Assessing the Clinical Efficacy of a Virtual Reality Tool for the Treatment of Obesity: Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) interventions, based on cognitive behavioral therapy principles, have been proven effective as complementary tools in managing obesity and have been associated with promoting healthy behaviors and addressing body image concerns. However, they have not fully addressed certain underlying causes of obesity, such as a lack of motivation to change, low self-efficacy, and the impact of weight stigma interiorization, which often impede treatment adherence and long-term lifestyle habit changes. To tackle these concerns, this study introduces the VR self-counseling paradigm, which incorporates embodiment and body-swapping techniques, along with motivational strategies, to help people living with obesity effectively address some of the root causes of their condition. OBJECTIVE: This study aims to assess the clinical efficacy of ConVRself (Virtual Reality self-talk), a VR platform that allows participants to engage in motivational self-conversations. METHODS: A randomized controlled trial was conducted with 68 participants from the bariatric surgery waiting list from the obesity unit of the Vall d'Hebron University Hospital in Barcelona, Spain. Participants were assigned to 1 of 3 groups: a control group (CG), which only received treatment as usual from the obesity unit; experimental group 1 (EG1), which, after intensive motivational interviewing training, engaged in 4 sessions of VR-based self-conversations with ConVRself, and underwent embodiment and body-swapping techniques; and experimental group 2 (EG2), which engaged in 4 VR-based sessions led by a virtual counselor with a prerecorded discourse, and only underwent the embodiment technique. In the case of both EG1 and EG2, the VR interventions were assisted by a clinical researcher. Readiness to change habits, eating habits, and psychological variables, as well as adherence and satisfaction with ConVRself were measured at baseline, after the intervention, 1 week after the intervention, and 4 weeks after the intervention. RESULTS: Regarding the primary outcomes, EG1 (24/68, 35%) and EG2 (22/68, 32%) showed significant improvements in confidence to lose weight compared to the CG (22/68, 32%) at all assessment points (ß=-.16; P=.02). Similarly, EG1 demonstrated a significant increase after the intervention in readiness to exercise more compared to the CG (ß=-.17; P=.03). Regarding the secondary outcomes, EG1 participants showed a significant reduction in uncontrolled eating (ß=.71; P=.01) and emotional eating (ß=.29; P=.03) compared to the CG participants, as well as in their anxiety levels compared to EG2 and CG participants (ß=.65; P=.01). In addition, participants from the experimental groups reported high adherence and satisfaction with the VR platform (EG1: mean 59.82, SD 4.00; EG2: mean 58.43, SD 5.22; d=0.30, 95% CI -0.30 to 0.89). CONCLUSIONS: This study revealed that using VR self-conversations, based on motivational interviewing principles, may have benefits in helping people with obesity to enhance their readiness to change habits and self-efficacy, as well as reduce dysfunctional eating behaviors and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT05094557; https://www.clinicaltrials.gov/study/NCT05094557.

The usefulness of the retina for identifying people with type 2 diabetes with prodromal stages of dementia.

Type 2 diabetes (T2D) is associated with cognitive impairment and dementia. The detection of cognitive impairment is important because this population is at higher risk of experiencing difficulties in the self-management of diabetes. Mild cognitive impairment (MCI) often remains undiagnosed due to lack of simple tools for screening at large scale. This represents an important gap in the patients' management because subjects with diabetes and MCI are at high risk of progressing to dementia. Due to its developmental origin as a brain-derived tissue, the retina has been proposed as a potential means of non-invasive and readily accessible exploration of brain pathology. Recent evidence showed that retinal imaging and/or functional tests are correlated with the cognitive function and brain changes in T2D. Simple retinal functional tests (i.e. retinal microperimetry) have proven to be useful as reliable tool for the cognitive evaluation and monitoring in patients with T2D>65 years. This review gives an overall update on the usefulness of retinal imaging in identifying patients with T2D at risk of developing dementia.

