Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Extensive versus focal lymphovascular invasion in squamous cell carcinoma of the cervix: A comprehensive international, multicenter, retrospective clinicopathologic study.

OBJECTIVE: We evaluated clinicopathologic parameters of patients with cervical squamous cell carcinoma (SCC) who were treated with initial surgical management and assessed their relation to survival outcomes. Specifically, we evaluated the relation between extent of lymphovascular invasion (LVI) and survival outcomes. METHODS: All available tumor slides from patients with initially surgically treated cervical SCC were collected from 10 institutions and retrospectively analyzed. Standard clinicopathological parameters, tumor stroma, and extent of LVI were assessed (focal: <5 spaces, extensive: ≥5 spaces). PFS and OS were evaluated using Kaplan-Meier methodology. Univariable and multivariable Cox proportional hazards models were created to determine prognostic survival-related risk factors. RESULTS: A total of 670 tumor samples were included in the analysis. Median age at diagnosis was 47 years (IQR: 38-60), 457 patients (72%) had a 2018 International Federation of Gynecology and Obstetrics (FIGO) stage I tumor, and 155 tumors (28%) were flat and/or ulcerated. There were 303 nonkeratinizing tumors (51%), 237 keratinizing tumors (40%), and 356 histologic grade 2 tumors (61%). Quantifiable LVI was present in 321 cases (51%; 23% focal and 33% extensive). On multivariable analysis for PFS, extensive and focal LVI had worse outcomes compared to negative LVI (HR: 2.38 [95% CI: 1.26-4.47] and HR: 1.54 [95% CI: 0.76-3.11], respectively; P = 0.02). The difference did not reach statistical significance for OS. CONCLUSION: Presence of LVI is a prognostic marker for patients with cervical SCC. Quantification (extensive vs. focal vs. negative) of LVI may be an important biomarker for oncologic outcome.

Day 5 versus day 3 embryo biopsy for preimplantation genetic testing for monogenic/single gene defects.

BACKGROUND: Assisted reproductive technology (ART) has allowed couples with a family history of a monogenic genetic disease, or a disease-carrying gene, to reduce the chance of them having a child with the genetic disorder. This is achieved by genetically testing the embryos using an advanced process called preimplantation genetic testing for monogenic or single gene disorders (PGT-M), such as Huntington's disease or cystic fibrosis. This current terminology (PGT-M) has replaced the formerly-known preimplantation genetic diagnosis (PGD). During PGT-M, one or more embryo cells are biopsied and analysed for genetic or chromosomal anomalies before transferring the embryos to the endometrial cavity. Biopsy for PGT-M can be performed at day 3 of cleavage-stage embryo development when the embryo is at the six- to the eight-cell stage, with either one or two blastomeres being removed for analysis. Biopsy for PGT-M can also be performed on day 5 of the blastocyst stage of embryo development when the embryo has 80 to 100 cells, with five to six cells being removed for analysis. Day 5 biopsy has taken over from day 3 biopsy as the most widely-used biopsy technique; however, there is a lack of summarised evidence from randomised controlled trials (RCTs) that assesses the effectiveness and safety of day 5 biopsy compared to day 3 biopsy. Since biopsy is an invasive process, whether it is carried out at day 3 or day 5 of embryo development may have different impacts on further development, implantation, pregnancy, live birth and perinatal outcomes. OBJECTIVES: To assess the benefits and harms of day 5 embryo biopsy, in comparison to day 3 biopsy, in PGT-M in women undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. SEARCH METHODS: We searched the following electronic bibliographic databases in December 2021 to identify relevant RCTs: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Trials Register; CENTRAL, MEDLINE, Embase and PsycINFO. We also handsearched grey literature, such as trial registers, relevant journals, reference lists, Google Scholar, and published conference abstracts. SELECTION CRITERIA: Eligible RCTs compared day 5 versus day 3 embryo biopsy for PGT-M.  DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live births and miscarriages. We calculated outcomes per woman/couple randomised and reported odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: We included one RCT involving 20 women. The evidence was of very low certainty; the main limitations of the study were serious risk of bias due to lack of blinding of study personnel, and imprecision. We are uncertain whether day 5 embryo biopsy compared to day 3 biopsy has an effect on live births (OR 1.50, 95% CI 0.26 to 8.82; 1 RCT, 20 women; very low-certainty evidence). The evidence suggests that if the chance of live birth following day 3 biopsy was assumed to be 40%, then the chance with day 5 biopsy is between 15% and 85%. It is also uncertain whether day 5 embryo biopsy compared to day 3 biopsy has an effect on miscarriages (OR 1.00, 95% CI 0.05 to 18.57; 1 RCT, 20 women; very low-certainty evidence).  We are uncertain whether day 5 embryo biopsy compared to day 3 biopsy has an effect on other secondary outcome measures, including viable intrauterine pregnancies (OR 2.25, 95% CI 0.38 to 13.47; 1 RCT, 20 women; very low-certainty evidence), ectopic pregnancies (OR 0.16, 95% CI 0.01 to 3.85; 1 RCT, 20 women; very low-certainty evidence), stillbirths (OR not estimable as no events in either group; 1 RCT, 20 women; very low-certainty evidence) or termination of pregnancies (OR 3.32, 95% CI 0.12 to 91.60; 1 RCT, 20 women; very low-certainty evidence). No studies reported on gestational age at birth, birthweight, neonatal mortality and major congenital anomaly. AUTHORS' CONCLUSIONS: We are uncertain if there is a difference in live births and miscarriages, viable intrauterine pregnancies, ectopic pregnancies, stillbirths or termination of pregnancies between day 5 and day 3 embryo biopsy for PGT-M. There was insufficient evidence to draw any conclusions regarding other adverse outcomes. The results should be interpreted with caution, as the evidence was of very low certainty due to limited studies, high risk of bias in the included study, and an overall low level of precision.

