Meta-regression of sulcal patterns, clinical and environmental factors on neurodevelopmental outcomes in participants with multiple CHD types.

Congenital heart disease affects 1% of infants and is associated with impaired neurodevelopment. Right- or left-sided sulcal features correlate with executive function among people with Tetralogy of Fallot or single ventricle congenital heart disease. Studies of multiple congenital heart disease types are needed to understand regional differences. Further, sulcal pattern has not been studied in people with d-transposition of the great arteries. Therefore, we assessed the relationship between sulcal pattern and executive function, general memory, and processing speed in a meta-regression of 247 participants with three congenital heart disease types (114 single ventricle, 92 d-transposition of the great arteries, and 41 Tetralogy of Fallot) and 94 participants without congenital heart disease. Higher right hemisphere sulcal pattern similarity was associated with improved executive function (Pearson r = 0.19, false discovery rate-adjusted P = 0.005), general memory (r = 0.15, false discovery rate P = 0.02), and processing speed (r = 0.17, false discovery rate P = 0.01) scores. These positive associations remained significant in for the d-transposition of the great arteries and Tetralogy of Fallot cohorts only in multivariable linear regression (estimated change ß = 0.7, false discovery rate P = 0.004; ß = 4.1, false discovery rate P = 0.03; and ß = 5.4, false discovery rate P = 0.003, respectively). Duration of deep hypothermic circulatory arrest was also associated with outcomes in the multivariate model and regression tree analysis. This suggests that sulcal pattern may provide an early biomarker for prediction of later neurocognitive challenges among people with congenital heart disease.

Date Vinegar: First Isolation of Acetobacter and Formulation of a Starter Culture.

There is a lack of scientific analysis and control over the production of date vinegar in Oman, despite its growing demand in the worldwide market. Traditional production of date vinegar may lead to elevated amounts of ethanol (≥0.5%) and reduced content of acetic acid (<4%) compared to the standard acceptable levels. This study aimed to isolate non-Gluconobacter species from date vinegar produced by spontaneous fermentation and formulate starter cultures for quick and efficient production of date vinegar. In spontaneous fermentation date vinegar samples, the highest concentration of acetic acid was 10.42% on day 50. Acetobacter malorum (5 isolates), A. persici (3 isolates), and A. tropicalis (3 isolates) were identified based on 16S rRNA gene sequences for the first time in date vinegar. For date vinegar prepared with a starter culture of Acetobacter and yeast, the highest concentration of acetic acid was 4.67%. In conclusion, spontaneous fermentation resulted in the production of date vinegar with a high concentration of acetic acid, acceptable concentrations of ethanol and methanol, and the first isolation of three Acetobacter species. The formulated starter culture produced acceptable amounts of acetic acid and the time of fermentation was reduced 10 times (from 40 days to 4 days). This can provide the basis for producing a personalized or commercial product that ensures the production of good-quality date vinegar in an easier, faster, safer, and more efficient way from low-quality and surplus dates.

Applications of Artificial Intelligence for Pediatric Cancer Imaging.

Artificial intelligence (AI) is transforming medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent data scarcity associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatrics compared to adults could also contribute to this challenge, as market size is a driver of commercialization. This article provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. While current developments are promising, impediments due to diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer-learning of adult-based AI models to pediatric cancers, multi-institutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking AI's full potential for clinical translation and improved outcomes for these young patients.

Genomic testing and molecular diagnosis among infants with congenital heart disease in the neonatal intensive care unit.

OBJECTIVE: To evaluate patterns of genetic testing among infants with CHD at a tertiary care center. STUDY DESIGN: We conducted a retrospective observational cohort study of infants in the NICU with suspicion of a genetic disorder. 1075 of 7112 infants admitted to BCH had genetic evaluation including 329 with CHD and 746 without CHD. 284 of 525 infants with CHD admitted to CMHH had genetic evaluation. Patterns of testing and diagnoses were compared. RESULTS: The rate of diagnosis after testing was similar for infants with or without CHD (38% [121/318] vs. 36% [246/676], p = 0.14). In a multiple logistic regression, atrioventricular septal defects were most high associated with genetic diagnosis (odds ratio 29.99, 95% confidence interval 2.69-334.12, p < 0.001). CONCLUSIONS: Infants with suspicion of a genetic disorder with CHD had similar rates of molecular diagnosis as those without CHD. These results support a role for genetic testing among NICU infants with CHD.

