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Methods
PMC10464068
Study design
HD, deaths
DER
In this randomized controlled pilot trial, we tested the effects of NMES combined with VR distraction in HD patients in the German dialysis care setting in a 12-week long intervention. In addition to muscle strength and structure indicators, we analysed body composition, functional capacity, and serum biochemistry (alb...
PMC10464068
Study participants
thrombosis, dementia, acute infectious diseases, nausea or dizziness, drug dependence
THROMBOSIS, CARDIOVASCULAR DISEASES, DISEASE, MOTION SICKNESS, INFLUENZA
The inclusion criteria were as follows: age of 18 years or older, haemodialysis duration more than 6 months, signed informed consent and sufficient eyesight. The exclusion criteria included cardiovascular diseases, electrical implants, metallic implants in the treatment area, susceptibility to nausea or dizziness (so-c...
PMC10464068
Study procedures and training protocol
quadriceps femoris muscle
The eligible patients were randomly assigned to one of the three groups: neuromuscular electrical stimulation (NMES), NMES combined with a VR distraction (NMES + VR) or control (CO) group. Randomization was generated by random.org online software [All patients underwent the standard HD care, but patients in the NMES an...
PMC10464068
Endpoints
PMC10464068
Baseline questionnaire
primary disease
The self-created baseline questionnaire included the demographic variables (age, gender, weight, duration on HD, primary disease of dialysis) and three questions on technical interest and physical condition which were rated on a 5-point Likert scale. The written questionnaire was answered by the patient at the time poi...
PMC10464068
Muscle strength
quadriceps femoris muscle, ®2
Using a digital handheld dynamometer microFET®2 (HOGGAN SCIENTIFIC LLC, USA) the muscle strength in both lower extremities (especially quadriceps femoris muscle (QFM) left and right) was measured by isometric knee extensor strength testing. To perform the measurement, the patient sat upright on a patient couch (approx....
PMC10464068
Muscle circumference
A tape measure was used to determine the location of the greatest circumference of the thigh at t0 and t1 (in centimetres).
PMC10464068
Body composition
Weight, fat, water, and muscle proportion were collected using the Beurer BF 185 body scale with bioelectrical impedance analysis (Beurer, Germany) at t0 and t1 after dialysis. We tried to measure at the same day of the week. Due to illness, quarantine, and study staff turnover during pandemic we could not adhere it fo...
PMC10464068
Functional capacity
To measure the effects of NMES on functional capacity we decided for using the 1-Minute Sit-to-Stand Test (STS-60), because it is a reliable, valid and responsive measurement, especially if space and time are limited, as it was in our pilot study [
PMC10464068
Serum biochemistry
muscle mass, PEW
BLOOD
Blood samples were drawn from the patients at t0 and t1 to measure the serum albumin level, as among others, an independent indicator for loss of muscle mass and PEW [We did the to-/t1-measurements mostly after dialysis. If the t0-tests had to be conducted before dialysis in a few cases, then the t1-test was also condu...
PMC10464068
Virtual reality distraction – effects
nausea, pain
The patients of the NMES and NMES + VR group rated their subjective feeling on the unpleasant tingling sensation caused by the current along the limb after every intervention on a Visual Analog Scale (VAS). It is a standardized measuring instrument for the evaluation of subjective sensations, such as pain, nausea, or s...
PMC10464068
Statistical analysis
primary disease
All data were reported as estimates of arithmetic mean and standard deviation except from ordinal scaled variables and those who violated normal distribution. For these we used the median and interquartile range (IQR). Fisher’s exact test was applied to explore the differences in age and primary disease between the gro...
