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International Journal of Colorectal... May 2024A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that... (Observational Study)
Observational Study
BACKGROUND AND AIMS
A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice.
METHODS
Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined.
RESULTS
Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated.
CONCLUSIONS
The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.
Topics: Humans; Sucralfate; Hemorrhoids; Female; Suppositories; Male; Middle Aged; Ointments; Prospective Studies; Treatment Outcome; Patient Satisfaction; Adult; Aged; Administration, Rectal
PubMed: 38750150
DOI: 10.1007/s00384-024-04642-7 -
La Tunisie Medicale Apr 2024Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. (Review)
Review
INTRODUCTION
Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab.
AIM
Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab.
METHODS
A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded.
RESULTS
Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated.
CONCLUSION
Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.
Topics: Humans; Crohn Disease; Rectal Fistula; Infliximab; Treatment Failure; Gastrointestinal Agents
PubMed: 38746955
DOI: 10.62438/tunismed.v102i4.4699 -
Stem Cell Research & Therapy May 2024Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of...
A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.
BACKGROUND
Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.
METHODS
An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.
RESULTS
Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.
CONCLUSIONS
Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.
TRIAL REGISTRATION
The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .
Topics: Humans; Crohn Disease; Male; Adult; Female; Mesenchymal Stem Cell Transplantation; Rectal Fistula; Mesenchymal Stem Cells; Young Adult; Transplantation, Homologous; Adolescent; Middle Aged; Magnetic Resonance Imaging; Treatment Outcome; Quality of Life
PubMed: 38745184
DOI: 10.1186/s13287-024-03746-9 -
American Journal of Veterinary Research May 2024This study aimed to compare the effects of low-dose subarachnoid injections of 2% lidocaine (LIDO) and 0.5% bupivacaine (BUPI) in goats.
OBJECTIVE
This study aimed to compare the effects of low-dose subarachnoid injections of 2% lidocaine (LIDO) and 0.5% bupivacaine (BUPI) in goats.
ANIMALS
6 healthy, privately owned female goats.
METHODS
In this randomized blind crossover clinical trial, each goat received 0.05 mL/kg-1 of LIDO, BUPI, or sterile saline solution into the lumbosacral subarachnoid space, with a seven-day washout. Cardiorespiratory variables, rectal temperature, and somatosensory (pinprick) and motor (ataxia) functions were recorded at baseline (time 0) and 2, 5, 10, 15, and 30 minutes after injection, then every 20 minutes until the goat was standing and able to walk. Time to regain somatosensory and motor functions was compared between treatments using Kaplan-Meier survival curves and the Cox proportional hazards model. Linear mixed-effects models were used to compare cardiorespiratory variables between treatments and over time. A P value ≤ .05 was considered significant.
RESULTS
Somatosensory recovery was longer with BUPI, though not statistically significant. The median time to stand was 50 (50, 67) minutes after LIDO injection and 104 (101, 156) minutes after BUPI injection (P = .031). The median time to walk was 72 (54, 85) minutes after LIDO versus 225 (220, 245) minutes after BUPI injection (P = .031). Cardiovascular and respiratory variables showed no significant differences between treatments.
CLINICAL RELEVANCE
Despite prolonged ataxia with BUPI, pinprick sensation recovery did not differ. At reduced doses, both LIDO and BUPI are deemed acceptable for short procedures of the flank, pelvic limb, or tail in healthy goats.
PubMed: 38744307
DOI: 10.2460/ajvr.24.02.0030 -
American Journal of Cancer Research 2024Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including...
Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including colorectal carcinoma (CRC), yet the concomitant radiation-induced colorectal fibrosis (RICF) has caused chronic toxicity and stenosis in the colorectal mucosa of patients. Mesenchymal stem/stromal cells (MSCs) with unique bidirectional immunoregulation and anti-fibrotic effect have been recognized as splendid sources for regenerative purposes including intestinal diseases. Herein, we are aiming to verify the feasibility and variations of MSC-based cytotherapy for the remission of RICF from the pathological features and the potential impact upon the transcriptomic signatures of RICF rats. For the purpose, we utilized our well-established RICF Sprague-Dawley (SD) rats by radiation for five weeks, and conducted consecutive intraperitoneal injection of two distinct MSCs for treatment, including MSCs derived from adult adipose tissue (AD-MSCs) and perinatal umbilical cord (UC-MSCs). On the one hand, the efficacy of AD-MSCs and UC-MSCs was assessed by diverse indicators, including weight change, pathological detections (e.g., H&E staining, Masson staining, EVG staining, IF staining, and IHC staining), and proinflammatory and fibrotic factor expression. On the other hand, we turned to RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses (e.g., GOBP, Venn Map, KEGG, and GSEA) to compare the impact of AD-MSC and UC-MSC treatment upon the gene expression profiling and genetic variations. RICF rats after consecutive AD-MSC and UC-MSC administration revealed comparable remission in histopathogenic features and significant suppression of diverse proinflammatory and fibrotic factors expression. Meanwhile, RICF rats after both MSC treatment revealed decrease and variations in the alterations in diverse gene expression and somatic mutations compared to RICF rats. Collectively, our data indicated the comparable therapeutic effect of AD-MSCs and UC-MSCs upon RICF in SD rats, together with the conservations in gene expression profiling and the diverse variations in genetic mutations. Our findings indicated the multifaceted impact of MSC infusion for the supervision of RICF both at the therapeutic and transcriptomic levels, which would provide novel references for the further evaluation and development of MSC-based regimens in future.
PubMed: 38726273
DOI: 10.62347/DRAE5818 -
Journal of Medical Case Reports May 2024Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP...
BACKGROUND
Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy.
CASE PRESENTATION
A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect.
CONCLUSIONS
M-B enema and suppository may be an effective treatment for chronic RP.
Topics: Humans; Male; Proctitis; Aged; Enema; Metformin; Prostatic Neoplasms; Radiation Injuries; Chronic Disease; Treatment Outcome; Butyrates; Gastrointestinal Hemorrhage; Suppositories
PubMed: 38725071
DOI: 10.1186/s13256-024-04551-x -
BMJ Open May 2024Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the...
Perfusion outcomes with near-infrared indocyanine green imaging system in laparoscopic total mesorectal excision for mid-rectal or low-rectal cancer (POSTER): a study protocol.
INTRODUCTION
Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the extravasation of intestinal contents into the intra-abdominal or pelvic cavity. It is a serious complication of rectal cancer surgery, accounting for a considerable increase in morbidity and mortality. The use of fluorescence imaging technology in surgery allows surgeons to better evaluate blood perfusion. However, the conclusions of some existing studies are not consistent, so a consensus on whether the near-infrared indocyanine green (NIR-ICG) imaging system can reduce the incidence of AL is needed.
METHODS
This POSTER trial is designed as a multicentre, prospective, randomised controlled clinical study adhering to the "population, interventions, comparisons, outcomes (PICO)" principles. It is scheduled to take place from August 2019 to December 2024 across eight esteemed hospitals in China. The target population consists of patients diagnosed with rectal cancer through pathological confirmation, with tumours located≤10 cm from the anal verge, eligible for laparoscopic surgery. Enrolled patients will be randomly assigned to either the intervention group or the control group. The intervention group will receive intravenous injections of ICG twice, with intraoperative assessment of anastomotic blood flow using the near-infrared NIR-ICG system during total mesorectal excision (TME) surgery. Conversely, the control group will undergo conventional TME surgery without the use of the NIR-ICG system. A 30-day follow-up period postoperation will be conducted to monitor and evaluate occurrences of AL. The primary endpoint of this study is the incidence of AL within 30 days postsurgery in both groups. The primary outcome investigators will be blinded to the application of ICG angiography. Based on prior literature, we hypothesise an AL rate of 10.3% in the control group and 3% in the experimental group for this study. With a planned ratio of 2:1 between the number of cases in the experimental and control groups, and an expected 20% lost-to-follow-up rate, the initial estimated sample size for this study is 712, comprising 474 in the experimental group and 238 in the control group.
ETHICS AND DISSEMINATION
This study has been approved by Ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2019-P2-055-02). The results will be disseminated in major international conferences and peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT04012645.