Retraction: Colonic Angiolipoma: An Extremely Rare Tumor Clinically Masquerading as Acute Appendicitis.

[This retracts the article DOI: 10.7759/cureus.20659.].

Trends in Management of Anal Fissures.

BACKGROUND: It is unclear how patients with anal fissures are treated in real-world settings, particularly since patients may not see colorectal surgeons. This study describes trends in treatment with medical therapies (calcium-channel blockers [CCBs], nitroglycerin [NTG], and narcotics) and surgical treatments. METHODS: Cohorts were created within the TriNetX database platform using codes for anal fissures and surgical interventions. Demographics were compared between patients that received surgical intervention within 1 year of diagnosis, CCB or NTG within 1 year (or preoperatively), or narcotics within 30 days or postoperatively vs those who did not. RESULTS: 121,213 patients were included of which 4.0% had surgical intervention. Factors associated with surgical intervention were male sex (OR 1.40), White race (OR 1.17), and Hispanic ethnicity (OR 1.11). Male patients were more likely to undergo sphincterotomy (OR 1.49). Female (OR 1.27), non-Hispanic (OR 1.34), and White patients (OR 1.41) were more likely to have chemodenervation. Regarding nonoperatively managed patients, non-Hispanic (OR .91) and White patients (OR .89) were less likely to receive CCB/NTG. Male (OR 1.21), non-Hispanic (OR 1.08), and Black patients (OR 1.20) were more likely to receive narcotics. Male patients that required surgery were more likely to be prescribed CCB/NTG preoperatively (OR 1.27). Non-Hispanic surgical patients were more likely to receive narcotics (OR 1.84). DISCUSSION: Male fissure patients were more likely to undergo surgical intervention other than chemodenervation. Differences in the rates of surgery and medical therapy (especially narcotics) between races and ethnicities require exploration to enhance the care of patients with anal fissures.

The role of prefrontal cortex and temporoparietal junction in interpersonal comfort and emotional approach.

Our perception of physical distance to individuals and stimuli is influenced by our mental distance and relatedness. The present study aimed to investigate the role of the dorsolateral prefrontal cortex (dlPFC), ventromedial prefrontal cortex (vmPFC), and right temporoparietal junction (rTPJ) in interpersonal comfortable distance and approach behaviors towards emotional stimuli. Twenty healthy volunteers received brain stimulation in four separate sessions with a one-week interval, including anodal left dlPFC, anodal right vmPFC, anodal rTPJ, and sham condition, with an extracranial return electrode. Our results revealed an increase in interpersonal distance during anodal rTPJ stimulation and a decrease in distance to positive pictures during anodal vmPFC stimulation. These findings suggest that the rTPJ plays a role in the perceptual component of self-other distancing, while the vmPFC is involved in approaching positive emotions.

Patient Satisfaction With Dental Services.

Patient satisfaction is an integral aspect of healthcare quality assessment, and it plays a crucial role in evaluating the effectiveness of healthcare services. This systematic review investigates patient satisfaction with dental services provided by public dental hospitals in rural and remote areas of Saudi Arabia. The study conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) standards. It involved a comprehensive search across multiple databases, including Medline, Cochrane, Embase, and CINAHL, with tailored search strategies for each database using MeSH terms and keywords. To ensure inclusivity, the search covered publications in both English and Arabic and included Google Scholar for gray literature. Inclusion criteria focused on empirical studies conducted in rural and remote public hospitals in Saudi Arabia, published between 2013 and January 2023, assessing patient satisfaction in oral or dental care for adult patients. Data screening and extraction followed a rigorous two-step process, and a narrative synthesis was used to analyze and summarize the findings. The findings reveal a complex landscape of patient satisfaction in these settings, with varying levels of contentment reported. While more than 50% of patients expressed satisfaction with the quality of dental care, significant challenges related to accessibility were evident. Patients residing in remote and rural areas often had to travel long distances to access dental clinics, resulting in dissatisfaction. Demographic factors, particularly education and age, were identified as significant influencers of patient satisfaction, with more educated individuals tending to be less satisfied. This study emphasizes the importance of continuous monitoring of patient satisfaction to enhance service delivery, particularly in public dental clinics serving remote and rural areas. Addressing issues related to access, availability, clinical quality, and effective communication is vital for improving patient satisfaction in these healthcare settings. The study concludes with recommendations for policymakers, including the development of quality assurance policies, cost mitigation strategies, and targeted interventions to address demographic disparities and enhance patient satisfaction with dental care services.

