HAV) immunization program for children, which began in 1999 in Israel, HAV infections in the country have occurred mostly in adults. HAV infection in adults is usually symptomatic and may present with hepatic, as well as extrahepatic, abdominal complications.

Objectives: To estimate the prevalence of extrahepatic abdominal complications in patients diagnosed with HAV.

Methods: Most extrahepatic abdominal complications corresponding to HAV infection have ultrasonographic manifestations; therefore, we retrospectively collected findings from ultrasound examinations in addition to laboratory data from adult patients with HAV infection who were admitted to our medical center between 2004 and 2016. Associations between ultrasonographic findings and laboratory parameters that reflect disease severity were identified.

Results: A total of 43 consecutive adult patients were included in this study. None presented with fulminant hepatic failure. Thirty patients (70%) had at least one ultrasonographic finding. Ascites was noted in 8 patients, a thickened gallbladder wall was observed in 14, pericholecystic fluid was found in 8, and biliary sludge was observed in 4. Significant associations included the presence of any ultrasonographic finding and peak total bilirubin levels (P = 0.021), the presence of ascites with peak aspartate and alanine aminotransferase levels (P = 0.041 and P = 0.038, respectively), and the presence of biliary sludge and nadir albumin during the HAV disease course (P = 0.037).

Conclusions: Abdominal ultrasonographic findings, such as ascites and gallbladder abnormalities, are frequently observed during acute HAV infection and are significantly associated with disease severity.

Background: Early identification of patients with a likelihood of cardiac improvement has important implications for management strategies.

Objectives: To evaluate whether tissue Doppler imaging (TDI) and two-dimensional (2D) strain measures may predict left ventricular (LV) improvement in patients with recent onset dilated cardiomyopathy (ROCM).

Methods: Clinical and comprehensive echo were performed at baseline and at 6 months. Patients who achieved an increase of ≥ 10 LV ejection fraction (LVEF) units and LV reverse remodeling (LVRR) (group 1) and those who improved beyond the device threshold achieving LVEF of ≥ 0.40 (group 2) were compared to patients who did not improve to this level.

Results: Among 37 patients with ROCM (mean age 56.3 ± 12.9 years and LVEF 29.1 ± 7.0%), 48% achieved LVEF ≥ 0.40 and 37.8% demonstrated LVRR. Patients with LVEF improvement ≥ 40% presented at diagnosis with higher LVEF (P = 0.006), smaller LV end-diastolic diameter (LVEDd) (P = 0.04), higher E’ septal (P = 0.02), lower E/E’ ratio (P = 0.02), increased circumferential strain (P = 0.04), and apical rotation (P = 0.009). Apical rotation and LVEDd were found to be independent predictors of LVRR. End-systolic LV volume was a significant predictor of LVEF improvement (≥ 40%).

Conclusions: Nearly half of the patients with ROCM demonstrated cardiac function improvement beyond the device threshold by 6 months. Apical rotation was introduced in our study as 2D strain prognostic parameter and found to be an independent predictor of LVRR. LV size and volume were predictors of LV improvement.

Background: Different clinical and sonographic parameters have been suggested to identify patients with retained products of conception. In suspected cases, the main treatment is hysteroscopic removal.

Objectives: To compare clinical, sonographic, and intraoperative findings in cases of hysteroscopy for retained products of conception, according to histology.

Methods: The results of operative hysteroscopies that were conducted between 2011 and 2016 for suspected retained products of conception were evaluated. Material was obtained and evaluated histologically. The positive histology group (n=178) included cases with confirmed trophoblastic material. The negative histology group (n=26) included cases with non-trophoblastic material.

Results: Patient demographics were similar in the groups, and both underwent operative hysteroscopy an average of 7 to 8 weeks after delivery/abortion. A history of vaginal delivery was more common among the positive histology group. The main presenting symptom in all study patients was vaginal bleeding, and the majority of cases were diagnosed at their routine postpartum/abortion follow-up visit. Sonographic parameters were similar in the groups. Intraoperatively, the performing surgeon was significantly more likely to identify true trophoblastic tissue as such than to correctly identify non-trophoblastic tissue (P < 0.001).

Conclusions: Suspected retained trophoblastic material cannot be accurately differentiated from non-trophoblastic material according to clinical, sonographic, and intraprocedural criteria. Thus, hysteroscopy seems warranted in suspected cases.

Background: Adverse drug events (ADEs) are a major cause of morbidity and mortality worldwide. Hence, identifying and monitoring ADEs is of utmost importance. The Trigger Tool introduced by the Institute of Healthcare Improvement in the United States has been used in various countries worldwide, but has yet to be validated in Israel.

