[Effect of autologous platelet-rich plasma perfusion on cytokines in uterine drainage fluid of patients with intrauterine adhesions following hysteroscopic adhesiolysis].

Objective: To investigate the effect of autologous platelet-rich plasma (PRP) perfusion on the levels of cytokines in uterine drainage fluid in patients with moderate to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Methods: Thirty patients with moderate to severe IUA who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from November 2020 to March 2021 were randomly divided into two groups: the PRP group (15 patients with placement of intrauterine-suitable balloons and PRP infusion) and the control group (15 patients with placement of intrauterine-suitable balloons only). For all patients, the channel switch was opened 48 hours after the surgery. The drainage fluid of the uterine cavity was collected using syringes through the proximal end of the drainage channel switch at 24 hours after the surgery and through the drainage channel directly at 48, 72, 96, and 120 hours after the surgery, and the levels of related cytokines including platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1) and transforming growth factor-ß1 (TGF-ß1) in the drainage fluid of the uterine cavity were evaluated, respectively. Results: (1) The changes in volumes of uterine cavity drainage fluid: the total drainage fluid volumes of the PRP group and the control group in 120 hours after the surgery were (21.8±2.9) and (22.7±2.7) ml, respectively, and there was no statistically significant difference between the two groups (t=-0.847, P>0.05). No significant differences were found in the volumes of drainage fluid between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). (2) Variation in cytokine levels in the uterine cavity drainage fluid: ① PDGF-BB: median PDGF-BB levels at 24 and 48 hours after the surgery in the PRP group (6.6 and 9.6 µg/L, respectively) were significantly higher than those in the control group (4.7 and 2.7 µg/L, respectively; all P<0.05). There were no significant differences in PDGF-BB levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ② VEGF-A: median VEGF-A levels at 24 and 48 hours after the surgery in the PRP group (3.5 and 2.8 µg/L, respectively) were significantly higher than those in the control group (1.6 and 1.2 µg/L, respectively; all P<0.05). There were no significant differences in VEGF-A levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ③ IGF-1: median IGF-1 level at 48 hours after the surgery in the PRP group was significantly higher than that in the control group (39.5 vs 8.6 µg/L, P<0.05). No significant differences were found in IGF-1 levels at 24, 72, 96, and 120 hours after the surgery between the two groups (all P>0.05). ④ TGF-ß1: There were no significant differences in TGF-ß1 levles between the two groups at 24, 48, 72, 96, and 120 hours after the surgery (all P>0.05). Conclusions: PRP perfusion following hysteroscopic adhesiolysis may increase the levels of PDGF-BB, VEGF-A, and IGF-1 in the uterine cavity drainage fluid, which plays a beneficial role in improving wound microvascular formation, reducing adhesion reformation, and promoting endometrial regeneration and repair.

Improved quantification of tumor adhesion in meningiomas using MR elastography-based slip interface imaging.

Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing resection and causing postoperative complications. Surgery remains the primary therapeutic approach, and when combined with adjuvant radiotherapy, it effectively controls residual tumors and reduces tumor recurrence when complete removal may cause a neurologic deficit. Previous studies have indicated that slip interface imaging (SII) techniques based on MR elastography (MRE) have promise as a method for sensitively determining the presence of tumor-brain adhesion. In this study, we developed and tested an improved algorithm for assessing tumor-brain adhesion, based on recognition of patterns in MRE-derived normalized octahedral shear strain (NOSS) images. The primary goal was to quantify the tumor interfaces at higher risk for adhesion, offering a precise and objective method to assess meningioma adhesions in 52 meningioma patients. We also investigated the predictive value of MRE-assessed tumor adhesion in meningioma recurrence. Our findings highlight the effectiveness of the improved SII technique in distinguishing the adhesion degrees, particularly complete adhesion. Statistical analysis revealed significant differences in adhesion percentages between complete and partial adherent tumors (p = 0.005), and complete and non-adherent tumors (p<0.001). The improved technique demonstrated superior discriminatory ability in identifying tumor adhesion patterns compared to the previously described algorithm, with an AUC of 0.86 vs. 0.72 for distinguishing complete adhesion from others (p = 0.037), and an AUC of 0.72 vs. 0.67 for non-adherent and others. Aggressive tumors exhibiting atypical features showed significantly higher adhesion percentages in recurrence group compared to non-recurrence group (p = 0.042). This study validates the efficacy of the improved SII technique in quantifying meningioma adhesions and demonstrates its potential to affect clinical decision-making. The reliability of the technique, coupled with potential to help predict meningioma recurrence, particularly in aggressive tumor subsets, highlights its promise in guiding treatment strategies.

