Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study.

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial ( NCT03269071 , EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale ≥6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients.

The risk of malignancy in uterine polyps: A systematic review and meta-analysis.

BACKGROUND: Endometrial polyps are a common condition. The risk of malignancy has often led to an overtreatment with high health care costs and huge psychological distress. OBJECTIVE: We conducted a systematic review and a meta-analysis in order to estimate the prevalence of premalignant and malignant lesions in women undergoing hysteroscopic polypectomy. DATA SOURCE: We developed the search using PubMed/MEDLINE and EMBASE databases to identify papers published between 2000- January 2019. The research strategy used on Pubmed was: ("polyps" (MESH) OR "endometrial polyp*") AND ("malignancy" OR "cancer" OR "histopathology" OR "hysteroscopy" OR "ultrasound", OR "sonohysterography"). The same search was modified for EMBASE. STUDY ELIGIBILITY: We included all observational retrospective and prospective studies and studies were selected for the review if they met following inclusion criteria: pre-operative diagnosis of benign-looking endometrial polyps at ultrasound examination or at hysteroscopy, excision of endometrial polyps via surgical hysteroscopy, histopathological diagnosis of benign polyps, or hyperplasia without atypia, or premalignancy (atypical hyperplasia) or malignancy (endometrial cancer). Moreover, studies were included if number or percentage of subjects with and without malignancy was provided and if they reported data about menopausal and/or bleeding status. We excluded data presented exclusively as abstracts in national and international meetings, or case report or review articles that did not include original data and papers published in other than English language. Our primary outcome was the prevalence of endometrial premalignant or malignant polyps in the total series, among premenopausal and postmenopausal women and among women with or without abnormal bleeding and then in subgroup analysis according to study design, diagnostic method, study region and calendar year of publication. RESULTS: A total of 51 studies reporting data on 35,345 women were included in this review. The prevalence of malignant polyps was 2.73% (95% CI 2.57-2.91) with very high heterogeneity among studies. The rates were lower for premenopausal women (1.12%) than post-menopausal ones (4.93%) and the difference was statistically significant (chi-square = 397.21. p < .0001). The risk of malignancy was higher among symptomatic (5.14%) than asymptomatic ones (1.89%) (chi-square = 133.13 p < .001). We observed higher rate of malignant polyps in prospective studies. In the meta-analysis selecting 10 prospective studies the random pooled estimate was 5.88 (95% CI: 4.06-7.97) with heterogeneity among studies (heterogeneity chi square = 17.55 P = .025) whereas in retrospective studies the random pooled estimate was 2.94 (95% CI:2.24-3.71) with high heterogeneity among studies (P < .001). This finding can be due to more strict diagnostic criteria in prospective studies. CONCLUSION: Symptomatic vaginal bleeding and postmenopausal status in women with endometrial polyps increased the risk of malignancy. This finding could be an useful evidence to select patients who need to undergo hysteroscopic resection of endometrial polyps and women to whom, instead, an expectant management can be offer.

Intimate partner violence and repeat induced abortion in Italy: A cross sectional study.

OBJECTIVE: To investigate the impact of intimate partner violence (IPV) on the risk of repeat induced abortion (RIA), we compared IPV history among women with and without previous induced abortion (IA). METHODS: All consecutive women aged 18 years or more requiring IA in 12 Italian abortion clinics were eligible for inclusion in the study. They were asked to fill in an anonymous, self-developed questionnaire assessing sociodemographic data and their history of different types of violence and related risk factors. RESULTS: The analysis included 1030 women, 624 (60.6%) of whom reported a previous IA. Past or current IPV was reported by 19.3%: 7.0% reported sexual violence, 11.3% physical abuse and 12.1% psychological abuse. Past or current IPV was reported by 22.3% of women with RIA and 14.8% of those undergoing their first IA (adjusted odds ratio 1.57, 95% confidence interval 1.07-2.30; p = 0.02). When we considered sexual, psychological and physical abuse separately, we found that any kind of abuse was more frequent in women with RIA than in women with no previous IA. CONCLUSION: This study underlines the impact of IPV on the risk of RIA and suggests the need for screening for IPV among women requiring abortion, in order to identify women at risk of RIA and to improve their general and reproductive health.

Endometrial polyps detected at ultrasound and rate of malignancy.

PURPOSE: The vast majority of the evidence on the prevalence of malignancy in endometrial polyps was obtained irrespectively of the time of diagnosis, i.e. including both women who were diagnosed at pre-surgical ultrasound and those who were diagnosed at the time of hysteroscopy. We hypothesize that this may represent an inaccuracy of potential clinical relevance since physicians have to take decisions regarding the need of surgery at the time of ultrasound diagnosis. MATERIALS AND METHODS: Medical records of 2,245 patients who underwent hysteroscopy during a 4-year period were reviewed. Inclusion criterion was a pre-operative diagnosis of endometrial polyps. RESULTS: 1,284 women (57 % of the cohort) were selected, of whom 36 were diagnosed with malignancies (2.8 %, 95 % CI 2.0-3.8). This prevalence markedly differ in pre- and post-menopause, being higher in the latter group (OR = 9.0, 95 % CI 2.6-30.3, p < 0.001). Six out of 803 resulted positive in the pre-menopausal group (0.7 %, 95 % CI 0.3-1.5) compared to 30 out of 481 in the post-menopausal group (6.2 %, 95 % CI 4.3-8.6). In the pre-menopausal group, a younger age resulted protective. The risk of malignancy in women younger than 50 years was 0.3 % (95 % CI 0.04-0.9). In the post-menopausal group, abnormal uterine bleeding (AUB) was associated with a diagnosis of malignancy (OR = 4.0, 95 % CI 1.9-8.5). The prevalence of malignancy in symptomatic and asymptomatic post-menopausal women was 11.8 % (95 % CI 7.6-17.1) and 3.0 % (95 % CI 1.4-5.3), respectively. CONCLUSIONS: The prevalence of malignancy among endometrial polyps detected at ultrasound is low and in line with the evidence obtained for a diagnosis made at the time of surgery. Some simple anamnestic information such as menopausal status, age and AUB helps identify women at higher risk and should be used in the decision-making process guiding the choice of surgery.

Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial.

OBJECTIVE: To evaluate the efficacy of laparoscopic resection of the uterosacral ligaments in women with endometriosis and predominantly midline dysmenorrhea. DESIGN: Randomized controlled trial. SETTING: Two academic departments. One hundred eighty patients undergoing operative laparoscopy as first-line therapy for stage I to IV symptomatic endometriosis. INTERVENTION(S): Operative laparoscopy including uterosacral ligament resection or conservative surgery alone. MAIN OUTCOME MEASURE(S): Proportion of women with recurrence of moderate or severe dysmenorrhea 1 year after surgery. RESULT(S): No complications occurred. Among the patients who were evaluable 1 year after operative laparoscopy, 23 of 78 (29%) women who had uterosacral ligament resection and 21 of 78 (27%) women who had conservative surgery only reported recurrent dysmenorrhea. The corresponding numbers of patients at 3 years were 21 of 59 (36%) women and 18 of 57 (32%) women, respectively. Time to recurrence was similar in the two groups. Pain was substantially reduced, and patients in both groups experienced similar and significant improvements in health-related quality of life, psychiatric profile, and sexual satisfaction. Overall, 68 of 90 (75%) patients in the uterosacral ligament resection group and 67 of 90 (74%) patients in the conservative surgery group were satisfied at 1 year. CONCLUSION(S): Addition of uterosacral ligament resection to conservative laparoscopic surgery for endometriosis did not reduce the medium- or long-term frequency and severity of recurrence of dysmenorrhea.