Israel Medical Association Journal

Background: The single-breath diffusing capacity of the lungs (DLCO_SB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VA_SB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCO_SB) is the DLCO_SB divided by VA_SB. Cystic fibrosis (CF) disease comprises progressive airway obstruction with bronchiectasis and parenchyma fibrosis. Yet, the KCO_SB appears insignificant in the assessment of pulmonary function in CF.

Objectives: To challenge the precision of normal KCO_SB in CF.

Methods: The authors collected pulmonary function tests (PFT) data from 74 confirmed CF patients (mean age 26 ± 10 years) with various levels of pulmonary disease severity. Tests included spirometry, DLCO_BP, and body plethysmography (_BP). Anatomical dead space was calculated by deducting anatomical dead space from total lung capacity TLC(_BP) to establish alveolar volume (VA_BP) and to determine KCO_BP. We also included individual data of arterial pCO₂ blood-gas level.  

Results: KCO_SB values were normal or higher in most patients, regardless of patient FEV1 value (R² = 0.2204; P < 0.02). In contrast, the measurements of KCO_BP were low corresponding with low FEV1 values, and negatively correlated with the elevation of trapped air and pCO₂ levels (R² = 0.1383; P = 0.0133, P > 0.05, respectively).

Conclusions: The 10- second perfusion time of the inert gas during DLCO_SB represent the communicative alveolar volume in CF patients with advanced pulmonary disease. The findings justify the use of DLCO_SB with the deterioration of FEV1 and elevation of pCO₂ levels.

Background: Transbronchial cryobiopsy (TBC) has recently emerged for the assessment of diffuse parenchymal lung disease (DPLD) as a less invasive procedure than surgical lung biopsy. The diagnostic usefulness and safety of TBC is still controversial.

Objectives: To evaluate the safety and diagnostic yield of TBC in a peripheral community medical center.

Methods: We retrospectively reviewed the charts of all patients with DPLD who underwent TBC from January 2015 to January 2020.

Results: The study comprised 97 patients. Three samples were taken from each patient with an average diameter of 0.59 cm. The histologic diagnostic yield was 54% (52 of 97 procedures). The most frequent histopathologic diagnoses were usual interstitial pneumonia in 13 patients (13%). Bleeding was observed in 19 cases (19%) and only one patient (1%) had severe bleeding. Pneumothorax developed in seven patients (7%) and one patient (1%) suffered from Interstitial lung disease exacerbation.

Conclusions: TBC was found to be safe; however, the diagnostic yield was rather low compared to other studies, which emphasizes the need for interstitial lung disease centers with expert in this field.

Background: The incidence of gestational diabetes mellitus (GDM) is increasing in parallel to the worldwide obesity and type 2 diabetes pandemic. Both GDM and pre-gestational diabetes mellitus (PGDM) are associated with short- and long-term consequences in the offspring. There are few recent studies addressing outcomes of newborns born to women diagnosed with GDM and PGDM in Israel.

Objectives: To assess perinatal complications in offspring of women with GDM and PGDM.

Methods: The authors conducted a single-center retrospective case-control study of outcomes of all newborns whose mothers had been diagnosed with diabetes in pregnancy compared to randomly assigned controls born on the same date, whose mothers had no diabetes.

Results: In the study period 2015–2017, 526 mothers diagnosed with GDM or PGDM and their newborn infants were identified. The authors randomly assigned 526 control infants. The rate of women with diabetes in pregnancy was 5.0%. Mothers with GDM and PGDM had higher rates of pre-eclampsia, multiple pregnancies, and preterm deliveries. Mothers with PGDM had significantly higher rates of intrauterine fetal demise (4.3%), congenital anomalies (12.8%), and small-for-gestational-age neonates (10.6%) compared to controls (0%, 3.2%, and 4.2%, respectively, P < 0.001). The risks for preterm or cesarean delivery, large-for-gestational-age neonate, respiratory morbidity, hypoglycemia, and polycythemia were increased in offspring of mothers with diabetes, especially PGDM.

