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OBJECTIVE: To demonstrate the use of surgical intelligence to routinely and automatically assess the proportion of time spent outside of the patient's body (out-of-body-OOB) in laparoscopic gynecological procedures, as a potential basis for clinical and efficiency-related insights. DESIGN: A retrospective analysis of videos of laparoscopic gynecological procedures. SETTING: Two operating rooms at the Gynecology Department of a tertiary medical center. PARTICIPANTS: All patients who underwent laparoscopic gynecological procedures between January 1, 2021 and December 31, 2022 in those two rooms. INTERVENTIONS: A surgical intelligence platform installed in the two rooms routinely captured and analyzed surgical video, using AI to identify and document procedure duration and the amount and percentage of time that the laparoscope was withdrawn from the patient's body per procedure. RESULTS: A total of 634 surgical videos were included in the final dataset. The cumulative time for all procedures was 639 hours, of which 48 hours (7.5%) were OOB segments. Average OOB percentage was 8.7% (SD = 8.7%) for all the procedures and differed significantly between procedure types (p < .001), with unilateral and bilateral salpingo-oophorectomies showing the highest percentages at 15.6% (SD = 13.3%) and 13.3% (SD = 11.3%), respectively. Hysterectomy and myomectomy, which do not require the endoscope to be removed for specimen extraction, showed a lower percentage (mean = 4.2%, SD = 5.2%) than the other procedures (mean = 11.1%, SD = 9.3%; p < .001). Percentages were lower when the operating team included a senior surgeon (mean = 8.4%, standard deviation = 9.2%) than when it did not (mean = 10.1%, standard deviation = 6.9%; p < .001). CONCLUSION: Surgical intelligence revealed a substantial percentage of OOB segments in laparoscopic gynecological procedures, alongside associations with surgeon seniority and procedure type. Further research is needed to evaluate how laparoscope removal affects postoperative outcomes and operational efficiency in surgery.
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Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)-participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2-3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns.
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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.
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Colposcopía , Papillomaviridae , Infecciones por Papillomavirus , Triaje , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Adulto , Triaje/métodos , Infecciones por Papillomavirus/diagnóstico , Papillomaviridae/aislamiento & purificación , Persona de Mediana Edad , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Coito , Sensibilidad y Especificidad , Hemorragia Uterina , Frotis Vaginal , Virus del Papiloma HumanoRESUMEN
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.
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Neoplasias Endometriales , Histerectomía , Humanos , Femenino , Estudios Retrospectivos , Neoplasias Endometriales/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Recurrencia Local de Neoplasia/epidemiología , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) play a pivotal role in ovarian cancer management. With medical cannabis emerging as a novel component of supportive care, this study investigated the impact of medical cannabis use on oncological outcomes in patients with ovarian cancer undergoing PARPi therapy. METHODS: The study included patients from a single institution database treated for ovarian cancer between January 2014 and January 2020 who received PARPi maintenance therapy in a first-line or recurrent disease setting after a confirmed response to platinum-based treatment. The study categorized patients as cannabis users and cannabis-naïve. Univariate and multivariate Cox regression analysis and the Kaplan-Meier method were used to assess the effects of medical cannabis use on the duration of PARPi therapy, progression-free survival, and overall survival. RESULTS: Among the eligible patients (n=93), most were cannabis-naïve (69%, n=64) while the rest used medical cannabis (31%, n=29). Medical cannabis use rates were comparable for patients receiving PARPi therapy post-primary treatment or for recurrence (42%, n=9, vs 27%, n=20; p=0.1). Both groups exhibited similar median duration for PARPi therapy (12.1 vs 9.5 months; p=0.89) and progression-free survival (20 vs 21 months; p=0.83). Kaplan-Meier analysis detected no differences in progression-free survival associated with cannabis use. Although cannabis users had an extended overall survival compared with the cannabis-naïve group (129.3 vs 99 months; p=0.03), cannabis use was insignificant for overall survival on multivariate analysis (p=0.10). Multivariate analysis showed stage IV at diagnosis (p=0.02) to be the sole factor associated with progression-free survival (p=0.02). CONCLUSION: Medical cannabis usage in patients receiving PARPi treatment showed no association with duration of PARPi therapy, progression-free survival, or overall survival.
