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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 -
Andrology Jun 2024Erectile dysfunction (ED) is prevalent not only among older males but also in younger. The physical activity has been considered a potential protective factor against... (Review)
Review
BACKGROUND
Erectile dysfunction (ED) is prevalent not only among older males but also in younger. The physical activity has been considered a potential protective factor against ED. However, there is a lack of comprehensive research on the impact of exercise interventions specifically on ED patients.
OBJECTIVES
This study aimed to assess the effectiveness of the physical activity in addressing ED symptoms among adult males, without the use of the phosphodiesterase-5 inhibitors (PDE5i) therapy. Additionally, subgroup analysis was performed to evaluate the effects of different exercise modes.
METHODS
Employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic literature search. A registered protocol is available at PROSPERO (CRD42023441717). Our search spanned PubMed, Web of Science, Embase, and Cochrane Library, with data collection ending on 11 April 2024. The Cochrane Risk of Bias tool was applied by two independent authors to assess randomized controlled trial (RCT) quality. The primary endpoint was determined as the International Index of Erectile Function (IIEF) scores.
RESULTS
A total of seven RCTs were included. Utilizing a random-effects model, the estimated standardized mean difference (SMD) was 0.69 (95% confidence interval [CI] 0.37 to 1.02, p < 0.0001) for the overall impact of the physical activity. Subgroup analysis revealed SMDs of 0.81 (95% CI 0.56 to 1.06; p < 0.00001) for aerobic training alone. However, no significant improvement was observed with pelvic floor muscle training (PFMT) (SMD 0.03; 95% CI -0.68 to 0.75; p = 0.93) and a combination of aerobic and resistance training (SMD 0.84; 95% CI -0.41 to 2.09; p = 0.19) CONCLUSION: The findings of this study highlight a significant improvement in the erectile function following exercise interventions for adult men with ED, who are not receiving the PDE5i therapy, especially in conducting aerobic training alone. However, PFMT and a combination of aerobic and resistance training did not show significant improvements in erectile function from this study.
PubMed: 38937909
DOI: 10.1111/andr.13682 -
American Journal of Obstetrics and... Mar 2024Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with...
BACKGROUND
Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity.
OBJECTIVE
This study aimed to test whether specific urinary or vaginal microbiome community types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence.
STUDY DESIGN
This planned secondary, cross-sectional analysis evaluated associations between the urinary and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and Urinary Distress Inventory questionnaires collected at baseline. Catheterized urine samples and vaginal swabs were concurrently collected before treatment at baseline to assess the urinary and vaginal microbiomes. Of note, 16S rRNA V4 to V6 variable regions were sequenced, characterizing bacterial taxa to the genus level using the DADA2 pipeline and SILVA database. Using Dirichlet multinomial mixtures methods, samples were clustered into community types based on core taxa. Associations between community types and severity measures (Urinary Distress Inventory total scores, Urinary Distress Inventory subscale scores, and the number of urinary incontinence episodes [total, urgency, and stress] from the bladder diary) were evaluated using linear regression models adjusted for age and body mass index. In addition, alpha diversity measures for richness (total taxa numbers) and evenness (proportional distribution of taxa abundance) were analyzed for associations with urinary incontinence episodes and community type.
RESULTS
Overall, 6 urinary microbiome community types were identified, characterized by varying levels of common genera (Lactobacillus, Gardnerella, Prevotella, Tepidimonas, Acidovorax, Escherichia, and others). The analysis of urinary incontinence severity in 126 participants with mixed urinary incontinence identified a Lactobacillus-dominated reference group with the highest abundance of Lactobacillus (mean relative abundance of 76%). A community characterized by fewer Lactobacilli (mean relative abundance of 19%) and greater alpha diversity was associated with higher total urinary incontinence episodes (2.67 daily leaks; 95% confidence interval, 0.76-4.59; P=.007) and urgency urinary incontinence episodes (1.75 daily leaks; 95% confidence interval, 0.24-3.27; P=.02) than the reference group. No significant association was observed between community type and stress urinary incontinence episodes or Urogenital Distress Inventory total or subscores. The composition of vaginal community types and urinary community types were similar but composed of slightly different bacterial taxa. Vaginal community types were not associated with urinary incontinence severity, as measured by bladder diary or Urogenital Distress Inventory total and subscale scores. Alpha diversity indicated that greater sample richness was associated with more incontinence episodes (observed genera P=.01) in urine. Measures of evenness (Shannon and Pielou) were not associated with incontinence severity in the urinary or vaginal microbiomes.