Conclusions: Despite all the advancements in prenatal care, diabetes in pregnancy, both PGDM and GDM, is still associated with significant morbidities and complications in offspring. Better preconception and inter-pregnancy care might reduce these risks

Background: Social distancing, implemented to decrease the spread of coronavirus disease-2019 (COVID-19), forced major changes in medical practices, including an abrupt transition from face-to-face to remote patient care. Pre-clinical medical studies were concomitantly switched to electronic distance learning.

Objectives: To explore potential implications of COVID-19 on future pre-clinical medical studies.

Methods: We examined responses of pre-clinical medical students to the remote electronic learning in terms of quality of and satisfaction with teaching and technical support, attendance to classes, and the desire to continue electronic learning in the post-epidemic era. A survey of responses from first-year students at the Adelson School of Medicine was conducted. To optimize the reliability of the survey, a single research assistant conducted telephone interviews with each student, using a structured questionnaire concerning aspects of participation and satisfaction with teaching and with technical components of the remote electronic learning.

Results: With 100% response rate, the students reported high satisfaction with the electronic learning regarding its quality, online interactions, instructions given, technical assistance, and availability of recording for future studies. Most of the students (68.6%) noted a preference to continue < 90% of the learning online in the post-outbreak era. A high level of overall satisfaction and a low rate of technical problems during electronic learning were significantly correlated with the desire to continue online learning (P < 0.01).

Conclusions: The high satisfaction and the positive experience with the electronic distance learning imposed by the COVID-19 epidemic implied a successful transition and might induce future changes in pre-clinical medical studies.

Background: Methylene blue (MB), an inhibitor of nitric oxide synthesis and its effects is a potentially effective treatment against distributive shock states such as septic shock and vasoplegic syndrome. MB has been shown to alleviate vasoplegia and promote an increase in blood pressure. It may reduce mortality. However, in the pediatric population, there are few case reports and only one controlled study on administration of MB use for vasoplegia, sepsis, or shock in general.

Objectives: To summarize the experience of administering MB for vasoplegic shock in a tertiary care pediatric intensive care unit.

Methods: A retrospective chart review of seven pediatric cases treated with MB for vasoplegic shock was conducted. MB was administered as a bolus followed by continuous infusion. The authors measured blood pressure, vasopressor, and inotropic support. Patient outcome was monitored.

Results: The authors observed a favorable hemodynamic response with an increase in blood pressure and a reduction in vasopressor and inotropic support needed following MB administration in six patients. No side effects were observed. Three patients eventually died one to two days later, secondary to their underlying disease.

Conclusions: This case series adds to the small body of evidence in the pediatric population supporting the use of MB for distributive shock states and emphasizes the need for larger, randomized trials evaluating its role in vasoplegic shock treatment.

Background: Cardiac rehabilitation (CR) is underutilized globally despite evidence of clinical benefit. Major obstacles for wider adoption include distance from the rehabilitation center, travel time, and interference with daily routine. Tele-cardiac rehabilitation (tele-CR) can potentially address some of these limitations, enabling patients to exercise in their home environment or community.

Objectives: To evaluate the clinical and physiological outcomes as well as adherence to tele-CR in patients with low cardiovascular risk and to assess exercise capacity, determined by an exercise stress test, using a treadmill before and following the 6-month intervention.

Methods: A total of 22 patients with established coronary artery disease participated in a 6-month tele-CR program. Datos Health (Ramat Gan, Israel), a digital health application and care-team dashboard, was used for remote monitoring, communication, and management of the patients.

Results: Following the 6-month tele-CR intervention, there was significant improvement in exercise capacity, assessed by estimated metabolic equivalents with an increase from 10.6 ± 0.5 to 12.3 ± 0.5 (P = 0.002). High-density lipoproteins levels significantly improved, whereas low-density lipoproteins, triglyceride, glycosylated hemoglobin, and systolic and diastolic blood pressure levels were not significantly changed. Exercise adherence was consistent among patients, with more than 63% of patients participating in a moderate intensity exercise program for 150 minutes per week.