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Marihuana Medicinal , Neoplasias Ováricas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Marihuana Medicinal/uso terapéutico , Proteína BRCA1 , Proteína BRCA2 , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
OBJECTIVES: To determine the feasibility and safety of resectoscopic treatment for uterine evacuation of first-trimester miscarriage. METHODS: A single-centre prospective study performed between April 2021 and October 2021 at a university-affiliated tertiary medical centre. Patients diagnosed with early miscarriage of up to 12 weeks from the last menstrual period were eligible for participation. Recruited patients underwent hysteroscopic uterine evacuation under general anaesthesia by a Versapoint 2 bipolar resectoscope 24Fr (Johnson and Johnson, Germany). RESULTS: A total of 15 patients were recruited for the study. The procedural characteristics as well as intra- and postoperative adverse events were recorded. The mean duration of the procedure was 14.3 ± 3.7 minutes. The achievement of complete evacuation was recorded in all cases, and no adverse events occurred during any procedure. Post-procedure follow-up 6 weeks after treatment was conducted by office hysteroscopy in 10 women and by ultrasonography in 4 women. One woman had conceived prior to her scheduled follow-up visit. In total, 2 (13.3%) cases of retained products of conception were diagnosed during office hysteroscopy and they were removed by the "see-and-treat" technique without anaesthesia. The diagnosis was confirmed pathologically. No intrauterine adhesions were detected and none of the women required a second hysteroscopy under anaesthesia due to retained products of conception. CONCLUSIONS: Hysteroscopic evacuation of first-trimester miscarriage by a standard resectoscope is a safe and feasible technique.
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Objective: To evaluate the effectiveness and safety of standard chemotherapy administered to patients >70 years with advanced ovarian cancer (OC). Methods: Medical records of 956 advanced-stage patients with OC treated between 2002-2020 with standard surgery and paclitaxel-carboplatin chemotherapy in a three-weekly (PC-3W) or weekly (PC-1W) regimen were reviewed. Treatment response and tolerability were compared between patients ≤70 years (N=723) and >70 years (N=233) with stratification to septuagenarians (>70-80 years) and octogenarians (>80 years). Results: Median overall survival (mOS) in patients >70 was 41.26 months (95% confidence interval [Cl], 37.22-45.14) and median progression-free survival (mPFS) was 11.04 months (95% Cl, 8.97-15.74). No statistically significant differences in mPFS and mOS were observed between septuagenarians and octogenarians. Patients >70 treated with PC-1W versus PC-3W had significantly longer mOS (57.17 versus 30.00 months) and mPFS (19.09 versus 8.15 months). Toxicity rates were mostly similar between younger and older patients. Among patients >70 treated with PC-1W, the rate of neutropenia (75.7% versus 51.8%, p=0.0005), thrombocytopenia (41.0% versus 22.2%, p=0.0042) and anemia (78.1% versus 51.9%, p<0.0001) were significantly higher and the rate of grade 2 alopecia was statistically significantly lower compared with those >70 treated with PC-3W. Significantly more patients treated with PC-1W completed ≥6 chemotherapy cycles, suggesting better tolerability of this regimen. Conclusions: Older patients with OC may benefit from improved OS with reasonable toxicity if treated with standard chemotherapy. Older patients treated with PC-1W are more likely to complete the full chemotherapy course and survive longer compared with those treated with conventional PC-3W.