CONCLUSION
In the urobiome of women with mixed urinary incontinence, a community type with fewer Lactobacilli and more diverse bacteria was associated with more severe urinary incontinence episodes (total and urgency) compared with a community type with high predominance of a single genus, Lactobacillus. Whether mixed urinary incontinence severity is due to lesser predominance of Lactobacillus, greater presence of other non-Lactobacillus genera, or the complement of bacteria consisting of urobiome community types remains to be determined.
Topics: Humans; Female; Microbiota; Vagina; Middle Aged; Cross-Sectional Studies; Severity of Illness Index; Urinary Incontinence; Adult; Urine; Aged; RNA, Ribosomal, 16S; Urinary Incontinence, Stress; Urinary Incontinence, Urge
PubMed: 38937257
DOI: 10.1016/j.ajog.2023.10.036 -
Sexual Medicine Reviews Jun 2024One of the changes caused by pelvic cancers is the decrease in patients' sexual function, which influences their quality of life (QoL) during and after treatment. Sexual...
INTRODUCTION
One of the changes caused by pelvic cancers is the decrease in patients' sexual function, which influences their quality of life (QoL) during and after treatment. Sexual dysfunction (SD) is associated with severe ejaculatory dysfunction, sexual dissatisfaction, reduced libido and sexual desire, decreased intensity of orgasm, difficulty in erection, and lower sexual frequency.
OBJECTIVES
This systematic review investigated the effectiveness of conservative treatments (nonsurgical and nonpharmacologic) for SD in males with pelvic cancer.
METHODS
Systematic searches were performed in the Cochrane Library, PubMed, CINAHL, PEDro, Embase, and VHL databases in September 2023 by using MeSH terms related to population, study design, intervention, and outcome.
RESULTS
Only prostate cancer studies were included due to a lack of studies in other treatments. Studies used pelvic floor muscle training (8 studies); biofeedback (1 study); a penile vibrator (1 study); electrostimulation (2 studies); shock wave therapy (2 studies); aerobic, resistance, and flexibility exercises (2 studies); and a vacuum erection device (1 study). All articles assessed sexual function and reported improvements in the intervention group, including 5 with no differences between the groups. Articles involving shock wave therapy described improvements in SD but were not clinically relevant. Studies evaluating QoL reported benefits in the experimental groups. Adverse effects of a vacuum erection device and penile vibrator were reported.
CONCLUSION
Conservative treatments are more effective than others in treating SD in men with prostate cancer. Further studies are needed to assess the unwanted effects of these treatments. In this study, we found evidence that this type of therapy improves sexual function and QoL in this population.
PubMed: 38936816
DOI: 10.1093/sxmrev/qeae045 -
JMIR Formative Research Jun 2024Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the...
BACKGROUND
Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the recommended first-line treatment. However, multiple individual and institutional barriers impede women's access to skilled care. Evidence suggests that digital health solutions are acceptable and may be effective in delivering first-line incontinence treatment, although these technologies have not yet been leveraged at scale.
OBJECTIVE
The primary objective is to describe the effectiveness and safety of a prescribed digital health treatment program to guide PFMT for UI treatment among real-world users. The secondary objectives are to evaluate patient engagement following an updated user platform and identify the factors predictive of success.
