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2.4. General Procedure
During the 3 consecutive study days, participants were instructed to refrain from strenuous physical activity, to consume a standard dinner (100 g chicken, 50 g rice, 50 g white bread and one apple; 503 kcal, 7 g fat, 82 g carbohydrates, 30 g protein) the night before, to fast overnight and to eat a standard breakfast ...
PMC10221585
2.5. Interventions
PMC10221585
2.5.1. Probe Meal
hummus, digestive sensations
The probe meal consisted of 150 g low-fat hummus (219 Kcal; 12 g fat, 82 g carbohydrates, 13 g protein; Hummus Classic, Ametller Origen, Barcelona, Spain) served at a controlled temperature (20 °C), 20 g toasts (81 Kcal; 0.9 g fat, 15.2 g carbohydrates, 2.4 g protein; Mini Tostas, Bimbo, Barcelona, Spain) and 120 mL wa...
PMC10221585
2.5.2. Duodenal Infusion
bloating, nausea,, pain
Aversive conditioning (2nd study day in aversive conditioning group only) was produced by infusion of lipids (300 mg/mL purified soybean oil; Intralipid, Fresenius Kabi, Barcelona, Spain) into the duodenum via the nasoduodenal catheter. Lipids were continuously infused starting 3 min before, during and 60 min after ing...
PMC10221585
2.6. Outcomes
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2.6.1. Perception of Homeostatic and Hedonic Sensations
nausea, pain, fullness, abdominal bloating
Five 10-cm scales graded from −5 to +5 were used to measure: (a) meal wanting (impossible/eagerly), (b) meal liking (very disagreeable/very agreeable), (c) hunger/satiety (extremely hungry/completely satiated), (d) digestive well-being (extremely unpleasant sensation/extremely pleasant sensation) and (e) mood (negative...
PMC10221585
2.6.2. Physiological Parameters
The following physiological parameters were measured at 4 time points: before meal ingestion (baseline) and at the beginning, mid and end of the postprandial observation period (0 min, 30 min and 60 min after ingestion) (Gastric emptying was measured by ultrasonography, as previously described [Changes in abdominal gir...
PMC10221585
2.7. Statistical Analysis
Calculations were performed using SPSS Statistics for Windows (Version 25.0, IBM Corp, Armonk, NY, USA). A significance level of 5% (two tails) was used for comparisons. In each group, the means and standard errors of the measured variables were calculated. In each experiment, the effects of the intervention on sensati...
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3. Results
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3.1. Demographics
Participants were 30.9 ± 2.3 years of age (range 23–49 years), had a 21.3 ± 0.5 kg/m
PMC10221585
3.2. Responses to the Probe Meal before Conditioning (Study Day 1)
nausea, discomfort/pain
Pre-ingestion. Before the probe meal (baseline fasting period), subjects reported hunger, neutral digestive well-being and positive mood without the sensations of abdominal fullness/bloating, discomfort/pain or nausea (Ingestion phase. All participants ingested the meal at a fixed rate (12 min). Participants found the ...
PMC10221585
3.3. Effect of Aversive Stimulation (Study Day 2 vs. Day 1)
bloating, sensations, nausea, satiety
Pre-ingestion and ingestion phase. The sensations measured before and during meal ingestion on the second study day were not different from those on the first day in both groups (Postprandial phase. In the control group, sham infusion on the second study day did not modify the postprandial experience as compared to the...
PMC10221585
3.4. Effect of Conditioning (Study Day 3 vs. Day 1)
bloating, nausea
Pre-ingestion and ingestion phase. No significant differences were detected in the sensations measured before and during meal ingestion on the study day 3 as compared to day 1 in both groups (Postprandial phase. In the control group, sham conditioning (duodenal sham infusion on the previous day) did not modify the post...
PMC10221585
3.5. Physiological Parameters
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3.5.1. Responses to the Probe Meal before Conditioning (Study Day 1)
Ingestion of the probe meal was associated with gastric filling (increase in antral cross-sectional area) and abdominal accommodation (elevation of the diaphragm with limited increase in girth) (
PMC10221585
3.5.2. Effect of Aversive Stimulation (Study Day 2 vs. Day 1)
gastric retention
GASTRIC RETENTION
In the control group, sham infusion on the second study day had no effects on any of the physiological parameters as compared to the first study day. By contrast, in the test group, lipid infusion (effect measured as the change in the area under the curve in day 2 minus day 1 vs. sham infusion) was associated with gast...
