BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective:To explore the safety and long-term efficacy of transvaginal reconstructive pelvic surgery (TVRPS) in ≥70-year-old women with severe pelvic organ prolapse (POP).Methods:A single-center, prospective cohort study was conducted on 343 elderly women patients with severe POP who received TVRPS at the Fourth Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA from March 2007 to September 2024. There were 297 cases (86.6%, 297/343) of Ⅲ degree and 46 cases (13.4%, 46/343) of Ⅳ degree prolapse respectively. Among them, anterior pelvic prolapse accounted for 80.8% (277/343), and those with prolapse in two or more sites accounted for 30.0% (103/343). The age was (74.2±3.4) years (range: 70 to 89 years old). There were 300 cases (87.5%, 300/343) with more than one internal medicine disease. Preoperative general conditions were assessed using American Society of Anesthesiologists physical status classification system (ASA) and American College of Surgeons National Surgical Quality Improvement Program-frailty index (ACS NSQIP-FI). TVRPS surgeries included transvaginal hysterectomy, salpingooophorectomy, high uterosacral ligament suspension, sacrospinous ligament fixation, native tissue and mesh repair of the anterior and posterior vaginal walls, mid-urethral sling for anti-urinary incontinence, and levator anal muscle folding suture and perineal repair. Perioperative complications were evaluated using Clavien-Dindo classification system. The objective effect of TVRPS was determined based on pelvic organ prolapse quantification system (POP-Q), and the subjective results were evaluated using pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form 7 (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients had a preoperative ASA grade of ≤gradeⅡ, and ACS NSQIP-FI score of ≤0.27. All patients safely and successfully underwent all TVRPS surgeries. The operation time was (154.2±43.2) minutes. The perioperative morbidity and mortality rate were 0.6% (2/343) and 0 (0/343) respectively. None of the patient needed blood transfusion. The follow-up time was (7.5±4.3) years, with the longest being 17 years. Thirty-four cases (9.9%, 34/343) were lost to follow-up, and 22 cases (6.4%, 22/343) died of internal diseases during the follow-up period. The point values of Aa, Ba, C, Ap and Bp in the POP-Q system were significantly decreased after the operation (all P<0.01), the genital hiatus was significantly shortened (all P<0.01), and the perineal body was significantly elongated (all P<0.01). The scores of PFDI-20 and PFIQ-7 were significantly lower than those before the operation (all P<0.01). There were 332 cases (96.8%, 332/343) with an overall symptom impression improvement score of PGI-I≤2. Conclusion:The results on 343 elderly women with severe POP aged an average of 74.2 years show that for elderly POP patients who still have the desire to preserve the vagina and do not meet the conditions for colpocleisis, as long as there is a comprehensive understanding and strict evaluation of the overall condition before the operation, TVRPS is a safe, feasible and long-lasting therapeutic procedure.

Objective:To explore the safety and long-term efficacy of transvaginal reconstructive pelvic surgery (TVRPS) in ≥70-year-old women with severe pelvic organ prolapse (POP).Methods:A single-center, prospective cohort study was conducted on 343 elderly women patients with severe POP who received TVRPS at the Fourth Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA from March 2007 to September 2024. There were 297 cases (86.6%, 297/343) of Ⅲ degree and 46 cases (13.4%, 46/343) of Ⅳ degree prolapse respectively. Among them, anterior pelvic prolapse accounted for 80.8% (277/343), and those with prolapse in two or more sites accounted for 30.0% (103/343). The age was (74.2±3.4) years (range: 70 to 89 years old). There were 300 cases (87.5%, 300/343) with more than one internal medicine disease. Preoperative general conditions were assessed using American Society of Anesthesiologists physical status classification system (ASA) and American College of Surgeons National Surgical Quality Improvement Program-frailty index (ACS NSQIP-FI). TVRPS surgeries included transvaginal hysterectomy, salpingooophorectomy, high uterosacral ligament suspension, sacrospinous ligament fixation, native tissue and mesh repair of the anterior and posterior vaginal walls, mid-urethral sling for anti-urinary incontinence, and levator anal muscle folding suture and perineal repair. Perioperative complications were evaluated using Clavien-Dindo classification system. The objective effect of TVRPS was determined based on pelvic organ prolapse quantification system (POP-Q), and the subjective results were evaluated using pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form 7 (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients had a preoperative ASA grade of ≤gradeⅡ, and ACS NSQIP-FI score of ≤0.27. All patients safely and successfully underwent all TVRPS surgeries. The operation time was (154.2±43.2) minutes. The perioperative morbidity and mortality rate were 0.6% (2/343) and 0 (0/343) respectively. None of the patient needed blood transfusion. The follow-up time was (7.5±4.3) years, with the longest being 17 years. Thirty-four cases (9.9%, 34/343) were lost to follow-up, and 22 cases (6.4%, 22/343) died of internal diseases during the follow-up period. The point values of Aa, Ba, C, Ap and Bp in the POP-Q system were significantly decreased after the operation (all P<0.01), the genital hiatus was significantly shortened (all P<0.01), and the perineal body was significantly elongated (all P<0.01). The scores of PFDI-20 and PFIQ-7 were significantly lower than those before the operation (all P<0.01). There were 332 cases (96.8%, 332/343) with an overall symptom impression improvement score of PGI-I≤2. Conclusion:The results on 343 elderly women with severe POP aged an average of 74.2 years show that for elderly POP patients who still have the desire to preserve the vagina and do not meet the conditions for colpocleisis, as long as there is a comprehensive understanding and strict evaluation of the overall condition before the operation, TVRPS is a safe, feasible and long-lasting therapeutic procedure.