Diagnostic accuracy of preoperative adhesion mapping by ultrasonography for laparoscopic surgery in patients with past abdominal surgery with special reference to loose adhesion.

PURPOSE: Endoscopic surgery is widely accepted for both elective and emergent abdominal surgery. This study was performed to assess the accuracy of preoperative adhesion mapping by abdominal ultrasonography (US). METHODS: Intra-abdominal intestinal adhesions on the abdominal wall in 50 patients with a history of abdominal surgery were prospectively assessed by the visceral slide test with US before laparoscopic surgery from 2019 to 2022. Adhesion was assessed in six separate abdominal zones during US. Actual adhesion on the abdominal wall was confirmed during laparoscopic surgery. RESULTS: The sliding distances in upper right, upper central, upper left, lower right, lower central, and lower left zones in patients with versus without intestinal adhesion were 4.4 versus 1.4 cm (P = .004), 3.4 versus 2.5 cm, 4.3 versus 1.3 cm (P = .011), 3.1 versus 1.5 cm (P = .0014), 3.3 versus 1.1 cm (P = .013), and 3.4 versus 0.8 cm (P = .0061), respectively. Receiver operating characteristic analysis revealed the optimal value of sliding distance as 2.5 cm and the area under the curve as 0.86. The specificity of US assessment of adhesion was lower in the central zone than in lateral zones. Loose adhesion mostly seen around the scar was attributed to either filmy tissue or omental adhesion, leading to visceral sliding during US. CONCLUSION: This study revealed the reason for insufficient accuracy of preoperative US assessment of intestinal adhesion around the scar area because of loose adhesion. The upper lateral area might be optimal for first port insertion.

CuSO4/H2O2induced polydopamine/polysulfobetaine methacrylate co-deposition on poly(amino acid) membranes for improved anti-protein adsorption and antibacterial activity.

Stopping postoperative soft tissue adhesions is one of the most challenging clinical problems that needs to be addressed urgently to avoid secondary injury and pain to patients. Currently, membrane materials with anti-protein adsorption and antibacterial activity are recognized as an effective and promising anti-adhesion barrier to prevent postoperative adhesion and the recurrent adhesion after adhesiolysis. Herein, poly(amino acid) (PAA), which is structurally similar to collagen, is selected as the membrane base material to successfully synthesize PAA-5 membranes with excellent mechanical and degradation properties by in-situ melt polymerization and hot-melt film-forming technology. Subsequently, the co-deposition of polydopamine/polysulfobetaine methacrylate (PDA/PSBMA) coatings induced by CuSO4/H2O2on PAA-5 membranes results in the formation of PDC-5S and PDC-10S, which exhibit excellent hemocompatibility, protein antifouling properties, and cytocompatibility. Additionally, PDC-5S and PDC-10S demonstrated significant antibacterial activity againstEscherichia coliandStaphylococcus aureus, with an inhibition rate of more than 90%. As a result, this study sheds light on newly discovered PAA membranes with anti-protein adsorption and antibacterial activity can sever as one of the promising candidates for the prevention of postoperative peritoneum adhesions.

Fabrication of a modified bacterial cellulose with different alkyl chains and its prevention of abdominal adhesion.

Abdominal hernia mesh is a common product which is used for prevention of abdominal adhesion and repairing abdominal wall defect. Currently, designing and preparing a novel bio-mesh material with prevention of adhesion, promoting repair and good biocompatibility simultaneously remain a great bottleneck. In this study, a novel siloxane-modified bacterial cellulose (BC) was designed and fabricated by chemical vapor deposition silylation, then the effects of different alkyl chains length of siloxane on surface properties and cell behaviors were explored. The effect of preventing of abdominal adhesion and repairing abdominal wall defect in rats with the siloxane-modified BC was evaluated. As the grafted alkyl chains become longer, the surface of the siloxane-modified BC can be transformed from super hydrophilic to hydrophobic. In vivo results showed that BC-C16 had good long-term anti-adhesion effect, good tissue adaptability and histocompatibility, which is expected to be used as a new anti-adhesion hernia repair material in clinic.

Hyaluronic acid/PEO electrospun tube reduces tendon adhesion to levels comparable to native tendons - An in vitro and in vivo study.