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3.5.3. Effect of Conditioning (Study Day 3 vs. Day 1)
Neither aversive nor sham conditioning had consistent effects on the physiological response to meal ingestion (
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4. Discussion
digestive dysfunction
Our study shows that pairing a pleasant meal with an experimentally-induced aversive sensation conditions the postprandial response to subsequent consumption of the same meal. Interestingly, aversive conditioning impaired the hedonic experience without significant impacts on homeostatic sensations or the physiological ...
PMC10221585
5. Limitations
Our conditioning paradigm introduced a colour clue (coloured meal during and after conditioning versus non-coloured meal pre-conditioning), but we do not know whether conditioned postprandial dissatisfaction was selective to the colour or if it would also affect the non-coloured meal; indeed, other forms of conditionin...
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6. Conclusions and Inferences
obesity, dyspepsia, functional gut disorders, meal intolerance, diabetes
OBESITY, METABOLIC SYNDROME, HYPERCHOLESTEROLEMIA, DIABETES
Postprandial conditioning might have important implications and open relevant research avenues. Several conditions of great health impact, such as obesity, metabolic syndrome, diabetes or hypercholesterolemia, relate to consumption (or overconsumption) of specific foods, and in this context, aversive conditioning could...
PMC10221585
Author Contributions
A.N.: investigation, data curation, formal analysis, methodology, D.M.L.: conceptualisation (supporting), formal analysis (lead), investigation, methodology, visualisation, writing—draft preparation, F.A.: conceptualisation (lead), funding acquisition, methodology (lead), project administration, writing—review and edit...
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Institutional Review Board Statement
The clinical study was conducted according to the Declaration of Helsinki. The study protocol had previously been approved by the Institutional Review Board of the University Hospital Vall d’Hebron (Comitè d’Ètica d’Investigació Clinica, Vall d’Hebron Institut de Recerca; protocol number PR(AG)338/2016M approved 28 Oct...
PMC10221585
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
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Data Availability Statement
The data presented in this study will be shared upon reasonable request from the corresponding author.
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Conflicts of Interest
The authors declare no conflict of interest.
PMC10221585
References
DAY 3).Homeostatic sensations, nausea
BLIND, DELAYED GASTRIC EMPTYING
Experimental design and procedure. In a sham-controlled, parallel, randomised, blind study, a comfort meal was paired with duodenal lipid infusion to induce aversive conditioning (DAY 2) and the responses to the meal were compared before (DAY 1) and after conditioning (DAY 3).Homeostatic sensations. Concomitant duodena...
PMC10221585
Introduction and hypothesis
SUI
STRESS URINARY INCONTINENCE
The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients.
PMC10506953
Methods
ADVERSE EVENTS, PAD, INCONTINENCE
Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy wer...
PMC10506953
Results
SUI, dysuria
URINARY TRACT INFECTION
Ten female patients with SUI grades I–II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under...
PMC10506953
Conclusion
Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.
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Keywords
Open access funding provided by University of Zurich
PMC10506953
Introduction
urinary incontinence
URINARY INCONTINENCE
More than 400 million people worldwide suffer from urinary incontinence (UI), whereas the ratio between women and men is three to one [
PMC10506953
Patients and methods
PB_2017-00621) and Swissmedic (Ref.
We conducted a prospective and randomised phase I clinical trial using ultrasound-guided injections of autologous MPCs into the EUS. The aim of the study was to assess the safety and feasibility of this autologous cell therapy for the treatment of SUI in female patients. The local ethics committee (KEK-ZH-Nr. 2014-0547...
PMC10506953
Patient recruitment
RECRUITMENT
Initial recruitment was accomplished by specialist referral, online advertisements (study website
PMC10506953
Inclusion and exclusion criteria
neurological disease, incontinence, cystocele, prolapse, enuresis, DSD, fistula, urogenital cancer, acontractile detrusor, hypersensitivity, congenital abnormality
NEUROLOGICAL DISEASE, INCONTINENCE, URETHRAL STENOSIS, URINARY TRACT DISEASES, CYSTOCELE, PROLAPSE, ENURESIS, INCONTINENCE, PAD, MUSCULAR DISEASE, HYPERSENSITIVITY, DETRUSOR INSTABILITY
The main inclusion criteria were: female gender; age 20–60 years; a clinical diagnosis of SUI grade ≥I according to the Stamey classification for at least 6 months; and post-void residual (PVR) <100 ml.The main exclusion criteria were: a history of anti-incontinence or prolapse surgery; a previous diagnosis of urinary ...
