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Toxins May 2024Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat...
Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat chronic pelvic pain (CPP). Mindfulness interventions may reduce procedure-associated acute anxiety and pain. We applied mindfulness techniques to increase the tolerability of office-based pelvic floor BoNT injections in women with CPP. Women enrolled in a clinical trial of BoNT for endometriosis-associated CPP were offered a brief, guided mindfulness session before and/or after transvaginal injection. Anxiety, pain, and dysphoria were rated on a 0-10 numerical rating scale (NRS) before and after each mindfulness session. Eight women underwent mindfulness sessions. Five participants had a session before and two after the transvaginal injection. One participant had two sessions: one before and one after separate injections. All six women completing a session prior to injection had at least moderate anxiety, which lessened after the mindfulness session (median NRS change: -3.3/10). All three women reporting injection-associated pain experienced less intense pain following the post-injection session (median NRS change: -3/10). Three women experiencing dysphoria improved after the session (median NRS change: -3/10). A brief, guided mindfulness session may lessen acute pain, anxiety, and dysphoria associated with office-based transvaginal BoNT injection.
Topics: Humans; Female; Pelvic Pain; Mindfulness; Adult; Chronic Pain; Pelvic Floor; Anxiety; Middle Aged; Botulinum Toxins; Endometriosis
PubMed: 38787068
DOI: 10.3390/toxins16050216 -
Diseases (Basel, Switzerland) May 2024Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner... (Review)
Review
Dystrophic Epidermolysis Bullosa (DEB): How Can Pregnancy Alter the Course of This Rare Disease? An Updated Literature Review on Obstetrical Management with an Additional Italian Experience.
Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome.
PubMed: 38785759
DOI: 10.3390/diseases12050104 -
Frontiers in Pharmacology 2024Cap polyposis (CP) is a rare kind of benign disease, and the majority of previously published relevant articles involve a small number of patients. Hence, we summarized...
BACKGROUND AND AIMS
Cap polyposis (CP) is a rare kind of benign disease, and the majority of previously published relevant articles involve a small number of patients. Hence, we summarized our experience to contribute additional data, hoping to raise awareness of this disease.
METHODS
From 1 January 2017 to 1 November 2021, consecutive patients diagnosed with CP were retrospectively reviewed. Their medical histories, and laboratory, imaging, endoscopic, and pathology results were analyzed. We made telephone calls to the patients and searched for the information in our electronic medical records to obtain the follow-up results.
RESULTS
Forty-one patients were chosen for analysis. The median age of the patients was 20 years old, and 90.24% (37 patients) of the patients were male. The majority of the patients presented with hematochezia. The rectum was the most commonly affected site, and the infection rate was high. There were multiple and combined treatments for these patients. These treatments can be divided into 3 main categories: medical therapy, endotherapy and surgery. Medical therapy helped to diminish the size of but the polyps were difficult to resolve; however, the patients' symptoms could be diminished. Twenty-three patients underwent surgical resection, and 12 patients received endotherapy. We further compared the two methods of polyp resection. Both endotherapy and surgery were safe, and the recurrence risk was not significantly different between the two kinds of therapy ( = 0.321).
CONCLUSION
The clinical improvement of medical treatments was not satisfactory, and endotherapy or surgical resection could remove the polyposis and provide temporary relief, but the recurrence rates were high.
PubMed: 38783946
DOI: 10.3389/fphar.2024.1391367 -
Health Technology Assessment... May 2024Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend clinics for pessary care.
OBJECTIVES
To determine the clinical effectiveness and cost-effectiveness of vaginal pessary self-management on prolapse-specific quality of life for women with prolapse compared with clinic-based care; and to assess intervention acceptability and contextual influences on effectiveness, adherence and fidelity.
DESIGN
A multicentre, parallel-group, superiority randomised controlled trial with a mixed-methods process evaluation.
PARTICIPANTS
Women attending UK NHS outpatient pessary services, aged ≥ 18 years, using a pessary of any type/material (except shelf, Gellhorn or Cube) for at least 2 weeks. Exclusions: women with limited manual dexterity, with cognitive deficit (prohibiting consent or self-management), pregnant or non-English-speaking.
INTERVENTION
The self-management intervention involved a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a local clinic telephone helpline number. Clinic-based care involved routine appointments determined by centres' usual practice.
ALLOCATION
Remote web-based application; minimisation was by age, pessary user type and centre.
BLINDING
Participants, those delivering the intervention and researchers were not blinded to group allocation.