Intention and practice on personal preventive measures against COVID-19 among older adults in the Kingdom of Saudi Arabia: an epidemiological study using the Theory of Planned Behaviour.

Introduction: Older adults aged 65 years and above are among the most vulnerable to adverse outcomes and death following a COVID-19 infection. The weekly epidemiological updates by the World Health Organisation show that the continued emergence of concerning subtypes of the virus indicates that the pandemic remains a public health concern and the public should continue to comply with personal preventive measures (PPMs). This study applies the Theory of Planned Behaviour (TPB) which is rooted in the field of Public Health, Epidemiology, and Preventive Medicine to Saudi older adults to predict their health behaviour. Methods: This behavioural epidemiological study recruited older adult participants aged 65 years of age and above. A tool which consisted of sociodemographic and health-related questions, as well as questions regarding the components of the TPB, namely, Attitude, Subjective Norm, Perceived Behavioural Control was used. Bivariate analyses, followed by unadjusted and adjusted multivariable logistic regression analyses were performed to derive odds ratios and 95% confidence intervals. Results: The total number of participants was 502. The mean age was 70.34 years, with similar distributions between males and females. In total, 52.2% intended to practice PPMs, whereas only 48% had a good practice. Also, 56% had a favourable Attitude towards PPMs, 61.4% had a positive Subjective Norm and 39.8% had perceived they had a high control over their behaviour. Females, and high educational status were predictors for high intention to practice PPMs (OR = 1.59, 95% CI = 1.01-2.52 and OR = 2.72, 95% CI = 1.44-5.16 respectively). Further predictors included Attitudes, Subjective Norm and Perceived Behavioural Control. Results also show that intention to practice was significantly associated with a lower odd of practicing PPMs (OR = 0.06, 95% CI = 0.04-0.10). Conclusion: Current findings highlight the need to continue with public health efforts targeting vulnerable older adults. Also, the fact that intention negatively predicted practice highlights the need for further behavioural epidemiological studies addressing the intention-behaviour gap.

The bidirectional relationship between opioids and the gut microbiome: Implications for opioid tolerance and clinical interventions.

Opioids are widely used in treating patients with acute and chronic pain; however, this class of drugs is also commonly abused. Opioid use disorder and associated overdoses are becoming more prevalent as the opioid crisis continues. Chronic opioid use is associated with tolerance, which decreases the efficacy of opioids over time, but also puts individuals at risk of fatal overdoses. Therefore, it is essential to identify strategies to reduce opioid tolerance in those that use these agents. The gut microbiome has been found to play a critical role in opioid tolerance, with opioids causing dysbiosis of the gut, and changes in the gut microbiome impacting opioid tolerance. These changes in turn have a detrimental effect on the gut microbiome, creating a positive feedback cycle. We review the bidirectional relationship between the gut microbiome and opioid tolerance, discuss the role of modulation of the gut microbiome as a potential therapeutic option in opioid-induced gut dysbiosis, and suggest opportunities for further research and clinical interventions.

Bilateral Pheochromocytoma and Paraganglioma Tumors Due to Von Hippel-Lindau Syndrome in a 15-Year-Old Boy: A Case Report.

