Israel Medical Association Journal

Background: Uterine tachysystole during labor can lead to a decrease in fetal oxygen saturation and intracerebral oxygen saturation. Acute tocolysis using atosiban can inhibit uterine smooth muscle activity, potentially improving fetal status and facilitating vaginal delivery or allowing time to prepare for operative delivery.

Objectives: To compare maternal and neonatal outcomes in cesarean and vaginal deliveries following atosiban administration during fetal prolonged deceleration and tachysystole at gestational age 37 0/7 to 43 0/7 weeks.

Methods: We conducted a single-center, descriptive retrospective cohort study at a large tertiary referral center.

Results: Of the 275 patients treated with atosiban, 186 (68%) delivered vaginally (either spontaneous delivery or instrumental delivery) and 89 (32%) underwent a cesarean delivery. In a univariate analysis, cesarean delivery was associated with higher body mass index (27.9 ± 4.3 vs. 30.2 ± 4.8, P = 0.003). Second stage atosiban administration was associated with vaginal delivery (89.3% vs. 10.7%, P = 0.01). Cesarean delivery was associated with lower Apgar at 1 and 5 minutes and a higher rate of neonatal intensive care unit admissions. The incidence of PPH among women treated with atosiban in our study (2.3–4.3%) was higher than the incidence reported in the literature (1–3%)  

Conclusions: Atosiban may be an effective acute intervention for non-reassuring fetal heart rate during tachysystole, increasing the rate of vaginal delivery and potentially reducing the need for cesarean delivery. However, the potential risk of postpartum hemorrhage should be taken into consideration.

Background: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR.

Objectives: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer.

Methods: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival.

Results: For 124 patients the median follow-up was 23 months (range 1–88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS.

Conclusions: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis and usually constitutes a diagnostic challenge. There are many causes for recurrent and chronic pancreatitis, with the main etiology being alcohol and choledocholithiasis [1]. However, the association between pancreatic divisum (PD), a common congenital anomaly of the pancreas that is rarely symptomatic, and complications of pancreatitis is still not firmly established [2]. Furthermore, the optimal management of PPF is still uncertain due to its rarity [3]. We describe a rare case of a 45-year-old woman with recurrent pancreatitis that presented with a PPF on the background of PD, successfully managed with conservative treatment. The purpose of this report is to highlight the rare association between PPF and PD together with the excellent response to conservative therapy.

Background: Physiotherapy can help treat of trigger fingers (TF).

Objectives: To compare efficacy of fascial manipulation (FM) and traditional physiotherapy (TP) techniques in treatment of TF.

Methods: Nineteen patients were randomized in the FM group and 15 in the TP group. All patients underwent eight physiotherapy sessions. The Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and visual analogue scale (VAS) scores, staging of stenosing tenosynovitis (SST) classification, triggering frequency, grip and pinch strength were recorded before and after treatment. We surveyed participants at 6 months for recurrence, further treatment, and the VAS and QuickDASH scores. The primary outcome measure was reduction in QuickDASH and VAS scores.

Results: Both FM and TF improved the QuickDASH and VAS scores at 6 months follow-up, without a significant difference. The QuickDASH score in the FM group improved from 28.4 ± 17.1 to 12.7 ± 16.3; TF scores improved from 27 ± 16.7 to 18.8 ± 29.4 (P = 0.001). The VAS score improved from 5.7 ± 2.1 to 1.2 ± 2.1 and from 4.8 ± 1.8 to 2 ± 2.6 for both groups, respectively (P < 0.001). SST and grip strength also improved following treatment, regardless of modality. At 6 months, four patients (22%) with an SST score of 1, three (30%) with a score of 2, and two (40%) with a score of 3A underwent additional treatment.

Conclusions: Both FM and TP techniques are effective for the treatment of TF and should be considered for patients who present with SST scores of 1 or 2.

Stevens-Johnson Syndrome (SJS), or toxic epidermal necrolysis, is a rare syndrome that develops after an allergic reaction to a medication [1,2]. It affects the skin and the mucocutaneous tissue. Individuals diagnosed with SJS are rarely referred to a rehabilitation medicine (RM) facility.

