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Objective: To evaluate the use of manipulators on the outcome of women who had minimally invasive surgery for endometrial cancer. Methods: Retrospective analysis of patients operated with or without an intrauterine manipulator. Results: Six hundred ninety-nine patients were included. The median follow-up was 44 months (range, 29–67). Nineteen (8.8%) patients had positive cytology in the manipulator group versus 21 (4.4%) in the comparison group (p = 0.02). Total recurrence rate was similar between the groups (12.3% vs. 11.9%; p = 0.8). Vaginal vault recurrence was the most common site of recurrence with higher incidence in the manipulator group (4.5% vs. 1.3%; p = 0.007). Subgroup analysis of low-risk patients who did not receive adjuvant treatment showed higher recurrence rate (8.3% vs. 3%; p = 0.023) and worse disease-free survival (p = 0.01) for the manipulator group. After controlling for other variables, the use of a manipulator did not affect the risk of recurrence for the whole cohort (hazard ratio [HR], 1.28; confidence interval [95% CI], 0.7–2.1, p = 0.3) and for the low-risk subgroup of patients who did not receive adjuvant treatment (HR, 2.47; 95% CI, 0.8–7, p = 0.08). Conclusion: The use of a manipulator increases the risk of positive cytology as well as vaginal vault recurrences, but it does not reduce the overall survival of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with early-stage cervical cancer treated by minimally invasive surgery show shorter progression-free and overall survival compared to open surgery. This study integrated minimally invasive and open surgery survival data with surgery costs and utilities and conducted a cost-effectiveness analysis, using a Markovian decision analysis model, to compare the two surgical approaches. Our results show that open radical hysterectomy is not only oncologically superior but also more cost-effective. Until new data regarding the safety of minimally invasive surgery and surgery costs are presented, open radical hysterectomy should be the preferred approach from both the oncological and financial standpoint. We aimed to investigate the cost-effectiveness of open surgery, compared to minimally invasive radical hysterectomy for early-stage cervical cancer, using updated survival data. Costs and utilities of each surgical approach were compared using a Markovian decision analysis model. Survival data stratified by surgical approach and surgery costs were received from recently published data. Average costs were discounted at 3%. The value of health benefits for each strategy was calculated using quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio, calculated using the formula (average cost minimal invasive surgery—average cost open surgery)/(average QALY minimal invasive surgery—average QALY open surgery), was used for cost-effectiveness analysis. One-way sensitivity analysis was conducted for all variables. Open radical hysterectomy was found to be cost-saving compared to minimally invasive surgery with an incremental cost-effectiveness ratio of USD −66 and USD −373 for laparoscopic and robotic surgery, respectively. The most influential parameters in the model were surgery costs, followed by the disutility involved with open surgery. Until further data are generated regarding the survival of patients with early-stage cervical cancer treated by minimally invasive surgery, at current pricing, open radical hysterectomy is cost-saving compared to minimally invasive radical hysterectomy, both laparoscopic and robotic. [ABSTRACT FROM AUTHOR]

Introduction: Lower uterine segment scarring after cesarean section can decrease intraoperative bleeding during subsequent surgery. We examined whether first elective cesarean section is associated with greater average blood loss compared to repeated surgery. Methods: Decrease in maternal hemoglobin and hematocrit after surgery was retrospectively compared between three study groups, women in their first, second and third or more cesarean section. Surgery length and need for blood transfusion were also compared. Results: Out of 9401 cases reviewed between January 2010 November 2020, 3917 had a first cesarean section, 3159 s cesarean section and 2325 had a third or more cesarean section. Hemoglobin and hematocrit drops were highest after first cesarean section (1.1 vs 1.0 vs 1.0 mg/dL, P < 0.001 and 3.3 vs 3.0, vs 2.9%, P < 0.001, respectively). Surgery length was significantly longer and more patients after third cesarean section required blood transfusions (2.5% vs 1.4% vs. 0.8%, P < 0.001). First cesarean section, younger age and BMI >35 were associated with increased hemoglobin drop in univariate and multivariate analysis. Conclusions: Although repeated cesarean section is associated with longer surgery and higher need for blood transfusion, average hemoglobin drop after first cesarean section is higher. Scarring of the lower uterine segment can explain this paradoxical finding. Synopsis: First elective cesarean section is associated with a higher average hemoglobin decline compared to higher order surgery. [ABSTRACT FROM AUTHOR]