Recommendations on the management of severe obesity in patients with inflammatory bowel disease of the Spanish Group on Crohn's Disease and Ulcerative Colitis (GETECCU), Spanish Society of Obesity (SEEDO), Spanish Association of Surgery (AEC) and Spanish Society of Digestive Endoscopy (SEED). / Recomendaciones sobre el manejo de la obesidad grave en pacientes con enfermedad inflamatoria intestinal del Grupo Español de Trabajo en Enfermedad Inflamatoria Intestinal (GETECCU), Sociedad Española de Obesidad (SEEDO), Asociación Española de Cirugía (AEC) y Sociedad Española de Endoscopia Digestiva (SEED).

Obesity is a multifactorial, chronic, progressive and recurrent disease considered a public health issue worldwide and an important determinant of disability and death. In Spain, its current prevalence in the adult population is about 24% and an estimated prevalence in 2035 of 37%. Obesity increases the probability of several diseases linked to higher mortality such as diabetes, cardiovascular disease, hyperlipidemia, arterial hypertension, non-alcoholic fatty liver disease, several types of cancer, or obstructive sleep apnea. On the other hand, although the incidence of inflammatory bowel disease (IBD) is stabilizing in Western countries, its prevalence already exceeds 0.3%. Paralleling to general population, the current prevalence of obesity in adult patients with IBD is estimated at 15-40%. Obesity in patients with IBD could entail, in addition to its already known impact on disability and mortality, a worse evolution of the IBD itself and a worse response to treatments. The aim of this document, performed in collaboration by four scientific societies involved in the clinical care of severe obesity and IBD, is to establish clear and concise recommendations on the therapeutic possibilities of severe or typeIII obesity in patients with IBD. The document establishes general recommendations on dietary, pharmacological, endoscopic, and surgical treatment of severe obesity in patients with IBD, as well as pre- and post-treatment evaluation.

Revisional Robotic Bariatric Surgery. Largest Single Centre Prospective Cohort Study and Review of the Literature.

Introduction: Robotic bariatric surgery (RBS) has seen a surge in popularity in recent years, yet questions persist about its utility concerning postoperative complications, costs, and technical aspects. RBS, while increasing in number, presents a greater technical challenge associated with more post-operative complications compared to primary bariatric surgery. In this study, we present our single institution experience and review the literature to assess the value of robotic revisional surgery. Material and Method: The retrospective review involved 42 patients (31 females, 11 males) who underwent various procedures, with the most frequent being the conversion of sleeve gastrectomy to gastric bypass (n=30). Encouragingly, no leaks or severe complications were identified. Furthermore, a systematic review indicated comparable outcomes, with decreased complication rates favoring robotic revisional surgery. Results: In direct comparison to standard laparoscopic revisional bariatric surgery, revisional robotic surgery demonstrated superior results in terms of efficacy, safety, and reduced hospital stay. However, rates of mortality, morbidity, and reintervention did not significantly differ between the two approaches. Conclusions: Considering these findings, we advocate for surgeons to acquire proficiency in the robotic technique, as part of the broader process of democratization and standardization of bariatric surgery. Embracing revisional robotic bariatric surgery can lead to improved patient outcomes, and its wider implementation may lead to enhanced surgical care and patient satisfaction in the field of bariatric procedures.

Accuracy of a sequential algorithm based on FIB-4 and ELF to identify high-risk advanced liver fibrosis at the primary care level.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, and liver fibrosis is the strongest predictor of morbimortality. We aimed to assess the performance of a sequential algorithm encompassing the Fibrosis 4 (FIB-4) and Enhanced Liver Fibrosis (ELF) scores for identifying patients at risk of advanced fibrosis. This cross-sectional study included one hospital-based cohort with biopsy-proven NAFLD (n = 140) and two primary care cohorts from different clinical settings: Type 2 Diabetes (T2D) follow-up (n = 141) and chronic liver disease (CLD) initial study (n = 138). Logistic regression analysis was performed to assess liver fibrosis diagnosis models based on FIB-4 and ELF biomarkers. The sequential algorithm retrieved the following accuracy parameters in predicting stages F3-4 in the biopsy-confirmed cohort: sensitivity (85%), specificity (73%), negative predictive value (79%) and positive predictive value (81%). In both T2D and CLD cohorts, a total of 28% of patients were classified as stages F3-4. Furthermore, of all F3-4 classified patients in the T2D cohort, 80% had a diagnosis of liver disease and 44% were referred to secondary care. Likewise, of all F3-4 classified patients in the CLD cohort, 71% had a diagnosis of liver disease and 44% were referred to secondary care. These results suggest the potential utility of this algorithm as a liver fibrosis stratifying tool in primary care, where updating referral protocols to detect high-risk F3-4 is needed. FIB-4 and ELF sequential measurement is an efficient strategy to prioritize patients with high risk of F3-4 in populations with metabolic risk factors.