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Cervical cancer (CC) screening and prevention are crucial responsibilities of obstetrician-gynecologists (OB/GYNs). Our study aimed to investigate whether knowledge impacts OB/GYNs' (n = 42) adherence to CC prevention measures by comparing them to non-OB/GYN physicians (n = 80). An anonymous questionnaire collected demographic information, personal screening habits and evaluated their knowledge of CC prevention. Results revealed that OB/GYNs exhibited superior knowledge of CC risk factors and prevention compared to non-OB/GYNs. Of note, a lower percentage of OB/GYN residents correctly identified the recommended upper age limit for cervical screening and for HPV vaccination compared to attending OB/GYNs (50% vs. 83%, p = 0.04 and 11% vs. 50%, p = 0.01, respectively). Despite these findings, most physicians from both groups recommended HPV vaccination. Cervical screening rates were similar between OB/GYNs and non-OB/GYNs (75% vs. 83%, p = 0.3). Half of OB/GYNs initiated their own cervical screening, similar to non-OB/GYNs. Interestingly, residents had higher HPV vaccination rates compared to attending physicians, irrespective of specialty (OB/GYNs - 38.89% vs. 4.76%, p = 0.0149; non-OB/GYNs - 51.06% vs. 15.38%, p = 0.0028). In conclusion, contrary to the assumption that physicians prioritize personal well-being, our study reveals the opposite. While skilled in guiding patients through CC screening and prevention, female OB/GYNs often neglect their own health. OB/GYNs must also be educated and supported in safeguarding their health, setting an essential example for patients.
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Infecciones por Papillomavirus , Médicos , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Encuestas y CuestionariosRESUMEN
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.
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OBJECTIVE: To investigate the prognostic significance of near-complete metabolic response on initial follow-up PET/CT after primary chemoradiation treatment of cervical cancer. METHODS: Survival data were retrospectively compared between patients who had complete metabolic response on first follow-up PET/CT, 3 months after chemoradiation (group 1) with those who had near-complete metabolic response on first PET/CT and later showed complete metabolic response at subsequent PET/CT, 6 months or more after treatment (group 2). RESULTS: Of the 108 patients included in the final analysis, 74 (68.5%) showed complete metabolic response on initial PET/CT, 3 months after treatment, and 34 patients (31.5%) showed complete metabolic response on subsequent PET/CT, 6 months after treatment. Tumor characteristics were comparable between groups. Group 1 had higher percent of stage 1 (12% vs 0%) and lower percent of stage 4 disease (3% vs 14%) than those of group 2. Group 2 patients had significantly fewer cases of recurrences and deaths than group 1 patients (6% vs 26%, p=0.018; 0% vs 20%, p=0.003, respectively), with comparable 3-year survival rates (group 1, 90% vs group 2, 100%, p=0.31). Twelve patients had progressive disease on first follow-up PET/CT; these patients had significantly worse overall survival compared with all other patients (log-rank test, p<0.001). Younger age and delayed complete metabolic response were associated with lower chance of recurrence and death on univariate analysis. On multivariate analysis, delayed complete metabolic response remained significantly associated with no recurrence HR=0.14 (95% CI 0.25 to 0.84), p=0.031. CONCLUSIONS: Survival outcome of patients with cervical cancer who show residual 18F-fluorodeoxyglucose uptake on initial PET/CT after treatment, but reach complete metabolic response on follow-up PET/CT, is not inferior compared with survival of patients who show complete metabolic response on initial PET/CT 3 months after treatment. Watchful waiting with follow-up PET/CT seems a safe option for these patients.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Cuello Uterino , Femenino , Humanos , Pronóstico , Neoplasias del Cuello Uterino/patología , Estudios Retrospectivos , Fluorodesoxiglucosa F18 , Radiofármacos , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy. METHODS: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination. RESULTS: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster. CONCLUSIONS: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated.