To determine the impact of deciding against medical advice and refusing labor induction in post-term pregnancies on pregnancy outcome. Maternal and neonatal outcomes of women who refused induction of labor due to post term pregnancy (study group) were retrospectively compared to a control group of women who agreed labor induction (1:2 ratio) in a university-affiliated tertiary single medical center. A total of 83 women who refused labor induction were identified and compared to 166 womenwho consented to labor induction. Women who refused labor induction had higher rates of cesarean deliveries (21.7 vs. 10.2% p =.04), longer post-delivery hospitalization (2.9 vs. 2.4 days p <.05) and more advanced gestational age at delivery (41 + 6 vs. 41 + 4 days, p <.05). No significant differences were found in the rate of operative vaginal deliveries, need for antibiotics treatment or blood transfusion between the studied groups. Adverse neonatal outcomes among women who refused labor induction were significantly higher with higher rates of meconium (44.6 vs. 15.7%, p <.01), admission to NICU (9.6 vs. 5%, p <.01) and need for mechanical ventilation (4.8 vs. 0.6%, p <.01). Refusing induction of labor due to post- term pregnancy is associated with higher rate of adverse maternal and neonatal outcomes, with a significant higher risk for cesarean section. [ABSTRACT FROM AUTHOR]

Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women's' sexual health. To assess the effect of cervical conization on women's sexual function and psychological wellbeing. Patients undergoing conization of the cervix were assessed before, and 6 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression, was assessed using the Hospital Anxiety and Depression Scale (HADS). FSDS-r, FSFI and HADS scores before and after conization From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, P=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization, (26.8 vs. 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization, P=0.388. A high percent of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization, p=1.0. A high percent of patients undergoing conization suffer from sexual distress, sexual dysfunction and general anxiety, both before and after conization. The conization procedure itself did not seem to effect questionnaire scores. This was a prospective cohort, with comprehensive assessment of female sexual and psychological wellbeing after conization. Not all subjects reported sexual intercourse prior to questionnaire completion. Gynecologists should be aware of the psychological and sexual effect of the diagnosis and treatment of cervical pre-cancerous lesions, patients should be counselled accordingly. Michaan N, Loboda N, Ochshorn I, et al., The Effect of Cervical Conization on Women's' Sexual Function and Psychological Health, A Prospective Observational Study. J Sex Med 2022;19:257–262. [ABSTRACT FROM AUTHOR]

Background: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. Results: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Conclusions: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers. [ABSTRACT FROM AUTHOR]

Background: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. Results: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Conclusions: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers. [ABSTRACT FROM AUTHOR]

Objective: To propose a treatment algorithm, after the LACC trial, of laparoscopic sentinel lymph node biopsy with frozen section, followed by immediate open radical hysterectomy in node‐negative cases, for early stage cervical cancer. Methods: We retrospectively collected all cases of cervical cancer that were surgically treated between 2019–2020. In all cases, surgery began with laparoscopic sentinel lymph node biopsy ± ovarian transposition. Node‐negative cases continued with open radical hysterectomy. In node‐positive cases, surgery was discontinued, sparing the patient a laparotomy incision. Results: Nine patients with cervical cancer were referred for surgery. Laparoscopic bilateral lymph node identification was achieved in all. In two cases, sentinel lymph nodes were positive for metastatic cancer and surgery was discontinued. For the other seven, node‐negative patients, open radical hysterectomy was completed. Four patients had laparoscopic ovarian transposition. There were no cases where nodes were negative on frozen section but positive on final pathology. Conclusion: Laparoscopic sentinel lymph node biopsy before open radical hysterectomy may spare a considerable number of laparotomies on the one hand and bi‐modal treatment with surgery and radiation on the other, for node‐positive patients. The oncological safety of this approach is yet to be determined. Laparoscopic sentinel lymph node biopsy before open radical hysterectomy is feasible and could prevent a considerable number of unnecessary laparotomies. [ABSTRACT FROM AUTHOR]