Large ovarian endometriomas are associated with high pre-operative anti-Müllerian hormone concentrations.

RESEARCH QUESTION: Are large ovarian endometriomas associated with high pre-operative anti-Müllerian hormone (AMH) concentrations? DESIGN: Data from 332 women who underwent AMH measurement before surgery for endometriosis were prospectively recorded in a large database. Univariate analysis compared AMH concentrations in terms of the patients' baseline characteristics. A multivariate model was used to identify variables having an independent relationship with AMH concentration. RESULTS: Among 332 women included in the study, 47.6% were aged 18-30 years, 67.8% were infertile and 85.5% were nulliparous. A total of 66.3% had ovarian endometriomas, and 10.8% had cysts measuring over 6 cm. Bilateral cysts over 3 cm were recorded in 24.7% of the women. Univariate analysis identified two variables that had a statistically significant relationship with AMH concentration: the woman's age (P = 0.01) and cyst size (P < 0.001). Multivariate analysis revealed that ages of 36-40 years and over 40 years showed a significant association with lower AMH concentrations (P = 0.02 and P = 0.009, respectively), while a cyst size of over 6 cm was statistically associated with high AMH concentrations (P < 0.001), after adjustment for smoking, parity, rectosigmoid endometriotic nodules and a bilateral location of endometriomas. CONCLUSIONS: Pre-operative AMH concentration was significantly increased in women with large endometriomas of over 6 cm, independent of their age or the presence of bilateral endometriomas. This is relevant for both surgeons and patients when planning surgery in women with an intention to conceive post-operatively.

Clinical and Pathological Significance of Cellular Atypia in Endometriosis.

Objective: To highlight the most frequent localization of ovarian endometriosis, the presence of atypical endometriosis, and recurrences. Retrospective review of 259 patients diagnosed with ovarian endometriosis treated at Tîrgu-Mures Emergency County Hospital, Obstetric Gynecology Clinic, between January 2014 and December 2018. Methods: Data were collected and analyzed for demographics, size of ovarian endometriotic cyst, and recurrences. Results: Out of 259 patients, 51 patients presented atypia, 20 on the right, 24 on the left, and seven patients were diagnosed with endometriosis with bilateral atypia. Higher susceptibility for left localization was noted. Thirty-nine patients (15.1%) presented recurrence. A statistically significant correlation (p = 0.006) was noted between patients with recurrence and atypia compared with those without atypia and endometriotic cysts larger than 7 cm. Patients with relapse under the age of 40 were noted to have mainly atypia with localization on the right (p = 0.025, OD = 4.107). Conclusions: The presence of endometrioma was not statistically significant correlated with left or right sided localization; recurrent endometriomas larger than 7 cm represents a risk for atypical endometriosis development. Recurrence and atypia appear more often in patients under the age of 40 and are right-sided. The total removal of the endometriomas can prevent the recurrence and subsequently the appearance of atypia and secondary neoplastic conditions.