A major problem after tendon injury is adhesion formation to the surrounding tissue leading to a limited range of motion. A viable strategy to reduce adhesion extent is the use of physical barriers that limit the contact between the tendon and the adjacent tissue. The purpose of this study was to fabricate an electrospun bilayered tube of hyaluronic acid/polyethylene oxide (HA/PEO) and biodegradable DegraPol® (DP) to improve the anti-adhesive effect of the implant in a rabbit Achilles tendon full laceration model compared to a pure DP tube. Additionally, the attachment of rabbit tenocytes on pure DP and HA/PEO containing scaffolds was tested and Scanning Electron Microscopy, Fourier-transform Infrared Spectroscopy, Differential Scanning Calorimetry, Water Contact Angle measurements, and testing of mechanical properties were used to characterize the scaffolds. In vivo assessment after three weeks showed that the implant containing a second HA/PEO layer significantly reduced adhesion extent reaching levels comparable to native tendons, compared with a pure DP implant that reduced adhesion formation only by 20 %. Tenocytes were able to attach to and migrate into every scaffold, but cell number was reduced over two weeks. Implants containing HA/PEO showed better mechanical properties than pure DP tubes and with the ability to entirely reduce adhesion extent makes this implant a promising candidate for clinical application in tendon repair.

Can direct bilirubin-to-lymphocyte ratio predict surgery for pediatric adhesive small bowel obstruction?

OBJECTIVE: Estimating which patients might require surgical intervention is crucial. Patients with complete bowel obstructions exhibit disrupted enterohepatic cycles of bile and bacteremia due to bacterial translocation. The goal of this study was to develop a prediction index using laboratory inflammatory data to identify patients who may need surgery. MATERIALS AND METHODS: The patients were divided into two groups based on their management strategy: Non-operative management (Group 1) and surgical management (Group 2). RESULTS: The indirect bilirubin, direct bilirubin, and total bilirubin were significantly higher in Group 2 than in Group 1 (p = 0.001, p < 0.001, and p < 0.001, respectively). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-NLR (PNLR), and direct bilirubin-to-lymphocyte ratio (DBR) were significantly higher in Group 2 compared to Group 1 (p = 0.041, p = 0.020, and p < 0.001, respectively). In group 2, 78% have viable bowels. Resection was performed in 40% of cases, with 12% mortality and a 10-day average hospital stay. DLR performs the best overall accuracy (72%), demonstrating a well-balanced sensitivity (62%) and specificity (81%). CONCLUSIONS: This study suggested that DBR is a more accurate predictive index for surgical intervention in pediatric adhesive small bowel obstruction patients compared to NLR and PNLR, providing valuable guidance for treatment strategies.

OBJETIVO: Desarrollar un índice de predicción utilizando datos inflamatorios de laboratorio para identificar qué pacientes podrían necesitar cirugía. MÉTODO: Los pacientes se dividieron en dos grupos según su estrategia de manejo: no quirúrgico (grupo 1) o quirúrgico (grupo 2). RESULTADOS: Las bilirrubinas indirecta, directa y total fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.001, p < 0.001 y p < 0.001, respectivamente). Las relaciones neutrófilos-linfocitos, plaquetas-neutrófilos-linfocitos y bilirrubina directa-linfocitos fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.041, p = 0.020 y p < 0.001, respectivamente). En el grupo 2, el 78% tenían intestino viable. Se realizó resección en el 40% de los casos, con un 12% de mortalidad y una estancia hospitalaria promedio de 10 días. La relación bilirrubina directa-linfocitos tuvo la mejor precisión general (72%), demostrando una sensibilidad bien equilibrada (62%) y una buena especificidad (81%). CONCLUSIONES: Este estudio sugiere que la relación bilirrubina directa-linfocitos es un índice predictivo más preciso para la intervención quirúrgica en pacientes pediátricos con obstrucción adhesiva de intestino delgado en comparación con la de neutrófilos-linfocitos y la de plaquetas-neutrófilos-linfocitos, proporcionando una valiosa orientación para las estrategias de tratamiento.

Abdominal cocoon syndrome (sclerosing encapsulated peritonitis) causing small bowel occlusion in a patient with gastric bypass.