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Varicela , Poliomielitis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Vacunas , Tos Ferina , Niño , Humanos , Inmunización Secundaria , Vacunas/uso terapéutico , Vacunación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
OBJECTIVE: Our study aimed to explore the effect of body mass index (BMI) change on cancer recurrence risk during the routine surveillance of endometrial cancer patients. METHODS: Data on patients with endometrial adenocarcinoma that had a staging procedure and continued follow-up was retrospectively collected. We compared patients' BMI at time of surgery and during the last clinic follow-up. Univariate and multivariate analyses were performed to examine the effect of predictors on BMI change and the risk of recurrence. RESULTS: A total of 211 patients were included in the final analysis. The majority of patients had stage I disease (n=176, 89%) and endometrioid histology (n=178, 86%). Median follow-up time was 53.4 (standard deviation (SD) 40) months. The mean BMI was 30.4 kg/m2 (interquartile range (IQR) 25-34) at surgery compared with 30.9 kg/m2 (IQR 26-36) at last follow-up (p<0.001). The BMI increase was most pronounced in patients with endometroid histology that recurred, 31.6 (IQR 24-35) kg/m2 at surgery compared with 33.5 (IQR 27-36) kg/m2 at last follow-up (p=0.016). On multivariate analysis, age and BMI change were the only predictors that were significantly associated with the risk of recurrence (overall response (OR 1.07 (0.99-1.14), p=0.05, OR 1.37 (1.12-1.67), p=0.002, respectively). CONCLUSION: Patients with endometroid endometrial cancer that had an increase in BMI during follow-up were at an increased risk for cancer recurrence compared with patients that did not change or had a decrease in BMI.
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Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Índice de Masa Corporal , Estudios Retrospectivos , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Neoplasias Endometriales/patología , Carcinoma Endometrioide/patologíaRESUMEN
OBJECTIVE: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic. METHODS: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure. RESULTS: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia. CONCLUSIONS: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics.
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COVID-19 , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Humanos , Niño , Pandemias , Israel/epidemiología , Virus del Papiloma Humano , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , VacunaciónRESUMEN
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.
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Cesárea , Cicatriz , Humanos , Femenino , Embarazo , Cesárea/efectos adversos , Estudios Retrospectivos , Cesárea Repetida , Hemoglobinas/análisis , HemorragiaRESUMEN
High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T cells to directly bind to tumor-associated antigens in a major histocompatibility complex-independent manner, thereby inducing tumor rejection. While CAR-T cell therapy shows great promise in hematological malignancies, its use in solid tumors is limited. Therefore, innovative approaches are needed to increase the specificity of CAR-modified T cells against solid tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal (IP) versus intravenous (IV) CAR-T cell therapy in the treatment of HGSOC. We constructed a CAR that targets the ErbB2/HER2 protein (ErbB2CAR), which is overexpressed in HGSOC, and evaluated the functionality of ErbB2CAR on ovarian cancer cell lines (OVCAR8, SKOV3, and NAR). Our findings show that an IP injection of ErbB2CAR-T cells to tumor-bearing mice led to disease remission and increased survival compared to the IV route. Moreover, we found that IP-injected ErbB2CART cells circulate to a lesser extent, making them safer for non-tumor tissues than IV-injected cells. Further supporting our findings, we show that the effect of ErbB2CAR-T cells on primary HGSOC tumors is correlated with ErbB2 expression. Together, these data demonstrate the advantages of an IP administration of CAR-T cells over IV administration, offering not only a safer strategy but also the potential for counteracting the effect of ErbB2CAR in HGSOC. Significance: IP-injected ErbB2CAR-T cells led to disease remission and increased survival compared to the IV route. These findings demonstrate the advantages of IP administration, offering a safe treatment strategy with the potential for counteracting the effect of ErbB2CAR in HGSOC.