METHODS
This retrospective cohort study of women who initiated device use between January 1, 2022, and June 30, 2023, included users aged ≥18 years old with a diagnosis of stress, urgency, or mixed incontinence or a score of >33.3 points on the Urogenital Distress Inventory Short Form (UDI-6). Users are prescribed a 2.5-minute, twice-daily, training program guided by an intravaginal, motion-based device that pairs with a smartphone app. Data collected by the device or app include patient-reported demographics and outcomes, adherence to the twice-daily regimen, and pelvic floor muscle performance parameters, including angle change and hold time. Symptom improvement was assessed by the UDI-6 score change from baseline to the most recent score using paired 2-tailed t tests. Factors associated with meeting the UDI-6 minimum clinically important difference were evaluated by regression analysis.
RESULTS
Of 1419 users, 947 met inclusion criteria and provided data for analysis. The mean baseline UDI-6 score was 46.8 (SD 19.3), and the mean UDI-6 score change was 11.3 (SD 19.9; P<.001). Improvement was reported by 74% (697/947) and was similar across age, BMI, and incontinence subtype. Mean adherence was 89% (mean 12.5, SD 2.1 of 14 possible weekly uses) over 12 weeks. Those who used the device ≥10 times per week were more likely to achieve symptom improvement. In multivariate logistic regression analysis, baseline incontinence symptom severity and maximum angle change during pelvic floor muscle contraction were significantly associated with meeting the UDI-6 minimum clinically important difference. Age, BMI, and UI subtype were not associated.
CONCLUSIONS
This study provides real-world evidence to support the effectiveness and safety of a prescribed digital health treatment program for female UI. A digital PFMT program completed with visual guidance from a motion-based device yields significant results when executed ≥10 times per week over a period of 12 weeks. The program demonstrates high user engagement, with 92.9% (880/947) of users adhering to the prescribed training regimen. First-line incontinence treatment, when implemented using this digital program, leads to statistically and clinically substantial symptom improvements across age and BMI categories and incontinence subtypes.
PubMed: 38935967
DOI: 10.2196/58551 -
Sensors (Basel, Switzerland) Jun 2024Pelvic floor dysfunction is a common problem in women and has a negative impact on their quality of life. The aim of this review was to provide a general overview of the... (Review)
Review
Pelvic floor dysfunction is a common problem in women and has a negative impact on their quality of life. The aim of this review was to provide a general overview of the current state of technology used to assess pelvic floor functionality. It also provides literature research of the physiological and anatomical factors that correlate with pelvic floor health. This systematic review was conducted according to the PRISMA guidelines. The PubMed, ScienceDirect, Cochrane Library, and IEEE databases were searched for publications on sensor technology for the assessment of pelvic floor functionality. Anatomical and physiological parameters were identified through a manual search. In the systematic review, 114 publications were included. Twelve different sensor technologies were identified. Information on the obtained parameters, sensor position, test activities, and subject characteristics was prepared in tabular form from each publication. A total of 16 anatomical and physiological parameters influencing pelvic floor health were identified in 17 published studies and ranked for their statistical significance. Taken together, this review could serve as a basis for the development of novel sensors which could allow for quantifiable prevention and diagnosis, as well as particularized documentation of rehabilitation processes related to pelvic floor dysfunctions.
Topics: Humans; Pelvic Floor; Pelvic Floor Disorders; Female; Quality of Life
PubMed: 38931784
DOI: 10.3390/s24124001 -
Journal of Personalized Medicine Jun 2024This study aims to characterize the clinical impact of endovascular treatment in Chronic Pelvic Pain (CPP) patients due to Pelvic Congestion Syndrome (PCS) and to assess...
BACKGROUND
This study aims to characterize the clinical impact of endovascular treatment in Chronic Pelvic Pain (CPP) patients due to Pelvic Congestion Syndrome (PCS) and to assess the diagnostic value of surface electromyography (sEMG) studies of pelvic floor musculature (PFM) in PCS patients pre- and post-endovascular treatment. Between January 2019 and July 2023, we studied consecutive patients who were referred for interventional radiology assessment and treatment to a tertiary trauma care hospital, had evidence of non-obstructive PCS from Magnetic Resonance Imaging (MRI), had sEMG of PFM and who had undergone endovascular treatment. The primary outcome was clinical, defined as a change in symptom severity after endovascular treatment. The secondary outcome was a difference in the sEMG values pre- and post-endovascular therapy.
