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A multicenter cross-sectional survey study involving four Italian University Hospitals was performed to test the hypothesis that negative affect and positive affect (affective dimensions) mediate the association between risk perception (perceived risk of infection and death; cognitive dimensions) and the feeling of work exhaustion (WE) among obstetrics healthcare providers (HCPs) during the Coronavirus Disease 2019 (COVID-19) pandemic. Totally, 570 obstetrics HCPs were invited to complete the 104-item IPSICO survey in May 2020. A theoretical model built on the tested hypothesis was investigated by structural equation modelling. The model explained 32.2% of the WE variance. Only negative affect mediated the association between cognitive dimensions and WE and also the association between WE and psychological well-being before the pandemic, experiences of stressful events, female gender, and dysfunctional coping. Non-mediated associations with WE were observed for work perceived as a duty, experience of stressful events, support received by colleagues, and the shift strategy. Only previous psychological well-being, support by colleagues, and shift strategies were inversely associated with WE. Based on study results, monitoring negative than positive affect appears superior in predicting WE, with practical implications for planning psychological interventions in HCPs at the individual, interpersonal, and organizational levels.

Mitochondrial dysfunction was observed in acute systemic inflammatory conditions such as sepsis and might be involved in sepsis-induced multi-organ failure. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2), also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1), a bi-organellar protein located in the mitochondria and the nucleus, is implicated in cell respiration, survival, and response to tissue hypoxia. Recently, the reduction of the cellular CHCHD2/MNRR1 protein, as part of mitochondrial dysfunction, has been shown to play a role in the amplification of inflammatory cytokines in a murine model of lipopolysaccharide-induced systemic inflammation. The aim of this study was to determine whether the plasma concentration of CHCHD2/MNRR1 changed during human normal pregnancy, spontaneous labor at term, and clinical chorioamnionitis at term. We conducted a cross-sectional study that included the following groups: 1) non-pregnant women (n = 17); 2) normal pregnant women at various gestational ages from the first trimester until term (n = 110); 3) women at term with spontaneous labor (n = 50); and 4) women with clinical chorioamnionitis at term in labor (n = 25). Plasma concentrations of CHCHD2/MNRR1 were assessed by an enzyme-linked immunosorbent assay. 1) Pregnant women at term in labor with clinical chorioamnionitis had a significantly higher plasma CHCHD2/MNRR1 concentration than those in labor without chorioamnionitis (p =.003); 2) CHCHD2/MNRR1 is present in the plasma of healthy non-pregnant and normal pregnant women without significant differences in its plasma concentrations between the two groups; 3) there was no correlation between maternal plasma CHCHD2/MNRR1 concentration and gestational age at venipuncture; and 4) plasma CHCHD2/MNRR1 concentration was not significantly different in women at term in spontaneous labor compared to those not in labor. CHCHD2/MNRR1 is physiologically present in the plasma of healthy non-pregnant and normal pregnant women, and its concentration does not change with gestational age and parturition at term. However, plasma CHCHD2/MNRR1 is elevated in women at term with clinical chorioamnionitis. CHCHD2/MNRR1, a novel bi-organellar protein located in the mitochondria and the nucleus, is released into maternal plasma during systemic inflammation. [ABSTRACT FROM AUTHOR]

Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI. This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester (n = 16); (2) term in labor (n = 37); (3) term not in labor (n = 22); (4) PTL without IAI who delivered at term (n = 25); (5) PTL without IAI who delivered preterm (n = 47); and (6) PTL with IAI who delivered preterm (n = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay. (1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester (p = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor (p = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm (p < 0.001) or term delivery (p = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI (p < 0.001); (5) among women with PTL and IAI, the amniotic fluid concentration of CHCHD2/MNRR1 correlated with that of interleukin-6 (Spearman's Rho = 0.7; p < 0.001); and (6) no correlation was observed between amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations among women with PTL. CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI. [ABSTRACT FROM AUTHOR]

