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International Journal of Molecular... May 2024Pelvic floor dysfunction encompasses a group of disorders that negatively affect the quality of women's lives. These include pelvic organ prolapse (POP), urinary...
Pelvic floor dysfunction encompasses a group of disorders that negatively affect the quality of women's lives. These include pelvic organ prolapse (POP), urinary incontinence, and sexual dysfunction. The greatest risk factors for prolapse are increased parity and older age, with the largest group requiring surgical intervention being post-menopausal women over 65. Prolapse recurrence rates following surgery were reported to be as high as 30%. This may be attributed to ineffective healing in the elderly. Autologous stem cell transplantation during surgery may improve surgical results. In our previous studies, we showed that the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) from young donor rats improved the healing of full-thickness vaginal surgical incision in the vaginal wall of old rats, demonstrated by both histological and functional analysis. In order to translate these results into the clinical reality of autologous MSC transplantation in elderly women, we sought to study whether stem cells derived from old donor animals would provide the same effect. In this study, we demonstrate that MSC transplantation attenuated the inflammatory response, increased angiogenesis, and exhibited a time-dependent impact on MMP9 localization. Most importantly, transplantation improved the restoration of the biomechanical properties of the vagina, resulting in stronger healed vaginal tissue. These results may pave the way for further translational studies focusing on the potential clinical autologous adjuvant transplantation of MSCs for POP repair for the improvement of surgical outcomes.
Topics: Animals; Female; Vagina; Mesenchymal Stem Cell Transplantation; Rats; Mesenchymal Stem Cells; Wound Healing; Matrix Metalloproteinase 9; Pelvic Organ Prolapse; Biomechanical Phenomena; Rats, Sprague-Dawley
PubMed: 38891914
DOI: 10.3390/ijms25115714 -
Cancer Medicine Jun 2024Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to...
BACKGROUND
Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies.
METHODS
In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics.
RESULTS
By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively).
CONCLUSIONS
Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.
Topics: Humans; Male; Female; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged; Colorectal Neoplasms; Fluorouracil; Immune Checkpoint Inhibitors; Pilot Projects; Bevacizumab; Antibodies, Monoclonal, Humanized; Leucovorin; DNA Mismatch Repair; Adult; Microsatellite Instability; Oxaliplatin; Neoadjuvant Therapy; Tumor Microenvironment; Organoplatinum Compounds; Programmed Cell Death 1 Receptor; Treatment Outcome
PubMed: 38888366
DOI: 10.1002/cam4.7224 -
Frontiers in Psychiatry 2024Increasing evidence suggests a correlation between intestinal microbiota and the gut-brain axis; however, the causal relationship between gut microbiota and postpartum...
BACKGROUND
Increasing evidence suggests a correlation between intestinal microbiota and the gut-brain axis; however, the causal relationship between gut microbiota and postpartum depression (PPD) remains unclear.
METHODS
In this study, a two-sample Mendelian randomization (MR) design was employed to analyze the GWAS data of gut microorganisms from the Mibiogen database and PPD data from the UK biobank. Various statistical methods, including inverse variance weighted, MR-Egger, weighted median, weighted model, and MR-PRESSO, were utilized to investigate the causal relationship between gut microbiota and PPD. Additionally, sensitivity analysis was conducted to assess the robustness of the findings.
RESULTS
Through MR analysis, it was found that phylum Actinobacteria (=0.014, OR=0.971, 95% CI=0.948-0.994) and genus Holdemanella (=0.023, OR=0.979, 95% CI=0.961-0.997) have protective effects on PPD, while the other two unknown genera, genus Unknown Ids 2001 (=0.025, OR=0.972,95% CI=0.947-0.996), and genus Unknown Ids 2755 (=0.012, OR=0.977, 95% CI=0.959-0.995) also has a protective effect on PPD. The sensitivity analysis results indicate that there is no heterogeneity or horizontal pleiotropy.
CONCLUSION
This study has identified a causal association between Actinomycetota, Holdemanella, and PDD through MR analysis. These findings offer significant contributions to the development of personalized treatment approaches for PPD, encompassing interventions such as dietary modifications or microbiome interventions.
PubMed: 38887725
DOI: 10.3389/fpsyt.2024.1282742 -
Heliyon May 2024[This corrects the article DOI: 10.1016/j.heliyon.2023.e14515.].