PMC10506953
One-hour pad test
Continence
PAD
The testing protocol was accomplished according to the standardised International Continence Society 1-h pad test [
PMC10506953
Urodynamic study
Continence
URETHRA
The urodynamic study was performed according to the International Continence Society (ICS) standards. To conduct urodynamic investigations, a multichannel urodynamic system (Laborie Medical Technologies Corp., Toronto, Canada) was used. Patients were assessed in a sitting position. UDI comprised same-session repeat fil...
PMC10506953
Magnetic resonance imaging of the pelvis
tumour, necrosis
TUMOUR, NECROSIS
Magnetic resonance imaging of the pelvis was performed at a field strength of 3 Tesla (Siemens MAGNETOM Skyra, Siemens Healthineers, Erlangen, Germany) using standard high-resolution T2-weighted turbo spin echo sequences with and without fat suppression and T1-weighted turbo spin echo sequences. An 18 Ch body coil was ...
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Muscle biopsy
To obtain an appropriate muscle specimen for MPC isolation and expansion, an open surgical biopsy coming from a striated skeletal muscle was performed in analgosedation on either the left or the right lower leg in each of the patients. After weighing the muscle biopsy in a cooled Falcon tube containing biopsy medium, i...
PMC10506953
Cell isolation, expansion and final product
Manufacturing of the MPCs was performed according to GMP standards in the clean room facility of the Wyss Translational Center Zurich (manufacturer authorisation number 512701-102673231). The manufacturing process consisted of MPC isolation, MPC expansion and final product preparation, including strict in-process and p...
PMC10506953
Injection of MPCs
URETHRA
The injection was performed according to a standardised procedure under general anaesthesia and in full lithotomy position. Before starting the operation, the batch number from the GMP facility was double-checked with the patient’s study ID. After insertion of a vaginal ultrasound probe (BK Medical®, Endocavity 3D 8838...
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Follow-up visits
The first follow-up visit was on the first postoperative day. After removal of the catheter in the morning, patients were seen for a physical examination, uroflowmetry and ultrasound including PVR measurement. Further visits in the ambulatory setting were arranged 1, 3 and 6 months after the intervention. The follow-up...
PMC10506953
Neuromuscular electromagnetic stimulation
SUI, pain
After the injection, the study nurse unveiled the 1:1 randomisation to the two treatment groups of either MPC vs MPC + NMES. NMES included two sessions per week for 20 min for 6 weeks with a total of 12 sessions on a BioCon-2000W™ chair (Marly Products®, Germany). Patients used its predefined program for SUI and the pe...
PMC10506953
Primary and secondary outcomes
incontinence, necrosis
NECROSIS, INCONTINENCE, ABERRANT TISSUE, PAD, ADVERSE EVENT, LEAKAGE, URETHRA
To analyse the safety and feasibility of our therapy, primary outcomes were defined as any adverse event (AE) during the follow-up period. AEs were classified according to Clavien–Dindo grade I–V. Secondary outcomes were chosen as objective and subjective outcome parameters. Objective parameters were uroflowmetry, PVR ...
PMC10506953
Statistical analysis
The statistical analysis was outsourced to an independent company (Hemex AG, Liestal, Switzerland) and performed using
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Results
STERILITY
Ten female patients were included in the study, 9 of whom received treatment and completed all follow-up visits during the study period between January 2020 and September 2021. One patient had to be excluded in between muscle biopsy and injection owing to an erroneous interpretation of a supposedly contaminated sterili...
PMC10506953
Functional outcome parameters
No relevant PVR (<50ml) was documented with sonography at baseline and follow-up visits in all patients. Median MUCP at rest decreased from 91 cmHBaseline and follow-up visits compared.
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Pad use
PAD
At baseline, 2 patients reported using no pads during daily routine, whereas 6 patients reported using 1 pad/day, and 1 patient using 2 pads/day. At the 6-month follow-up, 1 out of the 6 patients who needed 1 pad/day reported no longer needing any pads, 5 patients still used 1 pad/day, and the patient who needed 2 pads...
PMC10506953
ICIQ-UI-SF questionnaires
The ICIQ-UI-SF questionnaires showed a statistically significant improvement in scores from a median of 7 points at baseline to a median of 4 points at 6 months’ follow-up (difference: −3 points, 95% CI: −7 to −2.5,
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MRI of the pelvis
tumour, necrosis
ABERRANT TISSUE, TUMOUR, NECROSIS
The evaluation of MRI of the pelvis revealed no evidence of aberrant tissue formation (i.e. tumour) or necrosis. The diameter of the EUS was measured with a statistically significantly larger median of 1.8 mm at baseline and 1.9 mm at follow-up (difference: +0.1 mm, 95% CI: 0.10 to 0.25, MRI of the pelvis with a T2-wei...