Objective: To describe trends and ethnic differences in incidence of gynecologic cancer in Israel.Methods: In the present retrospective epidemiologic study, age-standardized rates (ASRs) rates of gynecologic malignancies that occurred between January 1, 1993, and December 31, 2013, were extracted from the Israeli National Cancer Registry. The annual percent change (APC) was calculated separately for Jewish and Arab patients for ovarian, endometrial, and cervical cancers.Results: Among Jewish patients, the ASR of ovarian cancer decreased (APC -2.27%, 95% confidence interval [CI], -2.7 to -1.84; P<0.001), the ASR of endometrial cancer increased (APC 1.50%, 95% CI 0.87-2.14; P<0.001), and the ASR of cervical cancer did not change (P=0.737). Among Arab patients, the ASRs of ovarian and cervical cancer did not change (P=0.181 and P=0.575, respectively), and the ASR of endometrial cancer increased (APC 1.98%, 95% CI 0.15-3.85; P=0.021).Conclusions: Between 1993 and 2013, the incidence of gynecologic malignancies showed different trends among Jewish and Arab populations. Endometrial cancer increased among both populations and ovarian cancer decreased among Jewish patients. ASR of cervical cancer was low and stable among both Jewish and Arab groups. These trends could reflect differences in lifestyle and exposure to risk factors associated with each malignancy. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women's sexual health. The study objective was to assess the effect of cervical conization on women's sexual function and psychological wellbeing using structured questionnaires. Methods: Patients undergoing conization of the cervix completed questionnaires before and 6-12 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Results: From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, p=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization (26.8 vs 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization (p=0.388). A high percentage of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization (p=1.0). Conclusions: A high percentage of patients undergoing conization suffer from sexual distress, sexual dysfunction, and general anxiety, both before and after conization. The conization procedure itself did not seem to affect questionnaire scores. Gynecologists should be aware of the psychological and sexual effects of the diagnosis and treatment of cervical pre-cancerous lesions; patients should be counseled accordingly. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods: The cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers, was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality-adjusted life years (QALYs'). All costs were discounted by 3%. Incremental cost-effectiveness ratio (ICER) compared to the willingness to pay threshold was used for cost-effectiveness analysis. A probabilistic sensitivity analysis (Monte Carlo simulation) was conducted with all variables, using 100 trials, each included 10,000 couples, to evaluate model uncertainties. Results: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Discount rate and uptake of risk reduction salpingo- oophorectomy (RRSO) are the most influential parameters that affect the ICER. Increasing uptake of RRSO would make the ICER highly cost-effective. Conclusions: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is costeffective and may be offered for selected couples with high BRCA mutation-related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers. [ABSTRACT FROM AUTHOR]

Background and Objectives: Accidental dural puncture (ADP) during epidural analgesia is a debilitating complication. Symptoms of ADP post-dural puncture headache (PDPH) are headache while rising from supine to upright position, nausea, and neck stiffness. While age, gender and needle characteristics are established risk factors for ADP, little is known about risk factors in laboring women.Methods: All cases of ADP during epidural analgesia treated with blood-patching during a 3-years period were retrospectively reviewed. Each case was matched to two controls according to delivery period.Results: Forty-nine cases of blood patches after ADP out 17 977 epidural anesthesia procedures were identified (0.27%). No differences were found between cases and controls with regards to body mass index, labor stage at time of epidural, length of second stage, location of epidural along the lumbar vertebrae, anesthesiologist's experience or time when epidural was done. In cases of ADP, significantly lower doses of local anesthetics were injected (10.9 versus 13.5 cc, p < 0.001); anesthesiologists reported significantly more trials of epidurals (70 versus 2.8% more than one trial, p < 0.001), more patient movement during the procedure (13 versus 0%, p < 0.001), more intra-procedure suspicion of ADP (69 versus 0%, p < 0.001) and more cases where CSF/blood was drawn with the syringe (57 versus 2.4%, p < 0.001).Conclusion: ADP during labor is a rare but debilitating complication. Risk factors for this iatrogenic complication include patient movement and repeated epidural trials. Intra-procedure identification of ADP is common, allowing early intervention with blood patching where indicated. [ABSTRACT FROM AUTHOR]