Assessment of obesity stigma and discrimination among Spanish subjects with a wide weight range: the OBESTIGMA study.

Introduction: This study aims to assess the extent of rejection and instances of stigmatization linked to obesity within the Spanish population, encompassing a diverse spectrum of weights ranging from normal weight to morbid obesity. Additionally, the study seeks to identify the primary factors influencing these experiences and further examines the impact of bariatric surgery on such dynamics. Materials and methods: Multicenter observational study with involving a total of 1,018 participants who were recruited from various Obesity Units. Negatives attitudes towards people with obesity were assessed through three questionnaires: (i) Antifat Attitudes Scale (AFA), (ii) Stigmatizing Situations Inventory (SSI) and (iii) Weight Bias Internalization Scale (WBIS). Subjects were categorized into four groups based on their BMI and history of prior bariatric surgery. Results: The cumulative score across all questionnaires (AFA, SSI and WBIS) exhibited a progressive increase, from participants with normal weight to those with obesity (p < 0.001 for all). Within the AFA questionnaire, males showed more rejection towards people with obesity than women, also perceiving obesity as a disease linked to a lack of willpower (p = 0.004 and p = 0.030, respectively). The overall SSI score was negatively associated with age (r = -0.080, p = 0.011), with young participants encountering more stigmatizing experiences than their adult counterparts. Neither employment status nor educational demonstrated a significant association with any of the questionnaires. Interestingly, patients who underwent lost weight following bariatric surgery did not exhibit improved outcomes. Conclusion: Individuals with obesity demonstrate a heightened level of aversion towards the disease compared to those with normal weight. Concurrently, the incidence of stigmatizing encounters displays a concerning escalation among younger individuals.

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.

Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS-/-) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS-/- mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS-/- livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Comparison of computed tomography and dual-energy X-ray absorptiometry in the evaluation of body composition in patients with obesity.

Objective: a) To evaluate the accuracy of the pre-existing equations (based on cm2 provided by CT images), to estimate in kilograms (Kg) the body composition (BC) in patients with obesity (PwO), by comparison with Dual-energy X-ray absorptiometry (DXA). b) To evaluate the accuracy of a new approach (based on both cm2 and Hounsfield Unit parameters provided by CT images), using an automatic software and artificial intelligence to estimate the BC in PwO, by comparison with DXA. Methods: Single-centre cross-sectional study including consecutive PwO, matched by gender with subjects with normal BMI. All the subjects underwent BC assessment by Dual-energy X-ray absorptiometry (DXA) and skeletal-CT at L3 vertebrae. CT images were processed using FocusedON-BC software. Three different models were tested. Model 1 and 2, based on the already existing equations, estimate the BC in Kg based on the tissue area (cm2) in the CT images. Model 3, developed in this study, includes as additional variables, the tissue percentage and its average Hounsfield unit. Results: 70 subjects (46 PwO and 24 with normal BMI) were recruited. Significant correlations for BC were obtained between the three models and DXA. Model 3 showed the strongest correlation with DXA (r= 0.926, CI95% [0.835-0.968], p<0.001) as well as the best agreement based on Bland - Altman plots. Conclusion: This is the first study showing that the BC assessment based on skeletal CT images analyzed by automatic software coupled with artificial intelligence, is accurate in PwO, by comparison with DXA. Furthermore, we propose a new equation that estimates both the tissue quantity and quality, that showed higher accuracy compared with those currently used, both in PwO and subjects with normal BMI.

