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Scientific Reports Sep 2023Colonoscopy is considered the standard procedure for early detection and prevention of colorectal cancer. Adequate bowel cleansing is an important determinant of the... (Randomized Controlled Trial)
Randomized Controlled Trial
Colonoscopy is considered the standard procedure for early detection and prevention of colorectal cancer. Adequate bowel cleansing is an important determinant of the efficacy of colonoscopy screening. Currently, there is no standard method of bowel preparation for patients with chronic constipation. The aim was to access the rate of adequate bowel cleansing achieved using split-dose polyethylene glycol electrolyte lavage solution (PEG-ELS) plus lubiprostone in comparison with split-dose PEG-ELS alone. A single-centre, endoscopist-blinded, randomized controlled trial was conducted. Seventy-eight constipated patients aged 18-75 years who were indicated for colonoscopy in the gastroenterology unit of Srinagarind Hospital, Khon Kaen University, between February 2020 and February 2021 were randomly allocated to receive either split-dose PEG-ELS in combination with lubiprostone (N = 39) or split-dose PEG-ELS alone (N = 39) before colonoscopy. Adequate bowel cleansing was defined as an Ottawa bowel preparation score ≤ 7. The rate of adequate bowel cleansing was comparable between the PEG-ELS plus lubiprostone group and the PEG-ELS alone group (50% vs. 52.9%, p value = 0.81) with a relative risk of 1.13 (95% CI = 0.43-2.91). There were no significant differences in adenoma detection rate (41.2% vs. 35.3%, p value = 0.62), adverse events, acceptance, compliance, or patient satisfaction between the 2 groups. No additional benefit to successful bowel preparation was achieved by the combination of lubiprostone and PEG-ELS in chronic constipation patients undergoing colonoscopy.
Topics: Humans; Lubiprostone; Polyethylene Glycols; Therapeutic Irrigation; Thailand; Constipation; Colonoscopy; Electrolytes
PubMed: 37759079
DOI: 10.1038/s41598-023-43598-6 -
Journal of Cerebral Blood Flow and... Dec 2023Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing... (Randomized Controlled Trial)
Randomized Controlled Trial
Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14-28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1-61.3) in the CL2020 group and 10.0% (0.3-44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke.Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103).
Topics: Humans; Ischemic Stroke; Alprostadil; Stroke; Double-Blind Method; Treatment Outcome; Brain Ischemia
PubMed: 37756573
DOI: 10.1177/0271678X231202594 -
Academic Radiology Mar 2024To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic...
RATIONALE AND OBJECTIVES
To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is feasible for staging Crohn's disease (CD) activity.
MATERIALS AND METHODS
A total of 65 CD patients were enrolled and analyzed in this retrospective study. The simplified endoscopic score for Crohn's disease (SES-CD) and magnetic resonance index of activity (MaRIA) were used as the reference. The MUSE-IVIM and DCE-MRI data were acquired at 3.0-T MRI scanner and processed by two radiologists. Three MUSE-IVIM parameters: fast apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (ADC), and the fractional perfusion (Fraction of ADC), as well as four DCE-MRI parameters: volume transfer constant (K), rate constant (K), extravascular extracellular volume fraction (V), and plasma volume fraction (V) were generated. Intraclass correlation coefficient (ICC), non-parametric test (Kruskal-Wallis H and Mann-Whitney U), logistic regression, receiver operating characteristic analysis, Delong test, and Spearman's correlation test were performed.
RESULTS
According to SES-CD, 116 ileocolonic segments with CD lesions were identified as: inactive, mild, and moderate to severe. With multivariable logistic regression analysis, ADC (p < 0.001), Fraction of ADC (p = 0.005), K (p < 0.001) and K (p = 0.003) were identified as significant factors for differentiating among the three groups. Binary logistic analyses identified ADC (p = 0.001), K (p = 0.014), and K (p = 0.029) as independent predictors for the active status. The combination of ADC, K, and K performed better than MaRIA score (p = 0.028), for differentiating inactive and active status. MaRIA score was positively correlated with ADC (p < 0.001), K (p < 0.001), K (p < 0.001), and V (p = 0.001), however, negatively correlated with Fraction of ADC (p < 0.001).
CONCLUSION
The combination of MUSE-IVIM and DCE-MRI has been demonstrated to accurately stage inflammatory activity in CD.