Objective:To explore the characteristics, prevention and treatment strategies of lower urinary tract injury in transvaginal reconstructive pelvic surgery (vRPS).Methods:A retrospective analysis was conducted on 24 patients who suffered lower urinary tract injuries occuring in vRPS from January 2005 to June 2021, among which 4 cases were referred to our hospital from other hospitals.Results:(1) In our hospital, 1 952 patients underwent vRPS for anterior and (or) middle pelvic organ prolapse during that study period, with a 1.0% (20/1 952) incidence of lower urinary tract injuries occurring in 20 cases. (2) Ureteral injuries were observed in 14 cases who underwent transvaginal high uterosacral ligament suspension (1.4%, 14/966). The symptoms were relieved after the removal of sutures. (3) Bladder injuries occurred in 6 cases in our hospital, with 4 cases (0.7%, 4/576) in anterior transvaginal mesh surgery (aTVM), one (0.4%, 1/260) in colpocleisis, and one (0.7%, 1/150) in apical suspension for fornix prolapse. An additional 4 cases of bladder injury were referred to our hospital after aTVM. Among the 8 cases of bladder injury during aTVM, 2 cases were intraoperative incidents. Cystoscopy confirmed that the superficial branch or puncture rod of anterior vaginal mesh had penetrated into the bladder. Re-puncturing and placement of the mesh were successfully performed. No abnormalities were observed during a follow-up period of 4-5 years. Postoperative bladder injuries were identified in 6 cases, characterized by mesh erosion into the bladder and formation of calculi. These injuries were confirmed between 6 months to 2 years after vRPS. The exposed mesh and calculi in the bladder were removed through laparotomy or cystoscopy, followed up for 2-12 years. One case experienced slight re-erosion of mesh to the bladder.Conclusions:Lower urinary tract injuries are difficult to avoid in vRPS, particularly in transvaginal high uterosacral ligament suspension and aTVM. However, the incidence is low. Lower urinary tract injuries during vRPS could be easily detected and managed intraoperatively because of the use of cystoscopy. As long-term postoperative complications, erosion of transvaginal mesh to lower urinary tract postoperatively could be treated correctly, seldom with severe sequelae.

Objective:To evaluate the indications, surgical skills and clinic outcomes of abdominal minimal incision sacrocolpopexy (AMISC) for treatment of advanced pelvic organ prolapse (POP).Methods:The retrospective study analyzed 30 women with advanced POP who underwent AMISC between June 2016 and October 2019, including 9 cases of recurrent prolapse and 10 cases of vault prolapse. AMISC was especially applicable to: (1) patients with several medical complications who was unable to tolerate general anesthesia or laparoscopic surgery, but able to tolerate combined spinal-epidural anesthesia and open surgery; (2) other abdominal procedures were indicated to perform with AMISC simultaneously, such as myomectomy, subtotal hysterectomy etc, the specimens were easy to get out of the abdominal cavity and morcellation was avoided; (3) surgeons preferring open surgery to laparoscopic surgery or skilled in open surgery; (4) patients with prior pelvic operations, presenting severe abdominal and pelvic adhesions. Objective outcomes were assessed by pelvic organ prolapse quantification (POP-Q) system. Subjective outcome were assessed by pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients with 1-3 medical complications were successfully performed with AMISC without stopping procedure, enlarging the incision or changing to other procedure, the operation duration was (110±19) minutes. The mean time of follow-up was (33.5±12.4) months (range: 8-49 months). The postoperative points of Aa, Ba, C, Ap, Bp reduced significantly and point C improved from (2.33±2.50) cm to (-7.54±1.18) cm after AMISC ( P<0.01). The objective cure rates were both 100% (30/30) in apex and posterior compartment, while 97% (29/30) in anterior compartment. Postoperative scores of PFDI-20 and PFIQ-7 were all significant decreased (all P<0.01). About PGI-I, 29 patients chose “significant improvement”, subjective satisfaction was 97% (29/30). Anterior sacral plexus hemorrhage occurred in 2 cases (7%, 2/30). There was no intestinal obstruction or injury of bladder, bowel and ureter intra- and postoperation. Two cases (7%, 2/30) had mesh exposure. Conclusion:AMISC is a safety, convenient, minimal traumatic and durable procedure for apical prolapse with short learning curve in the most of cases.