Patterns of Bowel Invisible Microscopic Endometriosis Reveal the Goal of Surgery: Removal of Visual Lesions Only.

STUDY OBJECTIVE: To document the presence of bowel invisible microscopic endometriosis implants and their relationship with deep endometriosis macronodule infiltrating the bowel. DESIGN: A series of consecutive patients with deep endometriosis infiltrating the rectum and/or sigmoid colon (Canadian Task Force classification II-2). SETTINGS: A university referral center. PATIENTS: Ten patients managed by colorectal resection. INTERVENTIONS: A microscopic study of endometriotic foci of the bowel involving 3272 microsection slides was established using a unique method of step serial sections using combined transverse and longitudinal macrosection. Two-dimensional reconstruction based on slide scanning highlighted the presence and localization of the deep endometriosis macronodule in contrast with bowel invisible microscopic endometriosis microimplants. MEASUREMENTS AND MAIN RESULTS: The distance separating the microimplants and the nodule and their histologic characteristics. The mean length of the colorectal specimens was 91 ± 19 mm. The maximum distance between the farthest microimplants was 7.2 cm. The maximum distance from the macroscopic nodule limit to the farthest microimplant was 31 mm. Bowel invisible microscopic endometriosis microimplants presented with similar features independently of the type of spread. They had an active appearance including stroma and glands, were sometimes decidualized, and were free of fibrosis. They were found on the distal/rectal limit of the specimen in 3 patients and on both limits (distal/rectal and proximal/sigmoid colon) in 1 patient. CONCLUSION: Invisible microscopic endometriosis implants surround the bowel macroscopic endometriosis nodule at variable distances, suggesting that complete surgical microscopic removal may be a challenging goal. These results may help to reconsider the principles and feasibility of the surgical management of bowel endometriosis.

Preoperative medical therapy before surgery for uterine fibroids.

BACKGROUND: Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive.Fibroid growth is stimulated by oestrogen. Gonadotropin-hormone releasing analogues (GnRHa) induce a state of hypo-oestrogenism that shrinks fibroids , but has unacceptable side effects if used long-term. Other potential hormonal treatments, include progestins and selective progesterone-receptor modulators (SPRMs).This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. OBJECTIVES: To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. SELECTION CRITERIA: We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low-quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD -175 mL, 95% CI -219.0 to -131.7; 13 studies; 858 participants; I² = 67%; low-quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate-quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate-quality evidence).Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (-9.59 minutes, 95% CI 15.9 to -3.28; 6 studies; 617 participants; I² = 57%; low-quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate-quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low-quality evidence).GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low-quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low-quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (-47% with GnRHa compared to -20% and -22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low-quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate-quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate-quality evidence) or haemoglobin levels (MD -0.2, 95% CI -0.6 to 0.2; 188 participants; moderate-quality evidence).There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI -5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low-quality evidence).The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB-2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high-quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low-quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low-quality evidence; asoprisnil: MD -166.9 mL; 95% CI -277.6 to -56.2; 1 study; 22 participants; low-quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. AUTHORS' CONCLUSIONS: A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid-related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost-effectiveness and distinguish between groups of women with fibroids who would most benefit.

Trends in outcomes of very preterm infants in Romania: A tale of three cities.