The annual prevalence of SJS is about one in one million. The skin is covered with blisters. Usually, it affects about 10 % of body surface area. The patients are treated usually by ophthalmologists, dermatologists, allergologists, and immunologists. When severe complications occur, plastic surgeons and intensive care physicians may also be involved. Few publications were found that linked SJS with comprehensive rehabilitation treatment [3-5].

Background: Implant-based breast reconstruction (IBR) is the most common method of reconstruction for breast cancer. Bacterial infection is a well-known risk with reported rates ranging from 1% to 43%. The most common pathogens of breast implant infection described in the literature are Staphylococcus aureus, Staphylococcus epidermidis, and coagulase-negative staphylococci. However, the prevalence of other pathogens and their antibiotic sensitivity profile differs profoundly in different parts of the world.

Objectives: To review the current literature and protocols with respect to our region and to determine a more accurate antibiotic protocol aimed at our specific local pathogens.

Methods: A retrospective review was conducted of all cases of clinically infected implant-based breast reconstruction in our institution from June 2013 to June 2019, as well as review of microbiologic data from around the world based on current literature.

Results: A total of 28 patients representing 28 clinically infected implant-based breast reconstruction were identified during the studied period. Thirteen patients (46.4%) had a positive bacterial culture growth, with P. aeruginosa being the most common microorganism identified (46.1%). Review of international microbiological data demonstrated significant variation at different places and time periods.

Conclusions: Microbiological data in cases of infected breast reconstructions should be collected and analyzed in every medical center and updated every few years due to the variations observed. These data will help to adjust the optimal empirical antibiotic regimens given to patients presenting with infections after breast reconstruction.

Background: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.

Objectives: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.

Methods: We reviewed charts of patients who were diagnosed with stage I–III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.

Results: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.

Conclusions: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Background: Serasis® (Serag-Wiessner KG, Naila, Germany) is a light-weight mid-urethral sling for treating stress urinary incontinence (SUI). Its insertion is considered less traumatic than other mid-urethral slings.

Objectives: To define postoperative outcomes following Serasis implantation. To compare the efficacy and complication rates of the implant to those of other common techniques.

Methods: Our retrospective study evaluated patients who underwent Serasis mid-urethral sling surgery for SUI. Data were collected from medical records prior to and at the time of surgery and by telephonic interview for postoperative pain and complications. Follow-up of patients was performed for up to one year postoperatively. Patients rated pain or discomfort according to the Visual Analogue Scale (VAS). The primary outcome was the development of early postoperative pain during the first month after surgery. Secondary outcomes were relief of SUI symptoms, groin pain or discomfort, and other postoperative complications up to 12 months after surgery.

Results: The study cohort included 50 consecutive patients aged 31 to 68 years. All patients underwent Serasis implantation procedures by a single surgeon and completed interviews. In total, 35 patients underwent concomitant anterior colporrhaphy. In the immediate postoperative period and at one month after the procedure, complaints were mild. No complaints were recorded during the 12-month follow-up period. Overall, 90% and 92% of the patients were free of SUI symptoms at one month and 12 months after surgery, respectively.

Conclusions: Serasis mid-urethral sling is safe, effective, and associated with mild postoperative pain and a low incidence of complications.

Coronavirus disease 2019 (COVID-19), first identified in 2019, constitutes a global major public health burden. Most of morbidity and mortality is derived by the severe inflammatory reaction (cytokine release syndrome) that ensues in later stages. Baricitinib, a selective JAK inhibitor primarily used for the treatment of rheumatoid arthritis (RA) [1], was shown to reduce mortality in COVID-19 hospitalized patients in combination with remdesivir [2].

Background: Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials, have become available in recent years. Comparative data among different drugs are scarce.

Objectives: To describe and compare the clinical outcomes of biological therapies in severe asthma patients treated at Shamir Medical Center.

Methods: We conducted a cohort study based on a review of cases treated with monoclonal antibodies for severe asthma at our center. Data were extracted for demographics, eosinophil count, lung function (FEV1), exacerbation rate, and median dose of oral prednisone. Between-drug comparison was conducted by repeated measures ANOVA.