PMC10464068
Functional capacity
The main effect of the NMES intervention was a statistically significant difference in the improvement of physical strength. This was evident in the 1-Minute Sit-to-Stand Test. While patients in the NMES and NMES + VR groups increased their numbers of repetitions, the number decreased in the CO group (Table
PMC10464068
Serum biochemistry
There was an increase in serum albumin levels in the NMES intervention groups from t0 to t1, while we observed none in the control group. For the NMES group the increase in serum albumin levels were significantly (0.233 ± 0.094 g/dL,
PMC10464068
Muscle strength
F(2,21
There was a statistically significant interaction between the intervention and time on left QFM force (F(2,21) = 4.24,
PMC10464068
Muscle cicumference
We observed no difference in the development of muscle circumference. The circumference tended to decrease in left as well as right QFM in all groups, except from QFM left in the NMES + VR group (t0: 42.06 ± 2.86 cm vs. t1: 42.89 ± 3.86 cm) (Table
PMC10464068
Body composition
Body composition did not change throughout our study. To avoid a Type I error rate due to no homogeneity of variance, two-way repeated measures analysis of variance was not run for the endpoint muscle proportion and interaction effect was not interpreted for the endpoint BMI due to violation of equality test of covaria...
PMC10464068
Effects of VR distraction in combination with NMES
cramping
ADVERSE EVENT
In 98 of the 228 interventions the patients in the NMES + VR group used to wear the VR-headsets, which means an adherece rate of 42.98%. 70.41% of the applications were of the category relaxation, 9.18% of the category interactive games and for 20.41% there was no documentation of the chosen VR applications. There were...
PMC10464068
Discussion
cognitive skills, illness, HD, cramping, Sarcopenia, malnutrition, depression, deaths
CATABOLIC STATE, ADVERSE EVENTS, SARCOPENIA, MALNUTRITION
Sarcopenia in dialysis patients is associated with physical limitations, hospitalizations, and depression. Thus, its onset and progression should be either fully prevented or at least slowed down. This randomized controlled trial design was used to evaluate the effects of intradialytic NMES combined with VR distraction...
PMC10464068
Conclusions
intradialytic NMES
The study results suggest that intradialytic NMES increases (1) functional capacity, (2) serum albumin level, (3) muscle strength in lower limb and (4) weight and BMI of HD patients. (5) Effects on VR distraction are inconclusive and must be proven in further studies. VR applications must be further optimized and expan...
PMC10464068
Acknowledgements
Kuratorium
DER
We are grateful for the support of our patients, healthcare workers of Klinikum rechts der Isar and Kuratorium and Kuratorium für Dialyse und Nierentransplantation as well as our study assistance Alina Simon, Anella Tomasevic, Esra Islertas, Melanie Mayr, and Sara Gerhardt.
PMC10464068
Authors’ contributions
LS, LH, KN, UH and CS contributed to the conception and design of the study. LH, CK and JS contributed to the acquisition. LS conducted the statistical analysis and wrote the draft of the manuscript with LH. All authors reviewed and approved the final manuscript.
PMC10464068
Funding
Open Access funding enabled and organized by Projekt DEAL. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
PMC10464068
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
PMC10464068
Declarations
PMC10464068
Ethics approval and consent to participate
DER
The study was approved by the Ethics Committee of the Klinikum rechts der Isar (MRI), Munich and was performed in accordance with the Declaration of Helsinki guidelines. Informed consents were obtained from all human research subjects for participation in this study.
PMC10464068
Consent for publication
Not applicable.
PMC10464068
Competing interests
The authors declare that they have no competing interests.
PMC10464068
References
PMC10464068
Key Points
PMC10623198
Question
Hypertension
HYPERTENSION
Can an adapted mindfulness training program improve interoception and adherence to the Dietary Approaches to Stop Hypertension (DASH) diet?
PMC10623198
Findings
BLOOD
This randomized clinical trial of 201 participants showed that by 6 months’ follow-up, the Mindfulness-Based Blood Pressure Reduction (MB-BP) program improved the Multidimensional Assessment of Interoceptive Awareness score by a statistically significant 0.54 points, and the DASH score by a significant 0.62 points, com...
