Randomized trial of screening for preterm birth in low-risk women - the preterm birth screening study.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth. OBJECTIVE: To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation. STUDY DESIGN: This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle. RESULTS: A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation. CONCLUSION: The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program.

Developing DPYD Genotyping Method for Personalized Fluoropyrimidines Therapy.

BACKGROUND: Fluoropyrimidine drugs are widely used in chemotherapy to treat solid tumors. However, severe toxicity has been reported in 10% to 40% of patients. The DPYD gene encodes the rate-limiting enzyme dihydropyrimidine dehydrogenase responsible for fluoropyrimidine catabolism. The DPYD variants resulting in decreased or no enzyme activity are associated with increased risk of fluoropyrimidine toxicity. This study aims to develop a pharmacogenetic test for screening DPYD variants to guide fluoropyrimidine therapy. METHODS: A multiplex allele-specific polymerase chain reaction (AS-PCR) assay, followed by capillary electrophoresis, was developed to detect 5 common DPYD variants (c.557A > G, c.1129-5923C > G, c.1679T > G, c.1905 + 1G > A, and c.2846A > T). Deidentified population samples were used for screening positive controls and optimizing assay conditions. Proficiency testing samples with known genotypes were analyzed for test validation. All variants detected were confirmed by Sanger sequencing. RESULTS: From the deidentified population samples, 5 samples were heterozygous for c.557A > G, 2 samples were heterozygous for c.1129-5923C > G (HapB3), and 1 sample was heterozygous for c.2846A > T. The 20 proficiency samples matched with their assigned genotypes, including 13 wild-type samples, 3 samples heterozygous for c.1679T > G, 2 samples heterozygous for c.1905 + 1G > A, and 2 samples heterozygous for c.2846A > T. One of the 3 patient samples was heterozygous for c.1129-5923C > G (HapB3). All the variants detected by the multiplex AS-PCR assay were concordant with Sanger sequencing results. CONCLUSIONS: A robust multiplex AS-PCR assay was developed to rapidly detect 5 variants in the DPYD gene. It can be used for screening DPYD variants to identify patients with increased risk of toxicity when prescribed fluoropyrimidine therapy.

Hysteroscopic Endometrial Ablation: From Indications to Instrumentation and Techniques-A Call to Action.

The development of minimally invasive techniques has led to the creation of innovative alternatives in cases where traditional methods are not applicable. In modern gynecology, hysteroscopy has become the gold standard for the evaluation and treatment of intrauterine pathology. Endometrial ablation (EA) is a procedure that uses different types of energy to destroy the endometrium and is currently used as an alternative technique in cases of heavy menstrual bleeding when medical treatment has failed and uterine preservation is desired. The aim of this review was to evaluate the feasibility, safety, and clinical outcomes of hysteroscopic EA as an alternative in patients with abnormal uterine bleeding. A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 1994 to June 2022, to evaluate the outcomes in patients with abnormal uterine bleeding (AUB) undergoing EA using hysteroscopic and non-hysteroscopic techniques. Only scientific publications in English were included. Twelve articles on the current use of endometrial ablation were included. Data on patient symptoms, tools used for EA, primary outcomes, and adverse events were recorded. EA should be considered an effective and safe approach in the management of patients with abnormal uterine bleeding caused by benign pathology, in whom medical treatment has failed or is contraindicated. Due to the lack of evidence, it would be interesting to determine whether EA would also have a role in the treatment of women with premalignant lesions, avoiding invasive surgical procedures or medical treatment in those patients for whom hysterectomy or the use of hormonal treatment is contraindicated.

Description and Disposition of Patients With Cancer Accessing a Novel, Pharmacist-Led Cannabis Consultation Service.