A rare condition, sclerosing encapsulating peritonitis, is characterized by a fibrotic membrane forming over the bowels, leading to intestinal obstruction. In this case of a 56-year-old male patient with a history of laparoscopic gastric bypass, a computed tomography scan showed findings indicative of the condition. Extensive adhesiolysis was performed, and biopsies confirmed the presence of fusiform cells (D2-40 positive on immunochemistry) resembling fibroblasts, within dense collagenous peritoneal tissue sheets, typical of sclerosing encapsulating peritonitis. The prevalence of this condition is uncertain, and diagnosis typically requires a peritoneal biopsy due to the nonspecific clinical presentation.

La peritonitis esclerosante encapsulada es una condición rara caracterizada por una membrana fibrótica que se genera sobre las asas intestinales causando cuadros de oclusión intestinal. Se presenta el caso de un paciente varón de 56 años con antecedente de derivación gastroyeyunal por laparoscopia que presenta oclusión intestinal. Se realizó tomografía computada que evidenció sitio de transición previo al sitio de anastomosis. Se realizó de anastomosis extensa y toma de biopsias. Histológicamente se observó engrosamiento de la membrana peritoneal, células fusiformes (D2-40 positivo en inmunohistoquímica) similares a fibroblastos con láminas de colágeno peritoneal denso. La peritonitis esclerosante encapsulada es una patología de prevalencia desconocida. El cuadro clínico es inespecífico y el diagnóstico definitivo es por patología con biopsia peritoneal.

Arthrofibrosis of the knee in pediatric orthopedic surgery.

Arthrofibrosis is a challenging complication associated with knee injuries in both children and adults. While much is known about managing arthrofibrosis in adults, it is necessary to understand its unique aspects and management strategies in the pediatric population. This paper provides an overview of arthrofibrosis in pediatric orthopedic surgery, focusing on its causes, implications, classifications, and management. This paper is a comprehensive review of the literature and existing research on arthrofibrosis in pediatric patients. Arthrofibrosis is characterized by excessive collagen production and adhesions, leading to restricted joint motion and pain. It is associated with an immune response and fibrosis within and around the joint. Arthrofibrosis can result from various knee injuries in pediatric patients, including tibial spine fractures, ACL and PCL injuries, and extra-articular procedures. Technical factors at the time of surgery play a role in the development of motion loss and should be addressed to minimize complications. Preventing arthrofibrosis through early physical therapy is recommended. Non-operative management, including dynamic splinting and serial casting, has shown some benefits. New pharmacologic approaches to lysis of adhesions have shown promise. Surgical interventions, consisting of arthroscopic lysis of adhesions (LOA) and manipulation under anesthesia (MUA), can significantly improve motion and functional outcomes. Arthrofibrosis poses unique challenges in pediatric patients, demanding a nuanced approach that includes prevention, early intervention with non-operative means, and improvements in surgical techniques. Modern pharmacological interventions offer promise for the future. Customized interventions and research focused on pediatric patients are critical for optimal outcomes.

La artrofibrosis es una complicación difícil asociada con lesiones de rodilla tanto en niños como en adultos. Si bien se sabe mucho sobre el manejo de la artrofibrosis en adultos, es necesario comprender sus aspectos únicos y estrategias de manejo en la población pediátrica. Este documento proporciona una visión general de la artrofibrosis en la cirugía ortopédica pediátrica, centrándose en sus causas, implicaciones, clasificaciones y manejo. Este documento es una revisión completa de la literatura y la investigación existente sobre artrofibrosis en pacientes pediátricos. La artrofibrosis se caracteriza por una producción excesiva de colágeno y adherencias, lo que conduce a un movimiento articular restringido y dolor. Se asocia con una inmunorrespuesta y fibrosis dentro y alrededor de la articulación. La artrofibrosis puede ser el resultado de varias lesiones de rodilla en pacientes pediátricos, incluyendo fracturas de columna tibial, lesiones de LCA y LCP, y procedimientos extraarticulares. Los factores técnicos en el momento de la cirugía desempeñan un papel en el desarrollo de la pérdida de movimiento y deben abordarse para minimizar las complicaciones. Se recomienda prevenir la artrofibrosis a través de la fisioterapia temprana. La gestión no operativa, incluyendo el empalme dinámico y la fundición en serie, ha mostrado algunos beneficios. Los nuevos enfoques farmacológicos a la lisis de adherencias han demostrado ser prometedores. Las intervenciones quirúrgicas, consistentes en lisis artroscópica de adherencias (LOA) y manipulación bajo anestesia (MUA), pueden mejorar significativamente el movimiento y los resultados funcionales. La artrofibrosis plantea desafíos únicos en los pacientes pediátricos, exigiendo un enfoque matizado que incluye prevención, intervención temprana con medios no operatorios y mejoras en las técnicas quirúrgicas. Las intervenciones farmacológicas modernas ofrecen una promesa para el futuro. Las intervenciones e investigaciones personalizadas centradas en pacientes pediátricos son fundamentales para obtener resultados óptimos.