PMC10623198
Meaning
HYPERTENSION
The results suggest that the MB-BP program may improve eating patterns, one of the primary drivers of hypertension.
PMC10623198
Importance
Hypertension
CARDIOVASCULAR DISEASE, HYPERTENSION
Hypertension is a major cause of cardiovascular disease, and although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP), adherence is typically low. Mindfulness training adapted to improving health behaviors that lower BP could improve DASH adherence, in part through improved interocept...
PMC10623198
Objective
BLOOD
To evaluate the effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on interoceptive awareness and DASH adherence.
PMC10623198
Design, Setting, and Participants
Parallel-group, phase 2, sequentially preregistered randomized clinical trials were conducted from June 1, 2017, to November 30, 2020. Follow-up was 6 months. Participants with elevated unattended office BP (≥120/80 mm Hg) were recruited from the population near Providence, Rhode Island. Of 348 participants assessed fo...
PMC10623198
Interventions
hypertension
HYPERTENSION
The 8-week MB-BP program was adapted for elevated BP, including personalized feedback, education, and mindfulness training directed to hypertension risk factors. Both MB-BP and control groups received home BP monitoring devices with instructions and options for referral to primary care physicians. The control group als...
PMC10623198
Main Outcomes and Measures
REGRESSION, SECONDARY, -11
The primary outcome was Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire scores (range 0-5, with higher scores indicating greater interoceptive awareness), and the secondary outcome was DASH adherence scores assessed via a 163-item Food Frequency Questionnaire (range 0-11, with higher scores ...
PMC10623198
Results
Among 201 participants, 118 (58.7%) were female, 163 (81.1%) were non-Hispanic White, and the mean (SD) age was 60.0 (12.2) years. The MB-BP program increased the MAIA score by 0.54 points (95% CI, 0.35-0.74 points;
PMC10623198
Conclusions and Relevance
A mindfulness program adapted to improving health behaviors to lower BP improved interoceptive awareness and DASH adherence. The MB-BP program could support DASH dietary adherence in adults with elevated BP.
PMC10623198
Clinical Trial Registration
BLOOD, HYPERTENSION
ClinicalTrials.gov Identifiers: This randomized clinical trial assesses the effects of a Mindfulness-Based Blood Pressure Reduction program on interoceptive awareness and adherence to the DASH (Dietary Approaches to Stop Hypertension) diet among adults with elevated unattended office blood pressure.
PMC10623198
Introduction
Hypertension
CARDIOVASCULAR DISEASE, HYPERTENSION
Hypertension is a primary cause of cardiovascular disease, which is the major cause of mortality in the US and worldwide.Mindfulness interventions have been tested in many diet studies, but often focus on eating disordersSelf-awareness can be defined as awareness of one’s thoughts, emotions, and physical sensations. On...
PMC10623198
Methods
PMC10623198
Study Design, Setting, and Participants
RECRUITMENT, BROWN
The MB-BP study was a parallel-group phase 2 RCT comparing group-based mindfulness meditation training adapted to improving health behaviors that lower BP vs an enhanced usual care control. Participants were recruited and enrolled from June 1, 2017, to November 30, 2020, through advertising in local communities and ref...
PMC10623198
Blinding and Randomization
Eligible participants who completed baseline assessments were randomly assigned to receive either the MB-BP or control condition (
PMC10623198
Intervention Descriptions and Theoretical Framework
The MB-BP program is based on, and time-matched to, the standardized Mindfulness-Based Stress Reduction (MBSR) program.
PMC10623198
Theoretical Framework of Mechanisms Through Which Mindfulness-Based Blood Pressure Reduction May Influence Dietary Patterns That Lower Blood Pressure
HEART
Participants assigned to the enhanced usual care control group received the same home BP device, training in home BP monitoring, and an option for referral to primary care as participants in the intervention group. They also received an American Heart Association brochure about high BP and how to treat it.