BACKGROUND: Although survival of preterm infants has improved, prematurity remains the second most frequent cause of death before 5 years of age in Romania. Data on the changing mortality of Romanian preterm infants born before 29 weeks of gestation have not been available. METHODS: Outcomes of infants of gestational age 25-28 weeks born in 2007-2010 (n = 247) were compared with those born in 2011-2014 (n = 235). Data were analyzed from three tertiary neonatal intensive care centers. Mortality rates and major morbidities were compared between these two epochs. RESULTS: Infants in the later epoch were more likely to have been born by cesarean section and had higher 1 and 5 min Apgar scores. Mortality rate decreased significantly with increasing gestational age at birth. Between the two epochs, the in-hospital mortality rate decreased from 65.6% to 29.4% (P < 0.001); death in the first 48 h decreased from 30.0% to 8.5% (P < 0.001); and prevalence of severe intraventricular hemorrhage decreased from 52.2% to 11.9% (P < 0.001). There were significant increases in the rates of necrotizing enterocolitis and bronchopulmonary dysplasia among survivors but no change in the rate of retinopathy of prematurity. The rate of antenatal corticosteroid use did not change and was only 47% in the more recent epoch (2011-2014). CONCLUSIONS: Overall mortality is decreasing, and infants admitted in the later epoch had substantially different rates of mortality and several serious morbidities. The low rate of antenatal corticosteroid use provides an opportunity for further reductions in mortality and morbidity among very preterm infants born in Romania.

Fertility Outcomes After Ablation Using Plasma Energy Versus Cystectomy in Infertile Women With Ovarian Endometrioma: A Multicentric Comparative Study.

STUDY OBJECTIVE: To compare the probability of postoperative pregnancy in infertile women with ovarian endometrioma larger than 3 cm in diameter, managed by either ablation using plasma energy or cystectomy. DESIGN: A multicentric case-control study (Canadian Task Force classification II-2). SETTING: Six surgical departments, affiliated with 4 university hospitals and 2 private facilities. PATIENTS: One hundred four infertile patients with ovarian endometrioma larger than 3 cm. INTERVENTIONS: Endometrioma ablation using plasma energy was performed in 64 patients (61.5%) and cystectomy in 40 patients (38.5%). MEASUREMENTS AND MAIN RESULTS: Patients were enrolled in the CIRENDO prospective cohort database (NCT02294825) from June 2009 to June 2014 and managed in 6 different facilities. The minimum length of follow-up was 1 year. Postoperative probabilities of pregnancy in patietns and control subjects were estimated using the Kaplan-Meier method with 95% confidence intervals (CIs) and compared using the log-rank test. The Cox model was used to assess independent predictive factors for pregnancy. Patients managed by plasma energy were significantly older than patients managed by cystectomy, had significantly higher overall revised American Fertility Society (rAFS) score, and had higher rate of Douglas pouch obliteration, deep endometriosis, and colorectal localizations. After a mean follow-up of 35.3 ± 17.5 months (range, 12-60), fertility outcomes were comparable between the groups. The probability of pregnancy at 24 and 36 months after surgery in plasma energy and cystectomy groups was, respectively, 61.3% (95% CI, 48.2%-74.4%) versus 69.3% (95% CI, 54.5%-83%) and 84.4% (95% CI, 72%-93.4%) versus 78.3% (95% CI, 63.8%-90%). The Cox's model revealed that the type of surgical procedure on ovarian endometrioma had no statistically significant impact on the probability of pregnancy, after adjustment for women's age, bilateral cysts larger than 3 cm, colorectal endometriosis, and rAFS stage of endometriosis. CONCLUSION: Postoperative pregnancy rates were comparable after management of ovarian endometrioma by either ablation using plasma energy or cystectomy despite an overall higher rate of unfavorable fertility predictive factors in women managed by ablation.

Ovarian Damage after Laparoscopic Cystectomy for Endometrioma.