Neutrophil to lymphocyte ratio predicts bowel ischemia in non-strangulated adhesive small bowel occlusions: a retrospective analysis from an acute care surgical service.

BACKGROUND: Adhesive small bowel obstruction (ASBO) is a leading cause of hospitalization in emergency surgery. The occurrence of bowel ischemia significantly increases the morbidity and mortality rates associated with this condition. Current clinical, biochemical and radiological parameters have poor predictive value for bowel ischemia. This study is designed to ascertain predictive elements for the progression to bowel ischemia in patients diagnosed with non-strangulated ASBO who are initially managed through conservative therapeutic approaches. METHODS: The study was based on the previously collected medical records of 128 patients admitted to the Department of Acute Care Surgery of Padua General Hospital, from August 2020 to April 2023, with a diagnosis of non-strangulated adhesive small bowel obstruction, who were then operated for failure of conservative treatment. The presence or absence of bowel ischemia was used to distinguish the two populations. Clinical, biochemical and radiological data were used to verify whether there is a correlation with the detection of bowel ischemia. RESULTS: We found that a Neutrophil-Lymphocyte ratio (NLR) > 6.8 (OR 2.9; 95% CI 1.41-6.21), the presence of mesenteric haziness (OR 2.56; 95% CI 1.11-5.88), decreased wall enhancement (OR 4.3; 95% CI 3.34-10.9) and free abdominal fluid (OR 2.64; 95% CI 1.08-6.16) were significantly associated with bowel ischemia at univariate analysis. At the multivariate logistic regression analysis, only NLR > 6.8 (OR 5.9; 95% CI 2.2-18.6) remained independent predictive factor for small bowel ischemia in non-strangulated adhesive small bowel obstruction, with 78% sensitivity and 65% specificity. CONCLUSIONS: NLR is a straightforward and reproducible parameter to predict bowel ischemia in cases of non-strangulated adhesive small bowel obstruction. Employing NLR during reevaluation of patients with this condition, who were initially treated conservatively, can help the acute care surgeons in the early prediction of bowel ischemia onset.

Neutrophil Extracellular Traps: A Crucial Factor in Post-Surgical Abdominal Adhesion Formation.

Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments.

Enhanced recovery programs following adhesive small bowel obstruction surgery are feasible and reduce the rate of postoperative ileus: a preliminary study.

PURPOSE: The recovery of gastrointestinal function and postoperative ileus are the leading goals for clinicians following surgery for adhesive small bowel obstruction. While enhanced recovery programs may improve recovery, their feasibility in emergency surgery has not yet been proven. We sought to assess the incidence of postoperative ileus in patients following surgery for ASBO and the feasibility of enhanced recovery programs, including their benefits in the recovery of gastrointestinal functions and reducing the length of hospitalization. METHODS: This prospective study includes the first 50 patients surgically treated for ASBO between June 2021 and November 2022. Their surgery was performed either as an emergency procedure or after a short course of medical treatment. The main aim was to compare the observed rate of postoperative ileus with a theoretical rate, set at 40%. The study protocol was registered in clinicaltrials.gov under the number NCT04929275. RESULTS: Among the 50 patients included in this study, it reported postoperative ileus in 16%, which is significantly lower than the hypothetical rate of 40% (p = 0.0004). The median compliance with enhanced recovery programs was 75% (95%CI: 70.1-79.9). The lowest item observed was the TAP block (26%) and the highest observed items were preoperative counselling and compliance with analgesic protocols (100%). The overall morbidity was 26.5%, but severe morbidity (Dindo-Clavien > 3) was observed in only 3 patients (6%). Severe morbidity was not related with the ERP. CONCLUSION: Enhanced recovery programs are feasible and safe in adhesive small bowel obstruction surgery patients and could improve the recovery of gastrointestinal functions. CLINICAL TRIAL REGISTRY: NCT04929275. WHAT DOES THE STUDY CONTRIBUTE TO THE FIELD?: Perioperative management of adhesive small bowel obstruction (ASBO) surgery needs to be improved in order to reduce morbidity. Enhanced recovery programs (ERP) are both feasible and safe following urgent surgery for ASBO. ERPs may improve the recovery of gastrointestinal (GI) functions.