Conclusions: Patients who participated in tele-CR adhered to the exercise program and attained clinically significant functional improvement. Tele-CR is a viable option for populations that cannot, or elect not to, participate in center-based CR programs.

Background: Left ventricular assist devices (LVADs) are used more commonly in patients with advanced-stage heart failure. Some of these patients may require elective or urgent abdominal surgical procedures.

Objectives: To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution.

Methods: A retrospective review was conducted on 93 patients who underwent LVAD implantation between August 2008 and January 2017. All abdominal surgeries in these patients were studied, and their impact on postoperative morbidity and mortality was evaluated.

Results: Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patients.

Conclusions: It is safe to perform elective abdominal procedures for LVAD-supported patients. The prognosis of these patients undergoing emergency surgery is poor and has high mortality and morbidity rates.

Background: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020.

Objectives: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel.

Methods: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented.

Results: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1%.

Conclusions: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.

Background: Although indwelling catheters are increasingly used in modern medicine, they can be a source of microbial contamination and hard-to-treat biofilms, which jeopardize patient lives. At times 70% ethanol is used as a catheter-lock solution due to its bactericidal properties. However, high concentrations of ethanol can result in adverse effects and in malfunction of the catheters.

Objective: To determine whether low concentrations of ethanol can prevent and treat biofilms of Pseudomonas aeruginosa.

Methods: Ethanol was tested at a concentration range of 0.625–80% against laboratory and clinical isolates of P. aeruginosa for various time periods (2–48 hours). The following parameters were evaluated following ethanol exposure: prevention of biofilm formation, reduction of biofilm metabolic activity, and inhibition of biofilm regrowth.

Results: Exposing P. aeruginosa to twofold ethanol gradients demonstrated a significant biofilm inhibition at concentrations as low as 2.5%. Treating pre-formed biofilms of P. aeruginosa with 20% ethanol for 4 hours caused a sharp decay in the metabolic activity of both the laboratory and clinical P. aeruginosa isolates. In addition, treating mature biofilms with 20% ethanol prevented the regrowth of bacteria encased within it.

Conclusions: Low ethanol concentrations (2.5%) can prevent in vitro biofilm formation of P. aeruginosa. Treatment of previously formed biofilms can be achieved using 20% ethanol, thereby keeping the catheters intact and avoiding complications that can result from high ethanol concentrations.

Background: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting.

Objective: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer’s guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds

Methods: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement.

Results: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer’s guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds.

Conclusions: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Background: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited.

Objectives: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function.

Methods: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250–500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids.

Results: Polyp tissue viability was retained for 2–3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production.

Conclusions: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.

Background: Older age is an independent predictor of worse outcome from traumatic brain injury (TBI). No clear guidelines exist for the management of TBI in elderly patients.

Objectives: To describe the outcomes of elderly patients presenting with TBI and intracranial bleeding (ICB), comparing a very elderly population (≥ 80 years of age) to a younger one (70–79).

Methods: Retrospective analysis of the outcomes of elderly patients presenting with TBI with ICB admitted to a level I trauma center.

Results: The authors analyzed 100 consecutive patients aged 70–79 and 100 patients aged 80 and older. In-hospital mortality rates were 9% and 21% for groups 70–79 and ≥ 80 years old, respectively (P = 0.017). Patients 70–79 years old showed a 12-month survival rate of 73% and a median survival of 47 months. In patients ≥ 80 years old, 12-month survival was 63% and median survival was 27 months (P = NS). In patients presenting with a Glasgow Coma Scale score of ≥ 8, the in-hospital mortality rates were 41% (n=5/12) and 100% (n=8/8). Among patients ≥ 80 years old undergoing emergent surgical decompression, in-hospital mortality was 66% (n=12/18). Survivors presented with a severe drop in their functional score. Survival was dismal in patients ≥ 80 years old who were treated conservatively despite recommended operative guidelines.

Conclusions: There is a lack of reliable means to evaluate the outcome in patients with poor functional status at baseline. The negative prognostic impact of severe TBI is profound, regardless of treatment choices.