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Neurourology and Urodynamics Jul 2024Studies show a significant association between the first vaginal delivery and injuries of the levator ani muscle (LAM), which can cause pelvic floor disorders (PFDs). (Review)
Review
BACKGROUND
Studies show a significant association between the first vaginal delivery and injuries of the levator ani muscle (LAM), which can cause pelvic floor disorders (PFDs).
OBJECTIVES
This study aims to identify the prevalence of short and long-term LAM injuries after vaginal delivery in primiparous women and its influence on PFDs.
METHOD
A systematic review was conducted according to the PRISMA methodology. The databases used were Pubmed, Cochrane, and PEDro. The quality assessment of the evidence was carried out using the Critical Appraisal Skills Programme (CASP). Both the selection of studies and their evaluation were done by two researchers and a third reviewer in cases of disagreement.
RESULTS
From the search, 57 articles were gathered, and 19 were included to match the eligibility criteria. The prevalence of avulsion of the LAM was found in association with vaginal delivery between 13% and 28% ≤ 1 year after delivery and between 16% and 29% > 1 year after delivery. Ballooning was detected between 20% and 37% ≤ 1 year, and 33% of women > 1 year after delivery, appearing to be more common when compared to avulsion. Pelvic organ prolapse (POP) was considered the most common disorder associated with injuries of the LAM, and there seems to be some connection with sexual dysfunction.
CONCLUSION
Avulsion of the LAM and ballooning of the hiatal area have a high prevalence in primiparous women after vaginal delivery and have a strong direct relation to the development of POP.
PubMed: 38948963
DOI: 10.1002/nau.25529 -
Oncoimmunology 2024Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic...
Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.
Topics: Animals; Male; Prostatic Neoplasms; Antigens, Neoplasm; Mice; Dendritic Cells; Adjuvants, Immunologic; RNA, Messenger; Cancer Vaccines; Humans; Mice, Inbred C57BL; Cell Line, Tumor; mRNA Vaccines; CD8-Positive T-Lymphocytes; T-Lymphocytes; Immunotherapy; Lymphocyte Activation
PubMed: 38948931
DOI: 10.1080/2162402X.2024.2373526 -
Frontiers in Surgery 2024Pelvic organs prolapse remains a significant health concern affecting millions of women worldwide. The use of native tissues to suspend the apex has acquired relevance...
INTRODUCTION
Pelvic organs prolapse remains a significant health concern affecting millions of women worldwide. The use of native tissues to suspend the apex has acquired relevance in urogynecologic surgery. One of the most commonly used procedures performed without mesh is the technique described by Shull, consisting of suturing the vaginal apex to the uterosacral ligaments. The objective of the study is to evaluate the learning curve of laparoscopic Shull's repair for the correction of pelvic floor defects, including the surgery time and surgical outcomes.
MATERIALS AND METHODS
This is a retrospective study conducted at the Policlinico G. Martino, University of Messina, Messina, Italy, and Policlinico Vanvitelli, Vanvitelli University, Naples, Italy. All patients affected by grade I-IV POP, consisting of apical prolapse with or without cystocele, and who underwent laparoscopic Shull's technique for prolapse correction were enrolled. The endpoints to estimate the learning curve for the procedure were the percentage of laparoscopic procedures completed, operative time, and the early complication rate.
RESULTS
A total of 31 laparoscopic Shull repairs were collected for the study. To evaluate the learning curve of the technique, we divided the 31 cases into three different groups: Procedures 0-10; 11-20; 21-31. The parameter for evaluating technique learning was the operative time. Group 21-31 demonstrated an operative time of 97 min (SD 20), compared with 121 min (SD 23) in group 0-10 and 120 min (SD 13) in group 11-20. A comparison of these means through ANOVA showed a -value of 0.01 for the entire system, and 0.95 for the comparison between 0 and 10 and 11-20, 0.04 for 0-10 vs. 21-31, and 0.02 between 11 and 20 and 21-31.
CONCLUSIONS
The rate of surgical improvement in terms of time became effective after an average of 20 procedures. However, the improvement seems to be effective case by case for surgeons skilled in basic endoscopy.
PubMed: 38948480
DOI: 10.3389/fsurg.2024.1396438 -
World Journal of Stem Cells Jun 2024Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the...
BACKGROUND
Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.
AIM
To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.
METHODS
Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined functional experiments . RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.
RESULTS
In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production . High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.
CONCLUSION
HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression . Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
PubMed: 38948096
DOI: 10.4252/wjsc.v16.i6.708 -
Contemporary Clinical Trials... Aug 2024Localized prostate cancer treated with radical prostatectomy is highly effective, though severe side-effects are common after the surgery. Prehabilitation is an approach...
BACKGROUND
Localized prostate cancer treated with radical prostatectomy is highly effective, though severe side-effects are common after the surgery. Prehabilitation is an approach to optimize patient's physical and mental resources before surgery, to improve postoperative outcomes. The feasibility of a multi-modal home-based prehabilitation program, delivered using telehealth in patients awaiting radical prostatectomy is unknown. This paper describes the development of a prehabilitation program for patients awaiting radical prostatectomy.
METHOD
A model by The Medical Research Council for developing and evaluating complex interventions (MRC Framework) was used in the development process. The Template for Intervention Description and Replication (TIDieR) checklist was applied for ensuring sufficient description of the interventions. A total of 40 patients will be randomized to either intervention or control group. Patients in the control group will follow standard care. The 4-week prehabilitation programme consists of exercise, pelvic floor exercise, sexual counseling, stress management and nutritional support. The interventions are home-based and delivered using telehealth. Feasibility outcomes will include recruitment, attrition rates, adherence, safety and suitability.
