Israel Medical Association Journal

Background: Dietary modifications and patient-tailored medical management are significant in controlling renal stone disease. Nevertheless, the literature regarding effectiveness is sparse.

Objectives: To explore the impact of dietary modifications and medical management on 24-hour urinary metabolic profiles (UMP) and renal stone status in recurrent kidney stone formers.

Methods: We reviewed our prospective registry database of patients treated for nephrolithiasis. Data included age, sex, 24-hour UMP, and stone burden before treatment. Under individual treatment, patients were followed at 6–8 month intervals with repeat 24-hour UMP and radiographic images. Nephrolithiasis-related events (e.g., surgery, renal colic) were also recorded. We included patients with established long-term follow-up prior to the initiation of designated treatment, comparing individual nephrolithiasis status before and after treatment initiation.

Results: Inclusion criteria were met by 44 patients. Median age at treatment start was 60.5 (50.2–70.2) years. Male:Female ratio was 3.9:1. Median follow-up was 10 (6–25) years and 5 (3–6) years before and after initiation of medical and dietary treatment, respectively. Metabolic abnormalities detected included: hypocitraturia (95.5%), low urine volume (56.8%), hypercalciuria (45.5%), hyperoxaluria (40.9%), and hyperuricosuria (13.6%). Repeat 24-hour UMP under appropriate diet and medical treatment revealed a progressive increase in citrate levels compared to baseline and significantly decreased calcium levels (P = 0.001 and 0.03, respectively). A significant decrease was observed in stone burden (P = 0.001) and overall nephrolithiasis-related events.

Conclusions: Dietary modifications and medical management significantly aid in correcting urinary metabolic abnormalities. Consequently, reduced nehprolithiasis-related events and better stone burden control is expected.

Background: Low folate levels are associated with megaloblastic anemia, neural tube defects, and an increased risk of cancer. Data are scarce regarding the sex aspect of this deficiency.

Objectives: To assess sex differences in folate levels in a large cohort of patients and to investigate the effect of low folate levels on homocysteine concentrations.

Methods: Data were collected from medical records of patients examined at a screening center in Israel between 2000 and 2014. Cross sectional analysis was conducted on 9214 males and 4336 females.

Results: The average age was 48.4 ± 9.5 years for males and 47.6 ± 9.4 years for females. Average folate levels were 19.2 ± 8.6 and 22.4 ±10.3 nmol/L in males and females, respectively (P < 0.001). The prevalence of folate levels below 12.2 nmol/L was 19.5% in males compared to 11.6% in females (P < 0.001). In patients with low folate levels and normal B12 levels, homocysteine levels above 15 μmol/L were found in 32.4% of males and 11.4% of females (P < 0.001). Males had a significantly higher odds ratio (OR) of having folate levels below 12.2 nmol/L: OR 1.84 (95% confidence interval [95%CI] 1.66–2.05) in a non-adjusted model, and OR 2.02 (95%CI 1.82–2.27) adjusted for age, smoking status, body mass index, kidney function, albumin, and triglycerides levels.

Conclusions: Folate levels are lower in males compared to females, which may contribute to the higher homocysteine levels found in males and thus to their increased risk of developing atherosclerosis and coronary artery disease.

Background: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines.

Objectives: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel.

Methods: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result.

Results: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment.

Conclusions: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

Background: The sonographic assessment of estimated fetal weight (EFW) is essential for identification of fetuses in weight extremes and aids in peripartum management. However, there are inconsistent reports regarding EFW accuracy.

Objective: To examine maternal and fetal determinants associated with unreliable EFW.

Methods: A retrospective case-control study was conducted at a single, tertiary medical center between 2011 and 2019. All term, singleton deliveries with a sonographic EFW within 2 weeks of delivery were included. Unreliable EFW was defined as > 500 grams discordance between it and the actual birth weight. We allocated the study cohort into two groups: unreliable EFW (cases) and accurate EFW (controls).

Results: Overall, 41,261 deliveries met inclusion criteria. Of these, 1721 (4.17%) had unreliable EFW. The factors positively associated with unreliable EFW included body mass index > 30 kg/m², weight gain > 20 kg, higher amniotic fluid index, pregestational diabetes, gestational age > 41^0/7, and birth weight ≥ 4000 grams. On multiple regression analysis, pregestational diabetes (odds ratio [OR] 2.22, 95% confidence interval [95%CI] 1.56–3.17, P < 0.001) and a higher birth weight (OR 1.91, 95%CI 1.79–2.04, P < 0.001) were independently associated with unreliable EFW. On analysis of different weight categories, pregestational diabetes was associated with unreliable EFW only among birth weights ≥ 3500 grams (OR 3.28, 95%CI 1.98–5.44, P< 0.001) and ≥ 4000 grams (OR 4.27, 95%CI 2.31–7.90, P < 0.001).

Conclusion: Pregestational diabetes and increased birth weight are independent risk factors for unreliable EFW and should be considered when planning delivery management.

Background: Adnexal torsion in pregnancy is often associated with functional adnexal cysts, especially in pregnancies conceived by ovulation induction (OI) or in-vitro fertilization (IVF). During laparoscopy for adnexal de-torsion, drainage of the functional cysts can be attempted, although this procedure may cause bleeding.

Objectives: To investigate the characteristics of ovarian torsion in pregnancy associated with functional cysts and to compare the rate of torsion recurrence following de-torsion alone versus cyst drainage.