Virtual self-conversation using motivational interviewing techniques to promote healthy eating and physical activity: A usability study.

Introduction: We aim to examine the usability of a Virtual Reality (VR) platform, called ConVRSelf, which has been designed to address the needs of People Living With Obesity (PLWO). Methods: Fourteen participants with a desire to eat healthier and exercise more (6 normal weight and 8 PLWO; Mean age = 41.86, SD = 13.89) were assigned to the experimental group (EG) or the control group (CG). EG participants, after being trained on motivational interviewing skills, engaged in a virtual self-conversation using embodiment and body swapping techniques, which aimed to normalize and resolve their ambivalence to change lifestyle habits. CG participants, embodied in their virtual bodies, participated in a pre-established discourse with a virtual counselor giving them psychoeducational advice about how to change lifestyle habits. A mixed-methods design was used, involving a semi-structured interview and self-report questionnaires, including readiness to change habits (Readiness Rulers), body ownership (Body Ownership Questionnaire, BOQ), and system usability (System Evaluation Questionnaire, SEQ). Thematic content analysis was carried out for qualitative data while statistical data analysis was carried out using SPSS 20.0. Results: Participants from both groups showed high readiness to change lifestyle (Readiness Rulers) before engaging with the virtual experiences, which was maintained at the same level after the interventions and their scores on the SEQ and BOQ were satisfactory. Regarding qualitative information obtained from the interviews, almost all participants found the VR experience to be novel, interesting, and enjoyable. A higher acceptability was observed among PLWO from the EG than normal weight participants from the same group, a promising finding for the ConVRSelf platform, which had been specifically designed to address the needs of PLWO. Conclusion: The ConVRSelf system is well-accepted by participants and is ready to be tested with PLWO in a clinical setting.

The Footprint of Type 1 Diabetes on Red Blood Cells: A Metabolomic and Lipidomic Study.

The prevalence of diabetes type 1 (T1D) in the world populations is continuously growing. Although treatment methods are improving, the diagnostic is still symptom-based and sometimes far after onset of the disease. In this context, the aim of the study was the search of new biomarkers of the disease in red blood cells (RBCs), until now unexplored. The metabolomic and the lipidomic profile of RBCs from T1D patients and matched healthy controls was determined by NMR spectroscopy, and different multivariate discrimination models were built to select the metabolites and lipids that change most significantly. Relevant metabolites were further confirmed by univariate statistical analysis. Robust separation in the metabolomic and lipidomic profiles of RBCs from patients and controls was confirmed by orthogonal projection on latent structure discriminant analysis (OPLS-DA), random forest analysis, and significance analysis of metabolites (SAM). The main changes were detected in the levels of amino acids, organic acids, creatine and phosphocreatine, lipid change length, and choline derivatives, demonstrating changes in glycolysis, BCAA metabolism, and phospholipid metabolism. Our study proves that robust differences exist in the metabolic and lipidomic profile of RBCs from T1D patients, in comparison with matched healthy individuals. Some changes were similar to alterations found already in RBCs of T2D patients, but others seemed to be specific for type 1 diabetes. Thus, many of the metabolic differences found could be biomarker candidates for an earlier diagnosis or monitoring of patients with T1D.

Integrative and Collaborative Approach in the Chronic Management of Obesity in Primary and Tertiary Care Setting: Vall Hebron-SAP Muntanya Healthcare Route.