PMC10623198
Outcomes
SECONDARY
The prespecified primary outcome was interoceptive awareness, measured using the validated Multidimensional Assessment of Interoceptive Awareness (MAIA) at 6 months from baseline assessment and randomization.Adherence to the DASH diet, the preregistered secondary outcome, was assessed with the Harvard 163-item 2007 Gri...
PMC10623198
Baseline Characteristics by Group
Facet Mindfulness
BLOOD, -11, HYPERTENSION
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); DASH, Dietary Approaches to Stop Hypertension; FFMQ, Five Facet Mindfulness Questionnaire; MAIA, Multidimensional Assessment of Interoceptive Awareness; MB-BP, Mindfulness-Based Blood Pressure Reduction; MET, me...
PMC10623198
Statistical Analysis
For statistical power considerations, an RCT of a similar program, Mindfulness-Based College, demonstrated a between-group MAIA scale effect size (SD) of 0.63 (0.83).We used generalized estimating equations to evaluate the effects of the MB-BP program on outcomes compared with the control program at 3 and 6 months usin...
PMC10623198
Results
Among 201 participants, 118 (58.7%) were female and 83 (41.3%) were male; 5 (2.5%) were Asian, 9 (4.5%) were Black or African American, 8 (4.0%) were Hispanic, 3 (1.5%) were Native American, 163 (81.1%) were non-Hispanic White, and 10 (5.0%) were of another race or ethnicity; 146 (72.6%) had a college or graduate degre...
PMC10623198
Effects of Mindfulness-Based Blood Pressure Reduction (MB-BP) vs Control on Interoceptive Awareness Assessed via Multidimensional Assessment of Interoceptive Awareness (MAIA) Score, and Dietary Approaches to Stop Hypertension (DASH) Diet Score Among All Participants and Among Participants With Poor DASH Adherence at Ba...
Poor DASH adherence was defined as a DASH score lower than 5.5. Error bars represent standard error of the mean.
PMC10623198
Between-Group Differences in Change of MAIA Scores From Baseline to Follow-Up, for MB-BP vs Control Groups
ADVERSE EVENTS, BLOOD, ADVERSE EVENT
Abbreviations: MAIA, Multidimensional Assessment of Interoceptive Awareness; MB-BP, Mindfulness-Based Blood Pressure Reduction.The 6-dimension mean excludes “not distracting” and “not worrying” dimensions.The intervention was associated with a 0.34-point improvement in the DASH diet score in MB-BP participants from bas...
PMC10623198
Discussion
Overall, the findings of this phase 2 RCT showed that the MB-BP program improved interoceptive awareness compared with an enhanced usual care control group through 6 months’ follow-up. There was evidence that MB-BP improved the DASH dietary pattern, with larger effects for participants with poor baseline DASH adherence...
PMC10623198
Limitations
This study has limitations. The first is a follow-up time of 6 months; the durability of intervention effects are unknown, although our prior single-group study of the MB-BP intervention demonstrated significant before vs after improvements in interoceptive awareness and the DASH diet through 1 year follow-up.
PMC10623198
Conclusions
hypertension
HYPERTENSION, CARDIOVASCULAR DISEASE
This phase 2 RCT offers evidence that an adapted mindfulness training for participants with elevated BP that targets diet and interoceptive awareness improves both. Given the high burden of hypertension on cardiovascular disease, the MB-BP program may offer an approach to improve self-awareness and adherence to evidenc...
PMC10623198
Purpose
renal toxicity
EPITHELIAL OVARIAN CANCER
Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary.
PMC10625947
Methods
A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m
PMC10625947
Results
Renal toxicities
SECONDARY
Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (
PMC10625947
Conclusions
toxicity, ovarian cancer, nephrotoxicity
OVARIAN CANCER
ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered.