Corrigendum to "MiR-423-5p is a novel endogenous control for the quantification of circulating miRNAs in human esophageal squamous cell carcinoma" [Heliyon Volume , Issue 4, April 2023, Article e14515].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14515.].
PubMed: 38887380
DOI: 10.1016/j.heliyon.2024.e31016 -
Plastic and Reconstructive Surgery.... Jun 2024In the past decades, reconstructive choices after female genital mutilation extended beyond de-infibulation and scar release. The current trend to expand techniques...
BACKGROUND
In the past decades, reconstructive choices after female genital mutilation extended beyond de-infibulation and scar release. The current trend to expand techniques addressing sexual and aesthetic aspects by reconstructing the clitoris and prepuce, and dissecting the clitoral nerves raises concern, as there is a paucity of evidence on the functional outcomes and suspected iatrogenic lacerations.
METHODS
A total of 128 female genital mutilation patients were included in the study. To evaluate clitoral sensitivity after elevation, the Semmes-Weinstein-monofilament test was performed before and after genital reconstruction.
RESULTS
Preoperatively, patients with a visually intact clitoris showed significantly better sensitivity compared with patients with a mutilated clitoris or infibulation ( < 0.0001). Surgery was performed in 84 patients. After clitoral reconstruction (CR), 70 of 73 patients were able to perceive 2.83 monofilaments (95.9%), whereas three perceived 3.61. Patients with a visually intact clitoris served as control, and 95.0% perceived 2.83 monofilaments. We showed a significant improvement of clitoral sensitivity ( = 0.0020) in the subgroup consisting of patients with a mutilated clitoris in whom the test was performed before and after reconstruction.
CONCLUSIONS
Clitoral sensitivity improves significantly after CR. Seventy of 73 patients attained the same sensitivity as unharmed women. No patient showed a decreased sensitivity compared with their preoperative findings. Therefore, our study supports the argument that CR offers sufficient improvement of objective clitoral sensitivity without additionally addressing clitoral nerves.
PubMed: 38881961
DOI: 10.1097/GOX.0000000000005851 -
Acta Biomaterialia Jun 2024Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound... (Review)
Review
Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.
PubMed: 38879102
DOI: 10.1016/j.actbio.2024.06.012 -
BMC Surgery Jun 2024Obstructive defecation syndrome (ODS) defines a disturbed defecation process frequently associated with pelvic organ prolapse (POP) in women that substantially...
Early safety and efficiency outcomes of a novel interdisciplinary laparoscopic resection rectopexy combined with sacrocolpopexy for women with obstructive defecation syndrome and pelvic organ prolapse: a single center study.
BACKGROUND
Obstructive defecation syndrome (ODS) defines a disturbed defecation process frequently associated with pelvic organ prolapse (POP) in women that substantially compromises quality of life. Conservative management offers limited relief and a surgical intervention may be required. This is characterized by individual approaches. AIM OF THE STUDY: This retrospective single center study evaluated the surgical and clinical short-term outcome of a novel interdisciplinary laparoscopic resection rectopexy (L-RRP) with mesh- sacrocolpopexy (L-SCP) for women suffering from ODS and POP.
METHODS
The study participants underwent surgery in an interdisciplinary laparoscopic approach. Safety was the primary endpoint, assessed via postoperative morbidity classified by Clavien-Dindo scale. Secondary outcomes included evaluation of bowel function, fecal and urinary incontinence and pelvic organ prolapse status at 12 months follow-up. Additionally, a biological mesh (BM) was offered to women, who asked for an alternative to synthetic mesh material (SM).
RESULTS
Of the 44 consecutive patients requiring surgery for ODS and POP, 36 patients underwent the interdisciplinary surgical approach; 28 patients with SM and 8 patients with BM. In total 5 complications occurred, four of them were classified as minor. One minor complication was observed in the BM group. One anastomotic leakage occurred in the SM group. The two ODS scores, the bowel dysfunction score, and the incontinence score improved significantly (p = 0.006, p = 0.003, p < 0.001, and p = 0.0035, respectively). Pelvic floor anatomy was fully restored (POP-Q 0) for 29 (80%) patients after surgery. 17 patients (47%) suffered from urinary incontinence before surgery, which was restored in 13 patients (76.5%).
CONCLUSIONS
The interdisciplinary approach with L-RRP and L-SCP and the use of a BM in a small subgroup were technically feasible, safe, and effective in this single center setting. The study's retrospective design, the small sample size and the lack of comparators limit the generalizability of the findings requiring future randomized trials.