Objective To evaluate the indications and clinic outcomes of vaginal high uterosacral ligament suspension (HUS) for treatment of recurrent advanced pelvic organ prolapse (POP). Methods This retrospective study analyzed 42 women with recurrent advanced POP who were referred to Fourth Medical Center of PLA General Hospital and underwent transvaginal HUS between November 2005 and January 2018. Primary surgeries included 30 vaginal colporrhaphy, 5 Manchester operation, 5 transvaginal mesh repair,2 sacrospinous ligament fixation.The median time for recurrence from primary pelvic floor repair surgery was 9 months, including 14 cases (33%, 14/42)≤3 months (median time was 2 months) and 25 cases (67%, 28/42) longer than 3 months (median time was 18 months).The rate of recurrent prolapse in stageⅢorⅣ was 79% (33 cases), 45% (19 cases) and 17%(7 cases) in anterior, apical and posterior compartment respectively. Results Transvaginal high bilateral uterosacral ligaments were identified and used for successful vaginal vault suspension after vaginal hysterectomy and residual cervical resection in all 42 consecutive patients. The cases of transvaginal mesh used in anterior wall and posterior wall were 25 (60%, 25/42) and 3 (7%, 3/42) respectively. There was no major intra-and postoperative complications,such as ureter and other pelvic organ injury. The median time of follow-up was 5.3 years after transvaginal HUS. The points of pelvic organ prolapse quantification system reduced significantly and point C improved from+0.3 cm to-8.2 cm after reoperation (P<0.01). The objective cure rate were 100% (42/42) both in apex and posterior compartment,while 93% (39/42) in anterior compartment. None had reoperation or pessary usage for recurrence of prolapse. Conclusion Transvaginal HUS with vaginal wall repair could be as a safety, cost-effective, minimal traumatic and durable procedure for recurrent POP in the most of cases.

Objective To assess the five?year effect of the transvaginal high uterosacral ligament suspension (HUS) with or without additional concomitant native?tissue anterior and (or) posterior repair in women suffering from middle compartment defect. Methods A retrospective review of records identified 79 women who underwent transvaginal HUS with or without additional concomitant native?tissue anterior and (or) posterior repair from January 2007 to January 2018 in Fourth Medical Center, General Hospital of People′s Liberation Army. The middle compartment defects were predominant in these patients with point C no less than point Ba or Bp if accompanied with anterior or posterior vaginal wall prolapse. Follow?up visits were performed 2,6 and 12 months after surgery and then annually. Anatomic results of pelvic organ prolapse (POP) was established by pelvic examination using pelvic organ prolapse quantitation system (POP?Q) staging. Funtional results were obtained by patient global impression of improvement (PGI?I) scale in POP, pelvic floor distress inventory?short form 20 (PFDI?20) and pelvic floor impact questionnaire short form (PFIQ?7). Surgical success required the fulfillment of all 3 criteria: (1) anterior or posterior vaginal wall prolapsed leading edge of 0 cm or less and apex of 1/2 total vaginal length or less; (2) the absence of POP symptoms as reported on the PFDI?20 question No.3 ("Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?"); and (3) no prolapse reoperations or pessary use during the study period. Results Of 79 women, 51(65%, 51/79) women completed the five?year follow?up during the study period. The median follow?up time was 5.2 years (2.8-8.3 years). The overall surgery success rate was 86% (44/51) according to above all 3 criteria. Prolapse recurrence rates were isolated anterior 8% (4/51), isolated apical 0, isolated posterior 2% (1/51) and multiple compartments 4% (2/51). Seven women (14%,7/51) developed anterior or posterior prolapse beyond the hymen with the leading edge≤1 cm. No apical prolapsed occurred. None of recurrent women underwent retreatment,including either surgery or pessary usage at last follow?up. The subjective satisfaction rate was 90% (46/51). There was a 1% (1/79) rate of intraoperative ureteral kinking and 3% (2/79) rate of postoperative morbidity. Conclusions The transvaginal HUS for middle compartment defect offers good long?term anatomical results with excellent vault suspension. With additional concomitant native?tissue anterior and (or) posterior repair, it will be a reconstructive surgery for the majority of moderate?to?severe POP. It is minimal traumatic and worthy of being popularized for clinical application.