INTRODUCTION: In the context of obesity pandemic, the health care providers involved in the primary care should have a significant role. Several guidelines for the management of obesity in primary care were proposed recently. In general lines, these guidelines include recommendation on the baseline assessment, therapy, and algorithm for referral to specialized obesity clinic and follow-up. Nevertheless, at present, there is no guideline or protocol that continuously and bidirectionally links the two settings: primary care and specialized obesity clinic. METHODS: We present a model of continuous, bilateral, and integrative interaction between primary care units and reference tertiary care setting in the chronic management of obesity that is already implemented in a public health system. RESULTS: The novelty of our algorithm is that incorporates the support and continuous communication with the specialized obesity clinic of the tertiary care setting from the beginning in the management of a patient with obesity, in a bidirectional manner. CONCLUSION: This kind of bidirectional and continuous collaboration will help engage health care providers in the management of obesity, optimize efforts, shorten the time until proper intervention, personalize the approach and, finally, save costs for the health system.

Outcomes of Patients with Severe Obesity and Cirrhosis with Portal Hypertension Undergoing Bariatric Surgery: a Systematic Review.

PURPOSE: Thus far, little attention has been paid to bariatric surgery (BS) in patients with severe obesity (SO) and cirrhosis with portal hypertension (PH). To address this knowledge gap, we systematically reviewed the available literature and evidence about BS in patients with SO and cirrhosis with PH. We inform on the perioperative and long-term outcomes of this intervention. MATERIALS AND METHODS: Articles were identified in MEDLINE, SCOPUS, LILACS, and SCIELO, and included if they analyzed SO patients with clinically significant PH and reported the characteristics and outcomes of BS. RESULTS: Six articles, including 32 patients, were included. The most frequent type of BS was sleeve gastrectomy performed in 27 patients. Perioperative transfusions were often not required, with only one case report describing the use of 1 unit of packed red blood cells post-operatively. Neither intraoperative nor post-op deaths were reported. All patients reported significant weight loss with improvements in comorbidities during the follow-up periods. Overall, 27 out of 29 patients had T2DM resolution, and 13 out of 23 had arterial hypertension resolution. One study reported improvements in the parameters of fibroscan. CONCLUSION: This systematic review described the outcomes of BS among patients with SO with cirrhosis and PH. Performing this kind of surgery among these patients appears safe and associated with acceptable perioperative and long-term outcomes. However, further studies are required to provide evidence-based, strong recommendations.

NAFLD as the metabolic hallmark of obesity.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, associated with a high risk of progression to NASH, liver cirrhosis and hepatocarcinoma. Its prevalence is closely related to obesity (understood as adipose-based disease and insulin resistance), which makes that at present NAFLD can be considered a metabolic dysfunction hallmark, regardless of the body mass index. Despite being such a prevalent condition, with such severe consequences, at present there are no reliable biomarkers for its diagnosis or specific treatment. Significant and sustained weight loss, as well as some antidiabetic treatments, has shown promising results for NAFLD but data needs confirmation in larger clinical trials and longer follow-up. Efforts should be made for a better and more accurate baseline diagnosis (including large-scale genetics), identification of patients at higher risk for progression to NASH as well as adequate treatment, to allow us to offer a personalized approach in NAFLD in the context of precision medicine.

New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes.

The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a "window" to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry.

Protein Supplementation with Short Peptides Prevents Early Muscle Mass Loss after Roux-en-Y-Gastric Bypass.

