Search

ImportanceTransvaginal mesh (TVM) can increase the durability of vaginal surgical procedures for pelvic organ prolapse (POP) and may be indicated in certain situations despite concerns about mesh-related complications. In addition, the expense of commercial mesh kits has limited their use. The effectiveness, safety, and cost of a self-cut mesh procedure compared with a commercial mesh-kit procedure for the surgical treatment of women with POP is unclear.ObjectiveTo assess the 1-year effectiveness and safety of self-cut titanium-coated polypropylene mesh compared with a precut commercial mesh kit for the transvaginal surgical treatment of women with severe symptomatic POP.Design, Setting, and ParticipantsThis multicenter randomized noninferiority clinical trial was conducted at 11 hospitals in 8 provinces of China. A total of 336 women with symptomatic stage 3 to 4 POP were enrolled between January 22, 2018, and November 11, 2019, with follow-up through December 11, 2020.InterventionsParticipants were randomized to receive a TVM procedure using either self-cut mesh (self-cut mesh group) or a precut commercial mesh kit (mesh-kit group), both of which used the same titanium-coated polypropylene mesh.Main Outcomes and MeasuresThe primary outcome measure was composite surgical success at 1 year, which was defined as the absence of vaginal bulge symptoms, no additional retreatment for POP, and no vaginal prolapse at or beyond the hymen. Secondary outcomes included symptom-specific pelvic floor function and quality-of-life measures as well as perioperative complications, including mesh-related complications and hospitalization costs. Complications were categorized using the Clavien-Dindo system (with grade 1 indicating any deviation from the normal postoperative course but not requiring grade 2-4 interventions; grade 2, need for pharmacological treatment, blood transfusion, and/or total parenteral nutrition; grade 3, the need for surgical, endoscopic, and/or interventional radiological procedures; and grade 4, life threatening).ResultsAmong 336 female participants (mean [SD] age, 63.3 [5.9] years; all of Chinese ethnicity), 169 patients were randomized to the self-cut mesh group, and 167 were randomized to the mesh-kit group. Three patients were unavailable for follow-up after 1 year. In the intention-to-treat analysis, 162 women (95.9%) in the self-cut mesh group had outcomes that met the definition of surgical success; this result was noninferior to the surgical success rate observed in the mesh-kit group (146 women [87.4%]; risk difference, 8.5%; 95% CI, 2.2%-14.3%; P = .006). The frequency of Clavien-Dindo grade 1 to 3 perioperative complications was not significant between groups (12 of 166 women [7.2%] in the self-cut mesh group vs 20 of 161 women [12.4%] in the mesh-kit group; P = .14). Vaginal mesh exposure rates in women examined at 1 year were similar (4 women [2.4%] in the self-cut mesh group vs 8 women [4.8%] in the mesh-kit group; P = .23). Median (IQR) total hospitalization costs were $3663.00 ($3258.90-$4495.10) in the self-cut mesh group vs $6144.00 ($5434.90-$7160.20) in the mesh-kit group (P Conclusions and RelevanceIn this clinical trial, the composite surgical success rate of a self-cut mesh procedure was noninferior to that of a commercial mesh-kit procedure using the same titanium-coated polypropylene mesh and reduced hospitalization expenses by 40.4%. These findings suggest that the use of self-cut mesh procedures may be advantageous for the surgical treatment of some women with severe POP, particularly those in countries with low and middle income.Trial RegistrationClinicalTrials.gov identifier: NCT03283124

