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Advanced Science (Weinheim,... Nov 2023Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells...
Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSC EVs) is developed to treat IBD. The MSC EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSC EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSC EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSC EVs-loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSC EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.
Topics: Rats; Animals; Interleukin-27; Extracellular Vesicles; Anti-Inflammatory Agents; Inflammatory Bowel Diseases; Mesenchymal Stem Cells
PubMed: 37759399
DOI: 10.1002/advs.202303349 -
Antimicrobial Resistance and Infection... Nov 2023Vancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk...
BACKGROUND
Vancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group.
METHODS
A retrospective, single center, case-control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (≥ 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization.
RESULTS
A total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively).
CONCLUSIONS
Antimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches.
Topics: Humans; Vancomycin; Case-Control Studies; Retrospective Studies; Gram-Positive Bacterial Infections; Vancomycin Resistance; Risk Factors; Vancomycin-Resistant Enterococci; Hospitals; Cross Infection
PubMed: 37957773
DOI: 10.1186/s13756-023-01332-x -
BMJ Open Gastroenterology Jan 2024Mpox is a viral infection caused by the monkeypox virus, a member of the Poxviridae family and Orthopoxvirus genus. Other well-known viruses of the Orthopoxvirus genus...
INTRODUCTION
Mpox is a viral infection caused by the monkeypox virus, a member of the Poxviridae family and Orthopoxvirus genus. Other well-known viruses of the Orthopoxvirus genus include the variola virus (smallpox), cowpox virus and vaccinia virus. Although there is a plethora of research regarding the dermatological and influenza-like symptoms of mpox, particularly following the 2022 mpox outbreak, more research is needed on the gastrointestinal (GI) effects.
OBJECTIVES
This systematic review is to outline the GI manifestations of the monkeypox virus.
METHODS
The authors conducted this systematic review using guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A search was conducted through the PubMed, EMBASE and MEDLINE databases from January 1958 to June 2023. The authors selected English language papers that discussed the GI symptoms in mpox patients. A manual search was also conducted in the reference sections of these publications for other relevant papers.
RESULTS
33 papers involving 830 patients were selected for this review. The GI manifestations in mpox patients are proctitis, vomiting, diarrhoea, rectal pain, nausea, tenesmus, rectal bleeding and abdominal pain. Although various papers explored transmission routes, one paper established a direct connection between anal-receptive sex transmission route and the development of a GI complication (proctitis). Another study reported that the mode of transmission could potentially impact the occurrence of GI symptoms and severity of the disease. The reviewed papers did not discover a relation between the severity of dermatological and influenza-like symptoms and the GI manifestations mentioned.
CONCLUSION
This systematic review confirms that GI manifestations are observed in mpox patients. GI symptoms of mpox are crucial for gastroenterologists and other healthcare professionals to recognise in order to address patient discomfort and further understand the pathophysiology of the virus.
Topics: Humans; Gastrointestinal Hemorrhage; Mpox (monkeypox); Proctitis; Vomiting
PubMed: 38184298
DOI: 10.1136/bmjgast-2023-001266 -
Journal of Traditional Chinese Medicine... Oct 2023In the study of the mechanism of wound healing after anal fistula surgery, how to scientifically and efficiently promote wound healing is of great significance. At...
In the study of the mechanism of wound healing after anal fistula surgery, how to scientifically and efficiently promote wound healing is of great significance. At present, modern medical treatment of wounds after anal fistula surgery mostly focuses on physical therapy intervention, new wound dressing and packing, and external application of growth factors. However, these therapies have many problems, and there is still no consensus on their clinical use. Traditional Chinese Medicine (TCM) has several methods to promote wound healing, such as oral administration, rubbing, and fumigation, which have a long history and obvious efficacy, but research in this area is relatively scattered and lacks classification and summarizing. Therefore, this paper analyzes and summarizes the existing research on TCM for promotion of wound healing after anal fistula surgery, carries out targeted analyses according to different clinical syndromes and treatment methods, and analyzes the defects in current research and anticipates future research trends in order to provide theoretical support for the advantages of TCM in promoting wound healing after anal fistula surgery.