PURPOSE: The Cannabis Consultation Service (CCS) is an innovative pharmacist-led resource at the Sunnybrook Odette Cancer Centre. Its mandate is to provide education and guide patients through access and appropriate use of high-quality plant-derived cannabinoids (PDCs). Our objective was to describe the CCS, explain its processes, and characterize patient disposition with respect to use of PDCs. METHODS: We retrospectively reviewed the charts of patients referred to the CCS from July 13, 2020, to March 05, 2021. We used descriptive statistics to report on the patient population and service metrics. RESULTS: During the 34-week period, 96 patients accessed the CCS (median age, 61 years). The top reasons for CCS consultation were management of cancer pain, insomnia, and general interest. Medical cannabis was supported as an option in 44/96 patients. Reasons for not supporting PDC use included lack of indication, potential drug interaction/contraindication, or requiring treatment with first-line therapy. Of the 40 patients requiring a medical document, 22 initiated therapy. The most common product used was a 2:50 THC:CBD (Tetrahydrocannabinol:Cannabidiol) cannabis oil. At the date of last contact, few patients remained on therapy because of lack of benefit, patient choice, and/or hesitancy. CONCLUSION: Despite patients with cancer having interest in seeking PDCs for symptom management, only a few initiated and continued therapy. Pharmacists have an opportunity to advise patients and the oncology team on the risks and benefits of PDCs. These results can be used to support the development of medical cannabis programs by oncology centers and focus future research priorities.

Effect of delayed versus immediate umbilical cord clamping in vaginal delivery at term: A randomized clinical trial.

OBJECTIVE: To compare maternal blood loss with immediate cord clamping versus delayed cord clamping in women undergoing spontaneous vaginal delivery at term. METHODS: Parallel group non-blinded randomized trial conducted at a single center in Italy. Women with singleton gestations who underwent spontaneous vaginal delivery at term were eligible and were randomized in a 1:1 ratio to either immediate or delayed cord clamping. In the immediate cord clamping group, cord clamping was within 15 s after birth. In the delayed cord clamping group, cord clamping was after more than 60 s, or when the cord had stopped pulsing. The primary outcome was change in maternal hemoglobin level from the day of delivery to day one after delivery. RESULTS: A total of 122 participants were enrolled in the trial. There were no significant differences in maternal blood loss as assessed by comparing the decrease in maternal hemoglobin level (mean difference - 0.10 g/dl, 95% confidence interval - 0.28 to 0.08) between the two groups. The mean hemoglobin level at postdelivery day 1 was 11.0 ± 1.5 g/dl in the delayed group and 11.3 ± 1.6 g/dl in the immediate group. CONCLUSIONS: Delayed umbilical cord clamping, compared with immediate umbilical cord clamping, resulted in no significant change in maternal hemoglobin level 1 day after delivery. TRIAL REGISTRATION: Clinicaltrials.gov NCT04353544.

The role of hysteroscopy in reproductive surgery: Today and tomorrow.

During the last decades, the number of couples with reproductive issues has substantially increased. Many different factors are implicated in reproductive failure, including uterine factors. Endometrial pathologies, such as endometrial polyps, hyperplasia, endometritis, and Mullerian anomalies, can also hinder embryo implantation. Hysteroscopy remains the gold standard for the evaluation and treatment of intrauterine pathology. Over the last few years, advances in hysteroscopic instrumentations and surgical techniques have significantly evolved, the refinement in technology, miniaturization of instruments, and improved image quality have rendered hysteroscopy a more patient and user-friendly procedure that has enhanced its use in reproductive medicine. Nowadays, hysteroscopy is essential in the evaluation and treatment of women with infertility. This article underscores the major technological breakthroughs achieved over the last few years with emphasis on the role of artificial intelligence, augmented reality, and 3D hysteroscopy, which can set new benchmarks in hysteroscopy applied to reproductive medicine.

Second stimulation in the same ovarian cycle: an option to fully-personalize the treatment in poor prognosis patients undergoing PGT-A.