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OBJECTIVE: This study aimed to compare the rates of positive specimen margins and postconization recurrent dysplasia between loop electrosurgical excision procedures (LEEPs) performed under general anesthesia (GA) and LEEP under local anesthesia (LA). METHODS: This retrospective cohort study included all consecutive women who underwent LEEP between 2011 and 2019. Collected data included demographics, LEEP indication, cone dimensions, and margin involvement as well as recurrence rate. Women who had undergone previous conization, cold-knife conization, or those who were lost to follow-up during the first 2 years after the procedure were excluded. RESULTS: Overall, 71 women who underwent LEEP under GA and 75 women under LA were included. Demographic characteristics were similar between the groups, as were the rates of preceding abnormal cytology and high-grade dysplasia before conization. Although cone depth and volume were higher for LEEP specimens done under GA compared with LA, the rate of positive specimen margins was comparable both for the endocervical margin (16/71 [22.5%] vs 16/75 [21.3%], respectively; p = .861) and the ectocervical margin (14/71 [19.7%] vs 11/75 [14.7%], respectively; p = .418). During the first 2 years after conization, the rates of high-grade dysplasia (cervical intraepithelial neoplasia ≥ 2) in repeat biopsy and the need for repeat conization were also not significantly different between the GA and LA groups (4.2% vs 1.3%, p = .356; 7.0% vs 9.3%, p = .614, respectively). CONCLUSIONS: Anesthesia mode does not seem to affect the rate of positive LEEP margins and the need for repeat conization. Our study findings suggest that LA should be preferred instead of GA in LEEP.
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Electrocirugia , Neoplasias del Cuello Uterino , Anestesia General/efectos adversos , Conización/efectos adversos , Conización/métodos , Electrocirugia/métodos , Femenino , Humanos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
BACKGROUND: The past decade has witnessed a rise in Fusobacterium infections. This study aimed to describe the epidemiology, clinical and demographic characteristics and outcomes associated with Fusobacterium infections in hospitalized children in central Israel. METHODS: We retrospectively analyzed the medical records of children <18 years old who had been admitted with a diagnosis of invasive Fusobacterium infection (IFI) between January 2010 and April 2020. Clinical, laboratory and microbiologic data were retrieved. IFI diagnosis was based upon microbiological identification in any specimen by culture or by 16S ribosomal RNA polymerase chain reaction. RESULTS: Fifty-one children (26 boys) with a median age of 3 years (range, 5-16 years) were included. Hospitalizations for IFI increased from 19 of 100,000 admissions between 2010 and 2015 to 50 of 100,000 between 2016 and 2020, representing a 2.5-fold increase. Most of the infections were from an otogenic source (n = 28, 55%) followed by an oropharyngeal/respiratory source (n = 21, 41%). The most common complications were subperiosteal and epidural abscesses (41% and 37%, respectively). Thrombosis was diagnosed in 11 children, 10 of whom had sinus vein thrombosis. All had an otogenic source. Children with otogenic compared with all other infection sources were significantly younger (median age of 1.9 vs. 3 years; P < 0.001). Forty-seven children (92%) underwent a surgical intervention. All patients survived, one with neurologic sequelae. CONCLUSIONS: The admissions for IFI in children increased 2.5-fold during the last decade. The most common source is otogenic, especially among younger children, and it is associated with high complication rates. Current management, including combinations of antibiotics and surgical interventions, leads to favorable outcome.
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Absceso Epidural , Infecciones por Fusobacterium , Adolescente , Antibacterianos/uso terapéutico , Niño , Preescolar , Absceso Epidural/complicaciones , Fusobacterium , Infecciones por Fusobacterium/diagnóstico , Humanos , Masculino , Estudios RetrospectivosRESUMEN
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). ß-hCG percentage change in the 48 h preceding MTX treatment and ß-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 ß-hCG; OR = 1.001, 95% CI = 1.0003-1.002 for every unit change in ß-hCG, respectively). In a decision tree analysis model, in women with ß-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 ß-hCG dynamics and level. The absolute risk for tubal rupture in women with ß-hCG increment<20% is low.
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Abortivos no Esteroideos , Embarazo Ectópico , Abortivos no Esteroideos/efectos adversos , Gonadotropina Coriónica Humana de Subunidad beta/uso terapéutico , Consejo , Femenino , Humanos , Masculino , Metotrexato/efectos adversos , Embarazo , Embarazo Ectópico/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
COVID-19 , Motilidad Espermática , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Masculino , Estudios Prospectivos , ARN Mensajero , SARS-CoV-2 , EspermatozoidesRESUMEN
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.