Israel Medical Association Journal

Background: Cases of second trimester pregnancy loss can be treated either pharmacologically or by surgical evacuation. Misoprostol, an E1-prostaglandin analog, is used to facilitate the evacuation of the uterus.

Objectives: To determine the risk factors associated with patients who were treated with five or more repeated doses of misoprostol.

Methods: We conducted a retrospective study of patients treated with vaginal misoprostol at our institution between December 2016 and October 2021 for second trimester pregnancy loss.

Results: In total, 114 patients were eligible for analysis; 83 were treated with < 5 doses and 31 with ≥ 5. We recorded each case in which repeated doses were administered, irrespective of predetermined conditions such as gravidity, parity, maternal age, or gestational age. Moreover, cases of five or more misoprostol dosing were not associated with an increased complications rate, except for the increased duration of hospitalization (3.1 vs. 2.2 days, P-value < 0.01).

Conclusions: Repeated dosing could not be predicted before treatment among those treated with vaginally administered misoprostol for second trimester pregnancy loss. However, low complication rates of repeated dosing may reassure both physicians and patients regarding safety, efficacy, and future fertility.

Background: Small left atria (LA) is associated with an increased risk of mortality.

Objectives: To determine whether the attributed risk of mortality is influenced by the underlying etiologies leading to decreased volumes.

Methods: We retrospectively evaluated patients with an available LA volume index (LAVI) as measured by echocardiography who came to our institution between 2011 and 2016. Individuals with small LA (LAVI < 16 ml/m²) were included and divided according to the etiology of the small LA (determined or indeterminate) and investigated according to the specific etiology.

Results: The cohort consisted of 288 patients with a mean age of 56 ± 18 years. An etiology for small LA was determined in 84% (n=242). The 1-year mortality rate of the entire cohort was 20.5%. Patients with indeterminate etiology (n=46) demonstrated a lower mortality rate compared with determined etiologies (8.7% vs. 22.7%, P = 0.031). However, following propensity score adjustments for baseline characteristics, there was no significant difference between the groups (P = 0.149). The only specific etiology independently associated with 1-year mortality was the presence of space occupying lesions (odds ratio 3.26, 95% confidence interval 1.02–10.39, P = 0.045).

Conclusions: Small LA serve as a marker for negative outcomes, and even in cases of undetected etiology, the prognosis remains poor. The presence of small LA should alert the physician to a high risk of mortality, regardless of the underlying disease.

Background: Diagnosing occult stress urinary incontinence (OSUI) prior to surgical intervention for pelvic organ prolapse (POP) repair may allow for adding an anti-incontinence procedure and thus prevent postoperative SUI.

Objectives: To compare preoperative detection rates for OSUI by either a multichannel urodynamic investigation or by a plain pelvic examination.

Methods: We retrospectively evaluated the medical charts of all women who underwent urodynamic investigation prior to surgical repair of advanced POP at our institution between 1 January 2006 and 31 December 2012.

Results: In total, 720 women underwent surgical POP repair during the study period, of whom 54 (7.5%) were diagnosed with OSUI preoperatively. Of these patients, 54 (100%) were detected by multichannel urodynamic investigation while only 27 (50%) were detected by a plain pelvic examination (P = 0.001). Bladder fullness during the pelvic examination was associated with higher detection rates for OSUI (P = 0.001). Women with OSUI who underwent concomitant tension-free vaginal tape and POP repair procedures did not develop de novo SUI or obstructive voiding symptoms (OVS) postoperatively.

Conclusions: Preoperative multichannel urodynamic investigation has significantly higher detection rates for OSUI than a plain pelvic examination. Utilizing this modality resulted in no cases of de novo SUI or OVS postoperatively.

Background: Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower healthcare costs.

Objectives: To evaluate the implementation of the ERAS protocol and the effect on recovery during the hospitalization period after gynecological laparotomy surgeries.

Methods: We compared demographic and clinical data of consecutive patients at a single institute who underwent open gynecological surgeries before (August 2017 to December 2018) and after (January 2019 to March 2020) the implementation of the ERAS protocol. Eighty women were included in each group.

Results: The clinical and demographic characteristics were similar among the women operated before and after implementation of the ERAS protocol. Following implementation of the protocol, decreases were observed in post-surgical hospitalization (from 4.89 ± 2.56 to 4.09 ± 1.65 days, P = 0.01), in patients reporting nausea symptoms (from 18 (22.5%) to 7 (8.8%), P = 0.017), and in the use of postoperative opioids (from 77 (96.3%) to 47 (58.8%), P < 0.001). No significant changes were identified between the two periods regarding vomiting, 30-day re-hospitalization, and postoperative minor and major complications.

