Dystrophic Epidermolysis Bullosa (DEB): How Can Pregnancy Alter the Course of This Rare Disease? An Updated Literature Review on Obstetrical Management with an Additional Italian Experience.

Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome.

Local anesthesia for Altis® single incision sling in women with stress urinary incontinence.

OBJECTIVE: Local anesthesia for single incision slings has shown a good objective and subjective cure rate in women with stress urinary incontinence. The aim of the present study was to verify the efficacy and safety of local anesthesia during Altis® single incision placement. MATERIAL AND METHODS: One hundred sixty-six consecutive patients (83 patients for each group: local resp. spinal anesthesia) were selected from our database for this retrospective study among women who underwent an Altis® implantation for SUI from September 2016 to June 2021, after unsuccessful previous conservative treatment. Primary endpoints were objective and subjective cure rates; secondary endpoint was the evaluation of complications linked to this procedure. RESULTS: A total of 155 included patients completed our 12 months follow-up. Baseline characteristics were similar between the groups. Operative time (percentage difference of 50%; p < 0.05) and the Intraoperative Difficulty Scale resulted lower in spinal patients. No differences were found between populations in terms of objective (cough stress test and urodynamics) and subjective (PGI-I and FSDS questionnaires) cure rate and postoperative complications. CONCLUSION: Local anesthesia for Altis® implantation could be considered a safe alternative to spinal anesthesia and an effective opportunity to avoid general anesthesia, increasing the possibility of outpatient implantation of this sling system.

Laparoscopic posterior vaginal plication plus sacral colpopexy for severe posterior vaginal prolapse: A randomized clinical trial.

AIM: A randomized clinical trial proposing a new laparoscopic prosthetic and fascial approach to severe posterior vaginal prolapse. The primary endpoint was to evaluate the objective and subjective outcomes of our laparoscopic posterior plication (LPP) combined to "two-mesh" sacral colpopexy (laparoscopic sacral colpopexy [LSC]) in severe posterior vaginal prolapse, with a 1-year follow-up. The secondary endpoint was to evaluate the safety of this surgical procedure. METHODS: This is single-center prospective randomized double-blinded clinical trial. A total of 130 consecutive patients with anterior and/or apical pelvic organ prolapse (POP) (POP-Q stage ≥II) and severe posterior vaginal prolapse (posterior POP-Q stage ≥III) were prospectively assessed for inclusion into the study from November 2018 to January 2020. Patients underwent "two-meshes" LSC and were randomized in Group A (LSC plus LPP) and Group A (LSC alone). Of the 130 included subjects, 8 were excluded, not meeting inclusion criteria. Cure rate was evaluated objectively, using POP-Q study, and subjectively using PGI-I, POPDI-6, and FSDS questionnaires. Complications were assessed intra-, peri-, and postoperatively. Twelve-month follow-ups were analyzed for the study. RESULTS: We found in LSC plus LPP Group a significant improvement of Ap and genital hiatus POP-Q points. Our subjective study showed, at 12 months, a statistical difference in PGI-I successful outcomes rate in favor of LPP. Also the FSDS resulted significantly much more improved in Group A. We observed no statistical differences in terms of postoperative complications. CONCLUSIONS: Our LPP approach to LSC could be considered an effective and safe technique to POP patients with severe posterior prolapse.

Laparoscopic ventral rectopexy plus sacral colpopexy: continuous locked suture for mesh fixation. A randomized clinical trial.

PURPOSE: Laparoscopic ventral rectopexy (LVR) plus sacral colpopexy (LSC) is a high-complexity surgical procedure. The aim of the present study was to evaluate a new approach to rectal-mesh fixation during LVR with continuous locked suture. METHODS: This is a prospective randomized double-blinded clinical trial enrolling 80 patients with severe POP and obstructed defecation syndrome (ODS) from November 2016 to January 2021. Patients underwent a "two-meshes" LSC plus LVR and were randomized, regarding rectal mesh fixation, in Group A (extracorporeal interrupted 0 delayed absorbable sutures) and Group B ("U-shaped" running locked 0 delayed absorbable suture). Our primary endpoints were the operative times (OT); the secondary endpoints were the incidence of anatomical failures, vaginal mesh erosions and surgical complications. RESULTS: A total of 75 patients completed the study. Baseline characteristics were similar between the groups. Overall OT (156 vs 138 min; p < 0.05; treatment reduction of 11.5%) and LVR mesh fixation time (29 vs 16 min; p < 0.05; treatment reduction of 44%), resulted in significantly lower in Group B. No differences were found in terms of anatomic failure, vaginal mesh erosion or intra- or post-operative complications. PGI-I, FSDS and Wexner questionnaires resulted significantly improved after surgery, without statistical differences between the studied surgical procedures. CONCLUSION: Laparoscopic continuous locked 0 absorbable suture for LVR mesh fixation guaranteed a faster and effective alternative to multiple interrupted sutures. The significant OT reduction linked to this technique should be considered even more helpful when performing a highly complex surgery such as LVR. CLINICAL TRIAL REGISTRATION: NCT05254860 (13/02/2017).