Background Pelvic organ prolapse (POP) is a common health problem and has significant negative effects on a woman’s quality of life. The transvaginal mesh procedure is a durable reconstructive surgery, but the mesh kits are expensive for underdeveloped countries. Our previous case-series study showed that the use of self-cut mesh had a good success rate (91.8% at 1-year follow-up) and low complication rate. This trial is designed to compare a self-cut titanium-coated polypropylene mesh procedure with a mesh kit for the treatment of symptomatic stage III–IV anterior or apical prolapse in terms of efficacy, safety and cost-effectiveness. Methods The trial is a randomized controlled multicenter non-inferiority trial. The primary outcome measure is the composite success rate at 1-year follow-up. The secondary outcomes are anatomic outcomes of each vaginal segment (anterior, posterior and apical) using the POP-Q score, subjective improvement of quality of life according to questionnaires, intraoperative parameters, complications and costs. Analysis will be performed according to the intention-to-treat principle. Based on a comparable success rate of 90% and 10% as the margin (β = 0.2 and one-sided α = 0.025), about 312 patients in total from 11 centers will be recruited including 10% dropout. The aims of the research are to demonstrate whether the self-cut mesh procedure is non-inferior to the mesh-kit procedure and to investigate the performance of titanium-coated mesh for vaginal prolapse repair. Discussion This multicenter non-inferiority trial will evaluate whether the efficacy and safety of self-cut mesh is non-inferior to mesh kits in women with severe symptomatic stage III–IV anterior or apical prolapse. If we are able to show that the self-cut mesh procedure is non-inferior to the mesh-kit procedure in success rates, then the self-cut mesh procedure may be more cost-effective. Trial registration ClinicalTrials.gov, NCT03283124. Registered on 17 January 2018.

Revolutionary CART therapy still faces the challenge of severe cytokine release syndrome (CRS). While IL6 and IL1 have been demonstrated as essential contributors, GM-CSF is one of the most abundant inflammatory cytokines secreted by CART and has also been suggested in contributing to CRS. To minimize GM-CSF production from CART to reduce its associated toxicity, we conducted a pilot study (ChiCTR2000032124) of CRISPR-edited GM-CSF knockout (KO) in CART secreting anti-IL6 scFv and IL1RA, with additional TCR KO for tracing edited CART. The initial results of three patients (1 Non-Hodgkin lymphoma (NHL) and 2 multiple myelomas (MMs)) are summarized as: 3/3 complete response, 2/3 none CRS, 1/3 grade 2 CRS, and 0/3 neurotoxicity. The analysis revealed low levels of GM-CSF, IL6 and IL1B at the time of interferon-gamma (IFNG) peaks, and elevated IL1RA. We also observed significant expansion of CD3– CART during treatment and no aberrant expansion of CD3– CART in the follow-up. Re-expansion of CD3– CART was observed in two patients while recurring CD19+ cells were eradicated in the patient with NHL. In summary, our study supported the safety and durable potency of CRISPR-edited CART in patients, providing a novel platform for developing autologous or allogeneic CART to minimize GM-CSF-associated toxicity in addition to autonomous IL6/IL1 blockade.

Additional file 1: Supplementary Table 1. The efficacy analysis of patients with high-grade serous cancer. ORR, objective response rate; DCR, disease control rate; a Twelve patients receiving less than 2 cycles of PLD and 4 patients without efficacy assessments after 2 cycles of PLD were excluded. Moreover, 1 patient had a postbaseline efficacy assessment that could not be confirmed and was thus excluded; b Including patients with complete and partial responses; c Including patients with complete and partial responses and stable disease.

Additional file 2:Supplementary Table 2. Predictive impact of factors on efficacy evaluated by the RECIST or the GCIG criteria. ECOG, Eastern Cooperative Oncology Group; FIGO, International Federation of Gynecology and Obstetrics; RECIST, Response Evaluation Criteria in Solid Tumors version 1.1; GCIG, Gynecologic Cancer InterGroup.