Objective To explore the clinical management and outcomes of polypropylene mesh and sling exposure after reconstructive pelvic surgery(RPS). Methods A total of 110 cases of mesh and sling exposure after RPS were analyzed, who admitted between Jan. 2002 and Oct. 2017 in First Affiliated Hospital of PLA General Hospital, in which 3 cases were referred from other hospitals. Mesh and sling exposures were identified in the outpatient clinic and categorized and managed according to International Continence Society and International Urogynecology Association(ICS-IUGA)classification about category, time and site(CTS)of mesh complication. Outpatient management included observation, topical estrogen use and mesh removal. Management in hospital included surgical removal of exposed mesh and repair of the resulting defects under the anesthesia. Seventy-four cases were managed in the outpatient setting, and 36 cases required inpatient management. Follow-up was consecutively performed from 1 month to 10 years. Objective outcome included the surgeon′s assessment of the healing state of the vaginal mucosa. Subjective outcome was evaluated with patient global impression of improvement questionnaire(PGI-I). Results One hundred and ten patients with mesh exposure were classified according to the different RPS underwent. There were 95 cases from transvaginal mesh surgery, 5 cases from anti-stress urinary incontinence sling surgery, and 10 cases from sacrocolpopxy. The outpatient group healed at an average of(3.0 ± 1.8)months. Of the 36 patients who required inpatient management, 21 cases healed completely at an average of 7 days after one surgery. The remaining 8 cases required either two or three times surgeries or conservative management. In the outpatient group, the PGI-I scale very much better was found in 65 cases(87.8％)and much better in 9 cases(12.2％). In the inpatient surgery group, the scale was very much better in 30 cases (83.3％), and much better in 6 cases(16.7％). Conclusions Among patients with mesh exposure after mesh-augmented RPS, 2/3 of patients with a CTS classification 1-3 could be managed in the office,and remaining 1/3 with CTS classification 4-6 need operation under anesthesia in hospital. If the mesh and sling exposure could be scientifically classified, according to the size, site and accompany symptoms, as well as pain, most of the mesh complications after explosure could be resolved. Using the pelvic floor repair and polypropylene mesh sling, the majority of the patients could get a better outcome, without affecting the effect of the original operation.

Objective To assess the long-term effectiveness of the transvaginal high uterosacral ligament suspension (HUS) in women suffering from advanced pelvic organ prolapse (POP).Methods A retrospective review of records identified 118 women who underwent transvaginal HUS with or without additional concomitant anterior and (or) posterior repairs from June 2003 to August 2009 in the First Affiliated Hospital,General Hospital of People's Liberation Army.Of 118 women,104 women completed the follow-up during study period;these 104 women were analysed.Follow-up visits were performed 2,6 and 12 months after surgery and then annually.Anatomic results of POP was established by pelvic examination using pelvic organ prolapse quantitation system (POP-Q) staging.Funtional results were obtained by patient global impression of improvement (PGI-I),pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7).Surgical success required the fulfillment of all 3 criteria:(1) prolapse leading edge of 0 cm or less and apex of 1/2 total vaginal length or less;(2) the absence of pelvic organ prolapse symptoms as reported on the PFDI-20 question No.3 (Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?);and (3) no prolapse reoperations or pessary use during the study period.Results The mean follow-up time was (9.1 ± 1.5) years.The overall surgery success rate was 91.3％ (95/104) according to above all 3 criteria.Prolapse recurrence rates were isolated anterior 6.7％ (7/104),isolated apical 0,isolated posterior 2.9％ (3/104) and multiple compartments 1.0％ (1/104).Five women (4.8％,5/104) developed bothersome vaginal bulge symptoms.None of recurrent women underwent retreatment,including either surgery or use of a pessary at last follow-up.The subjective satisfaction rate was 90.4％ (94/104).PFDI-20 and PFIQ-7 scores showed a statistically significant improvement from preoperative 72 and 65 points to postoperative 17 and 9 points respectively (all P＜0.01).There was a 2.9％ (3/104) rate of intraoperative ureteral kinking and 3.8％ (4/104) rate of postoperative morbidity.Conclusions The transvaginal HUS for vault prolapse offers good long-term anatomical results with excellent vault suspension.With additional concomitant anterior and (or) posterior repairs,it will be a reconstructive surgery for the majority of advanced POP.It is minimal traumatic and appropriate for different type of POP,especially for the eldly patients.It is worthy of being popularized for clinical application.