Altis® Adjustable Single Incision Sling System for Treatment of Intrinsic Sphincteric Deficiency: A 3-Year Follow-up Observational Study.

IMPORTANCE: This article is a long-term follow-up study on the Altis adjustable single incision sling (Coloplast Corp.) in patients with isolated intrinsic sphincteric deficiency (ISD). OBJECTIVES: The primary end-points were to evaluate the subjective and objective outcomes of the Altis for the treatment of ISD, with a 3-year follow-up. The secondary end-point was to evaluate the safety of this surgical procedure. STUDY DESIGN: This is a retrospective single-arm study. A total of 123 consecutive patients with ISD were selected from our database among women who underwent an Altis implantation for ISD from March 2015 to June 2017, after unsuccessful previous conservative treatment. Of the 123 included patients, 16 were excluded, not meeting inclusion criteria. Cure rate was evaluated objectively, using a standardized cough stress test and urodynamics, and subjectively using the Patient Global Impression of Improvement. Complications were assessed intraoperatively, perioperatively, and postoperatively. Six, 12, and 36 months of follow-ups were analyzed for the study. RESULTS: The 3-year objective cure rate was 86.9%, and the subjective cure rate was 81.5%. We observed no intraoperative complications. No women were obstructed. Ten patients reported postoperative complications, although most of them were Clavien-Dindo grade I and self-limited. CONCLUSIONS: Altis system could be considered an effective and safe alternative to traditional midurethral slings as treatment for women with ISD.

Laparoscopic sacral colpopexy and a new approach to mesh fixation: a randomized clinical trial.

PURPOSE: Laparoscopic sacral colpopexy (LSC) plus supracervical hysterectomy (LSH) for pelvic organ prolapse (POP) is a high-complexity surgical procedure. The aim of the present study was to evaluate a new approach to vaginal-mesh fixation during LSC with continuous locked suture. METHODS: This is a prospective randomized double-blinded clinical trial enrolling 90 patients with severe POP from January 2016 to April 2017. Patients underwent LSH plus a "two-meshes" LSC and were randomized, regarding mesh fixation, in Group 1 (extracorporeal interrupted 3-0 delayed absorbable sutures) and Group 2 (running locked 3-0 delayed absorbable suture). Our primary endpoints were the operative times and the secondary endpoints the incidence of intra- or post-operative complications. RESULTS: A total of 42 patients for group completed the study. Baseline characteristics were similar between the groups. Overall mesh fixation time (24 vs. 39 min; p < 0.01), and operative time (121 vs. 138 min; p < 0.05) resulted significantly lower in Group 2. No differences were found in terms of anatomic failure, vaginal mesh erosion or intra- or post-operative complications. CONCLUSIONS: Laparoscopic continuous locked 3-0 absorbable suture for anterior and posterior mesh fixation during LSC guaranteed a faster and effective alternative to multiple interrupted sutures. The significant operative time reduction linked to this technique should be considered even more helpful when performing a highly complex surgery such as LSC.

Prostaglandin: cervical ripening in hypertensive pregnancies.

BACKGROUND: To determine the outcome of cervical ripening with intracervical prostaglandin E2 (PEG2) in hypertensive and non-hypertensive high-risk pregnancies in terms of successful ripening, mode of delivery, time intercorring between ripening and the beginning of labor or parturition and, at least, duration of labor. METHODS: A total of 63 women with a diagnosis of hypertensive disorders were included in the study protocol. These 63 women were compared with 71 consecutive high-risk pregnancies requiring induction of labor for maternal and/or fetal indications. Cervical ripening was performed with single or multiple doses of 0.5 mg of intracervical PGE2 gel. RESULTS: The rate of successful ripening was 84% for non-hypertensive patients (60/71) and 69% (43/63) for hypertensive patients ( p < 0.03). Twenty-four out of 63 hypertensive patients (38%) and 21 out of 71 non-hypertensive patients (30%) ( p < 0.05) were delivered by cesarean section. After stratification of hypertensive patients, the time interval from the first PGE2 administration to the onset of labor or vaginal delivery was significantly longer for preeclamptic patients vs. non-hypertensive patients or non-preeclamptic hypertensive patients. There were no differences in the duration of labor. CONCLUSIONS: Among hypertensive patients, only preeclamptic patients showed a lower rate of successful ripening and vaginal delivery if compared with non-preeclamptic or non-hypertensive patients; however, a vaginal delivery might be obtained in most preeclamptic patients when suitable cervical ripening was performed in the presence of clinician-perceived urgency to delivery.

