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: 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: 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.

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: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced.                    

Objectives: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3).

Methods: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively

Results: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs. 

Conclusions: Most women with vulvar carcinoma are older than 70 years old. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma. 

 

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.