Topics: Humans; Medicine, Chinese Traditional; Administration, Oral; Wound Healing; Rectal Fistula
PubMed: 37679994
DOI: 10.19852/j.cnki.jtcm.20230630.002 -
World Journal of Surgical Oncology Jul 2023To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging.
METHODS
PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies.
RESULTS
This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study.
CONCLUSIONS
For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.
Topics: Humans; Metformin; Neoadjuvant Therapy; Chemoradiotherapy; Rectal Neoplasms; Diabetes Mellitus; Treatment Outcome
PubMed: 37491250
DOI: 10.1186/s12957-023-03087-6 -
Clinical Gastroenterology and... Oct 2023Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely... (Review)
Review
BACKGROUND & AIMS
Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings.
METHODS
Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations.
RESULTS
ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices.
CONCLUSIONS
Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.
Topics: Humans; Fecal Incontinence; Defecation; Quality of Life; Manometry; Constipation; Rectum; Rectal Diseases; Anal Canal; Biofeedback, Psychology
PubMed: 37302444
DOI: 10.1016/j.cgh.2023.05.025 -
The Journal of Pharmacology and... Apr 2024One cannot survive without regularly urinating and defecating. People with neurological injury (spinal cord injury, traumatic brain injury, stroke) or disease (multiple...
One cannot survive without regularly urinating and defecating. People with neurological injury (spinal cord injury, traumatic brain injury, stroke) or disease (multiple sclerosis, Parkinson's disease, spina bifida) and many elderly are unable to voluntarily initiate voiding. The great majority of them require bladder catheters to void urine and "manual bowel programs" with digital rectal stimulation and manual extraction to void stool. Catheter-associated urinary tract infections frequently require hospitalization, while manual bowel programs are time-consuming (1-2 hours), stigmatizing, and cause rectal pain and discomfort. Laxatives and enemas produce defecation, but onset and duration are unpredictable, prolonged, and difficult to control, which can produce involuntary defecation and fecal incontinence. Patients with spinal cord injury (SCI) consider recovery of bladder and bowel function a higher priority than recovery of walking. Bladder and bowel dysfunction are a top reason for institutionalization of elderly. Surveys indicate that convenience, rapid onset and short duration, reliability and predictability, and efficient voiding are priorities of SCI individuals. Despite the severe, unmet, medical need; there is no literature regarding on-demand, rapid-onset, short-duration, drug-induced, voiding therapies. This article provides in depth discussion of recent discovery and development of two candidates for on-demand voiding therapies. The first, DTI-117, a neurokinin receptor agonist, induces both urination and defecation after systemic administration. The second, DTI-301, is a TRPV1 receptor agonist that induces defecation after intrarectal administration. The review also presents clinical studies of a combination drug therapy administered via iontophoresis and preclinical studies of neuromodulation devices that induce urination and defecation. Safe, effective, on-demand, rapid-onset, short-duration, drug-induced, voiding therapy could eliminate or reduce need for bladder catheters, manual bowel programs, and colostomies in patient populations that are unable to voluntarily initiate voiding. People with spinal injury place more importance on restoring bladder and bowel control than restoring their ability to walk. This paradigm-changing therapy would reduce stigmatism and healthcare costs while increasing convenience and quality of life.
PubMed: 38641354
DOI: 10.1124/jpet.123.002073 -
The Cochrane Database of Systematic... Dec 2023Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory... (Review)
Review
BACKGROUND
Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs), specifically cyclo-oxygenase (COX) inhibitors such as diclofenac, can be used to treat pain and reduce inflammation. There is uncertainty regarding diclofenac's benefits and harms compared to placebo or other drugs for postoperative pain.
OBJECTIVES
To assess the efficacy and safety of diclofenac (any dose) for acute postoperative pain management in children compared with placebo, other active comparators, or diclofenac administered by different routes (e.g. oral, rectal, etc.) or strategies (e.g. 'as needed' versus 'as scheduled').