CONCLUSION
We have developed a multimodal prehabilitation programme, which has the potential to bring tangible health benefits to men with prostate cancer awaiting radical prostatectomy. The results of the feasibility study will inform the design of a fully powered randomized controlled trial.
PubMed: 38947984
DOI: 10.1016/j.conctc.2024.101319 -
Case Reports in Women's Health Jun 2024Pain after vaginal prolapse repair surgery with mesh is generally attributed to the mesh fixation, particularly to mesh erosion, dislocation or the development of...
Pain after vaginal prolapse repair surgery with mesh is generally attributed to the mesh fixation, particularly to mesh erosion, dislocation or the development of hematoma. However, once all the causes have been excluded, the urinary system, bladder and ureters should be accurately examined by means of endovaginal ultrasound. This report concerns the case of a 72-year-old woman who had undergone mesh-supported prolapse surgery 3 months prior, with no other relevant diseases, who visited the emergency department complaining of dull, right-sided colic pain. The endovaginal ultrasound examination revealed a prevesical ureteral calculus on the right side with consequent dilatation of the proximal ureter. Computed tomography of the abdomen and pelvis confirmed the calculus in the distal right ureter and revealed a right renal lower pole calculus. The patient underwent treatment via an operative ureterorenoscopy with removal of stones and placement of a double-J-stent. Two months later, a second ureterorenoscopy was performed with double-J-stent removal and concomitant stone extraction. It appears that no similar cases have been reported in the literature. This is why, during the urogynecological postoperative follow-up, it is of paramount importance to examine the entire urogenital system with endovaginal ultrasound. This case report highlights how, through a simple, non-invasive, radiation-free examination, like ultrasound, most of the post-operative complications of vaginal prolapse repair surgery using mesh, including urolithiasis, can be excluded.
PubMed: 38946844
DOI: 10.1016/j.crwh.2024.e00627 -
Science Bulletin Jun 2024
PubMed: 38945749
DOI: 10.1016/j.scib.2024.06.017 -
Trials Jun 2024Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to...
Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial.
BACKGROUND
Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction.
METHODS
Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study's primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle.
DISCUSSION
The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery.
TRIAL REGISTRATION
ChiCTR2200064041, registered on 24th September, 2022.
Topics: Humans; Hysterectomy; Female; Urinary Bladder; Laparoscopy; Recovery of Function; Uterine Cervical Neoplasms; Randomized Controlled Trials as Topic; Urinary Catheters; Intermittent Urethral Catheterization; Time Factors; Device Removal; Treatment Outcome; Quality of Life; Urodynamics; Middle Aged; Urinary Retention; Adult; Urinary Catheterization; Catheters, Indwelling
PubMed: 38943177
DOI: 10.1186/s13063-024-08266-8 -
Cell Reports. Medicine Jun 2024Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD....
Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.
PubMed: 38942021
DOI: 10.1016/j.xcrm.2024.101624 -
Gastroenterology Report 2024The oncological safety of transanal total mesorectal excision (taTME) remains uncertain, and its special surgical approach may contribute to tumor cell dissemination....
Changes to circulating tumor cells in the central vein during laparoscopic versus transanal endoscopic surgeries for rectal cancer: can surgical approach make a difference?
BACKGROUND
The oncological safety of transanal total mesorectal excision (taTME) remains uncertain, and its special surgical approach may contribute to tumor cell dissemination. Thus, we conducted a study to investigate the impact of surgical approach on circulating tumor cell (CTC) counts and phenotypes in rectal cancer.
METHODS
This is a prospective randomized controlled study (ClinicalTrials: NCT05109130). The patients were randomized to either the taTME (=49) or laparoscopic TME (laTME) (=48) groups. Blood samples were collected from the central vein to measure CTC counts and phenotypes at three time points: preoperative (t1), immediately post-tumor removal (t2), and one week post-surgery (t3). The effect of surgical procedure on CTCs at each time point was analyzed, with the primary endpoint being the change in CTC counts from t1 to t3 for each surgical approach. This study adheres to Consolidated Standards of Reporting Trials Guidelines.
RESULTS
The baseline clinicopathologic characteristics of the laTME and taTME groups were balanced. The change in CTC count from t1 to t3 was 1.81 ± 5.66 in the laTME group and 2.18 ± 5.53 in the taTME group. The taTME surgery was non-inferior to laTME in terms of changing CTC counts (mean difference [MD]: -0.371; 95% confidence interval [CI]: -2.626 to 1.883, upper-sided 95% CI of 1.883 < 2, non-inferiority boundary value). Compared with that at t1, the CTC count at t2 did not change significantly. However, higher CTC counts were detected at t3 than at t2 in the taTME (=0.032) and laTME (=0.003) groups. From t1 to t3, CTC counts significantly increased in both the taTME (=0.008) and laTME (=0.031) groups. There were no significant differences in CTC phenotype changes between the two groups from t1 to t3.
CONCLUSIONS
Compared with laTME, taTME did not affect CTC counts and phenotypes. Our findings indicate that taTME is not inferior to laTME in terms of CTC changes from an oncological perspective.
PubMed: 38939193
DOI: 10.1093/gastro/goae062