PMC10506953
Discussion
tumour, necrosis
PAD, TUMOUR, COMPLICATIONS, NECROSIS
Our phase I clinical trial demonstrates that the implantation of autologous MPCs in combination with or without NMES for the treatment of SUI grade ≥I in women is safe and feasible. Therapy was well tolerated by patients and no relevant or unexpected AEs and no need for consecutive surgical or interventional treatments...
PMC10506953
Conclusion
SEQUELAE
The transurethral ultrasound-guided injection of autologous MPCs into the EUS for the treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected AEs were documented, and all AEs were easily treatable and healed without sequelae. No severe or unexpected AEs were diagnosed...
PMC10506953
Acknowledgements
We thank Prof. Dr. K. Schallmoser (Paracelsus Medical University, Salzburg, Austria) and Prof. Dr. W. Aicher (University of Tübingen, Germany) for material supply and monitoring during the study. We thank the Wyss Translation Center Zurich for the usage of their clean rooms and their support while conducting the trial.
PMC10506953
Authors’ contributions
protocol/project
F.A.S.: protocol/project development, data collection and management, data analysis, manuscript writing and editing; J.A.P: protocol/project development, data collection and management, data analysis, manuscript writing and editing; M.K.: data collection, data analysis, manuscript editing; C.B.: data collection, manusc...
PMC10506953
Funding
Open access funding provided by University of Zurich This project has received funding from the European Union‘s Horizon 2020 research and innovation program under grant agreement No. 731377.
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Declarations
PMC10506953
Conflicts of interest
F.A.S., M.K., C.B., R.A.S., N.S., M.H., F.L., M.V., R.G., A.L., A.M.H., A.B.: none. The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: J.A.P., D.M.H. and D.E. own stocks in the company MUVON Therapeutics AG, aimed at further ...
PMC10506953
References
PMC10506953
Methods
NAFLD, liver stiffness, cirrhosis, virologically-suppressed HIV-1
LIVER FIBROSIS, CIRRHOSIS, RECRUITMENT
We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characte...
PMC10348519
Results
ADVERSE REACTION, TYPE 2 DIABETES MELLITUS
Fifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6–7.8) kPa, 325 (IQR 279–351) dB/m and 9.1 (IQR 8.6–9.6) respectively. Primary outcomes: all individuals eligible aft...
PMC10348519
Conclusions
hepatic steatosis, fibrosis
RECRUITMENT, HEPATIC STEATOSIS, FIBROSIS
This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis.
PMC10348519
Data Availability
Data are available within the publicly accessible University of Sussex Figshare DOI
PMC10348519
Introduction
NAFLD, inflammation, MVC, fibrosis
INFLAMMATION, SECONDARY, FIBROSIS, NON-ALCOHOLIC FATTY LIVER DISEASE
Non-alcoholic fatty liver disease (NAFLD), defined as fat accumulation in ≥5% of hepatocytes without a secondary cause, [Lifestyle changes, including physical activity and dietary modification, are the mainstay of therapy [Chemokine (C-C motif) ligand 5 (CCL5)/ Regulated upon Activation, Normal T cell Expressed and Sec...
PMC10348519
Materials and methods
PMC10348519
Study design and participants
WEST
This was a phase IV, open-label, dual, parallel arm, randomised, multi-centre, feasibility trial comparing MVC plus optimised background therapy (MVC+OBT) versus OBT alone in HIV-NAFLD over 96 weeks. The sites were hospitals in London (Barts, Chelsea and Westminster), the Midlands (Nottingham), North (Liverpool, South ...
PMC10348519
Randomisation
Participants were randomised 1:1 in accordance with a computer-generated randomization schedule using Sealed Envelope [
PMC10348519
Procedures
NAFLD, AIDS toxicity
INFECTIOUS DISEASES, ADVERSE EVENT, ALLERGY, LIVER FIBROSIS, CHRONIC LIVER DISEASE
MVC was prescribed twice daily at the licensed dose for HIV-1 therapy, adjusted according to co-medications according to the Summary of Product Characteristics. Participants attended every 24 weeks for 96 weeks plus a week 4 safety visit for those receiving maraviroc. All participants received advice on lifestyle and d...