SEARCH METHODS
We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, and trial registries on 11 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in children under 18 years of age undergoing surgery that compared diclofenac (delivered in any dose and route) to placebo or any active pharmacological intervention. We included RCTs comparing different administration routes of diclofenac and different strategies.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were: pain relief (PR) reported by the child, defined as the proportion of children reporting 50% or better postoperative pain relief; pain intensity (PI) reported by the child; adverse events (AEs); and serious adverse events (SAEs). We presented results using risk ratios (RR), mean differences (MD), and standardised mean differences (SMD), with the associated confidence intervals (CI).
MAIN RESULTS
We included 32 RCTs with 2250 children. All surgeries were done using general anaesthesia. Most studies (27) included children above age three. Only two studies had an overall low risk of bias; 30 had an unclear or high risk of bias in one or several domains. Diclofenac versus placebo (three studies) None of the included studies reported on PR or PI. We are very uncertain about the benefits and harms of diclofenac versus placebo on nausea/vomiting (RR 0.83, 95% CI 0.38 to 1.80; 2 studies, 100 children) and any reported bleeding (RR 3.00, 95% CI 0.34 to 26.45; 2 studies, 100 children), both very low-certainty evidence. None of the included studies reported SAEs. Diclofenac versus opioids (seven studies) We are very uncertain if diclofenac reduces PI at 2 to 24 hours postoperatively compared to opioids (median pain intensity 0.3 (interquartile range (IQR) 0.0 to 2.5) for diclofenac versus median 0.7 (IQR 0.1 to 2.4) in the opioid group; 1 study, 50 children; very low-certainty evidence). None of the included studies reported on PR or PI for other time points. Diclofenac probably results in less nausea/vomiting compared to opioids (41.0% in opioids, 31.0% in diclofenac; RR 0.75, 95% CI 0.58 to 0.96; 7 studies, 463 participants), and probably increases any reported bleeding (5.4% in opioids, 16.5% in diclofenac; RR 3.06, 95% CI 1.31 to 7.13; 2 studies, 222 participants), both moderate-certainty evidence. None of the included studies reported SAEs. Diclofenac versus paracetamol (10 studies) None of the included studies assessed child-reported PR. Compared to paracetamol, we are very uncertain if diclofenac: reduces PI at 0 to 2 hours postoperatively (SMD -0.45, 95% CI -0.74 to -0.15; 2 studies, 180 children); reduces PI at 2 to 24 hours postoperatively (SMD -0.64, 95% CI -0.89 to -0.39; 3 studies, 300 children); reduces nausea/vomiting (RR 0.47, 95% CI 0.25 to 0.87; 5 studies, 348 children); reduces bleeding events (RR 0.57, 95% CI 0.12 to 2.62; 5 studies, 332 participants); or reduces SAEs (RR 0.50, 95% CI 0.05 to 5.22; 1 study, 60 children). The evidence certainty was very low for all outcomes. Diclofenac versus bupivacaine (five studies) None of the included studies reported on PR or PI. Compared to bupivacaine, we are very uncertain about the effect of diclofenac on nausea/vomiting (RR 1.28, 95% CI 0.58 to 2.78; 3 studies, 128 children) and SAEs (RR 4.52, 95% CI 0.23 to 88.38; 1 study, 38 children), both very low-certainty evidence. Diclofenac versus active pharmacological comparator (10 studies) We are very uncertain about the benefits and harms of diclofenac versus any other active pharmacological comparator (dexamethasone, pranoprofen, fluorometholone, oxybuprocaine, flurbiprofen, lignocaine), and for different routes and delivery of diclofenac, due to few and small studies, no reporting of key outcomes, and very low-certainty evidence for the reported outcomes. We are unable to draw any meaningful conclusions from the numerical results.