Topics: Humans; Alprostadil; Multiparametric Magnetic Resonance Imaging; Crohn Disease; Retrospective Studies; Contrast Media; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 37730492
DOI: 10.1016/j.acra.2023.08.028 -
Plastic and Reconstructive Surgery.... Sep 2023Hematoma-induced vasospasm is a significant factor that can compromise the success of flap reconstructive surgery. Despite advances in microsurgical techniques and...
Hematoma-induced vasospasm is a significant factor that can compromise the success of flap reconstructive surgery. Despite advances in microsurgical techniques and knowledge, vasospasm remains a direct cause of flap loss. Hematoma-induced vasospasm occurs due to the presence of blood breakdown products, which can lead to arterial constriction and reduced blood flow to the transplanted tissue. A 77-year-old man with a history of coronary angina developed soft tissue sarcoma on the right groin. Postoperative hematoma-induced vasospasm occurred subsequent to the reconstruction using a pedicled anterolateral thigh flap for the defect after wide resection. The hematoma was evacuated, and blood flow to the flap was restored with topical application of warm saline and vasodilators. Postoperative administration of intravenous alprostadil was used to counteract the vasospasm, and the flap completely survived without any problems with blood flow. It is important to recognize the triggers of vasospasm, such as hematomas, which may occur intra- or postoperatively, and to take appropriate measures to prevent or treat them. Treatment of vasospasm includes the intraoperative topical application of warm saline or vasodilators and the administration of intravenous alprostadil or 4% lidocaine postoperatively. Nevertheless, in the case of hematoma-induced vasospasm, it is important to remove the hematoma.
PubMed: 37711725
DOI: 10.1097/GOX.0000000000005271 -
Scientific Reports Sep 2023Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ...
Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic-ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 10 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.
Topics: Humans; Animals; Rats; Animals, Newborn; Alprostadil; Hypoxia-Ischemia, Brain; Hypoxia; Excipients; Brain Injuries
PubMed: 37696826
DOI: 10.1038/s41598-023-41026-3 -
Stem Cell Research & Therapy Aug 2023Human multilineage-differentiating stress enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be easily obtained from various adult...
BACKGROUND
Human multilineage-differentiating stress enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be easily obtained from various adult or fetal tissues. Regenerative effects of Muse cells have been shown in some disease models. Muse cells specifically home in damaged tissues where they exert pleiotropic effects. Exposition of the small intestine to high doses of irradiation (IR) delivered after radiotherapy or nuclear accident results in a lethal gastrointestinal syndrome (GIS) characterized by acute loss of intestinal stem cells, impaired epithelial regeneration and subsequent loss of the mucosal barrier resulting in sepsis and death. To date, there is no effective medical treatment for GIS. Here, we investigate whether Muse cells can prevent lethal GIS and study how they act on intestinal stem cell microenvironment to promote intestinal regeneration.
METHODS
Human Muse cells from Wharton's jelly matrix of umbilical cord (WJ-Muse) were sorted by flow cytometry using the SSEA-3 marker, characterized and compared to bone-marrow derived Muse cells (BM-Muse). Under gas anesthesia, GIS mice were treated or not through an intravenous retro-orbital injection of 50,000 WJ-Muse, freshly isolated or cryopreserved, shortly after an 18 Gy-abdominal IR. No immunosuppressant was delivered to the mice. Mice were euthanized either 24 h post-IR to assess early small intestine tissue response, or 7 days post-IR to assess any regenerative response. Mouse survival, histological stainings, apoptosis and cell proliferation were studied and measurement of cytokines, recruitment of immune cells and barrier functional assay were performed.
RESULTS
Injection of WJ-Muse shortly after abdominal IR highly improved mouse survival as a result of a rapid regeneration of intestinal epithelium with the rescue of the impaired epithelial barrier. In small intestine of Muse-treated mice, an early enhanced secretion of IL-6 and MCP-1 cytokines was observed associated with (1) recruitment of monocytes/M2-like macrophages and (2) proliferation of Paneth cells through activation of the IL-6/Stat3 pathway.
CONCLUSION
Our findings indicate that a single injection of a small quantity of WJ-Muse may be a new and easy therapeutic strategy for treating lethal GIS.
Topics: Adult; Mice; Humans; Animals; Cell Differentiation; Alprostadil; Mesenchymal Stem Cells; Interleukin-6; Intestines
PubMed: 37568164
DOI: 10.1186/s13287-023-03425-1 -
Biomolecules Jul 2023Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets...
Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist), or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen and sedimented in multiwell plates, and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, prolonged the lag phase and decreased the maximum rate of plasma clotting and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.