PURPOSE: Our primary objective was to assess whether immediately undergoing a second stimulation in the same ovarian cycle (DuoStim) for advanced-maternal-age and/or poor-ovarian-reserve (AMA/POR) patients obtaining ≤ 3 blastocysts for preimplantation-genetic-testing-for-aneuploidies (PGT-A) is more efficient than the conventional-approach. METHODS: All AMA/POR patients obtaining ≤ 3 blastocysts after conventional-stimulation between 2017 and 2019 were proposed DuoStim, and 143 couples accepted (DuoStim-group) and were matched for the main confounders to 143 couples who did not accept (conventional-group). GnRH-antagonist protocol with recombinant-gonadotrophins and agonist trigger, intra-cytoplasmatic-sperm-injection (ICSI) with ejaculated sperm, PGT-A and vitrified-warmed euploid single-blastocyst-transfer(s) were performed. The primary outcome was the cumulative-live-birth-delivery-rate per intention-to-treat (CLBdR per ITT) within 1 year. If not delivering, the conventional-group had 1 year to undergo another conventional-stimulation. A cost-effectiveness analysis was also conducted. RESULTS: The CLBdR was 10.5% in the conventional-group after the first attempt. Only 12 of the 128 non-pregnant patients returned (165 ± 95 days later; drop-out = 116/128,90.6%), and 3 delivered. Thus, the 1-year CLBdR was 12.6% (N = 18/143). In the DuoStim-group, the CLBdR was 24.5% (N = 35/143; p = 0.01), 2 women delivered twice and 13 patients have other euploid blastocysts after a LB (0 and 2 in the conventional-group). DuoStim resulted in an incremental-cost-effectiveness-ratio of 23,303€. DuoStim was costlier and more effective in 98.7% of the 1000 pseudo-replicates generated through bootstrapping, and the cost-effectiveness acceptability curves unveiled that DuoStim would be more cost-effective than the conventional-approach at a willingness-to-pay threshold of 23,100€. CONCLUSIONS: During PGT-A treatments in AMA/POR women, DuoStim can be suggested in progress to rescue poor blastocyst yields after conventional-stimulation. It might indeed prevent drop-out or further aging between attempts.

Use of calendula ointment after episiotomy: a randomized clinical trial.

OBJECTIVE: Episiotomy is associated with an increased risk of postpartum pain, bleeding, and dyspareunia. The hypothesis of this trial was that in women with singleton pregnancy, and spontaneous labor at term, use of calendula ointment would reduce pain after episiotomy. METHODS: This was a single-center parallel group randomized trial of women with singleton pregnancies and spontaneous labor at term who were randomized to either use of calendula ointment (i.e. intervention group) or standard care (i.e. control group) after episiotomy. Eligible women were those with singleton gestations in spontaneous labor and vertex presentation at term. Women with premature rupture of membranes were excluded from the study. Women in the intervention group were recommended use of calendula ointment 4 h after the episiotomy and then every 8 h for 10 days. The primary outcome was the pain level. Pain level was self-reported and recorded using the verbal rating scale (VRS). The effect of the calendula ointment was quantified as mean difference (MD) with 95% confidence interval (CI). RESULTS: During the study, 100 women agreed to take part in the study, underwent randomization, and were enrolled in this trial. Of the 100 randomized women, 50 were randomized to the calendula ointment group, and 50 to the control group. No women were excluded after randomization or lost to follow up.Women who received calendula ointment after episiotomy compared to standard care had a significantly lower pain level starting from day two and during all the follow-up. Calendula ointment also improve wound healing in terms of redness and edema. CONCLUSIONS: Use of calendula ointment significantly reduce pain after episiotomy.

Ursodeoxycholic acid in the treatment of pregnancy cholestasis: a data-set available for Meta-analyses.

BACKGROUND: The recent literature on intrahepatic cholestasis of pregnancy raises questions on the best management of such a disease. Improved evidence might be achieved by meta-analyses. AIM: Providing data for allowing individual patients meta-analyses and aggregate data meta-analyses. METHODS: Data were collected retrospectively at the Fabia Mater Hospital of Rome (Italy), between 2013 and 2018. Several variables were collected and analyzed according to low-level bile acid (less than 40 µmol/L) and high-level bile acid (at least 40 µmol/L). Eighty-three cases of pregnancy cholestasis, diagnosed according to itching symptoms and excluding bile diseases, were collected and analyzed, both descriptively and inferentially. CONCLUSION: The analyzed data do not provide significant evidence supporting the use of ursodeoxycholic acid to prevent composite adverse fetal outcomes but they can be included in further meta-analyses.

Osseous metaplasia of the endometrium: A multicenter retrospective study.