OUTCOMES
The patient-reported primary outcome (measured using the Pelvic Floor Impact Questionnaire-7) was prolapse-specific quality of life, and the cost-effectiveness outcome was incremental cost per quality-adjusted life-year (a specifically developed health Resource Use Questionnaire was used) at 18 months post randomisation. Secondary outcome measures included self-efficacy and complications. Process evaluation data were collected by interview, audio-recording and checklist. Analysis was by intention to treat.
RESULTS
Three hundred and forty women were randomised (self-management, = 169; clinic-based care, = 171). At 18 months post randomisation, 291 questionnaires with valid primary outcome data were available (self-management, = 139; clinic-based care, = 152). Baseline economic analysis was based on 264 participants (self-management, = 125; clinic-based care, = 139) with valid quality of life and resource use data. Self-management was an acceptable intervention. There was no group difference in prolapse-specific quality of life at 18 months (adjusted mean difference -0.03, 95% confidence interval -9.32 to 9.25). There was fidelity to intervention delivery. Self-management was cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, with an estimated incremental net benefit of £564.32 and an 80.81% probability of cost-effectiveness. At 18 months, more pessary complications were reported in the clinic-based care group (adjusted mean difference 3.83, 95% confidence interval 0.81 to 6.86). There was no group difference in general self-efficacy, but self-managing women were more confident in pessary self-management activities. In both groups, contextual factors impacted on adherence and effectiveness. There were no reported serious unexpected serious adverse reactions. There were 32 serious adverse events (self-management, = 17; clinic-based care, = 14), all unrelated to the intervention. Skew in the baseline data for the Pelvic Floor Impact Questionnaire-7, the influence of the global COVID-19 pandemic, the potential effects of crossover and the lack of ethnic diversity in the recruited sample were possible limitations.
CONCLUSIONS
Self-management was acceptable and cost-effective, led to fewer complications and did not improve or worsen quality of life for women with prolapse compared with clinic-based care. Future research is needed to develop a quality-of-life measure that is sensitive to the changes women desire from treatment.
STUDY REGISTRATION
This study is registered as ISRCTN62510577.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/82/01) and is published in full in ; Vol. 28, No. 23. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Female; Pessaries; Pelvic Organ Prolapse; Cost-Benefit Analysis; Self-Management; Middle Aged; Quality of Life; Aged; United Kingdom; Quality-Adjusted Life Years; Adult
PubMed: 38767959
DOI: 10.3310/NWTB5403 -
Revista Brasileira de Ginecologia E... 2024To show the experience of a Latin American public hospital, with SNM in the management of either OAB, NOUR or FI, reporting feasibility, short to medium-term success...
OBJECTIVE
To show the experience of a Latin American public hospital, with SNM in the management of either OAB, NOUR or FI, reporting feasibility, short to medium-term success rates, and complications.
METHODS
A retrospective cohort was conducted using data collected prospectively from patients with urogynecological conditions and referred from colorectal surgery and urology services between 2015 and 2022.
RESULTS
Advanced or basic trial phases were performed on 35 patients, 33 (94%) of which were successful and opted to move on Implantable Pulse Generator (GG) implantation. The average follow-up time after definitive implantation was 82 months (SD 59). Of the 33 patients undergoing, 27 (81%)reported an improvement of 50% or more in their symptoms at last follow-up. Moreover, 30 patients (90%) with a definitive implant reported subjective improvement, with an average PGI-I "much better" and 9 of them reporting to be "excellent" on PGI-I.
CONCLUSION
SNM is a feasible and effective treatment for pelvic floor dysfunction. Its implementation requires highly trained groups and innovative leadership. At a nation-wide level, greater diffusion of this therapy among professionals is needed to achieve timely referral of patients who require it.
Topics: Humans; Female; Retrospective Studies; Hospitals, Public; Middle Aged; Electric Stimulation Therapy; Adult; Aged; Pelvic Floor Disorders; Latin America; Feasibility Studies; Fecal Incontinence; Treatment Outcome
PubMed: 38765538
DOI: 10.61622/rbgo/2024AO11 -
Revista Brasileira de Ginecologia E... 2024To analyze data of patients with symptomatic pelvic organ prolapse evaluated with PFDI20 and its subscales to report the prevalence of lower gastrointestinal symptoms...
OBJECTIVE
To analyze data of patients with symptomatic pelvic organ prolapse evaluated with PFDI20 and its subscales to report the prevalence of lower gastrointestinal symptoms and anal incontinence in the population of a public hospital and analyze its impact on quality of life.