Effects of pioglitazone and metformin on abdominal adhesion formation in an experimental model.

BACKGROUND: This study evaluated the use of metformin or pioglitazone in preventing or reducing the development of post-operative intra-abdominal adhesion (PIAA) by employing histopathological, immunohistochemical, and biochemical analyses in an experimental adhesion model. METHODS: Fifty Wistar-Albino rats were divided into five groups: Group I (Control), Group II (Sham Treatment), Group III (Hy-aluronic Acid), Group IV (Metformin), and Group V (Pioglitazone). Adhesions were induced in the experimental groups, except for the sham group, using the scraping method. After 10 days, rats were euthanized for evaluation. Macroscopic adhesion degrees were assessed using Nair's scoring system. Immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods were utilized to assess serum, peritoneal lavage, and intestinal tissue samples. Fructosamine, interleukin-6 (IL-6), transforming growth factor-beta (TGF-ß), and fibronectin levels were measured in serum and peritoneal lavage samples. RESULTS: The groups exhibited similar Nair scores and Type I or Type III Collagen staining scores (all, p>0.05). Pioglitazone significantly reduced serum IL-6 and TGF-ß levels compared to controls (p=0.002 and p=0.008, respectively). Both metformin and pioglitazone groups showed elevated IL-6 in peritoneal lavage relative to controls, while fibronectin levels in the lavage were lower in pioglitazone-treated rats compared to the sham group (all, p<0.005). CONCLUSION: Pioglitazone, but not metformin, demonstrated a positive biochemical impact on preventing PIAA formation in an experimental rat model, although histological impacts were not observed. Further experimental studies employing different dose/duration regimens of pioglitazone are needed to enhance our understanding of its effect on PIAA formation.

Analysis of the efficacy of retrodiscal approach percutaneous epidural adhesiolysis with WHIP catheter® in patients with lumbar radiculopathy: A retrospective study.

Percutaneous epidural adhesiolysis (PEA) is an effective treatment for patients with lumbar radiculopathy unresponsive to single steroid injections. Various approaches and instruments have been developed to access these lesions. This study aimed to evaluate the utility of a retrodiscal approach for epidural adhesiolysis using a WHIP catheter®. This retrospective study was conducted at Bundang Seoul National University Hospital, reviewing cases from January to December 2022. Forty-seven patients diagnosed with lumbar radiculopathy, aged 20 to 80 years, who underwent PEA with the WHIP catheter® were included. Outcomes assessed Numeric Rating Scale (NRS) for pain, Patients' Global Impression of Change (PGIC) scores, and the incidence of procedure-related complications. Follow-up evaluations occurred at 1, 3, and 6 months post-procedure. Among 47 patients, 41 completed the study, showing significant pain reduction at all follow-up points: 1 month (N = 41, 1.32 ±â€…1.68, P < .001), 3 months (N = 31, 1.90 ±â€…2.14, P < .001), and 6 months (N = 30, 2.50 ±â€…2.30, P < .001). PGIC scores indicated that 40% of the patients reported substantial improvement at one-month post-procedure. The complications were minimal, with only one case of intradiscal injection and 2 cases of vascular uptake. The retrodiscal approach PEA using the WHIP catheter® demonstrated significant efficacy in pain reduction with minimal safety concerns for patients with lumbar radiculopathy. These findings suggest that this procedure is a viable option for patients who are unresponsive to conservative treatment. However, the retrospective nature of this study and its small sample size necessitate further prospective controlled studies to confirm our results and establish long-term outcomes.

Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation.

BACKGROUND: Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA. METHODS: Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis. RESULTS: We successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor. CONCLUSIONS: Due to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA.

Human amnion mesenchymal stem cells promote endometrial repair via paracrine, preferentially than transdifferentiation.

BACKGROUND: Intrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA. METHODS: Human amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-ß1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection. RESULTS: qPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC. CONCLUSIONS: Our data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation.