OBJECTIVE: To describe clinical and demographic characteristics, ultrasound appearance, and hysteroscopic outcomes of patients with endometrial osseous metaplasia. STUDY DESIGN: We conducted a multicenter retrospective study. We retrospectively reviewed the medical records of all consecutive patients who were referred for hysteroscopy at fourteen institutions in Venezuela, Spain, Morocco, India, Ukraine, Argentina, the United States, and Italy between 1994 and 2018. We identified and included all patients who had a diagnosis of osseous metaplasia at the pathologic report, and data were retrieved from the medical records. RESULTS: Between January 1st, 1994, and December 31st, 2018, 63 patients out of a total of 419,673 women who underwent hysteroscopy had a diagnosis of osseous metaplasia (0.015%). Most patients were 31-40 years old (53.7%), were Caucasian or Hispanic (95.5%), and had at least one previous pregnancy (86.9%). Forty-one out of 63 patients (65.1%) had at least one miscarriage before the index hysteroscopy. Dysmenorrhea, abnormal uterine bleeding, and infertility were reported by 34.9%, 27.0%, and 23.8% of patients. 14.3% of women were asymptomatic. Preoperative transvaginal ultrasound was available and identified a hyperechoic area of variable size with posterior acoustic shadowing in all cases. Hysteroscopy was successful without complications in all 63 cases. Follow-up data were available in 30.2% of patients: 69.2% of patients were infertile, and 44.4% of them conceived and achieved a live birth; all other symptoms improved after hysteroscopic treatment in all patients. CONCLUSIONS: Osseous metaplasia appears associated with multiple unspecific gynecologic symptoms without the predominant role of infertility, as previously suggested. Although endometrial osseous metaplasia is rare, gynecologists should consider this pathologic condition when the characteristic ultrasound appearance is detected, being hysteroscopic treatment effective.

Perspectives of Italian pregnant women on pregnancy examinations and pregnancy care: is the caregiver more important than the care?

AIM: Assessing awareness of Italian low-risk pregnant patients on low-risk pregnancy care and what do they feel about their own pregnancy. METHODS: A questionnaire was administered to 382 low-risk pregnant women. This questionnaire assessed general knowledge of low-risk pregnancy, low-risk pregnancy care, and how much patients rated ten topics of low-risk pregnancy care. It would be expected that the knowledge of each topic would associates with the patient's perceived importance of that topic. RESULTS: Poor knowledge of pregnancy care was proven. Patients seem to incorrectly overrate vaginal examinations and obstetric and gynecologist-led care, while they attribute appropriate importance to midwife-led care. The more examinations performed (vaginal examinations, sonographic checks, cardiotocographies), the higher their rating. CONCLUSIONS: In Italy, expectations of pregnant women about their own pregnancy are incorrectly trusted in the obstetrics and gynecologists. Both poor knowledge of pregnancy care and cultural perspectives on the birth process amongst Italian people explain the finding. Referring low-risk pregnant women to midwives would help them to rate more the care than the caregiver.

Salivary gland-type mammary carcinoma arising in microglandular adenosis: A case report and clinicopathological review of the literature.

INTRODUCTION: Microglandular adenosis (MGA) is a rare benign proliferative lesion lacking a myoepithelial cell layer; 27% of all reported cases have progressed to invasive carcinoma. Salivary gland-type carcinomas of the breast are also uncommon, representing 2% of all breast cancers. This wide spectrum of neoplasms tends to be triple negative and generally has an excellent prognosis. Given the rarity of salivary gland-type carcinomas of the breast arising from MGA, there are few reports of these cases in literature. As such, there is uncertainty regarding their diagnosis and treatment strategies. PRESENTATION OF CASE: We report the rare case of a 66-year-old woman who presented with a triple negative, invasive carcinoma with salivary gland-type features, arising from MGA. The patient underwent mastectomy with sentinel lymph node biopsy, followed by Taxotere and Cyclophosphamide (TC) chemotherapy and 50 Gy in 25 fractions of radiation to her chest wall. We reviewed the available literature on salivary gland-type breast carcinomas arising from MGA. DISCUSSION: Despite the generally unfavourable characteristics associated with carcinoma arising in microglandular adenosis (MGACA), most patients with MGACA have favourable outcomes. CONCLUSIONS: The findings of the present case and reviewed cases are consistent with the literature on MGA, atypical MGA (AMGA), and MGACA. Future study of this rare entity is warranted to establish a consensus surrounding its clinical significance and treatment methods.

Pain descriptors of taxane acute pain syndrome (TAPS) in breast cancer patients-a prospective clinical study.