METHODS
Cross-sectional study of patients with symptomatic POP. Patients were evaluated with demographic data, POP-Q, pelvic floor ultrasonography, urological parameters, and pelvic floor symptoms (PFDI-20), and quality of life (P-QoL) surveys. Patients were classified as CRADI-8 "positive" for colorectal symptoms, with responses "moderate" in at least 3 and/or "severe" in at least 2 of the items in the CRADI-8 questionnaires.
RESULTS
One hundred thirteen patients were included. 42.5% (48) were considered positive for colorectal symptoms on CRADI-8. 53.4% presented anal incontinence. No significant differences were found in sociodemographic variables, POP-Q stage, ultrasound parameters, or urological parameters. Positive patients had a significantly worse result in PFDI-20, POPDI (48 vs 28; p<0.001), UDI6 (51 vs 24; p<0.001), and in the areas of social limitation (44.4 vs 22.2; p = 0.045), sleep- energy (61.5 vs 44.4; p = 0.08), and severity (56.8 vs 43.7, p=0.015) according to P-QoL.
CONCLUSION
Moderate or severe colorectal symptoms are seen in 40% of patients with symptomatic POP in our unit. Full evaluation of pelvic floor dysfunction symptoms should be performed routinely in urogynecology units.(FONIS SA12I2I53 - NCT02113969).
Topics: Humans; Female; Cross-Sectional Studies; Fecal Incontinence; Middle Aged; Prevalence; Pelvic Organ Prolapse; Aged; Quality of Life; Gynecology; Urology; Adult; Ambulatory Care
PubMed: 38765524
DOI: 10.61622/rbgo/2024AO10 -
Acta Obstetricia Et Gynecologica... Jun 2024
Topics: Humans; Female; Pregnancy; Pelvic Floor Disorders; Pelvic Floor; Delivery, Obstetric; Pregnancy Complications; Obstetric Labor Complications
PubMed: 38764284
DOI: 10.1111/aogs.14875 -
Therapeutic Advances in Gastroenterology 2024The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and...
BACKGROUND
The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and prognosis warrants further investigation. While high KRAS expression is commonly linked with poorer prognosis in other cancers, its role in CRC remains relatively understudied.
OBJECTIVE
To explore the correlation between KRAS expression, KRAS status, prognosis, and tumor-infiltrating T lymphocyte density in CRC.
DESIGN
Single-center retrospective study.
METHODS
Conducted between 2010 and 2020, this study utilized tumor samples to assess KRAS expression and quantify CD3+/CD8+ T lymphocytes. The Cox proportional hazards model and linear regression analysis were employed to examine the relationship between KRAS expression, prognosis, and tumor-infiltrating T lymphocytes.
RESULTS
This study included 265 CRC patients who underwent radical surgery. No significant association was observed between KRAS expression and KRAS status ( > 0.05). High KRAS expression was associated with poorer overall survival and disease-free survival ( < 0.05). Subgroup analysis revealed that high KRAS expression remained indicative of a worse prognosis in the group with mismatch repair-deficient (dMMR) and KRAS mutant type ( < 0.05). Multivariate analysis confirmed KRAS expression as an unfavorable prognostic factor ( < 0.05). However, the significance of KRAS expression was lost in the dMMR and KRAS mutant-type group regarding overall survival ( > 0.05). Notably, KRAS expression showed a negative correlation with the density of CD8+ T lymphocytes in tumor tissue ( < 0.05), a finding also observed in the dMMR group ( < 0.05).
CONCLUSION
No association was found between KRAS expression and KRAS mutation status in CRC. Higher KRAS expression was indicative of poorer prognosis for CRC patients, except for those with proficient mismatch repair and KRAS wild type. In addition, in patients with dMMR, KRAS expression was associated with a lower density of CD8+ T lymphocytes in tumor tissue.
PubMed: 38757097
DOI: 10.1177/17562848241249387 -
Gastroenterology Report 2024Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD), which still lacks of reliable markers and therapeutic options. Cellular senescence has...
BACKGROUND
Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD), which still lacks of reliable markers and therapeutic options. Cellular senescence has been considered an important mechanism of intestinal fibrosis, but the underlying molecular link remains elusive.
METHODS
Tissues were stained using α-smooth muscle actin (α-SMA), fibronectin, and collagen I as markers of myofibroblastic differentiation. Cellular senescence was confirmed through Lamin B1 staining, senescence-associated β-galactosidase staining, and the expression of senescence-associated secretory phenotype (SASP) factors. We explored the relationship between senescence of intestinal epithelial cells (IECs) and intestinal fibrosis, as well as the molecular mechanism underlying this interaction. The effects of irisin on cellular senescence and fibrosis were determined.
