Israel Medical Association Journal

Background: In the past decade, numerous new imaging and laboratory tests have been implemented that significantly contribute to improved medical diagnostic capabilities. However, inappropriate utilization, which occurs on a large scale, has significant ramifications for both patient care and health systems.

Objectives: To assess the impact of a novel clinical decision support system (CDSS) applied to our electronic medical records on abdominal ultrasonography utilization pattern.

Methods: We conducted a retrospective cohort study comparing patterns of abdominal ultrasound utilization in cases of liver enzyme elevation, with and without CDSS, between February and May in 2017 (before CDSS implementation) and during the same months in 2018 (after CDSS implementation). The following parameters were collected: number of tests ordered according to the guidelines, tests with a diagnostic value, and order forms completed with any data or a diagnostic question. The comparison was conducted using chi-square test.

Results: Of 152 abdominal ultrasound tests, 72 were ordered in the pre-implementation period and 80 in the post-implementation period. The system failed to reach statistical significance regarding the rates of ordered tests according to the guidelines and/or tests with a diagnostic value. However, the use of the CDSS had a statistically significant impact regarding completing the order form with data, including a specific diagnostic question.

Conclusions: The effect of the system on the efficiency of test utilization was partial. However, our findings strongly suggested that CDSS has the potential to promote proper usage of complementary technologies.

Common variable immunodeficiency (CVID) is a heterogeneous primary immune deficiency disorder characterized mainly by defective B lymphocyte differentiation, leading to hypogammaglobinemia and defective antibody production. It is often combined with cellular immune defects. A minority of patients present during childhood and adolescence. Infections are most often sinopulmonary but can affect any system. The noninfectious complications include progressive lung disease, autoimmunity, gastrointestinal inflammatory disease, liver disease, granulomatous disease, lymphoid hyperplasia and infiltrative disease, and the development of lymphoma and other cancers. In addition to recurrent infections and bronchiectasis, patients may develop chronic interstitial lung disease, granulomatous lung disease, lymphoma, and pulmonary hypertension.

Background: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation).

Objectives: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula.

Methods: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded.

Results: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group.

Conclusions: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.

Background: Guidelines for pandemic preparedness emphasize the role of sentinel and syndromic surveillance in monitoring pandemic spread.

Objectives: To examine advantages and obstacles of utilizing a sentinel influenza surveillance system to monitor community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity based on Israel's experience from mid-March to mid-May 2020.

Methods: Several modifications were applied to the influenza surveillance system. The clinical component relied mainly on pneumonia and upper respiratory infection (URI) consultations with primary care physicians as well as visits to emergency departments (ED) due to pneumonia. The virological data were based on nasopharyngeal swabs obtained from symptomatic patients who visited outpatient clinics.

Results: By week 12 of the pandemic, the crude and age-specific primary physician consultation rates due to URI and pneumonia declined below the expected level, reaching nadir that lasted from week 15 until week 20. Similarly, ED visits due to pneumonia were significantly lower than expected from weeks 14 and 15 to week 20. The virological surveillance started on week 13 with 6/253 of the swabs (2.3%) positive for SARS-CoV-2. There was a peak of 13/225 positive swabs on week 145.8%. During weeks 17–20, none of the swabs (47–97 per week) were positive for SARS-CoV-2. This trend was similar to national data.

Conclusions: The virological component of the surveillance system showed the SARS-CoV-2 community spread, but had low sensitivity when virus activity was low. The clinical component, however, had no yield. Sentinel surveillance can assist in monitoring future novel pandemics and should be augmented in revised preparedness plans.

Background: Recurrence of tracheoesophageal fistula (TEF) is reported in 8–20% patients. Factors that may influence recurrence of fistula beyond the postoperative period are not clear.

Objectives: To evaluate possible factors associated with recurrence of TEF beyond the immediate postoperative period.

Methods: A single center, retrospective comparison of patients with and without recurrence of TEF was conducted. Medical records of patients previously operated for TEF who were followed in our pediatric pulmonary institute between January 2007 and December 2016 were reviewed.