PMC10625947
Supplementary Information
AKI, ovarian cancer, CRS, acute kidney injury
OVARIAN CANCER, CAVITY, ADVERSE EFFECTS
The online version contains supplementary material available at 10.1245/s10434-023-14216-6.Open access funding provided by SCELC, Statewide California Electronic Library ConsortiumHyperthermic intraperitoneal chemotherapy (HIPEC) is the delivery of heated chemotherapy (42 °C) into the intraperitoneal (IP) cavity immedi...
PMC10625947
Methods
PMC10625947
Study Population
ONCOLOGY, DISEASE, FALLOPIAN TUBE CANCER
A single-institution, clinical trial was approved by the City of Hope Institutional Review Board (NCT01970722) to evaluate feasibility and safety of HIPEC with cisplatin in EOC and EC patients. All research was carried out in accordance with ethical principles as defined by the Declaration of Helsinki.Eligible patients...
PMC10625947
Trial Design
renal toxicity, gynecologic malignancies, tumor
TUMOR
This prospective, feasibility, clinical trial investigated the safety and molecular changes associated with HIPEC with cisplatin in patients with gynecologic malignancies. Initial protocol treatment did not include ST administration. However, after an interim analysis of the first 21 patients demonstrated a high rate o...
PMC10625947
Molecular Analysis
RNA from FFPE (miRNeasy RNA FFPE Kit, Qiagen) and snap-frozen tissues (miRNeasy RNA mini Kit, Qiagen) was extracted per standard manufacturer protocols. Concentration and purity were measured using NanoDrop One Spectrophotometer (Thermo Fisher Scientific) and Qubit 3.0 Fluorometer (Life Technologies). For whole transcr...
PMC10625947
Endpoints
The primary endpoint of the trial was safety and survival outcomes, which was previously reported.
PMC10625947
Statistical Analysis
CRS
GYNECOLOGIC CANCER
Baseline and postsurgical characteristics were compared between ST and nST patients by using the chi-square or Fisher’s exact test for categorical data, and the t-test (normally distributed) or Wilcoxon rank-sum (non-normally distributed) continuous variables. PFS was defined as the time in months from CRS and HIPEC to...
PMC10625947
Results
PMC10625947
Surgical and Clinical Outcomes
ovarian cancer, peritoneal carcinoma
POSTOPERATIVE COMPLICATION, PERITONEAL CARCINOMA, OVARIAN CANCER, COMPLICATIONS
Of the 40 enrolled patients, 38 (95%) underwent closed HIPEC technique, and two (5%) underwent laparoscopic technique. Twenty-eight of 40 (70%) patients underwent CCR0 resection, and 12 of 40 (30%) underwent CCR1 resection. Mean operative peritoneal carcinoma index (PCI) and median operative time were higher in the ST ...
PMC10625947
Renal Toxicities
Renal adverse
There were no grade 2 or 3 renal AEs in the ST group (Fig. Renal adverse events (AEs) and creatinine changes by ST exposure. Preoperative and postoperative Cr values were obtained and compared for patients in both groups. There was no statistically significant difference between preoperative and postoperative Cr among ...
PMC10625947
Toxicity-Related Gene and Mutational Signatures
Whole transcriptomic sequencing identified correlations between renal AEs and gene expression in normal samples from 13 patients in the nST group with available WTS (Fig. WTS data for the nST group.
PMC10625947
Discussion
ovarian cancer, nephrotoxicity, B-cell, toxicity, toxicities, nephrotoxicities, uterine cancer, renal toxicity, renal toxicities, acute renal failure, AKI, HIPEC-induced renal toxicities
OVARIAN CANCER, ACUTE INFLAMMATORY RESPONSE, UTERINE CANCER, RENAL FAILURE, RECRUITMENT, RECURRENT CANCER, ACUTE RENAL FAILURE, ONCOLOGY, DISEASE CHARACTERISTIC, COMPLICATIONS
Despite enthusiasm for HIPEC in EOC, routine use of HIPEC is marred by its toxicities and skepticism over its true clinical benefit. Despite a well-established incidence of nephrotoxicity from HIPEC with cisplatin, management and prevention of this toxicity vary widely. The Peritoneal Surface Oncology Group Internation...