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1–6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies. [ABSTRACT FROM AUTHOR]

To investigate whether benign or malignant cells are present in gas evacuated from the abdominal cavity during oncologic laparoscopic surgery. Thirty patients were included in this prospective observational study conducted at an academic, tertiary medical center. Fifteen patients underwent a laparoscopic staging procedure for high-grade uterine adenocarcinoma and 15 patients underwent laparoscopic nephrectomy for suspected renal cell carcinoma. The gas evacuated during laparoscopy was passed through a filter in order to capture any aerosolized cells formed during surgery. After surgery, the filter was rinsed backwards with 50 mL of saline, and the fluid was centrifuged and sent for cytological evaluation. The primary outcome was presence of benign or malignant cells in the rinsed fluid. Neither benign nor malignant cells were identified in evacuated gas in 29 cases (96.7%). In one endometrial cancer case, where macroscopic extra-uterine pelvic metastases were encountered intra-operatively, atypical epithelial cells were found in collected fluid of rinsed gas filter. Gas insufflation during laparoscopy for gynecologic and urologic malignancies apparently does not cause aerosolization and dissemination of malignant cells. However, laparoscopic surgery itself may cause cell spread possibly via surgical instruments when macroscopic, extra-organ tumor spread is encountered, the clinical significance of which remains undetermined. [ABSTRACT FROM AUTHOR]

Background: Exploratory laparotomy is considered the gold standard treatment for women with suspected uterine rupture. We aimed to investigate the feasibility and safety of laparoscopy as an alternative for laparotomy for the management of hemodynamically stable women with suspected postpartum uterine rupture. Study design: We conducted a case series study including all women who were diagnosed with postpartum uterine rupture following vaginal delivery in a university-affiliated tertiary hospital, between November 2012 and July 2021. Until 2016, all women with suspected post-partum uterine rupture underwent laparotomy. Following 2016, a new tailored protocol based on laparoscopy for the management of postpartum uterine rupture in hemodynamically stable women was implemented. A comparison was made between women who underwent emergent laparoscopy to laparotomy. Results: During the study period 17 women were diagnosed with postpartum uterine rupture. From January 2012 to January 2016, four cases of uterine rupture were diagnosed, all of whom underwent laparotomy. Since 2016, thirteen cases of uterine rupture were diagnosed, of whom seven women (54%) underwent laparoscopy and 6 (46%) laparotomy. The median time interval from delivery to surgery was 70.5 min IQR (40–179) in the laparotomy group and 202 min IQR (70–485) in the laparoscopy group. The median operative time for laparoscopic surgery was 80 min (IQR 60–114) and 78 min (IQR 58–114) for the laparotomy group. Four women who underwent laparotomy (40%) and one who underwent laparoscopy (14.2%) were admitted to the intensive care unit following surgery. Blood products transfusion was required in six women who had laparotomy (60%) and one who had laparoscopy (14.2%). Median hospitalization period was 5 d IQR (4–5) in the laparotomy group as compared to 3 d IQR (3–4) in the laparoscopy group. There were no conversions to laparotomy in the laparoscopy group. Conclusions: In hemodynamic stable women laparoscopic surgery for suspected postpartum uterine rupture is feasible and safe. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of the BNT162b, mRNA, SARS-CoV-2 virus vaccine on sperm quality. Methods: This was a prospective cohort study conducted on sperm donors at the sperm bank of a tertiary, university affiliated medical center. All sperm donors donated sperm repeatedly and the average sperm parameters of all available samples were compared before and after receiving the SARS-CoV-2 vaccine. Each donor served as his own control. For all participants, at-least one sperm sample was received 72 days after completing the second vaccine. Main outcome measures included total sperm count, total motile count and percent of motile sperm. Results: A total of 898 sperm samples from 33 sperm donors that were vaccinated with the Pfizer BNT162b, mRNA, SARS-CoV-2 virus vaccine were analyzed, 425 samples were received before the vaccine, while 473 samples were received after vaccination. Total sperm count and total motile count increased after the second vaccine compared to samples before vaccination. Percent of motile sperm did not change after vaccine. Conclusion: The Pfizer BNT162b, SARS-CoV-2 vaccine has no deleterious effect on sperm quality. Patients and physicians should be counseled accordingly. [ABSTRACT FROM AUTHOR]