INTRODUCTION: Despite extensive research endometriosis is an area with important controversies. The European Society of Human Reproduction and Embriology issued in 2014 the last Guideline for endometriosis management including the statement that among 83 recommendations in 32 cases the best available evidence was only based on good clinical practice, further research being necessary to solve the lack of evidence in this pathology. The prevalence of endometriosis is unknown in Romania but in the medical literature estimates range from 2 to 10% of women of reproductive age, to 50% of infertile women, worldwide. Ovarian endometrioma prevalence goes up to 44%. A Cochrane review published in 2008 by Hart et al. concluded that excisional surgery of ovarian endometriosis results in a more favorable outcome compared to drainage and ablation with regard to recurrence, pain symptoms and subsequent spontaneous pregnancy in subfertilewomen- so the gold standard was set. But several authors revealed that ovarian tissue was inadvertently excised together with the cyst wall and endometrioma cystectomy is associated with a significant decrease in residual ovarian volume that may result in diminished ovarian reserve and function. The aim of our retrospective study was to evaluate whether or not ovarian parenchyma is inadvertently removed during laparoscopic surgery for endometrioma in a Romanian academic center. MATERIAL AND METHOD: We performed a retrospective study including women having undergone endometrioma excision, between January 2009 to June 2014 in the Department of Gynecology and Obstetrics of Targu-Mures University Hospital. Histological specimens of excised endometriomas were reviewed by different pathologists, who carried out serial microscopic sections according to pathology protocol for diagnosis of ovarian mass but not specific for the ovarian parenchyma removed with the cyst. RESULTS: Among 202 endometriomas, drainage and ablation was done in 60 cases and excisional surgery in the remaining 152 cases. Ovarian parenchyma was found in 40% of cases of endometrioma cystectomy. DISCUSSION: We observed that endometrioma cystectomy leads to ovarian tissue removal in an important number of cases. Furthermore, at the time of surgery the amount of ovarian parenchyma loss may increases proportionally with increases in cyst diameter and patient age. Considering that most of the woman in our series were infertile and because of data from series using plasma energy, a shift in the endometrioma treatment paradigm is likely to occur.

Ulipristal acetate versus placebo for fibroid treatment before surgery.

BACKGROUND: The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain. METHODS: We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of ≤10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women). All patients received iron supplementation. The coprimary efficacy end points were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at week 13, after which patients could undergo surgery. RESULTS: At 13 weeks, uterine bleeding was controlled in 91% of the women receiving 5 mg of ulipristal acetate, 92% of those receiving 10 mg of ulipristal acetate, and 19% of those receiving placebo (P<0.001 for the comparison of each dose of ulipristal acetate with placebo). The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were -21%, -12%, and +3% (P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo, and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo). Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy. Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate (uterine hemorrhage) and in one patient during receipt of placebo (fibroid protruding through the cervix). Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo. CONCLUSIONS: Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids. (Funded by PregLem; ClinicalTrials.gov number, NCT00755755.).

Colorectal Endometriosis Responsible for Bowel Occlusion or Subocclusion in Women With Pregnancy Intention: Is the Policy of Primary in Vitro Fertilization Always Safe?

OBJECTIVE: To discuss the risk of bowel occlusion or subocclusion in patients with pregnancy wish and deep colorectal endometriosis, when surgery is postponed until after conception. DESIGN: A prospective series of consecutive patients managed for occlusion or subocclusion between January 2012 and January 2015 (Canadian Task Force classification II-2). Deep endometriosis had previously been diagnosed in all patients; however, they were advised to postpone surgery until after conception. SETTING: University tertiary referral center. PATIENTS: Twelve women with bowel occlusion or subocclusion due to deep endometriosis and desiring pregnancy. INTERVENTION: Surgical management including colorectal resection. MAIN OUTCOME MEASURES: Digestive symptoms, including standardized gastrointestinal questionnaires and preoperative imaging assessment of deep endometriosis. RESULTS: The patients enrolled in the series represent 5% of 241 patients with colorectal endometriosis managed over 37 consecutive months. Major digestive complaints were bloating, defecation pain, constipation, liquid stools, and a feeling of incomplete stool evacuation. The median length of digestive tract stenosis was 50 mm (range, 20-100 mm). In 8 patients (67%), computed tomography-based virtual colonoscopy revealed a virtual digestive lumen. The median length of colorectal specimen removed was 120 mm (range, 60-200 mm). Three patients (25%) had Clavien-Dindo IIIb and IVa postoperative complications with favorable outcomes within up to 20 days after surgery. CONCLUSION: Given the risk of bowel occlusion or subocclusion in young patients with colorectal endometriosis, an exhaustive assessment of deep disease and advice at a tertiary referral center appears to be mandatory before prioritizing primary in vitro fertilization instead of primary surgery.