PMC10625947
Conclusion
nephrotoxicities, toxicities
OVARIAN CANCER
We contribute to the growing pool of literature showing that ST abrogates nephrotoxicities induced by HIPEC with cisplatin and does not result in reduced PFS. The lack of renal toxicities associated with ST use and its stability in serum Cr, in contrast to the significant increase in serum Cr in patients without ST use...
PMC10625947
Acknowledgment
The authors thank Nicola Welch, PhD, CMPP (Whipbird Communications) for editorial assistance and critical review of the paper.
PMC10625947
Funding
Open access funding provided by SCELC, Statewide California Electronic Library Consortium.
PMC10625947
Disclosures
None.
PMC10625947
References
PMC10625947
Background
cancer
CANCER
The first-in-class brain-penetrating synthetic hydroxylated lipid idroxioleic acid (2-OHOA; sodium 2-hydroxyoleate), activates sphingomyelin synthase expression and regulates membrane-lipid composition and mitochondrial energy production, inducing cancer cell autophagy. We report the findings of a multicentric first-in...
PMC10449773
Methods
glioma
GLIOMA, SOLID TUMOUR
We performed an open-label, non-randomised trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of daily oral treatment with 2-OHOA monotherapy (BID/TID) in 54 patients with glioma and other advanced solid tumours. A dose-escalation phase using a standard 3 + 3 design ...
PMC10449773
Results
diarrhoea, DLTs, HGG, high-grade gliomas, gastrointestinal dose-limiting toxicities, nausea, vomiting
ADVERSE EVENTS
In total, 32 recurrent patients were enrolled in the dose-escalation phase (500–16,000 mg/daily). 2-OHOA was rapidly absorbed with dose-proportional exposure. Treatment was well-tolerated overall, with reversible grade 1–2 nausea, vomiting, and diarrhoea as the most common treatment-related adverse events (AEs). Four p...
PMC10449773
Conclusions
glioma, difficult-to-treat malignant brain-tumour
MALIGNANCIES, GLIOMA, SOLID TUMOUR
2-OHOA demonstrated a good safety profile and encouraging activity in this difficult-to-treat malignant brain-tumour patient population, placing it as an ideal potential candidate for the treatment of glioma and other solid tumour malignancies.
PMC10449773
Clinical trial registration
EudraCT registration number: 2012-001527-13; Clinicaltrials.gov registration number: NCT01792310.
PMC10449773
Subject terms
PMC10449773
Introduction
cancer, Gliomas
CANCER, GLIOMAS
Gliomas are the most common malignant brain tumour in adults [Cell membrane-lipid composition and structure are markedly altered in cancer cells with the resulting impact on intracellular oncogenic signalling [
PMC10449773
Results
diarrhoea, nausea, study-drug-related TEAEs, HGG, vomiting, Treatment-emergent adverse
DISEASE, DISEASE PROGRESSION, SOLID TUMOUR
Fifty-four patients were enrolled and treated at 5 investigational sites in the United Kingdom and Spain. Study design included two phases: Dose-escalation phase (DE) and Expansion Phase (EP) at the Maximum tolerated dose determined at the DE. No patient withdrew due to an AE or a serious AE (SAE) in either the dose es...
PMC10449773
Pharmacokinetic profiles of 2-OHOA at different doses.
HGG, tumour, SD
DISEASE, TUMOUR
The graphs represent log [2-OHOA] (ng/ml) in serum of patients after single dose (day 1, black) and steady state (day 21, black) at doses ranging from 500 mg/d to 16,000 mg/d (p.o.). Bottom/right panel: Linear relationship between the extent of systemic exposure (area under the curve, AUC) and dose following single (da...