To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1–25). β-hCG percentage change in the 48 h preceding MTX treatment and β-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04–1.12, p < 0.001 for every percent change in β-hCG; OR = 1.001, 95% CI = 1.0003–1.002 for every unit change in β-hCG, respectively). In a decision tree analysis model, in women with β-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to β-hCG dynamics and level. The absolute risk for tubal rupture in women with β-hCG increment<20% is low. [ABSTRACT FROM AUTHOR]

Aim: We examined the impact of insertion of the Rotavirus vaccine (RVV) into the Israeli National Immunisation Programme (NIP) on hospitalisations due to both acute gastroenteritis (AGE) and Rotavirus gastroenteritis (RVGE) in children. Methods: We retrospectively analysed the medical records of children aged <5 years admitted with a diagnosis of AGE between 2008 and 2016 in two children's hospitals in central Israel. Clinical, laboratory, microbiological data and RV immunisation status were retrieved. Data were compared before and after the introduction of the RVV into the NIP. Results: A total of 2042 children were admitted with AGE. Hospitalisations due to AGE and RVGE decreased from 3310 to 1950 and from 1027 to 585 per 100 000 admissions, respectively, after the RVV (relative risk reduction (RRR) of 41% and 43%, respectively). RV remained the most common pathogen in both study periods. There was no significant difference in the clinical course between immunised and non‐immunised children admitted with RVGE. Conclusion: The introduction of the RVV to the NIP significantly reduced the admissions due to both AGE and RVGE in children <5 years. However, RV is still the most common agent for admissions due to AGE in this age group. [ABSTRACT FROM AUTHOR]

Objective: Clinically suspected appendicitis is the most common nonobstetric surgical problem encountered in pregnancy. The diagnosis of appendicitis is hampered by equivocal symptoms during pregnancy. Ultrasonography (US) remains, as a rule, the imaging test of choice for the diagnosis of clinically suspected appendicitis during pregnancy and other imaging tools such as computed tomography (CT) or magnetic resonance imaging (MRI) are usually avoided. We evaluated the accuracy of US in the diagnosis of appendicitis during pregnancy. Methods: The clinical and sonographic findings of all pregnant women (n = 90), who underwent appendectomy between January 2005 and December 2017 at our institution, were retrospectively reviewed, analyzed, and compared to the clinical and sonographic findings similarly obtained for a control group of nonpregnant women matched for age and date of surgery (±6 months). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ultrasonic findings were calculated and compared between groups as well as within the three pregnancy trimesters. Results: The mean age of the patients was 31.3 ± 0.4. Right lower quadrant pain was present in almost all patients (99%). The sole imaging modality used in our study cohort was US. Among nonpregnant controls, CT scan was primarily used on more occasions (53.3%) compared to US (45.6%). Nonpregnant women underwent significantly more laparoscopies compared to pregnant women (83.3 versus 45.6%, p <.001). The rate of negative appendectomy was higher in pregnant women (31.1 versus 10%, p =.002). Among pregnant women operated there was a higher rate of inconclusive or negative imaging (43.3 versus 11.1%, p <.001). The rate of perforated appendix at surgery was similar in both groups (6.7 and 4.4%, respectively, p =.75). Conclusions: Ultrasonography (US) is of mediocre accuracy for the diagnosis of acute appendicitis in pregnant patients beyond the first trimester of pregnancy. Thirty percent of pregnant women with suspected appendicitis are futilely operated. Given the low yield of US, a second-line imaging should be considered in cases of inconclusive US before surgery. [ABSTRACT FROM AUTHOR]