IUA is the crucial cause of infertility in women of childbearing age, and no satisfactory treatment measures have been found in the clinic. hAMSCs can effectively treat intrauterine adhesions through paracrine and transdifferentiation mechanisms. This study confirmed in vitro and in vivo that amniotic mesenchymal stem cells preferentially inhibited endometrial fibrosis and promoted epithelial repair through paracrine, thus effectively treating intrauterine adhesions. The level of fibrosis marker proteins in IUA-THESCs decreased significantly after co-culturing with hAMSCs for 2 days in vitro. However, the level of epithelial marker proteins in hAMSCs increased significantly, requiring at least 6 days of co-culture. hAMSCs-CM had the same efficacy as hAMSCs in inhibiting fibrosis and promoting endometrial repair in IUA rats, supporting the idea that hAMSCs promoted endometrial remodeling through paracrine in vivo. In addition, GFP-labeled hAMSCs continuously colonized the endometrial stroma instead of the epithelium and gradually underwent apoptosis. These findings prove that hAMSCs ameliorate endometrial fibrosis of IUA via paracrine, preferentially than transdifferentiation, providing the latest insights into the precision treatment of IUA with hAMSCs and a theoretical basis for promoting the "cell-free therapy" of MSCs.

Mechanism of electroacupuncture in treating uterine endometrial fibrosis in intrauterine adhesions rats based on Wnt/ß-catenin pathway-mediated epithelial-mesenchymal transition. / 基于Wnt/ß-cateniné€šè·¯ä»‹å¯¼çš„ä¸Šçš®é—´è´¨è½¬åŒ–æŽ¢è®¨ç”µé’ˆæ²»ç–—å®«è ”ç²˜è¿žå¤§é¼ å­å®«å† è†œçº¤ç»´åŒ–çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins in rats with intrauterine adhesions (IUA), so as to explore the possible mechanisms of EA in repairing endometrial damage in IUA. METHODS: Female SD rats were randomly divided into blank, model, EA, and ICG-001 groups, with 10 rats in each group. The IUA model was established by using mechanical scraping combined with lipopolysaccharide infection for double injury. In the EA group, "Guanyuan" (CV4) was needled and EA (2 Hz/15 Hz, 1-2 mA) was applied to "Zusanli" (ST36) and "Sanyinjiao"(SP6) on both sides. In the ICG-001 group, ICG-001 (5 mg/kg), the inhibitor of ß-catenin was intraperitoneally injected. After intervention, samples were taken from 5 rats in each group, and uterine endometrium morphology, endometrial thickness, and gland counts were observed using HE staining. Masson staining was used to assess the degree of fibrosis in the endometrial tissue. Immunohistochemistry was used to detect the positive expression of transforming growth factor ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), fibronectin (FN), connective tissue growth factor (CTGF), type I collagen (Col- Ⅰ), glycogen synthase kinase-3ß (GSK-3ß), ß-catenin, E-cadherin, N-cadherin, and Vimentin in the endometrial tissue. Western blot was used to detect the relative expression of GSK-3ß, ß-catenin, E-cadherin, N-cadherin, and Vimentin proteins in the endometrial tissue. Another 5 rats from each group were placed in cages with male rats after intervention to record the number of embryo implantations. RESULTS: Necrosis and loss of endometrial tissue in the model group observed after HE staining were alleviated in the EA group, better than those in the ICG-001 group. Compared with the blank group, the numbers of glands and endometrial thickness in the uterine endometrial tissue, relative expression and positive expression of E-cadherin and GSK-3ß proteins in the uterine endometrial tissue, and embryo implantation numbers were reduced(P<0.000 1, P<0.001, P<0.01) in the model group, while fibrosis area ratio in the uterine endometrial tissue, TGF- ß 1, α -SMA, FN, CTGF, Col- Ⅰ positive expressions, N-cadherin, Vimentin, and ß-catenin proteins expression and positive expression were increased(P<0.000 1, P<0.001, P<0.01). Compared with the model group, the number of glands and endometrial thickness, E-cadherin and GSK-3ß proteins expression and positive expression, and embryo implantation numbers were increased (P<0.001, P<0.05, P<0.01) in the EA and ICG-001 groups, while the fibrosis area ratio in the uterine endometrial tissue, TGF-ß1, α-SMA, FN, CTGF, Col- Ⅰ positive expression, and N-cadherin, Vimentin, and ß-catenin proteins expression and positive expression were decreased(P<0.001, P<0.01, P<0.05). Compared with the EA group, the differences of the above-mentioned indicators in the ICG-001 group were not statistically significant. CONCLUSIONS: EA may reverse the EMT process and reduce the degree of fibrosis in endometrial tissue by inhibiting the Wnt/ß-catenin signaling pathway, thereby promoting the repair of endometrial damage in IUA.