PMC10449773
Waterfall plot responses during 2-OHOA monotherapy.
BEST
Best response after initial diagnosis.
PMC10449773
MRI scans over time of a patient with partial response.
glioblastoma, tumour, distal bile duct adenocarcinoma
SOLID TUMOUR, LUNG METASTASIS, LUNG ADENOCARCINOMA, MESOTHELIOMA, TUMOUR, REGRESSION, GLIOBLASTOMA, COLON ADENOCARCINOMA, PANCREATIC ADENOCARCINOMA
The patient showed a sustained tumour regression (partial response according to RANO criteria) over time for 3 years on monotherapy with 2-OHOA (500 mg BID, cohort 2). MRI transverse (upper scans) and sagittal (lower scans) brain images show the glioblastoma (red circle) reduction, which was determined to be ca. −93% o...
PMC10449773
Discussion
diarrhoea, nausea, death, HGG, cancer, vomiting, PD, tumour, Glioma, gliomas
PROLIFERATION, CANCER, EMA, TUMOUR, EVENTS, GLIOMA, GLIOMAS, MALIGNANT DISEASE
Given the lack of effective therapies for HGG, the investigation of novel therapies is a clinical priority. 2-OHOA is a synthetic lipid able to modulate the sphingolipids metabolism that in consequence modifies the membrane composition and properties impacting on the cell signalling and avoiding cancer cell proliferati...
PMC10449773
Supplementary information
The online version contains supplementary material available at 10.1038/s41416-023-02356-1.
PMC10449773
Acknowledgements
We thank the patients and their families for their participation in this study and the staff at the study sites. We also acknowledge the support we had from CRUK/NHS England as ECMC network members (Newcastle and ICR sites). We thank the late Mr. Antoine Périer for his fundamental assistance in the project.
PMC10449773
Author contributions
The contributions of each author to the manuscript is detailed as follows: Conceptualisation: RT, JR, RP and PVE. Methodology: JL, RT, GJV and PVE. Investigation: JL, LRM, LW, NT, DR, AA, JR, GJV, RP, AU, AL and KM. Formal analysis: JL, JL-K, LRM, LW, PF-G, VLL, AM, CAR, AA, JR, JS, GJV, RP and PVE. Writing - Review & ...
PMC10449773
Funding
Cancer
DEL, CANCER
This study was supported in part by Laminar Pharmaceuticals. Financial support was also provided by the Govern de les Illes Balears i del Fons Social Europeu (ES01/TCAI/53_2016, ES01/TCAI/21_2017, ES01/TCAI/24_2018 and PROCOE/5/2017), the European Commission (H2020 Framework Programmes Project CLINGLIO 755179), Cancer ...
PMC10449773
Data availability
The data are available on the Clinical Study Report of the trial.
PMC10449773
Competing interests
VL, PF-G, AM, CAR and PVE work for and are Laminar Pharmaceuticals shareholders, the sponsor of this study. RJT is a consultant to Laminar Pharmaceuticals. The remaining authors declare no competing interests.
PMC10449773
Ethics approval and consent to participate
All patients participating in the study provided written informed consent. The study got a favourable opinion from the Ethics Committees of the three centres participating in the study. Those were the Central Research Ethics Committee from London, Euskadi and Vall d’Hebrón. REC Reference is 13/LO/0062. The trial was co...
PMC10449773
Consent for publication
The written informed consent signed by all patients in the study includes authorisation of medical publications.
PMC10449773
References
PMC10449773
Background
anastomotic leak
ANASTOMOTIC LEAK
Large-scale quality improvement interventions demand robust trial designs with flexibility for delivery in different contexts, particularly during a pandemic. We describe innovative features of a batched stepped wedge trial, ESCP sAfe Anastomosis proGramme in CoLorectal SurgEry (EAGLE), intended to reduce anastomotic l...
PMC10184073