BACKGROUND: Taxane acute pain syndrome (TAPS) is a clinically significant side-effect of taxane chemotherapy, often described as arthralgia and myalgia that occurs 2-3 days after infusion. The aim of this study was to assess pain descriptors used by patients during their experience of TAPS. METHODS: A clinical prospective cohort study was conducted on breast cancer patients who had not received prior chemotherapy and were asked to complete diaries on three consecutive docetaxel treatment cycles on days 1-7, 14, and 21 (acute phase). Questionnaires to assess pain severity, descriptors of pain, and the interference in activities due to pain were adapted from the Brief Pain Inventory and the McGill Pain Questionnaire. Telephone questionnaire follow-up was done at 1, 3, 6, 9, and 12 months following docetaxel (delayed phase). RESULTS: The most commonly used descriptor for acute and chronic pain was "aching" (90-96%). However, in the delayed phase of the study, "burning" (32-50%), "radiating" (39-48%), and "sharp" (40-69%) were used more often. In both acute and chronic pain phases, most patients experienced moderate/severe pain regardless of the location. Pain in cycle 1 was predictive of pain in subsequent taxane cycles (p < 0.0001). Pain in cycle 3 was predictive of chronic pain (p < 0.002). CONCLUSIONS: The descriptors used by patients experiencing chemotherapy-induced pain (ChIP) may be reflective of the underlying mechanisms. It is suspected that TAPS initiates as an acute inflammatory pain, which over time develops into neuropathic pain, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the subjective pain experience varies from patient to patient.

Emergent Laparoscopic Removal of a Perforating Intrauterine Device During Pregnancy Under Regional Anesthesia.

STUDY OBJECTIVES: To describe and demonstrate a technique for laparoscopic removal of a perforating intrauterine device (IUD) during pregnancy, and to provide tips to facilitate safe laparoscopic surgery during pregnancy. DESIGN: Video presentation of the technique for laparoscopic removal of a perforating IUD in a pregnant woman. SETTING: Department of Neuroscience, Reproductive Sciences, and Dentistry, University of Naples Federico II, Naples, Italy. INTERVENTION: A 30-year-old woman, gravida 3, para 2, with a copper T IUD (Nova T 380; Bayer, Leverkusen, Germany) perforating the left adnexa presented to the emergency room complaining of left lower quadrant pain. The patient had the IUD inserted by her gynecologist 3 months before the onset of the symptoms. Ultrasound revealed a 6-week intrauterine pregnancy with the presence of fetal cardiac activity along with the IUD perforating the left adnexa. The patient returned at 11 weeks of gestation complaining of worsening abdominal pain and excruciating left lower quadrant pain. She was scheduled for laparoscopic excision of the perforating IUD [1-3]. Considering her pregnancy, laparoscopy under regional anesthesia was performed in the minimal Trendelenburg position at 12 degrees, through open laparoscopic access [4]. Intra-abdominal pressure of 8 mmHg and ultrasound energy to cut and coagulate, avoiding monopolar/bipolar energy owing to the presence of a copper IUD, were used. The IUD and tube were extracted in an endobag through umbilical access, under a 5-mm, 0-degree telescope in left lateral access [5]. The procedure was carried out uneventfully, and the IUD was removed. Fetal viability was confirmed after the procedure. At the time of this report, the patient was in the 23rd week of gestation, and the pregnancy was progressing without any problems. CONCLUSION: Laparoscopic removal of perforated IUD during pregnancy under regional anesthesia is a feasible and safe option that should be considered when needed.

Low endometrial beta-catenin and cadherins expression patterns are predictive for primary infertility and recurrent pregnancy loss.

Inadequate uterine receptivity is responsible for two-third of implanting failures. Aim of the study was to investigate the role of epithelial adherence and tight-junction molecules expressed by human endometrium in predicting womens' fertility outcome. A total of 76 consecutive women, including 24 fertile (G1), 40 primary infertile (G2), and 12 recurrent pregnancy loss (RPL, G3) women, who underwent diagnostic hysteroscopy plus endometrial biopsy between 2005 and 2016 at the Gynecology Division of Sant'Andrea Hospital, Sapienza University of Rome, in Italy, were retrospectively identified and included into the study. Endometrial biopsies were assessed for the immunohistochemical expression of beta-catenin (ß-catenin), E-cadherin and K-cadherin biomarkers. Expression profiles were compared between the three groups of patients and were correlated with patients' fertility outcome. In infertile patients there was a significant lower endometrial expression of ß-catenin (p = .001), E-cadherin (p = .001) and K-cadherin (p = .002), compared to the fertile ones. Furthermore, ß-catenin and E-cadherin intensity gradients of expression at glandular level were found totally reversed in infertile patients. Significant lower expression levels of K-catenin (p = .016) and E-cadherin (p < .0001) at glandular level were found in RPL patients. Results showed that the low endometrial expression of ß-catenin, E-cadherin and K-cadherin were associated to fertility-related problems, such as primary intertility and RPL.