Mortality and morbidity of very preterm infants in Romania: how are we doing?

BACKGROUND: Birth before 28 weeks of gestation is associated with high mortality and morbidity. The purpose of this study was to examine characteristics associated with in-hospital mortality and morbidity among extremely low-birthweight neonates admitted to three tertiary care centers in Romania. METHODS: The study was conducted in three Romanian hospitals with level-III neonatal intensive care units. We studied singleton live births at the established Romanian limit of viability (i.e., 25-28 weeks' gestational age) born between January 2007 and December 2010 (n = 227). Infants born in non-level-III facilities transferred to these three centers were included in our study (n = 39). Descriptive and multivariate statistical analyses were used to describe the population and examine outcomes and risk factors. RESULTS: During the study period, 62 neonates (27.3%) were delivered at 25 weeks, 56 (24.7%) were delivered at 26 weeks, 56 (24.7%) at 27 weeks, and 53 (23.3%) at 28 weeks. Overall in-hospital mortality was 65% (from 85% at 25 weeks to 35% at 28 weeks). The rates for major morbidities were necrotizing enterocolitis 8.8%, bronchopulmonary dysplasia 12.5%, and retinopathy of prematurity (stage higher than 2) 26.2%. CONCLUSIONS: During 2007-2010, in-hospital survival of infants admitted to three neonatal intensive care units in Romania was 35% and ranged from 14% at 25 weeks to 64% at 28 weeks.

Bowel dysfunction before and after surgery for endometriosis.

The relationship between deep fibrotic endometriosis of the rectum and digestive symptoms as well as the impact of surgical treatment on digestive complaints appears increasingly complex. With the exception of cases in which the disease leads to rectal stenosis, it seems likely that certain digestive symptoms are a result of cyclic inflammatory phenomena leading to irritation of the digestive tract and not necessarily the result of actual involvement of the rectum by the disease itself because they frequently occur in women free of rectal nodules. Functional or inflammatory bowel diseases and rectal hypersensitivity may be associated with pelvic endometriosis and consequently joepardize the hypothetical causal relationship between the presence of a rectal nodule and digestive complaints. Women treated surgically for rectal endometriosis may continue to experience postoperative digestive complaints, such as constipation. Despite successful surgery free of intra- and postoperative complications and significant improvement in well-being and pelvic pain, several unpleasant digestive symptoms may be incompletely cured by the surgery. Furthermore, de novo postoperative digestive complaints may occur after rectal surgery. Retrospective data suggest that performing colorectal resection is related to less favorable digestive functional outcomes than the use of conservative procedures such as shaving or full-thickness disc excision. These hypotheses need to be confirmed by prospective randomized trials comparing rectal radical and conservative approaches. Bearing in mind the complex relationship between rectal nodules, digestive symptoms and rectal surgery, particular care must be taken in the preoperative assessment of digestive function and in choosing the most suitable surgical procedure.

Postoperative recurrence and fertility after endometrioma ablation using plasma energy: retrospective assessment of a 3-year experience.