The natural history and patterns of ovarian cancer (OC) relapse are still unclear. Recurrent disease can be peritoneal, parenchymal, or nodal. This study aims to analyze the location and pattern of OC recurrence according to the primary site of disease and to the type of surgical approach used. All OC patients underwent primary debulking surgery (PDS) or interval debulking surgery (IDS), with 2014 FIGO stage III-IV, and with platinum-sensitive recurrence were included in the study. Primary disease location and site of recurrences were divided into peritoneal, parenchymal, and nodal, according to the presence of peritoneal carcinomatosis, parenchymal metastasis, and nodal involvement, respectively. A total of 355 patients were initially considered; of them, 295 met the inclusion criteria. Two hundred thirty-three patients obtained no macroscopic residual tumor at the end of primary surgical treatment. Primary parenchymal disease relapsed in 84.6% cases at a parenchymal site (p < 0.001), 97.2% of peritoneal diseases relapsed on the peritoneum (p < 0.001), and 100% of nodal diseases had a nodal recurrence (p < 0.001). Stratifying by the surgical approach all these correlations have been confirmed both in the PDS (p < 0.001) and IDS (p < 0.001) groups. Our study shows that the site of relapse in cases of platinum-sensitive OC recurrence is closely related to the primary location of the disease, regardless of the type of initial treatment. Therefore, more attention during followup should be paid to areas where the initial tumor was present. 1. In 84.6% of cases, parenchymal disease recurred to parenchymatous organs; 2. In 97.2% of cases, peritoneal disease relapsed on peritoneal surfaces; 3. In 100% of cases, nodal disease relapsed on the lymph nodes. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to describe a rare case of a serous borderline ovarian tumor (BOT) diagnosed during pregnancy in a 15-year old adolescent. Results  The suspect of BOT was raised at a transvaginal ultrasound scan in early first trimester (at 5 weeks of amenorrhea), due to the presence of a moderately vascularized irregular papilla in the context of a unilocular low-level right ovarian cyst. The patient and her parents required termination of pregnancy, irrespective of the diagnosis of an ovarian lesion. After termination of pregnancy, the patient underwent laparoscopic enucleation of the ovarian mass, omentectomy, and peritoneal biopsies. No intra-abdominal spillage of the ovarian mass occurred, and the surgical specimens were put in an endobag and extracted transvaginally. Final pathological examination confirmed the diagnosis of a serous borderline ovarian tumor. The patient of free of disease after 8 months of follow-up. Conclusion  Although rare, borderline ovarian tumors can be diagnosed in an adolescent during pregnancy. The combination of specific sonographic assessment and minimally invasive conservative surgery appears as a very effective approach in this type of patient. Key Points BOTs can occur in pregnant adolescents. Transvaginal ultrasound is crucial to suspect BOT. Laparoscopic conservative treatment is feasible. [ABSTRACT FROM AUTHOR]

Objectives The chemotherapy response score (CRS) has been developed for measuring response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. This study aimed to validate the ability of this three-tier scoring system of pathologic response on omental specimens to determine prognosis in a subgroups of patients who had clinical complete response to neoadjuvant chemotherapy. Methods This was a retrospective study, conducted in women receiving interval debulking surgery at the Division of Gynecologic Oncology, between December 2007 and April 2017. Inclusion criteria were: high-grade serous ovarian cancer, FIGO stage IIIC/IV, platinum-based neoadjuvant chemotherapy, and clinical complete response after neoadjuvant chemotherapy (normalization in CA125 levels, disappearance of all target and nontarget lesions according to RECIST 1.1). CRS was denned by a single pathology review and classified as previously reported: CRS1, no or minimal tumor response with fibroinflammatory changes limited to a few foci ranging from multifocal or diffuse regression-associated fibroinflammatory changes with viable tumor in sheets, or nodules to extensive regression-associated fibroinflammatory changes with multifocal residual tumor; CRS2, appreciable tumor response with viable tumor readily identifiable; and CRS3, complete absence of tumor or nodules with maximum size of 2 mm. CRS was analyzed according to clinical variables and survival. results A total of 108 patients were eligible for analysis. The average age was 65 (range 36-85) years. A total of 91 (84.3%) patients had stage IIIC disease and 17 (15.7%) patients had stage IV disease. No statistically significant differences were observed in terms of age, FIGO stage, CA125 serum levels, type of chemotherapy schedules, and number of cycles between the three groups. Patients in the CRS3 group had a longer median progression-free survival (25.8 months) compared with CRS2 or CRS 1 (20.3 vs 17.4 months, respectively; p=0.001). Median overall survival was 68.9 months for CRS3, 35.0 months for CRS2, and 45.9 months for CRS1 (p=0.034). Conclusion Complete or near-complete pathologic response assessed in the omental specimens of advanced epithelial ovarian carcinoma patients after neoadjuvant chemotherapy (CRS3) is predictive of prolonged progression-free and overall survival. In particular, this is true in women with a clinical complete response. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effects on oncologic outcomes of intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer. A systematic literature search was performed by an expert librarian in multiple electronic databases from inception to January 31, 2023. We included all studies in the English language that compared oncologic outcomes (recurrence-free, cause-specific, or overall survival) between endometrial cancer patients who underwent total laparoscopic or robotic hysterectomy for endometrial cancer with vs without the use of an intrauterine manipulator. Studies comparing only peritoneal cytology status or lymphovascular space invasion were summarized for completeness. No selection criteria were applied to the study design. Four reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled hazard ratios with 95% confidence intervals were estimated for oncologic outcomes using the random effect model. Heterogeneity was quantified using the I2 tests. Publication bias was assessed by funnel plot and Egger test. Out of 350 identified references, we included 2 randomized controlled trials and 12 observational studies for a total of 14 studies and 5,019 patients. The use of an intrauterine manipulator during hysterectomy for endometrial cancer was associated with a pooled hazard ratio for recurrence of 1.52 (95% confidence interval, 0.99–2.33; P =.05; I 2=31%; chi square P value=.22). Pooled hazard ratio for recurrence was 1.48 (95% confidence interval, 0.25–8.76; P =.62; I 2=67%; chi square P value=.08) when only randomized controlled trials were considered. Pooled hazard ratio for overall survival was 1.07 (95% confidence interval, 0.65–1.76; P =0.79; I 2=44%; chi square P value=.17). The rate of positive peritoneal cytology or lymphovascular space invasion did not differ using an intrauterine manipulator. Intrauterine manipulator use during hysterectomy for endometrial cancer was neither significantly associated with recurrence-free and overall survival nor with positive peritoneal cytology or lymphovascular space invasion, but further prospective studies are needed. [ABSTRACT FROM AUTHOR]