AUTHORS' CONCLUSIONS
We remain uncertain about the efficacy of diclofenac compared to placebo, active comparators, or by different routes of administration, for postoperative pain management in children. This is largely due to authors not reporting on clinically important outcomes; unclear reporting of the trials; or poor trial conduct reducing our confidence in the results. We remain uncertain about diclofenac's safety compared to placebo or active comparators, except for the comparison of diclofenac with opioids: diclofenac probably results in less nausea and vomiting compared with opioids, but more bleeding events. For healthcare providers managing postoperative pain, diclofenac is a COX inhibitor option, along with other pharmacological and non-pharmacological approaches. Healthcare providers should weigh the benefits and risks based on what is known of their respective pharmacological effects, rather than known efficacy. For surgical interventions in which bleeding or nausea and vomiting are a concern postoperatively, the risks of adverse events using opioids or diclofenac for managing pain should be considered.
Topics: Humans; Child; Adolescent; Diclofenac; Acetaminophen; Pain, Postoperative; Nausea; Vomiting; Analgesics, Opioid; Bupivacaine
PubMed: 38078559
DOI: 10.1002/14651858.CD015087.pub2 -
Brain, Behavior, and Immunity Aug 2023Inflammation and depressed mood constitute clinically relevant vulnerability factors for enhanced interoceptive sensitivity and chronic visceral pain, but their putative... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Inflammation and depressed mood constitute clinically relevant vulnerability factors for enhanced interoceptive sensitivity and chronic visceral pain, but their putative interaction remains untested in human mechanistic studies. We tested interaction effects of acute systemic inflammation and sad mood on the expectation and experience of visceral pain by combining experimental endotoxemia with a mood induction paradigm.
METHODS
The double-blind, placebo-controlled, balanced crossover fMRI-trial in N = 39 healthy male and female volunteers involved 2 study days with either intravenous administration of low-dose lipopolysaccharide (LPS, 0.4 ng/kg body weight; inflammation condition) or saline (placebo condition). On each study, day two scanning sessions were conducted in an experimentally induced negative (i.e., sad) and in a neutral mood state, accomplished in balanced order. As a model of visceral pain, rectal distensions were implemented, which were initially calibrated to be moderately painful. In all sessions, an identical series of visceral pain stimuli was accomplished, signaled by predictive visual conditioning cues to assess pain anticipation. We assessed neural activation during the expectation and experience of visceral pain, along with unpleasantness ratings in a condition combining an inflammatory state with sad mood and in control conditions. All statistical analyses were accomplished using sex as covariate.
RESULTS
LPS administration led to an acute systemic inflammatory response (inflammation X time interaction effects for TNF-α, IL-6, and sickness symptoms, all p <.001). The mood paradigm effectively induced distinct mood states (mood X time interaction, p <.001), with greater sadness in the negative mood conditions (both p <.001) but no difference between LPS and saline conditions. Significant main and interaction effects of inflammation and negative mood were observed for pain unpleasantness (all p <.05). During cued pain anticipation, a significant inflammation X mood interaction emerged for activation of the bilateral caudate nucleus and right hippocampus (all p < 0.05). Main effects of both inflammation and mood were observed in multiple regions, including insula, midcingulate cortex, prefrontal gyri, and hippocampus for inflammation, and midcingulate, caudate, and thalamus for mood (all p < 0.05).
CONCLUSIONS
Results support an interplay of inflammation and sad mood on striatal and hippocampal circuitry engaged during visceral pain anticipation as well as on pain experience. This may reflect a nocebo mechanism, which may contribute to altered perception and interpretation of bodily signals. At the interface of affective neuroscience and the gut-brain axis, concurrent inflammation and negative mood may be vulnerability factors for chronic visceral pain.
Topics: Female; Humans; Male; Affect; Brain; Healthy Volunteers; Inflammation; Lipopolysaccharides; Magnetic Resonance Imaging; Visceral Pain; Cross-Over Studies
PubMed: 37302437
DOI: 10.1016/j.bbi.2023.06.005 -
Annals of Surgical Treatment and... Nov 2023In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving... (Review)
Review
In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750-800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG's role, advantages, disadvantages, and potential clinical impact in colorectal surgery.
PubMed: 38023438
DOI: 10.4174/astr.2023.105.5.252