TRIAL REGISTRATION
Retrospectively registered at clinicaltrials.gov, trial number NCT05910021, date of registration 06/10/2023.
Topics: Humans; Female; Retrospective Studies; Pelvic Organ Prolapse; Laparoscopy; Middle Aged; Aged; Surgical Mesh; Treatment Outcome; Vagina; Rectum; Defecation; Postoperative Complications; Gynecologic Surgical Procedures; Syndrome; Constipation
PubMed: 38877450
DOI: 10.1186/s12893-024-02474-4 -
International Journal of Surgery Case... Jul 2024Perineal hernias are protrusions of intra-abdominal contents resulting from weakness of the pelvic floor muscles. They are an uncommon complication after ultraradical...
INTRODUCTION AND IMPORTANCE
Perineal hernias are protrusions of intra-abdominal contents resulting from weakness of the pelvic floor muscles. They are an uncommon complication after ultraradical pelvic surgeries, with no established gold standard for surgical treatment. This case describes a rare anterior perineal hernia that developed after radical surgery for bladder carcinoma.
CASE PRESENTATION
A 77-year-old Caucasian woman presented with a painful 10 cm bulge in the perineal region. The hernial sac involved the entire left labia majora and developed 4 years after radical surgery for bladder carcinoma. She had been misdiagnosed twice in the past with vaginal prolapse, leading to two unsuccessful vaginoplasty procedures due to recurrence. She underwent hernia repair with perineal approach and polypropylene mesh placement. The postoperative period was uncomplicated, and the patient was discharged after five days, with histology showing no malignancy.
CLINICAL DISCUSSION
Perineal hernias are protrusions of intra- or extraperitoneal contents into the perineum due to a defect in the pelvic musculature. Various surgical modalities exist for perineal hernia repair, which adhere to the fundamental principles of hernia surgery: sac mobilization, precise incision, sac debridement and excision, and defect repair. Here, we successfully applied the perineal approach in a complicated case of a misdiagnosed perineal hernia after radical surgery.
CONCLUSION
The perineal approach for hernia repair, involving an implantation of a polypropylene mesh and tissue flap was successfully applied, confirming its main place in the surgical treatment of perineal hernias. During the two-year follow-up no postoperative complications or recurrence hernia were registered.
PubMed: 38875825
DOI: 10.1016/j.ijscr.2024.109859 -
Open Research Europe 2023To be able to optimize pelvic healthcare, it would be helpful to specifically assess women's psychological burden with pelvic floor complaints. In the absence of such an...
BACKGROUND
To be able to optimize pelvic healthcare, it would be helpful to specifically assess women's psychological burden with pelvic floor complaints. In the absence of such an instrument, a new instrument was developed to measure this burden in women who seek help. In previous research, a comprehensive overview was yielded of women's restrictions and distress with pelvic floor complaints, and a conceptual model was developed of seven types of distress that were reflected by 33 statements. The present study was performed to investigate the psychometric properties of the new instrument, termed the Pelvic Floor Complaint-related Psychological Burden Inventory (PFC-PBI).
METHODS
In an online survey data was collected from women with and without pelvic floor complaints on the 33 statements. The internal consistency of the types of distress was tested using item-total correlation analysis, Principal Component and Confirmatory Factor Analyses were performed, and the convergent and divergent validity of the types of distress was examined against existing questionnaires using the Multi-Trait Multi-Method methodology.
RESULTS
Based on the factor analyses, a 10-item instrument was tested. Outcomes show excellent internal consistency of this instrument, comprising a single component. The PFC-PBI demonstrated satisfactory convergent and divergent validity.
CONCLUSIONS
This new measure appears to be a promising tool to inventory the psychological burden of women suffering from pelvic floor complaints. Research into its further development, implementation, and clinical use appears warranted.
PubMed: 38872842
DOI: 10.12688/openreseurope.15833.2 -
World Journal of Urology Jun 2024The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder...
BACKGROUND
The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS.
METHOD
In this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8).
RESULTS
Of the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively.
CONCLUSION
A highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS's might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.
Topics: Humans; Magnetic Resonance Imaging; Retrospective Studies; Urinary Bladder; Male; Urinary Bladder Neck Obstruction; Middle Aged; Aged; Severity of Illness Index; Lower Urinary Tract Symptoms; Symptom Assessment; Radiomics
PubMed: 38872048
DOI: 10.1007/s00345-024-05081-3