Homocysteine induces trophoblast cell death with apoptotic features.

Hyperhomocysteinemia has been suggested as a possible risk factor in women suffering from habitual abortions, placental abruption or infarcts, preeclampsia, and/or intrauterine growth retardation. However, little is known about the pathogenic mechanisms underlying the action of homocysteine. The present study investigated the in vitro ability of homocysteine to affect trophoblast gonadotropin secretion and to induce cell death. In primary human trophoblast cells, homocysteine treatment (20 micromol/L) resulted in cellular flattening and enlargement, extension of pseudopodia, and cellular vacuolization. Cellular detachment, apoptosis, and necrosis were favored. With in situ nick end labeling, we investigated DNA degradation, and we used M30 CytoDEATH to selectively stain the cytoplasm of apoptotic cells. Cytochrome c release from mitochondria to the cytosol and DNA cleavage in agarose gel have been investigated. Homocysteine, but not cysteine, induced trophoblast apoptosis and significantly reduced human chorionic gonadotropin secretion. These findings suggest that trophoblast cell death might represent a pathogenic mechanism by which homocysteine may cause pregnancy complications related to placental diseases.

Regulation of endometrial adenocarcinoma cell proliferation by Activin-A and its modulation by 17beta-estradiol.

A role for activins in regulating cellular transformation is suggested by the alpha-inhibin knockout mouse in which development of gonadal tumors is associated with elevated activin levels. It was the purpose of the current study to determine whether activin had similar actions on endometrial cell lines, specifically on a well differentiated estrogen-responsive endometrial adenocarcinoma cell line (ISH) and estrogen-unresponsive cells (HEC-50) obtained from a poorly differentiated endometrial adenocarcinoma. Activin was secreted by both adenocarcinoma cell lines. Using reverse transcription-PCR, messenger RNA type I and type II activin receptor subtypes were detected in both cell lines: expression of IB and IIB was approximately three- to fourfold greater in ISH cells than in HEC-50 cells, while activin receptor IA and IIA messenger RNA levels were approximately equal in both cell lines. Activin treatment (30-300 ng/ml) caused a dose- and time-dependent inhibition of ISH cells proliferation and resulted in a significant decrease in Bcl-2 protein and mRNA levels. No difference was observed in Bax expression. There was no significant effect of activin when the cultures of ISH cells were exposed to 17beta-estradiol. In contrast, activin showed a weak, but significant, mitogenic effect on HEC-50 cells without modifications in Bax and Bcl-2 mRNA and protein levels. The results demonstrate that activin is a regulator of endometrial cancer cell growth. 17beta-Estradiol may promote resistance of estrogen-responsive endometrial cancer cells to the growth-retarding effects of activin and one of the mechanisms might be a down-regulation of the activin receptors.

Antiphospholid antibodies regulate the expression of trophoblast cell adhesion molecules.

OBJECTIVE: To examine the effect of antiphospholipid antibodies on trophoblast expression of adhesion molecules. DESIGN: Primary cytotrophoblast cell cultures. SETTING: Department of Obstetrics and Gynecology, Catholic University, Rome, Italy. PATIENT(S): Five normal pregnant women underwent uncomplicated vaginal delivery at 36 weeks of gestation. INTERVENTION(S): IgG antibodies were isolated from a patient with antiphospholipid syndrome and from a normal control subject, using protein-G Sepharose columns. Cytotrophoblast cells were dispersed in bicarbonate buffer containing trypsin and DNAse I. MAIN OUTCOME MEASURE(S): We investigated the effects of antiphospholipid antibodies on trophoblast adhesion molecules (alpha1 and alpha5 integrins, E and VE cadherins), both at the protein and mRNA levels. RESULT(S): The alpha1 and alpha5 integrins were present in trophoblast cells from 24 hours of culture. Treatment with IgG that were obtained from the patient with antiphospholipid syndrome significantly decreased alpha1 integrin and increased alpha5 integrin at both the mRNA and protein levels. Furthermore, IgG with antiphospholipid antibodies activities induced VE-cadherin down-regulation and the E-cadherin up-regulation at protein and mRNA levels compared with control IgG or untreated cells. CONCLUSION(S): The results suggest that the inadequate trophoblastic invasion, induced by antiphospholipid antibodies, can be the result of abnormal trophoblast adhesion molecules expression.