RESULTS
Here, we identify engulfment and cell motility protein 1 (ELMO1) as a novel biomarker for intestinal cellular senescence and fibrosis. In fibrostrictured tissues from patients and murine models with IBD, significantly high levels of cellular senescence score and factors were noted, which positively correlated with the fibrotic regulator fibronectin. Senescent IECs, not fibroblast itself, released SASP factors to regulate fibroblast activation. Prolonging exposure to severe and persistent injurious stimuli decreased ELMO1 expression, which dampened SIRT1 deacetylase activity, enhanced NF-κB (p65) acetylation, and thereby accelerated cellular senescence. Deletion of ELMO1 led to senescent IECs accumulation and triggered premature fibrosis in murine colitis. Furthermore, irisin, inhibiting the degradation of ELMO1, could downregulate p65 acetylation, reduce IECs senescence, and prevent incipient intestinal fibrosis in murine colitis models.
CONCLUSIONS
This study reveals ELMO1 downregulation is an early symbol of intestinal senescence and fibrosis, and the altered ELMO1-SIRT1-p65 pathway plays an important role in intestinal cellular senescence and IBD-related fibrosis.
PubMed: 38756351
DOI: 10.1093/gastro/goae045 -
Cell Communication and Signaling : CCS May 2024Extracellular ATP-AMP-adenosine metabolism plays a pivotal role in modulating tumor immune responses. Previous studies have shown that the conversion of ATP to AMP is...
BACKGROUND
Extracellular ATP-AMP-adenosine metabolism plays a pivotal role in modulating tumor immune responses. Previous studies have shown that the conversion of ATP to AMP is primarily catalysed by Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39), a widely studied ATPase, which is expressed in tumor-associated immune cells. However, the function of ATPases derived from tumor cells themselves remains poorly understood. The purpose of this study was to investigate the role of colon cancer cell-derived ATPases in the development and progression of colon cancer.
METHODS
Bioinformatic and tissue microarray analyses were performed to investigate the expression of ATPase family members in colon cancer. An ATP hydrolysis assay, high-performance liquid chromatography (HPLC), and CCK8 and colony formation assays were used to determine the effects of ENTPD2 on the biological functions of colon cancer cells. Flow cytometric and RNA-seq analyses were used to explore the function of CD8 T cells. Immunoelectron microscopy and western blotting were used to evaluate the expression of ENTPD2 in exosomes. Double-labelling immunofluorescence and western blotting were used to examine the expression of ENTPD2 in serum exosomes and colon cancer tissues.
RESULTS
We found that ENTPD2, rather than the well-known ATPase CD39, is highly expressed in cancer cells and is significantly positively associated with poor patient prognosis in patients with colon cancer. The overexpression of ENTPD2 in cancer cells augmented tumor progression in immunocompetent mice by inhibiting the function of CD8 T cells. Moreover, ENTPD2 is localized primarily within exosomes. On the one hand, exosomal ENTPD2 reduces extracellular ATP levels, thereby inhibiting P2X7R-mediated NFATc1 nuclear transcription; on the other hand, it facilitates the increased conversion of ATP to adenosine, hence promoting adenosine-A2AR pathway activity. In patients with colon cancer, the serum level of exosomal ENTPD2 is positively associated with advanced TNM stage and high tumor invasion depth. Moreover, the level of ENTPD2 in the serum exosomes of colon cancer patients is positively correlated with the ENTPD2 expression level in paired colon cancer tissues, and the ENTPD2 level in both serum exosomes and tissues is significantly negatively correlated with the ENTPD2 expression level in tumor-infiltrating CD8 T cells.
CONCLUSION
Our study suggests that exosomal ENTPD2, originated from colon cancer cells, contributes to the immunosuppressive microenvironment by promoting ATP-adenosine metabolism. These findings highlight the importance of exosome-derived hydrolytic enzymes as independent entities in shaping the tumor immune microenvironment.
Topics: Humans; Exosomes; Adenosine; Adenosine Triphosphate; Colonic Neoplasms; CD8-Positive T-Lymphocytes; Apyrase; Animals; Mice; Cell Line, Tumor; Male; Female; Metabolic Reprogramming; Receptor, Adenosine A2A
PubMed: 38755598
DOI: 10.1186/s12964-024-01654-2