Pheochromocytomas and paragangliomas are catecholamine-secreting tumors that originate from chromaffin cells of the adrenal medulla and autonomic neural ganglia, respectively. Patients with pheochromocytomas and paragangliomas typically present with paroxysmal headache, sweating, tachycardia, and hypertension. Although most pheochromocytoma cases are sporadic, many of the cases occur as part of a genetic disorder. Here, we report the case of a 14-year-old male patient who presented with hypertension. Laboratory tests showed elevated levels of serum and urinary catecholamines, metanephrines, and chromogranin. Abdominal ultrasound and computed tomography studies revealed bilateral solid adrenal masses and an isolated splenic mass. Further assessment identified an underlying Von Hippel-Lindau syndrome. The patient was initially treated medically and later surgically. This case highlights the importance of always considering pheochromocytomas and paragangliomas as rare differentials of secondary hypertension, especially in the presence of episodic headaches, sweating, and tachycardia. Furthermore, screening for underlying genetic disorders, such as in our case, should be considered in cases of bilateral tumors, onset at a young age, and presence of extra-adrenal tumors.

Quantitative approaches for decoding the specificity of the human T cell repertoire.

T cell receptor (TCR)-peptide-major histocompatibility complex (pMHC) interactions play a vital role in initiating immune responses against pathogens, and the specificity of TCRpMHC interactions is crucial for developing optimized therapeutic strategies. The advent of high-throughput immunological and structural evaluation of TCR and pMHC has provided an abundance of data for computational approaches that aim to predict favorable TCR-pMHC interactions. Current models are constructed using information on protein sequence, structures, or a combination of both, and utilize a variety of statistical learning-based approaches for identifying the rules governing specificity. This review examines the current theoretical, computational, and deep learning approaches for identifying TCR-pMHC recognition pairs, placing emphasis on each method's mathematical approach, predictive performance, and limitations.

NaX Channel Is a Physiological [Na+] Detector in Oxytocin- and Vasopressin-Releasing Magnocellular Neurosecretory Cells of the Rat Supraoptic Nucleus.

The Scn7A gene encodes NaX, an atypical noninactivating Na+ channel, whose expression in sensory circumventricular organs is essential to maintain homeostatic responses for body fluid balance. However, NaX has also been detected in homeostatic effector neurons, such as vasopressin (VP)-releasing magnocellular neurosecretory cells (MNCVP) that secrete VP (antidiuretic hormone) into the bloodstream in response to hypertonicity and hypernatremia. Yet, the physiological relevance of NaX expression in these effector cells remains unclear. Here, we show that rat MNCVP in males and females is depolarized and excited in proportion with isosmotic increases in [Na+]. These responses were caused by an inward current resulting from a cell-autonomous increase in Na+ conductance. The Na+-evoked current was unaffected by blockers of other Na+-permeable ion channels but was significantly reduced by shRNA-mediated knockdown of Scn7A expression. Furthermore, reducing the density of NaX channels selectively impaired the activation of MNCVP by systemic hypernatremia without affecting their responsiveness to hypertonicity in vivo These results identify NaX as a physiological Na+ sensor, whose expression in MNCVP contributes to the generation of homeostatic responses to hypernatremia.SIGNIFICANCE STATEMENT In this study, we provide the first direct evidence showing that the sodium-sensing channel encoded by the Scn7A gene (NaX) mediates cell-autonomous sodium detection by MNCs in the low millimolar range and that selectively reducing the expression of these channels in MNCs impairs their activation in response to a physiologically relevant sodium stimulus in vitro and in vivo These data reveal that NaX operates as a sodium sensor in these cells and that the endogenous sensory properties of osmoregulatory effector neurons contribute to their homeostatic activation in vivo.

Antimicrobial Activity of Frankincense (Boswellia sacra) Oil and Smoke against Pathogenic and Airborne Microbes.

