Israel Medical Association Journal

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monoclonal antibody, was recently shown to be effective in treating resistant CSU.

Objectives: To investigated the treatment of CSU with omalizumab in Israel.

Methods: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012–2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients’ condition improved but required regular or intermittent doses of antihistamines.

Results: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 ± 12 years and CSU duration was 4.3 ± 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 ± 3.2 injections; 30 patients received 150 mg/month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005).

Conclusions: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy. 

Background: The primary diagnosis of functional dyspepsia (FD) is made on the basis of typical symptoms and by excluding organic gastrointestinal diseases that cause dyspeptic symptoms. However, there is difficulty reaching a diagnosis in FD.

Objectives: To assess the efficiency of the Usefulness Index (UI) test and history-taking in diagnosing FD.

Methods: A study on acute abdominal pain conducted by the World Organizati­on of Gast­roentero­logy Research Committee (OMGE) included 1333 patients presenting with acute abdo­minal pain. The clinical history-taking variables (n=23) for each pa­tient were recorded in detail using a prede­fined structured data collection sheet, and the collected data were compared with the final diagnoses.

Results: The most signifi­cant clinical history-taking variables of FD in univa­riate analysis were risk ratio (RR): location of pain at diagnosis (RR = 5.7), location of initial pain (RR = 6.5), previous similar pain (RR = 4.0), duration of pain (RR = 2.9), previous abdominal surgery (RR = 4.1), previous abdominal diseases (RR = 4.0), and previous indigestion (RR = 3.1). T­he sensi­tivity of the physicians’ initial de­cisi­on in detecting FD was 0.44, speci­fi­city 0.99 and effi­ciency 0.98; UI was 0.19 and RR 195.3. In the stepwise multivariate logistic regression analysis, the independent predictors of FD were the physicians’ initial decision (RR = 266.4), location of initial pain (RR = 3.4), duration of pain (RR = 3.1), previous abdominal surgery (RR = 3.7), previous indigestion (RR = 2.2) and vomiting (RR = 2.0).

Conclusions: The patients with upper abdominal pain initially and a previous history of abdominal surgery and indigestion tended to be at risk for FD. In these patients the UI test could help the clinician differentiate FD from other diagnoses of acute abdominal pain.

Background: Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications. 

Objectives: To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes.

Methods: We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated.

Results: Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination.

Conclusions: It is apparent that due to a lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops. 

Background: Contemporary therapies improve prognosis and may restore left ventricular (LV) size and function.

Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM).

Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by ≥ 10% concomitant with ≥ 10% decreased LV end-diastolic dimension.

Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the RR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, lower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose was related to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01).

Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures. 

Background: The role of routine active surveillance cultures (ASCs) in predicting consequent blood stream infections is unclear.

Objectives: To determine prospectively whether routine screening ASCs obtained on admission to the intensive care unit (ICU) can predict the causative agent of subsequent bloodstream infections.

Methods: We prospectively studied a cohort of 100 mechanically ventilated patients admitted consecutively to a 16-bed ICU. On admission, ASCs were obtained from four sites: skin cultures (swabs) from the axillary region, rectal swabs, nasal swabs, and deep tracheal aspirates. Thereafter, cultures were obtained from all four sites daily for the next 5 days of the ICU stay.

Results: Of the 100 recruited patients 31 (31%) had culture-proven bacteremia; the median time to development of bacteremia was 5 days (range 1–18). Patients with bacteremia had a longer median ICU stay than patients without bacteremia: 14 days (range 2–45) vs. 5 days (1–41) (P < 0.001). ICU and 28 day mortality were similar in patients with and without bacteremia. Most ASCs grew multiple organisms. However, there was no association between pathogens growing on ASCs and eventual development of bacteremia.

Conclusions: ASCs obtained on ICU admission did not identify the causative agents of most subsequent bacteremia events. Therefore, bloodstream infections could not be related to ASCs.

Background: Claudication is one of the sequelae of peripheral arterial disease (PAD). To date, no effective treatment has been found for this condition.

Objectives: To investigate a new device to treat PAD. The device administers pre-programmed protocols of oscillations to the foot.

Methods: Fifteen patients aged 40–70 years who suffered from intermittent claudication secondary to PAD were recruited to an open prospective study. Each patient was treated once for 30 minutes. The following parameters were evaluated: pain-free and maximal walking distances, skin blood flux by laser-Doppler, skin temperature, ankle-brachial and toe-brachial indices, transcutaneous oxygen pressure (tcpO₂) and transcutaneous carbon dioxide pressure (tcpCO₂). Non-parametric signed-rank test was applied for testing differences between baseline assessment and post-treatment assessments for quantitative parameters.

Results: Mean pain-free walking distance was 122 ± 33 m and increased to 277 ± 67 m, after the treatment session (P = 0.004). Mean maximal walking distance was 213 ± 37 m and it increased to 603 ± 77 m (P < 0.001). Foot skin perfusion also improved, as demonstrated by an increase in tcpO₂ by 28.6 ± 4.1 mmHg (P < 0.001), a decrease in tcpCO₂ by 2.8 ± 1.3 (P = 0.032), and up to twofold improvement in blood flux parameters, and an increase in skin temperature by 1.9 ± 0.5°C (P < 0.001). Ankle-brachial index increased by 0.06 ± 0.01 (P = 0.003) and toe-brachial index by 0.17 ± 0.02 (P < 0.001).

Conclusions: Preprogrammed oscillations applied to the foot had a positive effect on microcirculation, tissue oxygenation and CO₂ clearance; they had a smaller though significant effect on arterial blood pressure indices, and the change in the arterial-brachial index correlated with the change in the pain-free walking distance. 

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. 

Background: Ethiopian immigration to Israel was initiated in 1981. Most immigrants were rural dwellers who migrated first to Addis Ababa or Gondar, where they waited for eligibility status from Israel to leave Ethiopia. Soon after arriving in Israel, all immigrants were offered screening tests for human immunodeficiency virus (HIV) and syphilis.

Objectives: To evaluate the association of age, gender, marital status and length of time spent in urban areas in Ethiopia with the prevalence of HIV and syphilis seropositivity.

Methods: All adult Ethiopian immigrants who arrived at the Jerusalem immigration center between 1999 and 2002 and consented to HIV and syphilis screening tests were interviewed.

Results: Altogether, 678 immigrants (51% females) were screened; 39 (5.8 %) were seropositive for HIV and 33 (4.9%) for syphilis. The length of time the immigrants spent in Ethiopian cities before leaving for Israel was significantly associated with HIV: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.13–6.71, and syphilis seropositivity  OR 3.87, 95%CI  1.56–9.62.

Conclusions: The length of transit time Ethiopian immigrants from rural areas spend in Ethiopian cities is significantly associated with HIV and syphilis seropositivity. Efforts should be made to shorten this time in order to reduce the risk of infection