Methods: All cases of surgically diagnosed adnexal torsion occurring during pregnancy between January 2007 and April 2019 in our department were retrospectively analyzed. The cases of torsion associated with presumed functional ovarian cysts were selected. The rate of recurrent torsion during the same pregnancy was compared for de-torsion alone versus de-torsion and cyst aspiration.

Results: Of the 113 women who experienced adnexal torsion during pregnancy, 71 (67.0%) of torsion cases were caused by presumed functional ovarian cysts. Among women with torsion of functional ovarian cysts, the rate of torsion recurrence was significantly higher in patients who underwent de-torsion alone (n=28) compared to women who underwent aspiration and drainage of the ovarian cysts (n=43) (14.3% vs. 0, P = 0.021). There were no cases of intra- or post-operative bleeding in the study cohort.

Conclusions: Functional ovarian cysts are the most common adnexal pathology encountered in pregnant women with torsion. Intra-operative cyst aspiration and drainage may reduce the risk of recurrent torsion. Further multi-center studies are required to validate our data prospectively.

Background: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative.

Objectives: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold).

Methods: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant.

Results: The authors’ novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days.

Conclusions: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Background: Primary spontaneous pneumothorax (PSP) tends to occur in young adults without underlying lung diseases and is usually followed by limited symptoms, while secondary spontaneous pneumothorax (SSP) is a complication of a pre-existing lung disease. Surprisingly, for such common conditions, there is a considerable inconsistency regarding management guidelines.

Objectives: To evaluate the risk factors for spontaneous pneumothoraxes and to summarize outcomes and complications based on our clinical experience.

Methods: This retrospective study group was comprised of 250 consecutive patients older than 18 years of age who were diagnosed with spontaneous pneumothorax and hospitalized at the Meir Medical Center (2004–2017). Data on demographic characteristics, indicating symptoms, chest X-rays, and chest computed tomography (CT) results were collected. Our experience and outcomes were then compared to a large multicenter study.

Results: Most of the patients were male (85%) and past or current smokers; 69% presented with PSP, while the rest were SSP. No occupational relation was noted. About 55% of the cases presented with a moderate or large pneumothorax (over 1/3 hemithorax). Most patients (56%) required chest tube drainage and 20% undergone surgery. Nearly 10% presented with a recurrent pneumothorax with the mean time to recurrence being 11 ± 20 days. Although the length of hospital stay of patients that underwent surgery was the longest (P < 0.001) for both PSP and SSP, the recurrence rate was actually reduced, suggesting some benefit for the surgical treatment option.

Conclusions: Our experience showed that the traditional approach to the PSP treatment should be further considered, as previously suggested.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease caused by chronic obstruction of major pulmonary arteries, which can be cured by pulmonary endarterectomy. However, many CTEPH patients are not surgical candidates. Balloon pulmonary angioplasty (BPA) is an emerging technique used to treat inoperable CTEPH.

Objectives: To describe the first Israeli experience with BPA for inoperable CTEPH.

Methods: In 2017 we established a BPA program at our institution. We reviewed the outcomes to date of BPA in our center.

Results: Forty-seven BPA procedures were performed in five patients with inoperable CTEPH (4–17 procedures/patient). Mean pulmonary artery pressure improved in all patients (median decrease 17 mmHg, range 10–26 mmHg). Pulmonary vascular resistance also improved (median decrease 11 Woods Units/m², range 8–16 Woods Units/m²). Cardiac output increased in 4 of 5 patients and decreased in one. Functional capacity improved from New York Heart Association (NYHA) III to II in four patients; one patient was NYHA II at baseline without change after BPA. Six-minute walking distance improved by a median of 97 meters. (range 21–197 meters). Hemodynamic and functional improvements were sustained at follow-up 5–11 months after the last BPA procedure. BPA enabled 2 of 3 patients treated with parenteral prostanoids to be switched to oral therapy. There were no major complications.

Conclusions: We successfully established BPA as a treatment for inoperable CTEPH in our center. BPA resulted in hemodynamic and clinical improvements that were sustained over time.

Background: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets.

Objectives: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis.

Methods: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019.

Results: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects.

Conclusions: The efficacy of MyC injection should be studied prospectively.

Background: Chronic obstructive pulmonary disease(COPD) is a common and debilitating condition, often accompanied by other co-morbidities. The Hadassah Medical Center’smulti-disciplinary approach in treating COPD patients in a one-stop shopfor COPD patients is the first of its kind in Israel. It includes pulmonary physicians, a nurse coordinator, dietitian, psychotherapist, physiotherapist, and a smoking cessation program.

Objectives: To characterize efficacy of such a program in COPD patients

Methods: Demographic and clinical data from patients referred to the Hadassah COPD center, including co-morbidities, baseline symptoms (using the CAT questioner), spirometry results, 6-minute walking distance (6MWD) test and current treatment were collected and compared to the same data after 6–12 months of treatment.

Results: Some 154 patients were evaluated; mean age 64 years; 67% male; 53% current smokers. Only 74% received chronic treatment for COPD. Average body mass index was 28, CAT score 21.3, and mean FEV1 was 1.38 liters (53% of predicted).The mean exacerbation rate during the year prior to referral was 1.72 with a 1.07 annual admission rate. Following treatment, a small increase was noted in FEV1 to 1.47 liters, 54.4% of predicted; improvement in CAT scores to 16.5 with improvement seen in 70% of patients, and a 42 meter increase in the 6MWD (from 344 to 386 meters) with some improvement of effort capacity in 77% of patients. The rate of smokers decreased to 21%, and 97% of patients received medical treatment for COPD.

Conclusions: Multidisciplinary approach is feasible and efficacious in patients with COPD.