Introduction: Partial urethrectomy during radical surgery for vulvar cancer may help avoid adjuvant radiotherapy in some patients. This study aimed to evaluate surgical, oncologic, and urinary outcomes of a new surgical technique based on vaginal flap to perform neomeatus reconstruction after distal urethral resection in radical surgery for vulvar cancer. Methods: Retrospective cohort study between January 2005 and December 2017. We recorded data on pre- and post-operative urinary symptoms, surgical procedures, complications, adjuvant therapy, and follow-up of all patients who underwent surgery for vulvar cancer and had distal urethral resection and neomeatus reconstruction with the proposed technique. The reconstruction was based on the development of a vaginal flap in which a circular opening was created to become the neo-outlet of the urethra. Results: Of a total of 200 patients with vulvar cancer operated with curative intent, 33 (16.5%) underwent distal urethral resection and neomeatus reconstruction during surgery (median age 73 (range 57–89) years; median body mass index 25.3 (range 16.3–36.4) kg/m2). Urethrectomy allowed the avoidance of adjuvant radiotherapy in 15/33 (45.5%) patients. No case of dehiscence was reported at the site of neomeatus. After a median follow-up of 39 (range 14–151) months, only one case of deviated urinary stream (3%) and no cases of neomeatus stricture were reported. Six (18.2%) patients developed or worsened urinary incontinence after urethral resection and neomeatus reconstruction, and there was no difference in the prevalence of urethral compressor muscle involvement during urethrectomy (p=0.19) and adjuvant radiotherapy (p=1.00). No recurrences were reported at urethral margins. Conclusions: Distal urethral resection and neomeatus reconstruction seem to be associated with adequate healing and low complication rates, such as dehiscence, stenosis, and flux deviation/dribbling. New-onset or worsened urinary incontinence does not seem to be associated with urethral compressor muscle involvement during urethral resection or adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To review the published literature on vulvar Paget's disease (VPD) molecular bases, aiming to support the need for tailored treatment in women affected by this 'orphan' tumor. Methods: MEDLINE-PubMed and Scopus were interrogated using the following algorithm: (extramammary OR extra mammary OR vulvar) AND (paget OR pagets OR paget's) AND (molecular OR biological OR marker OR protein OR target OR expression). The inclusion criteria for papers were: peer-reviewed English-language journals, articles published in the last 30 years, studies focused on fixed research questions, quality assessment on the basis of the relevance and contribution to the selected topics. Results: A total of 42 studies were selected, providing the following results. Molecular markers implicated in cell cycle transitions seem to be related to prognosis and could help to tailor conventional treatments. Fragmented but consistent preliminary data exist on hormonal receptor expression, ERBB2 amplification/overexpression and abnormal vascular proliferation, offering a concrete possibility for target therapy trials. Conversely, other fields linked to the possible use of immunotherapy are currently relatively unexplored, such as the tumor 'immune contexture', programmed death ligand-1 (PD-L1) expression and defects in the mismatch repair system, which is involved in genomic instability and potentially promotes a consistent response to treatment. Conclusions: Additional effort is needed to further characterize these aspects. Centralization of patients in dedicated units would be beneficial for concentrating patient numbers, collecting valuable clinical data and conducting clinical trials. Interdisciplinary study platforms should be developed and integrated into wider multicentric networks. [ABSTRACT FROM AUTHOR]