STUDY OBJECTIVE: To assess recurrence and pregnancy rates in women with ovarian endometrioma treated via ablation using plasma energy. DESIGN: Retrospective non-comparative pilot study including 55 patients treated during 28 months, with prospective recording of data (Canadian Task Force classification II-2). SETTING: Tertiary referral center. PATIENTS: Fifty-five consecutive women with pelvic endometriosis in whom ovarian endometriomas were managed solely via ablation using plasma energy. The minimum follow-up was 1 year. INTERVENTION: Endometrioma ablation using plasma energy. MEASUREMENTS AND MAIN RESULTS: Information was obtained from the database of the North-West Inter Regional Female Cohort for Patients with Endometriosis, based on self-questionnaires completed before surgery, surgical and histologic data, and systematic recording of recurrences, pregnancy, and symptoms. Recurrences were assessed using pelvic ultrasound examination. Mean (SD) follow-up was 20.6 (7.2) months (range, 12-39 months). In 75% of patients, deep infiltrating endometriosis was treated, and 40% had colorectal involvement. Preoperative infertility was recorded in 42% of patients. The rate of postoperative recurrence was 10.9% for the entire series. Of 33 women who wished to conceive, 67% became pregnant, spontaneously in 59%. Time from surgery to the first pregnancy was 7.6 (4.3) months. After discontinuation of postoperative hormone therapy, the probability of not conceiving at 12 months was 0.36 (95% confidence interval, 0.19-0.53), and at 24 months was 0.27 (95% confidence interval, 0.12-0.44). CONCLUSIONS: Recurrence and pregnancy rates are encouraging in that they seem comparable to the best reported results after endometrioma cystectomy. Plasma energy may have an important role in the management of ovarian endometrioma in women seeking to conceive. Patients most in need of surgical procedures that can spare ovarian parenchyma, such as those with bilateral endometriomas or a history of ovarian surgery, may particularly benefit from ablation using plasma energy.

Pregnancy rate following endometriomas management by ablation using plasma energy, cystectomy and drainage: A three-arm comparative study.

OBJECTIVE: To compare differences in the postoperative pregnancy rate in women seeking to conceive and presenting with endometriomas larger than 3 cm in diameter, which were managed by ablation using plasma energy, cystectomy, or simple drainage. METHODS: A retrospective three-arm comparative study based on prospective collection of data evaluating 363 patients, undergoing endometrioma cystectomy, ablation using plasma energy, or simple drainage. RESULTS: In this series, 204 (56.2%) patients underwent endometrioma ablation using plasma energy, 121 (33.3%) received cystectomy, and 38 (10.5%) had a simple drainage. Postoperative follow up was 50 ± 26 months. Overall postoperative pregnancy rate was 60.3%. The probability of being pregnant after cystectomy, ablation, and drainage was respectively 27%, 32%, and 16% at 12 months, with a statistically significant difference between pregnancy rates among the three arms (P = 0.015). Simple drainage was associated with a probability of conception over 50% after 2 years, mainly based on postoperative assisted reproductive technology. CONCLUSIONS: We reveal good postoperative pregnancy rate after ablation using plasma energy or cystectomy for endometriomas. Surgical management should be carefully considered in women with endometriomas and pregnancy intention, because the postoperative pregnancy rate may be compared with that observed after first-line assisted reproductive technology management.

Neutrophil­to­lymphocyte, platelet­to­lymphocyte and lymphocyte­to­monocyte ratios are associated with amputation rates in patients with peripheral arterial disease and diabetes mellitus who underwent revascularization: A Romanian regional center study.

Inflammation plays an important role in peripheral artery disease (PAD), contributing to the onset and progression of atherosclerosis, as well as to the rupture of atherosclerotic plaques. Studies have revealed that due to their inflammatory nature, leucocytes play an important role in the development of atherosclerosis. A retrospective study was conducted involving 203 patients with PAD admitted to Targu Mures Emergency County Hospital for revascularization surgery between January 2017 and June 2019 (of which 47 were treated by endovascular intervention, and 156 underwent classical surgical intervention). Among all patients included in the study, 47 patients required amputation following the revascularization intervention. The results indicated that though the mean patient age in the non-amputation group was higher than that in the amputation group, that the difference was not significant. With regard to sex distribution, 72% of the patients from the amputation group were male, while from the non-amputation group, 74% were male. The neutrophil-to-lymphocyte ratio (NLR) cut-off value for the prediction of amputation in PAD was 3.485 (sensitivity, 60.42%; specificity 72.44%), whereas the platelet-to-lymphocyte ratio (PLR) value was 152, (sensitivity, 54.17%; specificity, 71.79%), and was 2.55 for the lymphocyte-to-monocyte ration (LMR; sensitivity, 56.25%; specificity, 66.88%). The study concluded that in patients with PAD, the NLR and PLR were increased, while the LMR was decreased, which was also associated with a higher rate of amputation after revascularization, despite the lack of correlation between these factors, Fontaine classification and the number of damaged vessels. Therefore, pre-operative alterations in NLR, PLR and LMR may predict the need for amputation in patients with PAD, or those who underwent a revascularization intervention.