Introduction: A significant reduction in fat-free mass (FFM) following bariatric surgery (BS) has been reported, and adequate protein intake is recommended for FFM preservation. Current guidelines of nutritional management after BS recommend complex protein (CP) compounds. However, Roux-en-Y-gastric bypass (RYGB) has a negative impact on CP digestion, leading to protein malabsorption. At present, there is no data regarding the impact of early supplementation with short peptide-based (SPB) or hydroxy methylbutyrate (HMB)-enriched formulas on the evolution of the FFM after the BS. Aim: The aim of this study is to evaluate the effect of nutritional products based on CP, HBM-enriched, or SPB formulas on the FFM of patients that undergo RYGB. Material and methods: This is a prospective interventional study, including three groups of patients (according to the type of protein product) as candidates for BS, recruited between December 2021 and April 2022, matched by age, gender, and BMI. All patients underwent evaluations at baseline and one month post-BS, including: medical history, physical and anthropometric evaluation, bioimpedance, and biochemical analysis. Results: A total of 60 patients were recruited: 63% women, mean age 43.13 ± 9.4 years, and BMI 43.57 ± 4.1 kg/m2. The % of FFM loss from total weight loss (TWL) was significantly lower in the SPB group than CP and HMB groups despite the major %TWL in this group (40.60 ± 17.27 in CP, 34.57 ± 13.15 in HMB, and 19.14 ± 9.38 in SPB, p < 0.001). TWL% was 9.98 ± 1.82 vs. 9.83 ± 2.71 vs. 13.56 ± 4.30, p < 0.001, respectively. Conclusion: In our study, the SPB supplementation prevented almost 50% FFM lost from the TWL than the CP- or HMB-enriched compounds at one month post-BS. These results are significant in the setting of muscle mass preservation after the BS, and have the potential to change the current guidelines for the management of nutritional supplementation after BS.

Risk of infections in patients with NAFLD and Type 2 Diabetes under treatment with SGLT2 inhibitors and relationship with liver outcomes: A retrospective case-control study.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries, with its incidence growing parallel to the epidemics of obesity and type 2 diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are becoming a cornerstone in the management of cardiovascular health and some studies suggest the potential role in NAFLD. However, patients under treatment with SGLT2i are at risk of developing genitourinary fungal infections (GFIs). Moreover, both NAFLD and SGLT2i have a strong influence on the immune system, and therefore the risk of infections other than GFIs could be increased in NAFLD patients treated with SGLT2i. We aimed to examine the possible association of SGLT2i with infections and hepatic outcomes in NAFLD patients. Methods: We conducted a case-control study including NAFLD patients with T2DM visited at the Liver Unit outpatient clinic from 2016 to 2021 with a minimum follow-up of 6 months by selecting 65 patients receiving SGLT2i and 130 matched patients with other types of antidiabetic treatment. Results: During follow-up, GFIs were significantly higher in the SGLT2i group (15.4% vs. 3.8%; p=0.008), whereas there were no differences in the occurrence of overall infections (41.5% vs. 30%; p=0.1) nor in other types of specific infections. In the multivariable analysis, treatment with SGLT2i was not independently associated with higher odds of overall infection. On the other hand, SGLT2i patients showed a significantly lower incidence of hepatic events (1.5% vs. 10.7%; p=0.02). There were no significant different in all-cause mortality between cases and controls. Conclusions: NAFLD patients with T2DM receiving SGLT2i more frequently presented GFIs, whereas the incidence of other types of infections was not found to be higher than in other patients with NAFLD and T2DM treated with other drugs. Moreover, SGLT2i-treated patients had a lower occurrence of hepatic events. Further studies are warranted to validate our data.

Enterohepatic Shunt-Driven Cholemia Predisposes to Liver Cancer.

BACKGROUND & AIMS: Pathogenesis of hepatocellular carcinoma (HCC), which kills millions annually, is poorly understood. Identification of risk factors and modifiable determinants and mechanistic understanding of how they impact HCC are urgently needed. METHODS: We sought early prognostic indicators of HCC in C57BL/6 mice, which we found were prone to developing this disease when fed a fermentable fiber-enriched diet. Such markers were used to phenotype and interrogate stages of HCC development. Their human relevance was tested using serum collected prospectively from an HCC/case-control cohort. RESULTS: HCC proneness in mice was dictated by the presence of congenitally present portosystemic shunt (PSS), which resulted in markedly elevated serum bile acids (BAs). Approximately 10% of mice from various sources exhibited PSS/cholemia, but lacked an overt phenotype when fed standard chow. However, PSS/cholemic mice fed compositionally defined diets, developed BA- and cyclooxygenase-dependent liver injury, which was exacerbated and uniformly progressed to HCC when diets were enriched with the fermentable fiber inulin. Such progression to cholestatic HCC associated with exacerbated cholemia and an immunosuppressive milieu, both of which were required in that HCC was prevented by impeding BA biosynthesis or neutralizing interleukin-10 or programmed death protein 1. Analysis of human sera revealed that elevated BA was associated with future development of HCC. CONCLUSIONS: PSS is relatively common in C57BL/6 mice and causes silent cholemia, which predisposes to liver injury and HCC, particularly when fed a fermentable fiber-enriched diet. Incidence of silent PSS/cholemia in humans awaits investigation. Regardless, measuring serum BA may aid HCC risk assessment, potentially alerting select individuals to consider dietary or BA interventions.