Background: Transvaginal mesh can increase the durability of surgery for pelvic organ prolapse. However, commercial mesh kits can be expensive. We assessed the efficacy of a much cheaper self-cut titanium-coated polypropylene mesh with a mesh-kit for treating symptomatic pelvic organ prolapse. Methods: We conducted a multicenter, randomized, non-inferiority trial. Patients were randomized to either self-cut mesh or commercial mesh-kit. Patients with symptomatic stage III-IV pelvic organ prolapse were enrolled at 11 centers between January 2018 and November 2019. The primary outcome measure was composite success at one year defined by absence of vaginal bulge symptoms, and no additional re-treatment for POP, and no vaginal prolapse at or beyond the hymen. Secondary outcomes included symptom-specific pelvic floor function and quality of life measures, complications and costs. Findings: A total of 336 participants were randomized. In the intention-to-treat analysis, 95∙9% (162/169) met the definition of surgical success in the self-cut group, which was noninferior to the 87∙4% (146/167) surgical success in the mesh-kit group (risk difference, 8∙5 [95%CI 2∙2 to 14∙3]). The frequency of Clavien-Dindo grade I-III complications were not significant between groups (12 [7∙2%] vs 20 [12∙4%], P=0∙14). Vaginal mesh exposure rates in women examined within 1 year [self-cut group 4/169 (2∙4%) vs mesh-kit group 8/167 (4∙8%)] were similar (P=0∙23). Interpretation: This trial demonstrated that composite surgical success of a self-cut mesh procedure was non-inferior to a commercial mesh-kit procedure using the same mesh. The use of self-cut mesh was effective and safe, while reducing the hospitalization expense by approximately 40%. Clinical Trial Registration Details: Clinicaltrials.gov, NCT03283124. Funding Information: Chinese Academy of Medical Science Initiative for Innovative Medicine(CAMS-2017-12M-1-002). Medstron Medical(shanghai) Co. Ltd, the agent of Tiloop® products in China, provided monetary support for this research including interim meeting and third party (LinkDoc Beijing company) EDC system. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by the Institutional Review Board of Peking Union Medical College Hospital (JS-1278).

Additional file 3:Supplementary Table 3. Predictive impact of a CA125 decrease after the first cycle on efficacy evaluated by the RECIST or the GCIG criteria. ORR, objective response rate; DCR, disease control rate; a chi-square test; b Including patients with complete and partial responses; c Including patients with complete and partial responses and stable disease. RECIST, Response Evaluation Criteria in Solid Tumors version 1.1; GCIG, Gynecologic Cancer InterGroup.

Background: Low-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, which has an indolent history with late recurrences. ESS usually spread through the lymph nodes and venous system but very seldom involve large vessels or the heart.Case presentation: A 38-year-old Chinese woman was admitted to our department due to pelvic mass found on physical examination. The superior and inferior vena cava CT angiography (CTA) showed an enlarged uterine as well as low density image in the left internal iliac vein, the left common iliac vein, the inferior vena cava, the left renal vein adjacent to the heart and the right atrium, with a range of 110*16mm. The filling defect of right atrium was about 30*14mm. The three-dimensional computed tomography reconstruction showed that the mass originated from the uterine and invaded into the reproductive vein, subsequently extended along the inferior vena cava to the right atrium. Needle biopsy of the pelvic mass was performed and the tissue indicates smooth muscle. The preoperative diagnosis was intravascular leiomyomatosis and the patient underwent radical resection: thrombectomy and total hysterectomy with bilateral salpingo-oophorectomy. Postoperative histopathology revealed low grade endometrial stromal sarcoma. Microscopically, the tumors in both original uterine lesions and intravascular and intracardiac metastases shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which small spiral artery differentiation was recognized and tumor tissue showed invasive growth pattern by inserting into the surrounding smooth muscle. Immunohistochemistry showed tumor cells were reactive to Estrogen Receptor, Progesterone Receptor,CD10. Primary uterine foci showed cyclin D1(5%+) and Ki-67(20%+),whereas metastatic lesions of the intracardiac and the intravascular component identified cyclin D1(negative) and Ki-67(2%+). The patient is alive without evidence of recurrence 3 months after surgery.Conclusions: Distant metastasis of low-grade endometrial stromal sarcoma is rare, especially involving large vessels or the heart. This case demonstrates that malignant tumor metastasis should be considered as a differential diagnosis of intracardiac and intravascular masses. The treatment rely on multidisciplinary cooperation.

Objective To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Additional file 1. SPIRIT Checklist: Recommended items to address in a clinical trial protocol and related documents.