Results: The medical records of 74/77 patients previously operated for TEF were evaluated. Nine patients (12%) had a recurrence of TEF and 65 did not. These groups had similar age and gender distribution and similar prevalence of VACTERL association. In addition, they had similar length of atretic gap, rates of thoracoscopic surgery, rates of prolonged need for respiratory assistance post-surgery, and frequency of gastrointestinal symptoms. Notably, the patients who had recurrent TEF had significantly more hospitalizations for respiratory symptoms (P = 0.011) and significantly more episodes of clinical bronchiolitis per patient (P < 0.0001). In addition, the patients with recurrent TEF had significantly more episodes of positive polymerase chain reaction for viruses (P = 0.009).

Conclusions: Hospitalizations for respiratory symptoms as well as clinical and/or viral bronchiolitis are associated with recurrence of TEF. Even though cause and effect cannot be established, these patients should undergo meticulous evaluation for the possibility of recurrence of TEF.

Background: The closure of an atrial septal defect is procedure that is frequently performed in both adults and children. Currently, the most commonly used devices are the Amplatzer® and Occlutech® Figulla® atrial septal occluders. Studies conducted in adults have shown that these devices all have similar performance efficiency for the closure of secundum atrial septal defects. No study to date has examined their performance in the pediatric population.

Objectives: To evaluate and compare the performance of Amplatzer® and Occlutech® Figulla® atrial septal occluders in the pediatric population.

Methods: A consecutive retrospective study of exclusively pediatric patients who underwent percutaneous closure of atrial septal defect with these devices was conducted at our institute. 

Results: The study comprised 110 children, 50 in the Amplatzer® device group and 60 in the Occlutech® Figulla® device group. The groups had similar demographic and defect characteristics, except for defect size per transesophageal echocardiography (TEE), which was 2.1 mm larger in the Amplatzer® device group (P = 0.02). No adverse events were recorded in either of the study groups. Complete defect closure at 12 months follow-up (procedural success) was achieved in all but one of the patients in the Amplatzer® group and all but two in the Figulla® group (P = 1). The residual shunt rates of fenestrated defects were similar in the two groups. 

Conclusions: For children with an isolated secundum atrial septal defect, percutaneous closure is equally safe and effective with either Amplatzer® or Occlutech® Figulla® devices.

Pseudoexfoliation syndrome (PES) is a common age-related disorder affecting 60–70 million people worldwide. Patients with PES have abnormal production and deposition of fibrillar material in the anterior chamber of the eye. These exfoliated fibrils, easily detected by ocular slit-lamp examination, have also been found to exist systematically in the skin, heart, lungs, liver and kidneys. Recently, myriad studies have associated PES with systemic conditions such as increased vascular risk, risk of dementia and inflammatory state. We review here the most current literature on the systemic implications of PES. Our aim is to encourage further studies on this important clinical entity.

Background: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. 

Objectives: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.

Methods: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.

Results: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.

Conclusions: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT. 

 

Clostridium difficile-associated diarrhea is a problem most hospital-based physicians will face in their career. This review aims to refresh current knowledge with regard to Clostridium difficile infection and bring physicians up to date with the latest developments in the growing field of fecal microbiota transplantation, the benefits it offers, and the promise this and other developments hold for the future. 

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: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.
 

Heart failure (HF) accompanied by renal failure, termed cardiorenal syndrome (CRS), encompasses both the development and worsening of renal insufficiency secondary to HF as well as the harmful effects of impaired renal function on the cardiovascular system, and remains a universal clinical challenge. CRS was recently classified into subtypes depending on the etiologic and chronologic interactions between cardiac and renal dysfunctions. The mechanisms underlying the CRS are multifactorial, including hemodynamic alterations, neurohormonal effects, and inflammatory components. However, despite enhanced understanding and awareness of CRS, further elucidation of the mechanisms involved and the appropriate treatment approaches are clearly warranted. CRS is a difficult condition to manage, as treatment to relieve congestive symptoms of HF is limited by a further decline in renal functions, itself a major independent predictor of long-term cardiac morbidity. In order to perform a proper clinical investigation and implement appropriate treatment that will minimize subsequent progression of heart and kidney injury, a comprehensive approach to these two pathologies is crucial. In the present review we discuss current theories behind the mechanistic evolution of the CRS as well as therapeutic issues regarding this multifaceted condition.