Objective: To validate the international Trigger Tool in Israel and to compare the results with those generated in various countries.

Methods: A retrospective descriptive correlative analysis surveying four general hospitals in Israel from different geographical regions was conducted. Patient medical charts (n=960) were screened for 17 established triggers and confirmed for the presence of an ADE. Trigger incidence was compared to the actual ADE rate. Further comparison among countries was conducted using published literature describing Trigger Tool validation in various countries.

Results: A total of 421 triggers in 279 hospitalizations were identified, of which 75 ADEs in 72 hospitalizations (7.5%) were confirmed. In addition, two ADEs were identified by chart review only. Mean positive predictive value was 17.81% and overall sensitivity was 97%. We found 1.54 ADEs for every 100 hospitalization days, 7.8 ADEs per 100 admissions, and 1.81 ADEs for every 1000 doses of medication. Of the 77 ADEs identified, 22.7% were defined as preventable.

Conclusions: Our results support the Trigger Tool validity in Israel as a standardized method. Further studies should evaluate between hospital and region differences in ADE rate, in particular for the preventable events.

Background: About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF.

Objectives: To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program.

Methods: Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6  months later.

Results: Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3).

Conclusions: An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

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: Since the introduction of the electrocardiogram (ECG) in 1902, the fundamentals of ECG data acquisition, display, and interpretation in the clinical arena have not changed much.

Objectives: To present a new method to enhance and improve acquisition, analysis, and display of the standard ECG.

Methods: We performed ECG enhancement by superimposition and summation of multiple standard ECG cycles of each lead, by temporal alignment to peak R wave and voltage alignment to an improved baseline, at the T-P segment.

Results: We enhanced ECG recordings of 504 patients who underwent coronary angiograms for routine indications. Several new ECG features were noted on the enhanced recordings. Examination of a subgroup of 152 patients with a normal rest 12-lead ECG led to the discovery of a new observation, which may help to distinguish between patients with and without coronary artery disease (CAD): namely, a spontaneous cycle-to-cycle voltage spread (VS) at the S-T interval, normalized to VS at the T-P interval. The mean normalized VS was significantly greater in those with CAD (n=61, 40%) than without (n=91, 60%), 5.61 ± 3.79 vs. 4.01 ± 2.1 (P < 0.05).

Conclusions: Our novel method of multiple ECG-cycle superimposition enhances the ECG display and improves detection of subtle electrical abnormalities, thus facilitating the standard rest ECG diagnostic power. We describe, for the first time, voltage spread at the S-T interval, an observed phenomenon that can help detect CAD among individuals with normal rest 12-lead ECG.

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.

Background: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy).

Objectives: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery.

Methods: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan–Meier method.

Results: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50–62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52–87%), LC was 84% (95%CI 65–93), and DFS 35% (95%CI 14–59). Grade 4–5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01).

Conclusions: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Background: Trials have shown superiority of primary percutaneous intervention (PPCI) over in-hospital thrombolysis in ST-elevation myocardial infarction (STEMI) patients treated within 6-12 hours from symptom onset. These studies also included high-risk patients not all of whom underwent a therapeutic intervention. 

Objectives: To compare the outcome of early-arriving stable STEMI patients treated by thrombolysis with or without coronary angiography to the outcome of PPCI-treated STEMI patients.

Methods: Based on six biannual Acute Coronary Syndrome Israeli Surveys comprising 5474 STEMI patients, we analyzed the outcome of 1464 hemodynamically stable STEMI patients treated within 3 hours of onset. Of these, 899 patients underwent PPCI, 383 received in-hospital thrombolysis followed by angiography (TFA), and 182 were treated by thrombolysis only.

Results: Median time intervals from symptom onset to admission were similar while door-to-reperfusion intervals were 63, 45 and 52.5 minutes for PPCI, TFA and thrombolysis only, respectively (P < 0.001). The 30-day composite endpoint of death, post-infarction angina and myocardial infarction occurred in 77 patients of the PPCI group (8.6%), 64 patients treated by TFA (16.7%), and 36 patients of the thrombolysis only group (19.8%, P < 0.001), with differences mostly due to post-infarction angina. One-year mortality rate was 27 (3%), 13 (3.4%) and 11 (6.1%) for PPCI, TFA and thrombolysis only, respectively (P = 0.12).

Conclusions: PPCI was superior to thrombolysis in early-arriving stable STEMI patients with regard to 30-day composite endpoint driven by a decreased incidence of post-infarction angina. No 1 year survival benefit for PPCI over thrombolysis was observed in early-arriving stable STEMI patients.