As they continuously evolve, plants will remain a renewable source for antimicrobial compounds. Omani frankincense is produced by B. sacra trees and is graded into Hojari, Nejdi, Shazri or Sha'bi. Air can be a source for pathogenic or food spoilage microbes; thus, inactivating airborne microbes is necessary in environments such as food and animal production areas. This study investigated the antimicrobial activity and the chemistry of steam-distilled oils of Hojari and Sha'bi grades. It also analyzed the antimicrobial activity of frankincense smoke and the size of its solid particles. Chemical analysis was performed using gas chromatography mass spectrometry (GC-MS). The antimicrobial activity of the oils against Staphylococcus aureus (NCTC 6571), Bacillus spp., Escherichia coli (NCTC 10418), Pseudomonas aeruginosa (NCTC 10662), Saccharomyces cerevisiae, Candida albicans, Aspergillus flavus, Aspergillus ochraceus, Aspergillus niger, Penicillium citrinum, Alternaria alternata and Fusarium solani was determined using well diffusion and micro-well dilution methods. A microscopic technique was used to determine the size of frankincense smoke solid particles. Microbes were exposed to frankincense smoke to test their susceptibility to the smoke. Hojari and Sha'bi oils were similar in composition and contained monoterpenes and sesquiterpenes. The Hojari and the Sha'bi oils possessed broad spectrum antimicrobial activity. The largest growth inhibition zones were obtained with S. cerevisiae and F. solani. An MIC of 1.56% (v/v) was found with E. coli, S. cerevisiae and F. solani. Frankincense smoke contained fine irregular solid particles with a diameter range of 0.8-2287.4 µm, and thus may pose a health risk to susceptible individuals. The smoke had potent antimicrobial activity against S. aureus, E. coli, and airborne bacteria, yeast and mold, with a maximum inhibition of 100%. It was concluded that Hojari and Sha'bi frankincense oils and smoke had significant antimicrobial activity that can be exploited in controlling human, animal and plant pathogenic microbes.

Tapping Into Skeletal Muscle Biomechanics for Design and Control of Lower Limb Exoskeletons: A Narrative Review.

Lower limb exoskeletons and exosuits ("exos") are traditionally designed with a strong focus on mechatronics and actuation, whereas the "human side" is often disregarded or minimally modeled. Muscle biomechanics principles and skeletal muscle response to robot-delivered loads should be incorporated in design/control of exos. In this narrative review, we summarize the advances in literature with respect to the fusion of muscle biomechanics and lower limb exoskeletons. We report methods to measure muscle biomechanics directly and indirectly and summarize the studies that have incorporated muscle measures for improved design and control of intuitive lower limb exos. Finally, we delve into articles that have studied how the human-exo interaction influences muscle biomechanics during locomotion. To support neurorehabilitation and facilitate everyday use of wearable assistive technologies, we believe that future studies should investigate and predict how exoskeleton assistance strategies would structurally remodel skeletal muscle over time. Real-time mapping of the neuromechanical origin and generation of muscle force resulting in joint torques should be combined with musculoskeletal models to address time-varying parameters such as adaptation to exos and fatigue. Development of smarter predictive controllers that steer rather than assist biological components could result in a synchronized human-machine system that optimizes the biological and electromechanical performance of the combined system.

Clinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex.

Turner syndrome (TS) leads to a characteristic phenotype, including premature ovarian insufficiency and infertility. Ovarian tissue cryopreservation (OTC) is becoming an established fertility preservation strategy for both pre- and post-pubertal females and may offer the chance of having a biological family to selected patients with TS. To date, women with TS have had ovarian tissue cryopreserved but there are few reports of autologous re-implantation and none of pregnancy. We herein report, to our knowledge, the first clinical pregnancy in a patient with TS, conceived naturally following re-implantation of cryopreserved ovarian tissue which had been removed soon after spontaneous puberty. This provides proof of concept for OTC as a means of fertility preservation in TS.

The Role of Hematological Parameters in Predicting the Death of Hospitalized Patients with COVID-19.

Background: The role of the hematologic indicators in the identification of severe or critical patients requires further investigation. In this study, we focused on predicting Covid-19 patients at risk of progression using blood parameters. Materials and Methods: We performed a retrospective study including 444 patients with confirmed Covid-19. Hematological parameters were evaluated. The logistic regression analysis was performed with step-wise method with dependent variables such as intensive care units admission, partial pressure of oxygen saturation, and mortality. Also, independent variables such as hematological parameters, age and sex to assess variables that are likely to predict patients at risk of progression. Results: Patients in intensive care units had significantly higher mean absolute neutrophil count than outpatients (P < 0.001). There was a statistically significant difference in the mean absolute lymphocyte count between dead and survived patients (P = 0.015). Multivariate analysis confirmed the positive association of the white blood cells (P < 0.001), absolute neutrophil count (P < 0.004), red cell distribution width (P < 0.001), and lactate dehydrogenase (P = 0.007) to be positively associated with the admission of Covid-19 patients in the intensive care units and the absolute monocyte count (P = 0.012, Odds ratios = 0.100, CI95% = 0.066-0.605) to be negatively associated with mortality. Conclusion: Based on the results of our study, it is recommended to use hematological data to make clinical decisions and evaluate the patient's prognosis.