PMC10348519
Outcome measures
ADVERSE REACTION, RECRUITMENT
The primary objective was to assess the safety, feasibility and acceptability of adding MVC to OBT in HIV-NAFLD. This was assessed through the following outcome measures and minimum target values to indicate feasibility: (1) proportion of eligible individuals who were recruited [target >50%] (2) monthly recruitment rat...
PMC10348519
Analyses
PMC10348519
Sample size
fibrosis
EVENT, FIBROSIS, CHRONIC LIVER DISEASE
This was a pilot study evaluating feasibility, with the intention that results would be used to estimate the variability of the treatment effect of MVC on the ELF score. This in turn would inform the sample size calculation for an RCT to evaluate drug efficacy. We based our sample size justification for this pilot stud...
PMC10348519
Statistical analyses
SECONDARY, RECRUITMENT
Reasons for screen failures are summarised in the CONSORT flowchart, according to the 2010 Statement extension to pilot and feasibility studies [Primary outcome measures are presented with 95% CI for the following measures, at 48 and 96 weeks: participant retention, the proportion of individuals for whom data are missi...
PMC10348519
Ethics
This study was approved by the London Dulwich Research Ethics Committee (Reference 17/LO/2093). The authors did not have access to information that could identify individual participants during or after data collection. Study data will be made available on reasonable request to the Brighton & Sussex Clinical Trials Uni...
PMC10348519
Results
PMC10348519
Participant flow
Eighty individuals were referred for screening, 21 (26%) and 6 (8%) of whom were excluded prior to and following attendance at the formal eligibility assessment, respectively. The remaining 53 (66%) individuals entered the randomized treatment portion of the trial and were included in analyses; 23 (43%) and 30 (57%) we...
PMC10348519
CONSORT flow diagram.
PMC10348519
Baseline characteristics
Baseline demographic and clinical characteristics were broadly similar across groups (
PMC10348519
Participant baseline characteristics.
liver stiffness
*Tropism testing from HIV proviral DNA sequencing was successful for 39/53 (74%)cART combination antiretroviral therapy, CAP controlled attenuation parameter, INSTI integrase strand transfer inhibitor, LS liver stiffness, MVC maraviroc, NNRTI Non-nucleoside reverse transcriptase inhibitor, OBT optimised background ther...
PMC10348519
Completion of assessments
All mandatory 48 and 96 week clinical assessments were completed by 41 (77%) and 39 (74%) participants, respectively. At 48 / 96 weeks, CLDQ-NAFLD, SF36 and WPAI: SHIP questionnaires were completed by 45 (85%) / 44 (83%), 43 (81%) / 43 (81%) and 25 (47%) / 25 (47%) participants, respectively. The incompletely answered ...
PMC10348519
Primary outcome measures–assessment of progression criteria against predefined targets
ADVERSE REACTION, RECRUITMENT
All individuals considered eligible after screening consented to participate, exceeding the target of 50%. The average recruitment rate was 2.9 per month over 18 months, exceeding the target of 2 per month. Participant retention was 45/53 (85%, 95% CI (72%, 93%)) and 44/53 (83%, 95%CI (70%, 92%)) by weeks 48 and 96, re...
PMC10348519
Adverse Reactions (AR) to maraviroc.
ADVERSE REACTION
AR Adverse Reaction, BL baseline visit, MVC maraviroc
PMC10348519
Adverse events
ideation, vomiting, SAEs, gastro-oesophageal reflux disease, urinary retention
GASTRO-OESOPHAGEAL REFLUX DISEASE, BENIGN PROSTATIC HYPERPLASIA, COVID-19 PNEUMONIA, DEGENERATIVE, COMMUNITY ACQUIRED PNEUMONIA, LISTERIA MENINGITIS
Two SAEs were observed in the MVC+OBT group (community acquired pneumonia and gastro-oesophageal reflux disease with vomiting) and four in the OBT group (fatal COVID-19 pneumonia, urinary retention from benign prostatic hyperplasia, suicidal ideation, listeria meningitis). One SAE was observed in a participant prior to...
PMC10348519
Difference in change from baseline in metabolic and liver parameters for the maraviroc + OBT versus OBT group with bootstrapped 95% confidence intervals.
LCL, lower confidence limit; UCL upper confidence limitSupplementary Table S4 in For QoL outcomes, comparing change from baseline through weeks 48 and 96 between treatment groups, 95% CI were wide indicating imprecise estimation of between-group differences. In all cases, 95% CI included zero, consistent with there bei...
PMC10348519
Difference in change from baseline in quality of life outcomes for the maraviroc + OBT versus OBT group with bootstrapped 95% confidence intervals.