Objective: Evaluate whether the incorporation of the refugees into the Israeli medical system resulted in improvements in perinatal outcomes, namely a reduction in the number of preterm deliveries and a decrease in NICU admissions.Methods: Retrospective cohort study. Electronic medical records of all African immigrants who delivered in our tertiary referral center between January 2018 and September 2019 were reviewed. African patients' demographics, maternal and perinatal outcomes were compared to those of native Israeli population. In addition, the results were compared to the cohort from our previous study from 2010.Results: A total of 20,796 deliveries took place at our labor and delivery department during the study period. Of these, 3% of all deliveries were of African refugees. Total rates of preterm deliveries <37 weeks was similar between groups, while rate of premature deliveries <34 week was higher among refugees. Rates of extreme prematurity <28 weeks were also similar between groups. Rate of meconium stained amniotic fluid, neonatal weight <2000 g as well as NICU admissions were significantly higher among refugees.Conclusion: Though perinatal results have not substantially improved with the incorporation of a refugee population into a healthcare system, some progression has indeed been achieved in some perinatal parameters. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the present study was to compare the incidence of endometrial carcinoma following hysterectomy in patients with presurgical diagnoses of atypical endometrial hyperplasia (non-polypoid) versus atypical endometrial hyperplasia confined to an endometrial polyp. Methods: Medical records of women who underwent staging surgery, including hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node dissection, for atypical endometrial hyperplasia or atypical endometrial polyp between 2016 and 2020 were reviewed. Results: Seventy-nine women who underwent surgery were included. Of those, 46 women were diagnosed with an atypical endometrial polyp that was resected via hysteroscopy (endometrial polyp group), and 33 women had non-polypoid atypical endometrial hyperplasia following endometrial tissue sampling (non-polypoid group). The mean age at diagnosis was 60.2 ± 9.9 years in the endometrial polyp group compared to 61.7 ± 12 years in the non-polypoid group (p=0.5). Most women (81.8%) in the non-polypoid group presented with post-menopausal bleeding, whereas 41.3% of the women in the endometrial polyp group were asymptomatic (p=0.001). Pathology results from the hysterectomy specimens revealed concurrent endometrial carcinoma in 23.9% of women in the endometrial polyp group compared to 51.5% of women in the non-polypoid group (p=0.001). Ninety-one percent of cancers were grade 1 in the endometrial polyp group compared to 53% of cancers in the non-polypoid group. Grade 2 was found in 9% of cancers in the endometrial polyp group compared to 35% of women in the non-polypoid group (p=0.04). Most women were diagnosed at stage IA, 91% in the endometrial polyp group compared to 82% in the non-polypoid group (p=0.6). In both groups, none of the sentinel lymph nodes harvested during surgery were involved by cancer. Conclusions: Concurrent cancer is less frequent with atypical endometrial polyp as compared to atypical endometrial hyperplasia. Still, the high incidence of endometrial carcinoma in both groups supports the current advice to perform a hysterectomy and bilateral salpingo- oophorectomy for peri and post-menopausal women. Our data do not support performing sentinel lymph node dissection for atypical endometrial hyperplasia. [ABSTRACT FROM AUTHOR]