Conclusions: Implementation of the ERAS protocol is feasible and was found to result in less postoperative opioid use, a faster return to normal feeding, and a shorter postoperative hospital stay. Implementation of the protocol implementation was not associated with an increased rate of complications or with re-admissions

Background: Early referral to palliative care services in patients with advanced cancer is widely accepted. In addition, the use of futile intervention at the end of life is a pivotal aspect of assessing quality of care at that time.

Objectives: To evaluate the use of palliative care and aggressive treatments during the last month of life in women with gynecological malignancies.

Methods: The study was designed in two steps. The first step included a retrospective analysis of a gynecologic oncology cohort that underwent end-of-life (EOL) care. In the second part, a questionnaire regarding EOL care was completed by family members. Since our palliative care service became more active after 2014, we compared data from the years 2013–2014 to the years 2015–2019.

Results: We identified 89 patients who died from gynecological malignancy during study period; 21% received chemotherapy and 40% underwent invasive procedures during their last month of life. A palliative care consultation was documented for 49% of patients more than one week before their death. No statistical difference was achieved between the two time periods regarding the use of chemotherapy or invasive procedures in the last month of life. Nonetheless, after the incorporation of palliative medicine more women had palliative care consultations and had EOL discussions. Most of the patients’ relatives were satisfied with EOL care.

Conclusions: Many aggressive interventions were given during the last month of life. EOL discussions were documented in the medical charts of most patients and the rates increased with time.

Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease that presents an urgent challenge to global health and economy.

Objectives: To assess the effects of population median age and mean ambient temperature on the COVID-19 global pandemic burden.

Methods: We used databases from open access public domains to record population median age, mean ambient temperature, and the numbers of COVID-19 cases and deaths on days 14 and 28 from the pandemic outbreak for each country in the world. We then calculated the correlation between these parameters.

Results: The analysis included 202 countries. A univariate analysis showed that population median age significantly correlated with the cumulative number of cases and deaths, while mean ambient temperature showed a significant inverse correlation with the cumulative number of deaths on days 14 and 28 from the epidemic outbreak. After a multivariate logistic regression analysis only population median age retained its statistically significant correlation.

Conclusions: Country population median age significantly correlated with COVID-19 pandemic burden while mean ambient temperature shows a significant inverse correlation only in univariate analysis. Countries with older populations encountered a heavier burden from the COVID-19 pandemic. This information may be valuable for health systems in planning strategies for combating this global health hazard.

Background: Peritoneal dialysis (PD) is a treatment option for patients with end-stage renal disease (ESRD) and cardiorenal syndrome (CRS).

Objectives: To evaluate the outcome of this patient population.

Methods: A retrospective study was conducted of patients who underwent an open or laparoscopic insertion of a PD catheter at our institution between 2009 and 2017. Data included demographics, peri-operative parameters, and long-term outcome. Patient and technique survival curves are presented, including subgroup analysis by method of catheter insertion and techniques for infection prevention.

Results: The study population included 95 men and 42 women, aged 65.7 ± 12.4 years. Mean follow-up was 34.6 ± 27.3 months. Open insertion was performed in 113 cases, while 24 underwent laparoscopic insertion. There was no difference in technique survival between these groups (P = 0.943). Removal of the catheter was required in 66% of patients. Median technique survival was 12.1 months. Two-year technique survival was 37% and 5-year technique survival was 12%. The leading cause for catheter removal was infection (69%). Application of measures for prevention of infections were significantly associated with prolonged technique survival (P = 0.001). Technique survival after 2 years was 38% with the application of a single measure and 57% with the application of two measures (P = 0.001). CRS patients (n=24) had a significantly lower overall survival rate (2-year survival 20% vs. 74%, P = 0.001).

Conclusions: The method of catheter insertion has no effect on technique survival. Prevention of infections is the most significant factor for improving the technique survival rates.

Background: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease.

Objectives: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA).

Methods: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization.

Results: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06–6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01–1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01–1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22–4.11).

Conclusions: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

Background: Falls are a common complication in persons with stroke (PwS). Reliable assessment of balance responses to unexpected loss of balance has the potential to identify risk for falls. 

Objectives: To examine inter-observer reliability of balance responses to unannounced surface perturbations in PwS and to explore the concurrent validity of a balance recovery assessment protocol.

Methods: Two observers evaluated balance recovery strategies and fall threshold (a fall into a harness system) in 15 PwS and 15 healthy adults who were exposed to forward, backward, right, and left unannounced surface translations in six increasing intensities while standing. 

Results: Observer agreement was 100% for the fall threshold. Kappa coefficients for step strategies were 0.960–0.988 in PwS and 0.886–0.938 in healthy adults, 0.905–0.988 for arm reactions in PwS and 0.754–0.926 in healthy adults. Significant correlations were found between fall threshold and Berg Balance Scale (r = 0.691), 6-minute walk test (r = 0.599), and fall efficacy scale-international (r= -0.581). 