Objective: Mixed gestational trophoblastic neoplasia (GTN) is a rare occurrence that refers to the coexistence of choriocarcinoma and/or placental site trophoblastic tumor and/or epithelioid trophoblastic tumor. The diagnosis and management of mixed GTN are challenging. We investigated the clinicopathological characteristics, diagnoses, treatments, and outcomes of patients with mixed GTN.Materials and Methods: The medical records and pathological sections of 16 patients with mixed GTN who were treated at Peking Union Medical College Hospital and The Second Xiangya Hospital of Central South University between January 2012 and December 2018 were reviewed.Results: Pretreatment serum human chorionic gonadotropin (hCG) levels ranged from 180 to 625,024 IU/L, and were >10,000 IU/L in 14 of the 16 patients, none of whom were diagnosed correctly at initial presentation. Two patients were diagnosed with choriocarcinoma coexisting with intermediate trophoblastic tumor (ITT) through dilation and curettage (D&C) before treatment. Another 5 patients were histologically confirmed to have placental site trophoblastic tumor (PSTT) by D&C but final pathological findings showed mixed PSTT and choriocarcinoma at subsequent hysterectomy. Seven post-chemotherapy patients with an initial clinical diagnosis of choriocarcinoma underwent surgery because of chemoresistance and their pathological findings revealed coexisting ITT. The remaining 2 patients were found to have choriocarcinoma coexisting with ITT following cervical biopsy and pulmonary lobectomy. All patients received chemotherapy: 14 underwent surgery combined with chemotherapy and 2 received chemotherapy alone to preserve fertility. Other than 1 patient who died of disease progression, 15 patients (93.8%) achieved complete remission (CR) after treatment, although 5 (33.3%) relapsed. Of these 5 patients with relapse, 3 achieved CR after additional treatment, 1 was receiving an immune checkpoint inhibitor, and 1 was lost to follow-up after refusing further therapy.Conclusion: Mixed GTN is difficult to diagnose on initial presentation. Overlap of the ITT component should be considered in refractory chemoresistant choriocarcinoma. Coexistence of choriocarcinoma should be suspected in ITT patients with high hCG levels. Surgery combined with chemotherapy is optimal treatment for choriocarcinoma mixed with ITT.

The transcription factor MEF2 promotes survival in various cell types and a number of studies indicate that abnormal regulation of MEF2 is linked to oncogenicity in several carcinomas. We have found that MEF2D, a member of the MEF2 family, is upregulated in Ovarian Cancer (OC). Immunohistochemistry analysis of tumor sections of 402 OC patients revealed that MEF2D is significantly elevated at the protein level. We have also found that the expression level of MEF2D is associated with cisplatin-resistance and poor prognosis by a retrospective analysis. Furthermore, Downregulation of MEF2D by siRNA reduces proliferation and invasiveness of OC cells SKOV3 and OVCAR3, induces apoptosis in vitro, and abolishes OVCAR3 tumorigenicity in xenograft model. Mechanistic study via ChIP analysis identified two of MEF2D-targeted genes, HPSE and IKBKE, which are associated with tumor invasion and chemotherapy-resistance, in accord with MEF2D expression in OC. Remarkably, knock-down of MEF2D invariably lead to the downregulation of IKBKE and reversed cisplatin (DDP)-resistance in cisplatin-resistant cells SKOV3-DDP. Our results suggest that MEF2D promotes malignant biological behaviors and cisplatin-resistance in OC and establish MEF2D as a new therapeutic target in OC treatment.

A nano-structured scaffold was designed for bone repair using collagen, hyaluronic acid (HYA) and nano-bioactive glass (NBaG) as its main components. The collagen-HYA/NBaG scaffold was prepared by using a freeze-drying technique and characterized by scanning electron microscopy (SEM). Osteoblastls were seeded on these scaffolds and their proliferation rate, alkaline phosphatase (ALP) activity and ability to form mineralized bone nodules were compared with those osteoblasts grown on cell culture plastic surfaces. The cross-section morphology shows that the collagen-HYA/NBaG scaffold possessed a three-dimensional (3D) interconnected homogenous porous structure. The results obtained from biological assessment show that this scaffold did not negatively affect osteoblasts proliferation rate and improves osteoblasts function as shown by increasing the ALP activity and calcium deposition and formation of mineralized bone nodules. Therefore, the composite scaffolds could provide a favorable environment for initia...