Background: To develop a diagnostic assessment tool, using clinical, biochemical and sonographic markers, to help clinicians in the differential diagnosis of functional oligomenorrhea (FO) and endocrine-metabolic oligomenorrhea (EMO). Methods: Sixty-two adolescents with oligomenorrhea without evident hormonal imbalances or severe energy deficit were selected. They were divided into two groups (EMO and FO) and they all underwent the following assessment: physical examination (height, weight, presence of hirsutism or acne), blood exams and transabdominal ultrasonography. The biochemical markers included: hemoglobin, thyrotropin stimulating hormone (TSH), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), free (FT) and total testosterone (TT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG). Uterine and ovarian volume, ovarian morphology, endometrial thickness and pulsatility index (PI) of uterine arteries were evaluated with ultrasound. Results: Body mass index (BMI), hemoglobin, LH levels and LH/FSH ratio were significantly higher in women with EMO than in those with FO. Increased androgens values were found in the EMO group, but only A and FT were significantly different (p=0.04). Ovarian volume and uterine artery PI were the only ultrasound features significantly different, with higher values in the EMO population (p<0.05). Considering these variables, with a receiving characteristic operating curve, new cut-offs were calculated, and a diagnostic assessment tool elaborated (area under curve [AUC] 0.88, specificity 99%, sensibility 59%, p<0.001]. Conclusions: This diagnostic tool, specific for adolescents, could be useful in the management of oligomenorrhea. Recognizing and distinguishing EMO and FO is very important in order to establish an appropriate treatment and a correct follow-up. [ABSTRACT FROM AUTHOR]

To demonstrate a laparoscopic technique to remove a scar pregnancy. Stepwise demonstration of the surgical technique. Santa Croce and Carle Hospital, Cuneo. Patient B.B. is a woman referred to our center for a suspected cesarean scar pregnancy (CSP) at 9 weeks gestation. CSP occurs approximately in 6% of all ectopic pregnancies. The estimated incidence is reported to be 1:1800 to 1:2500 in cesarean deliveries. Depending on its location, CSP can be categorized as either type 1, if the growth is in the uterine cavity, or type 2, if it expands toward the bladder and the abdominal cavity. If inadequately managed, it can lead to severe complications; most of them are hemorrhagic and can threaten the woman's life. There are several therapeutic approaches: local excision seems to be the most effective choice in type 2 CSP. In expert hands, the laparoscopic approach is perhaps the best surgical choice as tissue dissection, electrosurgical hemostasis, and vascular control can be effectively managed with minimal invasive access. Because severe intraoperative bleeding can occur, retroperitoneal vascular control is mandatory in this surgery. In type 1 CSP curettage, aspiration or hysteroscopic approach can be considered if the CSP is of small dimensions. A hysteroscopic approach can also be helpful in type 2 CSP during the laparoscopic removal, as intrauterine guidance. A potassium chloride local injection can be considered in a preoperative stage in the presence of a fetal heart rate. The systemic administration of methotrexate is usually ineffective as single agent, but it can be useful if administered as adjuvant therapy. Uterine artery embolization can be useful in an emergency setting to manage severe bleeding, but it can lead to complications in subsequent pregnancies and, more rarely, to premature ovarian failure. Considering poor bleeding at presentation, feasible dimensions, and the woman's desire for future pregnancy, ultrasound-guided aspiration and curettage was attempted. Because endouterine removal was incomplete, methotrexate injection was proposed as adjuvant therapy, but the administration was postponed as the patient tested positive for coronavirus disease 2019. A month later, beta-human chorionic gonadotropin level dropped from over 16 000 to 271 mU/mL, so an ultrasound and biochemical follow-up was performed. A month later, despite a low beta-human chorionic gonadotropin value, an increase in dimensions was observed at ultrasound, so surgical laparoscopic removal was offered. In this video article, laparoscopic removal of scar pregnancy is discussed in the following surgical steps: (1) Temporary closure of uterine arteries at the origin, using removable clips. (2) Retroperitoneal dissection to safely manage the scar pregnancy. (3) Dissection of the myometrial–pregnancy interface. (4) Double layer suture on the anterior uterine wall. Laparoscopic surgical management is a very effective surgical approach to remove CSP. Knowledge of retroperitoneal dissection and vascular control is necessary to carry out this surgical intervention safely and effectively. [ABSTRACT FROM AUTHOR]