RESULTS
We included 32 women (mean age 38 years). CPP was the leading symptom in 100% patients, followed by dysmenorrhea (75%) and post-coital pain (68.7%). Endovascular therapy included ovarian vein embolization in 28 patients (87.5%) and internal iliac vein embolization in only 2 patients (6.2%). After a median of 8 (range 6-10) months from endovascular treatment, 29 (90%) of patients reported an improvement of the main symptoms, and 15 (46%) were symptom-free. The sEMG values did not show a statistical difference pre- and post-PCS endovascular treatment.
CONCLUSIONS
Endovascular treatment appeared to be highly effective in CPP due to PCS and was associated with a low rate of complication. sEMG study could be useful in revealing alterations of PFM electrophysiology, but a difference pre- and post-embolization in PCS patients was not demonstrated.
PubMed: 38929881
DOI: 10.3390/jpm14060661 -
Journal of Translational Medicine Jun 2024Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to...
Intestinal mRNA expression profiles associated with mucosal healing in ustekinumab-treated Crohn's disease patients: bioinformatics analysis and prospective cohort validation.
BACKGROUND
Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD.
METHODS
The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset.
RESULTS
A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers.
CONCLUSIONS
Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients.
TRIAL REGISTRATION
Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www.
CLINICALTRIALS
gov .
Topics: Adult; Female; Humans; Male; Cluster Analysis; Computational Biology; Crohn Disease; Gene Expression Profiling; Gene Ontology; Intestinal Mucosa; Prospective Studies; Reproducibility of Results; RNA, Messenger; ROC Curve; Transcriptome; Ustekinumab
PubMed: 38926732
DOI: 10.1186/s12967-024-05427-w -
Lower Urinary Tract Symptoms Jul 2024To analyze the management strategies in the children who had treatment-resistant dysfunctional voiding (DV).
OBJECTIVES
To analyze the management strategies in the children who had treatment-resistant dysfunctional voiding (DV).
METHODS
Among 75 children with DV who underwent pelvic floor biofeedback therapy (BF) between 2013 and 2020, 16 patients (14 girls, 87.5%) with a mean age of 9.81 ± 2.53 years that showed incomplete clinical response following urotherapy and initial BF sessions were retrospectively reviewed. The demographic and clinical characteristics, DVSS, and uroflowmetry parameters were recorded before and after the initial BF sessions. Subsequent treatments after initial BF and clinical responses of patients were noted.
RESULTS
Clinical success was observed in one patient by addition of an anticholinergic and in three patients with combination of salvage BF sessions and anticholinergics, whom had predominant overactive bladder (OAB) symptoms. The success rate of TENS alone and in combination with other treatment modalities was 88.8% (8/9 patients). In addition, salvage BF sessions (range 2 to 3) enabled clinical success in five (50%) of 10 cases as a combination with anticholinergics or TENS. In case of incomplete emptying without OAB, adequate clinical response to Botulinum-A was observed during an average follow-up of 29 months in two boys who did not respond to alpha-blockers, even though one required repeat injection after 10 months. The total clinical success rate was 87.5% (14/16 patients) after a median follow-up of 24 months. VV-EBC and Qmax increased by a mean of 30.89% and 7.13 mL/min, respectively, whereas DVSS decreased by a mean of 8.88 points and PVR-EBC decreased by a median of 19.04%.
CONCLUSIONS
Our findings showed that clinical success in resistant DV was achieved by various combination treatments in the majority of children. However, a small group may still have persistent, bothersome symptoms despite multiple treatment modalities.
Topics: Humans; Female; Male; Biofeedback, Psychology; Child; Retrospective Studies; Urinary Bladder, Overactive; Urination Disorders; Cholinergic Antagonists; Treatment Outcome; Pelvic Floor; Combined Modality Therapy; Transcutaneous Electric Nerve Stimulation
PubMed: 38923750
DOI: 10.1111/luts.12528