Topics: Humans; Platelet Aggregation Inhibitors; Blood Platelets; Ticagrelor; Thrombin; Alprostadil; Blood Coagulation; Aspirin; Fibrin; Collagen
PubMed: 37509160
DOI: 10.3390/biom13071124 -
Cells Jun 2023Stem cell transplantation has recently demonstrated a significant therapeutic efficacy in various diseases. Multilineage-differentiating stress-enduring (Muse) cells are... (Review)
Review
Stem cell transplantation has recently demonstrated a significant therapeutic efficacy in various diseases. Multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant endogenous pluripotent stem cells that were first reported in 2010. Muse cells can be found in the peripheral blood, bone marrow and connective tissue of nearly all body organs. Under basal conditions, they constantly move from the bone marrow to peripheral blood to supply various body organs. However, this rate greatly changes even within the same individual based on physical status and the presence of injury or illness. Muse cells can differentiate into all three-germ-layers, producing tissue-compatible cells with few errors, minimal immune rejection and without forming teratomas. They can also endure hostile environments, supporting their survival in damaged/injured tissues. Additionally, Muse cells express receptors for sphingosine-1-phosphate (S1P), which is a protein produced by damaged/injured tissues. Through the S1P-S1PR2 axis, circulating Muse cells can preferentially migrate to damaged sites following transplantation. In addition, Muse cells possess a unique immune privilege system, facilitating their use without the need for long-term immunosuppressant treatment or human leucocyte antigen matching. Moreover, they exhibit anti-inflammatory, anti-apoptotic and tissue-protective effects. These characteristics circumvent all challenges experienced with mesenchymal stem cells and induced pluripotent stem cells and encourage the wide application of Muse cells in clinical practice. Indeed, Muse cells have the potential to break through the limitations of current cell-based therapies, and many clinical trials have been conducted, applying intravenously administered Muse cells in stroke, myocardial infarction, neurological disorders and acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection. Herein, we aim to highlight the unique biological properties of Muse cells and to elucidate the advantageous difference between Muse cells and other types of stem cells. Finally, we shed light on their current therapeutic applications and the major obstacles to their clinical implementation from laboratory to clinic.
Topics: Humans; Cell Differentiation; Alprostadil; COVID-19; SARS-CoV-2; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 37443710
DOI: 10.3390/cells12131676 -
BMJ Open Jun 2023Individuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing...
Use of a targeted, computer/web-based guided self-help psychoeducation toolkit for distressing hallucinations (MUSE) in people with an at-risk mental state for psychosis: protocol for a randomised controlled feasibility trial.
INTRODUCTION
Individuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing Unusual Sensory Experiences (MUSE) treatment is a brief symptom targeted intervention that draws on psychological explanations to help account for unusual experiences. Practitioners use formulation and behavioural experiments to support individuals to make sense of their experiences and enhance coping strategies. The primary objective of this feasibility trial is to resolve key uncertainties before a definitive trial and inform parameters of a future fully powered trial.
METHODS AND ANALYSIS
88 participants aged 14-35 accepted into ARMS services, experiencing hallucinations/unusual sensory experiences which are considered by the patient to be a key target problem will be recruited from UK National Health Service (NHS) sites and randomised using 1:1 allocation (stratified by site, gender, and age) to either 6-8 sessions of MUSE or time-matched treatment as usual. Participants and therapists will be unblinded, research assessors are blinded. Blinded assessment will occur at baseline, 12 weeks and 20 weeks postrandomisation. Data will be reported in line with Consolidated Standards of Reporting Trials. Primary trial outcomes are feasibility outcomes, primary participant outcomes are functioning and hallucinations. Additional analysis will investigate potential psychological mechanisms and secondary mental well-being outcomes. Trial progression criteria follows signal of efficacy and uses an analytical framework with a traffic-light system to determine viability of a future trial. Subsequent analysis of the NHS England Mental Health Services Data Set 3 years postrandomisation will assess long-term transition to psychosis.
ETHICS AND DISSEMINATION
This trial has received Research Ethics Committee approval (Newcastle North Tyneside 1 REC; 23/NE/0032). Participants provide written informed consent; young people provide assent with parental consent. Dissemination will be to ARMS Services, participants, public and patient forums, peer-reviewed publications and conferences.
TRIAL REGISTRATION NUMBER
ISRCTN58558617.
Topics: Humans; Adolescent; Alprostadil; State Medicine; Feasibility Studies; Treatment Outcome; Psychotic Disorders; Hallucinations; Computers; Internet; Randomized Controlled Trials as Topic
PubMed: 37399435
DOI: 10.1136/bmjopen-2023-076101