Conclusions: A trained examiner can reliably classify reactive balance responses to surface perturbations. The high frequency of falls observed in PwS highlights the importance of assessing reactive balance responses to different directions and intensities of surface translations.

Background: Pneumonia is a major cause of morbidity and mortality in burn patients with inhalation injuries. An increased risk of pneumonia has been demonstrated in trauma and burn patients urgently intubated in the field vs. emergency departments (EDs).

Objectives: To compare intubation setting (field vs. ED) and subsequent development of pneumonia in burn patients and to evaluate the indication for urgent intubation outside the hospital setting.

Methods: A retrospective medical records review was conducted on all intubated patients presenting with thermal (study group, 118 patients) or trauma (control group A, 74 patients) injuries and admitted to the intensive care unit of a level I trauma and burn center at a single institution during a 15 year period. Control group B (50 patients) included non-intubated facial burn patients hospitalized in the plastic surgery department.

Results: Field intubation was less frequent (37% field vs. 63% ED), although it was more frequent in larger burns (total body surface area > 50%; 43% field vs. 27% ED). More field intubated patients developed pneumonia during hospitalization (65% field vs. 36% ED [burns]; 81% field vs. 45% ED [multi-trauma]; 2% non-intubated, P < 0.05), with a significantly higher all-cause mortality (49% field vs. 24% ED, P < 0.05) and dramatically lower rates of extubation within 3 days (7% field vs. 27% ED, P < 0.05).

Conclusions: Field intubation is associated with a higher risk of subsequent development of pneumonia in burn and multi-trauma patients and should be applied with caution, only when airway patency is at immediate risk.

Because fragility fractures have an enormous impact on the practice of medicine and global health systems, effective screening is imperative. Currently, dual-energy X-ray absorptiometry (DXA), which has limited ability to predict fractures, is being used. We evaluated the current literature for a method that may constitute a better screening method to predict fragility fractures. A systematic review of the literature was conducted on computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound to evaluate screening methods to predict fragility fractures. We found that ultrasound had sufficient data on fracture prediction to perform meta-analysis; therefore, we analyzed prospective ultrasound cohort studies. Six study populations, consisting of 29,299 individuals (87,296 person-years of observation) and including 992 fractures, were analyzed. MRI was found to be sensitive and specific for osteoporosis, but its use for screening has not been sufficiently evaluated and more research is needed on cost, accessibility, technical challenges, and sensitivity and specificity. CT could predict fracture occurrence; however, it may be problematic for screening due to cost, exposure to radiation, and availability. Ultrasound was found to predict fracture occurrence with an increased risk of 1.45 (95% confidence interval 1.21–1.73) to fracture. Ultrasound has not replaced DXA as a screening tool for osteoporosis, perhaps due to operator-dependency and difficulty in standardization of testing.

Background: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean).

Objectives: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications.

Methods: We analyzed all gastrectomies for gastric cancer performed 2009–2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification.

Results: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05).

Conclusions: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

Background: Invasive cervical cancer is caused by human papillomavirus (HPV).

Objectives: To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia.

Methods: Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006–2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR).

Results: Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively.

Conclusions: This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.

Background: The goals of treatment for rheumatoid arthritis (RA) are remission and low disease activity (LDA). However, many patients do not reach or maintain these targets with regard to disease control. 

Objective: To identify predictive factors of remission/LDA in a cohort of RA patients who started treatment with first line tumor necrosis factor-inhibitors (TNF-i). 

Methods: We included 308 RA patients treated with first line TNF-i for 2 years to evaluate remission/LDA based on the 28-joint disease activity score (DAS28). Predictive factors considered for achievement of remission/LDA were: gender, age at the time of TNF-i treatment, early arthritis, baseline C-reactive protein (CRP) and erythrocyte sedimentation rate levels, RF/anti-citrullinated protein antibody positivity, good/moderate European League Against Rheumatism response at 6 months, co-morbidities, and concomitant disease modifying antirheumatic drugs (DMARDs). Intention to treat, receiver operating characteristic curve, and univariate and multivariate analyses by logistic regression were performed. 

Results: Positive predictors of remission/LDA in both the univariate and the multivariate analyses were: male gender, age at the time of TNF-i treatment ≤ 54 years, negative baseline CRP, and concomitant DMARDs. The presence of any co-morbidity resulted to be a negative predictor of remission/LDA in both the univariate and the multivariate analyses. 

Conclusions: Demographic and clinical features were identified as reliable predictors of both the achievement and the maintenance of treatment targets in a cohort of RA patients treated for 2 years with first line TNF-i.