Complications associated with two laparoscopic procedures used in the management of rectal endometriosis.

BACKGROUND: To evaluate intra- and postoperative complications associated with laparoscopic management of rectal endometriosis by either colorectal segmental resection or nodule excision. METHODS: During 39 consecutive months, 46 women underwent laparoscopic management of rectal endometriosis and were included in a retrospective comparative study. The distinguishing feature of the study is that the choice of the surgical procedure is not related to the characteristics of the nodule. RESULTS: Colorectal segmental resection with colorectal anastomosis was carried out in 15 patients (37%), while macroscopically complete rectal nodule excision was performed in 31 women (63%). No intraoperative complications were recorded. In the colorectal resection group, 3 women (18%) had a bladder atony (spontaneously regressive in 2 women), 4 women (24%) experienced chronic constipation, one had an anastomosis leakage (6%), while 2 women (13%) had acute compartment syndrome with peripheral sensory disturbance. In the nodule excision group, 1 woman (4%) developed transitory right obturator nerve motor palsy. Based on both postoperative pain and improvement in quality of life, all 29 women in the excision group (100%) and 14 women in the colorectal resection group (82%) would recommend the surgical procedure to a friend suffering from the same disease. CONCLUSION: Our study suggests that carrying out colorectal segmental resection in rectal endometriosis is associated with unfavourable postoperative outcomes, such as bladder and rectal dysfunction. These outcomes are less likely to occur when rectal nodules are managed by excision. Information about complications related to both surgical procedures should be provided to patients managed for rectal endometriosis and should be taken into account when a decision is being made about the most appropriate treatment of rectal endometriosis in each case.

Ultrasound pattern and diagnostic accuracy of primary ovarian endometrioma and its recurrence: a pictorial essay.

The authors present their experience in ultrasound patterns of primary and recurrent endometrioma and correspondence with histopathological results, using 2D and color Doppler ultrasound examination. Cases of primary and recurrent endometriomas, as well as other false positive diagnosis are presented. The presence of the peripheral, healthy ovarian tissue, is the principal difference between the primary endometrioma and their recurrence. The arousal of papillary projections or solid-type echostructure decreases the likelihood of an endometrioma without histological atypia. Postmenopause modifies the ultrasound features of endometrioma by decreasing homogeneity and echogenicity.

Pseudoglandular hepatoid differentiation in endometrioid carcinoma of the ovary simulates oxyphilic cell change.

A 42-year-old patient had a stage III ovarian endometrioid adenocarcinoma with areas of hepatoid carcinoma (HC) of clear cell and eosinophilic pseudoglandular type that was difficult to differentiate from endometrioid carcinoma of oxyphilic type and sex cord-stromal tumor. Immunohistochemically, endometrioid adenocarcinoma was positive for CA125, estrogen and progesterone receptors, CAM5.2, cytokeratin (CK) 7 and 19, and vimentin. HC areas were positive for hep par1, polyclonal carcinoembryonic antigens, CD10, alpha-fetoprotein, epithelial membrane antigens, and antimitochondrial antibodies and shared with endometrioid carcinoma focal CK7, and constant positive CK19, CAM5.2, and progesterone receptors. In the differential diagnosis, a hepatic immunophenotype of oxyphilic, mitochondriae-rich areas (demonstrated by antimitochondrial antibodies) was identified by HC specific (hep par1) and characteristic markers: canalicular, cytoplasmic and membranous polyclonal carcinoembryonic antigens, CD10 patterns, and alpha-fetoprotein). Trabecular and clear vacuolated areas of HC resembled luteinized cells of sex cord-stromal ovarian tumors, but the membranous positivity to CAM5.2 supported epithelial (hepatoid) identity. The partial preservation of an endometrioid immunophenotype in HC (positive CK7 and 19 and progesterone receptors) would support an origin from endometrioid carcinoma.