To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, Pcombined, stringently matched=9.69×10(-9), per-allele odds ratio (OR)stringently matched=1.26) and 17q12 (rs8067378, Pcombined, stringently matched=2.00×10(-8), per-allele ORstringently matched=1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched=4.52×10(-27), per-allele ORstringently matched=0.75). Our findings provide new insights into the genetic etiology of cervical cancer.

To evaluate the clinical efficacy of letrozole on ovulation induction and hormone replacement therapy (HRT) during endometrial preparation for frozen-thawed embryo transfer (FET).We analyzed totally 1,230 cycles of patients that underwent FET from October 2010 to September 2012. Seven hundred and thirteen cycles of patients with ovulation disorders that underwent FET were randomly assigned to two groups by case control study. 359 cycles received letrozole ovulation induction and 354 cycles received HRT during endometrial preparation for FET, respectively. In the corresponding period, 517 cycles of patients with normal ovulation in the natural cycle group for FET endometrial preparation served as controls. Reproduction-related clinical outcomes of patients in the three groups were compared.The embryo implantation rate of patients in letrozole group (30.4 %) was significantly higher than the HRT group (22.8 %, P0.05). The clinical pregnancy rate of patients in the letrozole group (53.2 %) was significantly higher than the HRT group (44.4 %, P0.05), while no significant difference was observed between the letrozole and natural cycle groups (51.3 %, P0.05). Estradiol levels on the day of human chorionic gonadotropin administration in the letrozole group were significantly lower than those in the natural cycle group (280.32 ± 125.39 pg/ml and 351.06 ± 123.03 pg/ml, respectively; P0.05). The live birth rate of patients in letrozole group (44.6 %) was significantly higher than the HRT group (32.5 %, P0.05), while abortion rate (12.0 %) was significantly lower than the HRT group (21.0 %, P0.05). There were no significant differences in number of mature follicles, endometrial thickness, duration of follicle growth between the letrozole and the natural cycle groups, and there were no significant differences in twin birth rate and ectopic pregnancy rate among the three groups (all P values0.05).Ovulation induction with letrozole during endometrial preparation for FET has a higher rate of pregnancy success and a lower abortion rate than HRT. Letrozole treatment exhibits clinical progression and outcomes similar to those patients undergoing a natural cycle or normal ovulation cycle. Therefore, letrozole treatment may be an effective option in endometrial preparation for FET in patients with ovulation disorders or irregular menstruation.

To evaluate the clinical effect of letrozole (LE) alone on the ovulation induction in endometrial preparation for frozen-thawed embryo transfer (FET).Totally 253 FET cycles were analyzed by case control study from October 2010 to June 2011. We divided ovulation disorders or menstrual disorders divided into 2 groups: a LE group on ovulation induction cycle (n=85), and a hormone replacement therapy (HRT) cycle group (n=84). Meanwhile those who ovulated normally were included in a natural cycle group (n=84). Demographics and clinical parameters of reproductive correlation of all patients were observed among these groups.The average clinical pregnancy rate of the LE group was higher than that of HRT cycle group (54.1% vs 44.04%; P0.05). The difference in the parameters such as patients' demographics and other clinical indexs had no statistical significance (P0.05). The estradiol level on human chorionic gonadotrophin (HCG) administration day in the natural cycle group [(341.19±113.14) pg/mL] was higher than that of the LE group [(279.70±127.80) pg/mL] (P0.05). There was no significant difference in the number of maturation follicles and endometrial thickness on the HCG administration day between the LE group and the natural cycle group (P0.05).Ovulation induction with LE alone for endometrial preparation is superior to HRT cycle in FET and has similar clinical process and outcome to those of the natural cycle. It can be applied in endometrial preparation for FET effectively for those with anovulation or menstrual disorder.