Results: The cohort included 62 patients receiving biological therapy. All biologic drugs were found to reduce exacerbation rate [F(1, 2) = 40.4, P < 0.0001] and prednisone use [F(1, 4) = 16, P < 0.001] significantly. ANOVA revealed no difference of efficacy endpoints between the different drugs. Eosinophil count was significantly reduced post-biologic treatment in the anti-interleukin-5 agents (P < 0.001) but not under treatment with omalizumab and dupilumab.

Conclusions: All of the biological therapies were effective for improving clinical outcomes. None of the agents was clearly superior to any other. These data emphasize the need for severe asthma patients to be seen by pulmonary medicine specialists and offered, where appropriate, biological therapies.

Background: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient’s skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping.

Objectives: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan.

Methods: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease.

Results: The study included 817 eligible patients, mean age 40 (2–95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02).

Conclusions: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

Background: Vaginal hysterectomy (VH) and colpocleisis are both used for the treatment of advanced pelvic organ prolapse (POP).

Objective: To compare short- and long-term outcomes of vaginal hysterectomy vs. colpocleisis for advanced POP.

Methods: Hospital and outpatient charts of patients who underwent VH or colpocleisis at our institution between January 2006 and December 2015 were reviewed. Clinical data were obtained and analyzed.

Results: In this study, 188 patients underwent VH and 32 patients underwent colpocleisis. The colpocleisis group was significantly older than the VH group (79.5 ± 4.5 vs. 69 ± 6.1 years respectively, P < 0.0001) and presented with significantly higher co-morbidity rates and a higher degree of POP. Perioperative blood loss was significantly lower (250 ± 7.6 ml vs. 300 ± 115 ml, P < 0.0001) and postoperative hospitalization was significantly shorter (2 ± 2.7 vs. 3 ± 2.2 days, P = 0.015) among the colpocleisis group. None of the patients from the colpocleisis group required an indwelling urethral catheter after discharge, compared to 27.5% of the patients from the VH group (P = 0.001). Total postoperative complication rate was significantly lower among the colpocleisis group (25% vs. 31% P < 0.0001). Objective recurrence of POP was significantly more common among the VH group (7% vs. 0% and 21% vs. 0% for the anterior and posterior compartments, respectively, P = 0.04).

Conclusions: Colpocleisis is associated with faster recovery, lower perioperative morbidity, and higher success rates than VH and should be considered for frail and elderly patients.

Background: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking.

Objectives: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents.

Methods: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses.

Results: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability.

Conclusions: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

Background: Diabetes mellitus (DM) is one of the risk factors for progression from latent to active tuberculosis. However, the effect of DM on subsequent tuberculosis treatment is still inconclusive.

Objectives: To compare tuberculosis treatment outcomes and the rate of drug resistance of tuberculosis patients with or without DM.

Methods: This case-control study was conducted between 2005 and 2015 at the only tuberculosis ward in Israel. All 80 tuberculosis patients who had DM and were hospitalized during the study period were included in this study, as were a randomized sample of 213 tuberculosis patients without DM. Demographic, clinical, and laboratory data were collected from patient files in the hospital and clinics after discharge.

Results: Tuberculosis patients with DM were more often older and more likely to be Israeli citizens with a lower socioeconomic status than patients without DM. No statistically significant differences were found in clinical presentation, radiological findings, and sputum smear tests between the two groups. Culture converting times were prolonged in patients with DM compared to normoglycemic patients. Multidrug drug resistance tuberculosis was more common among normoglycemic tuberculosis patients than tuberculosis patients with DM (9.2% vs. 1.6%, P = 0.12). Treatment success rates were 76.2% and 83.1% for tuberculosis patients with or without DM, respectively (P = 0.18). DM was not statistically significant in the multivariate analysis predicting treatment success, which controlled for age, citizenship, compliance, addictions, and chronic diseases.

Conclusions: The presence of DM does not necessarily affect tuberculosis treatment outcomes as long as treatment compliance is optimal.