Effectiveness of Hysteroscopic Techniques for Endometrial Polyp Removal: The Italian Multicenter Trial.

STUDY OBJECTIVE: To compare the effectiveness and safety of different techniques of hysteroscopic polypectomy. DESIGN: Multicenter, prospective observational trial (Canadian Task Force classification II-2). SETTING: Nineteen Italian gynecologic departments (university-affiliated or public hospitals). PATIENTS: Consecutive patients suffering from endometrial polyps (EPs). INTERVENTIONS: Hysteroscopic polypectomy, as performed through different techniques. MEASUREMENTS AND MAIN RESULTS: Included in the study were 1404 patients (with 1825 EPs). The setting was an ambulatory care unit in 40.38% of the cases (567 women), of whom 97.7% (554) did not require analgesia/anesthesia. In the remaining 59.62% of women (837 women), the procedures were performed in an operating room under mild sedation, local or general anesthesia. Minor complications occurred in 32 patients (2.27%), without significant differences between the techniques used (p = ns). Uterine perforation occurred in 14 cases, all performed in the operating room with some kind of anesthesia, only 1 with a vaginoscopic technique and the remaining during blind dilatation (odds ratio [OR], 19.98; 95% confidence interval [CI], 1.19-335.79; p = .04). An incomplete removal of EPs was documented in 39 patients. Logistic regression analysis showed that a higher risk of residual EPs was associated with the use of a fiber-based 3.5-mm hysteroscope (OR, 6.78; 95% CI, 2.97-15.52; p <.001), the outpatient setting (OR, 2.17; 95% CI, 1.14-4.14; p = .019), and EPs located at the tubal corner (OR, 1.98; 95% CI, 1.03-2.79; p = .039). No association between incomplete EP removal and EP size or number was recorded (p = ns), as well as with the other variables evaluated. CONCLUSION: Outpatient polypectomy was associated with a minimal but significantly higher risk of residual EPs in comparison with inpatient polypectomy. Conversely, inpatient polypectomy was associated with a considerably higher risk of uterine perforation and penetration in comparison with office hysteroscopy. Because of lower intraoperative risks and higher cost-effectiveness, office hysteroscopy may be considered, whenever possible, as the gold standard technique for removing EPs.

Synergistic antiproliferative and differentiating effect of 2,4-monofurfurylidene-tetra-O-methylsorbitol and 4,6-dimethyl-2-(3,4,5-trimethoxyphenylamino)pyrimidine on primary and immortalized keratinocytes.

Psoriasis is one of the most common chronic autoinflammatory skin disease, associated with hyperproliferation and abnormal differentiation of keratinocytes, inflammation, and angiogenesis. The available treatments for psoriasis are not curative and may have numerous side effects, and topical administration is preferred over systemic therapy due to the reduced systemic burden of the drug. Thus, novel and more efficacious formulations of anti-inflammatory and/or differentiating compounds for topical application could be very useful for the disease management and for improving the quality of life of the patients. Here we evaluated the potential as anti-psoriatic of an equimolar mixture of two compounds, 2,4-Monofurfurylidene-tetra-O-methylsorbitol (Compound A) and 4,6-dimethyl-2-(3,4,5-trimethoxyphenylamino)pyrimidine (Compound B), that, used individually, are known to possess immunomodulating properties (Compound A) and keratolitic and anti-inflammatory activity (Compound B). Human immortalized keratinocyte cell line (HaCaT cells) and primary human keratinocyte cells from adult donor (HEKa) were used as in vitro experimental models. We show that the mix A + B exhibits antiproliferative activity and induces terminal differentiation more efficiently than compounds A and B used individually. We confirm that the compound B is the active ingredient of the mixture and the mainly responsible for anti-psoriatic activity, but the mix A + B is more effective and possesses lower cytotoxicity than the compound B alone. This could be ascribable to the association with compound A, that is known to possess, in addition to the immunomodulating ability, antioxidant and antiradical action. Our results indicate that mix A + B could be a suitable candidate for a new cosmeceutical formulation for topical treatment of psoriasis.