NAFLD
CHRONIC LIVER DISEASE
LCL, lower confidence interval, UCL upper confidence intervalCLDQ-NAFLD Chronic Liver Disease Questionnaire for NAFLD, SF36 36-item Short Form Survey, WPAI:SHP Work Productivity and Activity Impairment: Specific Health Problem
PMC10348519
Protocol deviations
There were 263 protocol deviations due to missing a study assessment (96, 37%); COVID-19 pandemic related factors resulting in assessments out of window (67, 25%); assessment out of window for other reasons (46, 17%); scheduling of the whole visit out of window (36, 14%); other reason (wrong stratification, incorrect r...
PMC10348519
Discussion
NAFLD, non-AIDS-defining disease, PWH, inflammation, cirrhosis, fibrosis, TG
ADVERSE REACTIONS, INFLAMMATION, CIRRHOSIS, FIBROSIS, ADVERSE REACTION
These data provide preliminary evidence that add-on maraviroc as therapy for NAFLD without cirrhosis in PWH on effective cART may be safe, acceptable and feasible. We recruited ~90% of our target of 60 individuals, and, of those referred for possible participation, 66% were randomised, including all who met eligibility...
PMC10348519
Limitations
NAFLD, PWH, hepatic steatosis, fibrosis
DISEASE, HEPATIC STEATOSIS, FIBROSIS
We used non-invasive assessment methods for hepatic steatosis and fibrosis, whilst the gold standard, liver biopsy, would have permitted more accurate classification of disease. However, recruiting a sufficient sample of PWH and mild NAFLD to a randomised study requiring consecutive liver biopsies presents feasibility ...
PMC10348519
Considerations for an efficacy RCT of add-on MVC in HIV-NAFLD
NAFLD
Given conflicting data for associations between NAFLD development and different ART classes [
PMC10348519
Conclusions
NAFLD, PWH, fibrosis
HEPATIC STEATOSIS, FIBROSIS
This study provides preliminary evidence that add-on maraviroc as therapy for HIV-NAFLD may be safe, feasible and acceptable. Although there were differences in the trend for ALT and LSM scores, with improvement in the MVC+OBT versus OBT group, the 95% CI contained zero, which was consistent with there being no detecta...
PMC10348519
Supporting information
PMC10348519
CONSORT 2010 checklist of information to include when reporting a pilot or feasibility trial.
(DOC)Click here for additional data file.
PMC10348519
This file contains all supporting tables (S1-S4 Tables).
(DOCX)Click here for additional data file.
PMC10348519
Trial protocol.
(PDF)Click here for additional data file.The authors wish to acknowledge the participants who generously participated in this trial.
PMC10348519
References
PMC10348519
Abstract
PMC10512773
Introduction
AKI, sepsis, dysbiosis, acute kidney injury
SEPSIS
During acute kidney injury (AKI) due to sepsis, the intestinal microbiota changes to dysbiosis, which affects the kidney function recovery (KFR) and amplifies the injury. Therefore, the administration of probiotics could improve dysbiosis and thereby increase the probability of KFR.
PMC10512773
Methods
AKI, sepsis
ADVERSE EVENTS, SEPSIS, KIDNEY REPLACEMENT
In this double-blind clinical trial, patients with AKI associated with sepsis were randomized (1:1) to receive probiotics or placebo for 7 consecutive days, with the objectives of evaluate the effect on KFR, mortality, kidney replacement therapy (KRT), urea, urine volume, serum electrolytes and adverse events at day 7.
PMC10512773
Results
From February 2019 to March 2022, a total of 92 patients were randomized, 48 to the Probiotic and 44 to Placebo group. When comparing with placebo, those in the Probiotics did not observe a higher KFR (HR 0.93, 0.52–1.68,
PMC10512773
Conclusion
AKI, sepsis
SEPSIS
In AKI related to sepsis, probiotics for 7 consecutive days did not increase the probability of KFR, nor did other variables related to clinical improvement, although they were safe.
PMC10512773
Keywords
PMC10512773
Introduction
AKI, inflammation, endotoxemia
ENDOTOXEMIA, PROLIFERATION, INFLAMMATION, DISEASE, SYNDROME, IMMUNODEFICIENCY
The intestinal microbiota comprises 100 trillion microorganisms, such as bacteria, viruses, fungi, and protozoa, that interact with the human host during health and disease processes [During disease and inflammation, the intestinal microbiome undergoes changes in its composition, causing the proliferation of pathogenic...
PMC10512773