Objectives: Epithelial ovarian cancer is often diagnosed at an advanced stage due to intraperitoneal spread. Modern treatment strategies have only modestly improved the survival rates of this disease. Chimeric antigen receptor (CAR) T cells enable T cells to directly bind tumor-associated antigens in an MHC-independent manner inducing tumor rejection. A major barrier is the lack of true tumor-specific antigens followed by risk of "on-target off-tumor" toxicity. Innovative approaches are therefore needed to increase the specificity of CAR-modified T cells exclusively against tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal versus intravenous CAR T cell therapy. Our working hypothesis was that intraperitoneal CAR T cell therapy will demonstrate higher cytotoxic activity towards a tumor tissue while sparing non-tumor tissues. Methods: We have constructed CARs targeting HER2 (ErbB2) that are overexpressed in ovarian cancers. CARs were expressed in human lymphocytes, and their functionality toward human ovarian cancer cell lines was evaluated in-vitro and in a murine model. Results: We have found that the anti-ErbB2 CARs secreted IFN-g (600-1800pg/ml) after stimulation with OVCAR8, SKOV3, or NAR cells compared to untransduced lymphocytes CAR T cells (50pg/ml). Treatment with an intraperitoneal injection of anti-ErbB2 CAR T cells leads to remission of the tumor and increased survival compared to the intravenous route. Intraperitoneal treatment of anti-ErbB2 CARs was less toxic to non-tumor tissues compared to the intravenous treatment. Conclusions: Our results demonstrate that the intra-peritoneal approach of CAR T cells offers a safe strategy with a clinical potential for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Although non-inferior overall survival and reduced surgical morbidity with neoadjuvant therapy (NAC) compared to primary debulking surgery, upfront debulking surgery remains the treatment of choice for newly diagnosed advanced stage ovarian cancer (OC) in the US. This can be partially attributed to the association of aggressive surgical treatment with long term survival (LTS) demonstrated in high grade serous OC (HGSOC). On the contrary, NAC has been shown to lower the odds for LTS. We aimed to identify clinico-pathologic factors associated with LTS in advanced epithelial OC (EOC) treated with NAC. This is a retrospective case-control study. Women with FIGO stage III-IV high grade epithelial cancer of the ovary, fallopian tube or peritoneum diagnosed and treated with NAC prior to 2013 were extracted from consecutive patient records of the Tel-Aviv Sourasky Medical Center. Women surviving longer than 7 years from diagnosis (defined as long-term survivors, LTS) were compared to women surviving 6-24 months from diagnosis (defined as short-term survivors, STS). Patients with low grade or low malignant potential tumors were excluded. We identified 190 women with stage III/IV epithelial OC. Seventy-eight patients (41%) survived longer than 5 years from diagnosis and 47 (24%) survived longer than 7 years from diagnosis, significantly higher proportions compared to previous reports. Thirty-nine patients (20%) survived 6-24 months, similar to previous reports. Clinicopathologic and treatment characteristics of both groups are displayed in Table 1. CA125 pre-treatment or after 4 courses of chemotherapy and the number of adjuvant and total chemotherapy courses administered were similar between the groups. LTS were significantly younger than STS at diagnosis, with a mean age of 60.05 years vs 65.95 years, respectively (p=0.008). The majority of LTS received 3 courses of NAC or less compared to STS (59.6% vs 33.4%), implying a smaller disease burden or better response to NAC. LTS had a significantly longer disease-free interval (80.49 months vs 3.65 months, p<0.0001) and significantly less recurrences (68.1% vs 94.9%, p=0.002) compared to STS. Logistic regression model including age at diagnosis, germline BRCA mutation status, stage and histologic type showed that increased age lowers the odds for long term survivorship (OR-0.929 per 1 year of age, p=0.008). Endometroid carcinoma, compared to serous histology, lowers the odds for LTS as well (OR-0.295, p=0.046). Surprisingly, germline BRCA1 mutation carriers are 5.5 times more likely to survive more than 7 years compared to non-carriers (OR-5.508, p=0.034). Germline BRCA2 mutations do not change the odds for LTS compared to non-carriers p=0.99. Patients diagnosed at stage III have a significantly higher chance of long-term survivorship compared to stage IV, as previously reported for primary-debulked HGSOC patients (OR-7.89, p=0.016). [Display omitted] Our analysis, to the best of our knowledge, is the first to demonstrate that NAC does not compromise the odds of long-term survivorship in women with advanced EOC, further strengthening NAC as an equivalent alternative to primary debulking surgery. In addition, we identified basic clinicpathologic and treatment-related factors associated with long term survival of epithelial OC patients treated with NAC. Further investigation is needed to determine which factors should be integrated into treatment-related decisions. [ABSTRACT FROM AUTHOR]