The prevalence of pulmonary arterial hypertension in patients with mixed connective tissue disease: a systematic review and meta-analysis.

OBJECTIVES: The prevalence and outcome of mixed connective tissue disease-associated pulmonary arterial hypertension (MCTD-PAH) has not been well understood. Our aim was to review the current knowledge on the prevalence, severity, and mortality of MCTD-PAH. We also aimed to examine the prevalence trend of MCTD-PAH over the years. METHODS: PubMed/Medline, Embase, Scopus and Web of Science electronic databases were searched for the published randomised controlled clinical trials (RCTs) and observational/original studies on PAH in patients with MCTD from January 1972 to December 2020. RESULTS: The results were pooled using random-effects meta-analysis based on DerSimonian and Laird method. A total of 983 patients from eight studies were included in the meta-analysis (K=8, n=983). Pooled prevalence of PAH in MCTD patients was 12.53% [95% CI 8.30-18.48%] with significant level statistical heterogeneity (tau2=0.30, tau=0.55, i2 83.3%, H=2.13 Q(df,7)=31.90, p=0.001). There was no association between PAH and female gender or age. The percentage of deaths in MCTD patients due to PAH varied and reached up to 81.8%. CONCLUSIONS: This is the first systematic review and meta-analysis investigating the prevalence of PAH in patients with MCTD and it revealed an overall prevalence of PAH in patients with MCTD of 12.53%. Our results showed trends of reduced prevalence of MCTD-PAH over last four decade, reconfirmed the lower prevalence rate in recent studies, but revealed an increased mortality rate. We also determined the low impact of the age, gender, and interstitial lung disease on MCTD-PAH.

Sex-specific differences in the circadian pattern of action potential firing by rat suprachiasmatic nucleus vasopressin neurons.

The suprachiasmatic nucleus (SCN) of the hypothalamus serves as the master circadian clock in mammals. Most SCN neurons express the inhibitory neurotransmitter GABA (gamma amino butyric acid) along with a peptide cotransmitter. Notably, the neuropeptides vasopressin (VP) and vasoactive intestinal peptide (VIP) define two prominent clusters within the SCN: those located in the ventral core (VIP) and those forming the dorsomedial "shell" of the nucleus (VP). Axons emerging from VP neurons in the shell are thought to mediate much of the SCN's output to other brain regions as well as VP release into the cerebrospinal fluid (CSF). Previous work has shown that VP release by SCN neurons is activity dependent and SCN VP neurons fire action potentials at a higher rate during the light phase. Accordingly, CSF VP levels are higher during daytime. Interestingly, the amplitude of the CSF VP rhythm is greater in males than females, suggesting the existence of sex differences in the electrical activity of SCN VP neurons. Here we investigated this hypothesis by performing cell-attached recordings from 1070 SCN VP neurons across the entire circadian cycle in both sexes of transgenic rats that express green fluorescent protein (GFP) driven by the VP gene promoter. Using an immunocytochemical approach we confirmed that >60% of SCN VP neurons display visible GFP. Recordings in acute coronal slices revealed that VP neurons display a striking circadian pattern of action potential firing, but the characteristics of this activity cycle differ in males and females. Specifically, neurons in males reached a significantly higher peak firing frequency during subjective daytime compared to females and the acrophase occurred ~1 h earlier in females. Peak firing rates in females were not significantly different at various phases of the estrous cycle.

A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial.

BACKGROUND: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. METHODS: VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will be followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. DISCUSSION: VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. TRIAL REGISTRATION: ISRCTN67321719 . Prospectively registered on 14 September 2020.