When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD.

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.

Clinical efficacy of a virtual reality tool for the treatment of obesity: study protocol of a randomised controlled trial.

INTRODUCTION: Previous research has shown that it is feasible to integrate motivational interviewing techniques with behavioural and psychological interventions for the treatment of obesity. Moreover, these combined interventions have the potential to improve health-related outcomes of people living with obesity (PLWO) and to afford maintenance of behavioural changes over time. In addition, the use of virtual reality (VR) embodiment techniques in the treatment of eating disorders and obesity has promising preliminary effectiveness. The objective of this study is to assess the clinical efficacy of a VR intervention that uses embodiment and body-swapping techniques and has been specifically developed to cover the needs of PLWO. METHODS AND ANALYSIS: A randomised control trial will be carried out with an estimated sample of 96 participants with body mass index (BMI)>30. The whole duration of the trial will be 12 months. Participants will be recruited from the external consultations of the Vall d'Hebron University Hospital and be randomly assigned to three groups. The experimental group 1 will engage in a virtual self-conversation using the ConVRself platform, the experimental group 2 will participate in a 'pre-established discourse' provided by the virtual counsellor, who will give psychoeducation advice, and the control group will continue with treatment as usual. Readiness to change, BMI, eating habits and physical activity, psychological well-being, body image satisfaction, quality of life in relation to body image, and weight bias internalisation will be assessed at baseline, post intervention, 1-week and 4-week follow-up. Finally, variables related to adherence and satisfaction with the VR tool will be evaluated for the experimental groups. ETHICS AND DISSEMINATION: This study was approved by the Research Projects Committee of the Vall d'Hebron University Hospital. Findings will be disseminated through peer-reviewed journals, reports to the funding body, conferences and other events for the scientific and clinical community, and the general public. TRIAL REGISTRATION NUMBER: NCT05094557.

Influence of Type 2 Diabetes in the Association of PNPLA3 rs738409 and TM6SF2 rs58542926 Polymorphisms in NASH Advanced Liver Fibrosis.

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in western countries. Insulin resistance (IR), type 2 diabetes (T2D), and the polymorphisms patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 are independent risk factors of NASH. Nevertheless, little is known about the interaction between IR and T2D with these polymorphisms in the pathogenesis of NASH and the development of advanced fibrosis. Thus, our study aimed to investigate this relationship. This is a cross-sectional study including NASH patients diagnosed by liver biopsy, at the Vall d'Hebron University Hospital. A total of 140 patients were included (93 T2D, 47 non-T2D). T2D (OR = 4.67; 95%CI 2.13−10.20; p < 0.001), PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms (OR = 3.94; 95%CI 1.63−9.54; p = 0.002) were independently related with advanced liver fibrosis. T2D increased the risk of advance fibrosis on top of the two polymorphisms (OR = 14.69; 95%CI 3.03−77.35; p = 0.001 for PNPLA3 rs738409 and OR = 11.45; 95%CI 3.16−41.55; p < 0.001 for TM6SF2 rs58542926). In non-T2D patients, the IR (HOMA-IR ≥ 5.2, OR = 14.33; 95%CI 2.14−18.66; p = 0.014) increased the risk of advanced fibrosis when the polymorphisms were present (OR = 19.04; 95%CI 1.71−650.84; p = 0.042). The T2D and IR status increase the risk of advanced fibrosis in patients with NASH carrying the PNPLA3 rs738409 and/or TM6SF2 rs58542926 polymorphisms, respectively.