Topics: Humans; Indocyanine Green; Rectal Neoplasms; Laparoscopy; Prospective Studies; Anastomotic Leak; Coloring Agents; Female; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Male; China; Spectroscopy, Near-Infrared; Adult; Middle Aged
PubMed: 38724058
DOI: 10.1136/bmjopen-2023-079858 -
IDCases 2024Helicobacter cinaedi, a gram-negative spiral bacterium, has historically been associated with infections primarily in immunocompromised patients. Recently, however, its...
Helicobacter cinaedi, a gram-negative spiral bacterium, has historically been associated with infections primarily in immunocompromised patients. Recently, however, its potential to cause infections in immunocompetent individuals has been recognized. We report a unique case of a man in his 20 s who reported having sex with men. He presented with symptoms of fever and throat discomfort and was diagnosed with a peritonsillar abscess. While the rapid antigen test for Group A Streptococcus was positive and antibiotics were administered, a puncture fluid from the peritonsillar abscess taken the day after antibiotic treatment revealed the presence of Group C Streptococcus. By the fifth day, the blood culture taken on the first day detected a gram-negative spirochete, which was subsequently identified H. cinaedi. The patient had engaged in oral sex with his male partner, suggesting a potential transmission route. This is significant as H. cinaedi was initially identified from rectal cultures in men who have sex with men (MSM), raising the possibility of pharyngeal transmission through oral sex. In our patient, although H. cinaedi was not isolated from the aspirate of the peritonsillar abscess, its presence in the blood culture and lack of other potential sources of bacteremia make the abscess a likely primary site of infection. This case highlights the importance of considering H. cinaedi as a potential pathogen in immunocompetent patients, particularly in cases of MSM. The potential for H. cinaedi transmission through oral sex and its role in the development of peritonsillar abscesses, a previously unreported association, requires further investigation.
PubMed: 38721054
DOI: 10.1016/j.idcr.2024.e01975 -
The Journal of Pharmacology and... May 2024Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal...
Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal chemoreceptors and mechanoreceptors and are involved in various rectal hypersensitivity disorders with common features of colorectal overactivity. These stimulatory properties of TRPV1 receptors on colorectal function suggested that brief stimulation of TRPV1 might provide a means of pharmacologically activating the colorectum to induce defecation in patients with an "unresponsive" colorectum. The current studies explored the basic features of TRPV1 receptor-induced contractions of the colorectum in anesthetized rats with and without acute spinal cord injury (aSCI). Cumulative concentration-response curves to intrarectal (IR) capsaicin (CAP) solutions (0.003% to 3.0%) were performed in anesthetized aSCI and spinal intact rats. CAP produced an "inverted U", cumulative concentration-response curve with a threshold for inducing colorectal contractions at 0.01% and a peak response at 0.1% and slight decreases in responses up to 3%. Decreases in responses with concentrations > 0.1% are due to a rapid desensitization (i.e. 30 min) of TRPV1 receptors to each successive dose. Desensitization appeared fully recovered within 24 hours in spinal intact rats. Colorectal contractions were completely blocked by atropine, indicating a reflexogenic activation of parasympathetic neurons, and responses were completely unaffected by a neurokinin 2 receptor antagonist, indicating that release of neurokinin A (NKA) from afferent terminals and subsequent direct contractions of the smooth muscle was not involved. IR administration of 3 other TRPV1 receptor agonists produced similar results as CAP. Individuals with spinal cord injury often lose control of defecation. Time consuming and inconvenient bowel programs using digital stimulation of the rectum and manual extraction of stool are used to empty the bowel. We show that intrarectal administration of the TRPV1 receptor agonist, capsaicin, can induce rapid onset, short duration colorectal contractions capable of inducing defecation in spinal cord injured and intact rats. Therefore, TRPV1 agonists show promise as a potential therapeutics to induce defecation in individuals with neurogenic bowel.
PubMed: 38719479
DOI: 10.1124/jpet.123.001989 -
PLoS Medicine May 2024Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting.
METHODS AND FINDINGS
The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability.
CONCLUSIONS
In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored.
TRIAL REGISTRATION
NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.
Topics: Humans; Azithromycin; Niger; Child, Preschool; Anti-Bacterial Agents; Infant; Female; Drug Resistance, Bacterial; Male; Macrolides; Mass Drug Administration; Child Mortality
PubMed: 38709718
DOI: 10.1371/journal.pmed.1004386