Semaglutide May Ameliorate Fibrosis and Inhibit Epithelial-Mesenchymal Transition in Intrauterine Adhesion Models.

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-ß1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-ß1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial-mesenchymal transition in IUA models.

Multimodal learning system integrating electronic medical records and hysteroscopic images for reproductive outcome prediction and risk stratification of endometrial injury: a multicenter diagnostic study.

OBJECTIVE: To develop a multimodal learning application system that integrates electronic medical records (EMR) and hysteroscopic images for reproductive outcome prediction and risk stratification of patients with intrauterine adhesions (IUAs) resulting from endometrial injuries. MATERIALS AND METHODS: EMR and 5014 revisited hysteroscopic images of 753 post hysteroscopic adhesiolysis patients from the multicenter IUA database we established were randomly allocated to training, validation, and test datasets. The respective datasets were used for model development, tuning, and testing of the multimodal learning application. MobilenetV3 was employed for image feature extraction, and XGBoost for EMR and image feature ensemble learning. The performance of the application was compared against the single-modal approaches (EMR or hysteroscopic images), DeepSurv and ElasticNet models, along with the clinical scoring systems. The primary outcome was the 1-year conception prediction accuracy, and the secondary outcome was the assisted reproductive technology (ART) benefit ratio after risk stratification. RESULTS: The multimodal learning system exhibited superior performance in predicting conception within 1-year, achieving areas under the curves of 0.967 (95% CI: 0.950-0.985), 0.936 (95% CI: 0.883-0.989), and 0.965 (95% CI: 0.935-0.994) in the training, validation, and test datasets, respectively, surpassing single-modal approaches, other models and clinical scoring systems (all P<0.05). The application of the model operated seamlessly on the hysteroscopic platform, with an average analysis time of 3.7±0.8 s per patient. By employing the application's conception probability-based risk stratification, mid-high-risk patients demonstrated a significant ART benefit (odds ratio=6, 95% CI: 1.27-27.8, P=0.02), while low-risk patients exhibited good natural conception potential, with no significant increase in conception rates from ART treatment (P=1). CONCLUSIONS: The multimodal learning system using hysteroscopic images and EMR demonstrates promise in accurately predicting the natural conception of patients with IUAs and providing effective postoperative stratification, potentially contributing to ART triage after IUA procedures.

Prevention of post-operative adhesions: Model development and pilot outcomes of human placental stem cell-based interventions.

BACKGROUND: Abdominal adhesions are the most common surgical complication and without reliable prophylactics. This study presents a novel rat model for abdominal adhesions and reports pilot results of human placental stem cell (hPSC)-based therapies. METHODS: Forty-four (n = 44) male Sprague-Dawley rats (250-350 g) were used in the experiment. Of these, thirty-eight (n = 38) were included in a preliminary data set to determine a minimum treatment effect. Adhesions were created in a reproducible model to the abdominal wall and between organs. Experimental groups included the control group (Model No Treatment, MNT), Plasmalyte A (Media Alone, MA, 10 mL), hPSC (5 × 106 cells/10 mL Plasmalyte A), hPSC-CM (hPSC secretome, conditioned media) in 10 mL Plasmalyte A, Seprafilm™ (Baxter, Deerfield, IL), and sham animals (laparotomy only). Treatments were inserted intraperitoneally (IP) and the study period was 14 days post-operation. Results are reported as the difference between means of an index statistic (AIS, Animal Index Score) and compared by ANOVA with pairwise comparison. RESULTS: The overall mean AIS was 23 (SD 6.16) for the MNT group with an average of 75% of ischemic buttons involved in abdominal adhesions. Treatment groups MA (mean overall AIS 17.33 SD 6.4), hPSC (mean overall AIS 13.86 SD 5.01), hPSC-CM (mean overall AIS 13.13 SD 6.15), and Seprafilm (mean overall AIS 13.43 SD 9.11) generated effect sizes of 5.67, 9.14, 9.87, and 9.57 decrease in mean overall AIS, respectively, versus the MNT. DISCUSSION: The presented rat model and scoring system represent the clinical adhesion disease process. hPSC-based interventions significantly reduce abdominal adhesions in this pilot dataset.