Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

BACKGROUND: Perianal fistulas may affect 15% to 50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2). OBJECTIVE: Presenting real-world effectiveness data for darvadstrocel in a Spanish population. DESIGN: Observational retrospective cohort study with prospective data gathering. SETTINGS: The study was conducted at 14 institutions in Spain. PATIENTS: From November 2019 to April 2022, all patients (n = 73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery. INTERVENTIONS: Darvadstrocel treatment. MAIN OUTCOME MEASURES: Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, edema, or inflammation) evaluated 6 months after treatment. RESULTS: Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%), and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure, and vice versa. No serious adverse events were reported. LIMITATIONS: Retrospective nature of the study. CONCLUSIONS: Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract . USO DE DARVADSTROCEL TERAPIA CON CLULAS MADRE ALOGNICAS PARA FSTULA EN ENFERMEDAD DE CROHN EN LA PRCTICA CLNICA REAL EL PROYECTO NACIONAL PARA IMPLEMENTAR DE CLULAS MADRE MESENQUIMALES PARA EL TRATAMIENTO DE LA FSTULA DE CROHN PERIANAL EL ESTUDIO PRIME: ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco ).

Results of the national registry of patients diagnosed with inflammatory bowel disease candidates for bariatric surgery (ReNacEIBar).

BACKGROUND: Our aim is to carry out a national registry of patients with inflammatory bowel disease (IBD) who underwent bariatric surgery, as well as evaluate the results and management of this type of patients in the usual clinical practice. METHODS: National multicentric observational retrospective study, including patients, previously diagnosed with IBD who underwent bariatric surgery from January 2000 to December 2022. RESULTS: Forty-one patients have been included: 43,9% previously diagnosed with ulcerative colitis, 57,3% Crohn's disease, and an indeterminate colitis (2,4%). The preoperative BMI was 45.8 ± 6,1 kg/m2. Among the bariatric surgeries, 31 (75,6%) sleeve gastrectomy, 1 (2,4%) gastric bypass and 9 (22%) one anastomosis gastric have been carried out. During the postoperative period, 9.8% complications have been recorded. BMI was 29,5 ± 4,7 kg/m2 and percent total weight lost was 33,9 ± 9,1% at 12 months. CONCLUSIONS: Bariatric surgery in patients with inflammatory bowel disease can be considered safe and effective.

Multicentre, prospective, randomized control non-inferiority trial of bladder catheter management in colon surgery.

AIM: Perioperative bladder catheterization is a controversial issue. Most current recommendations are based on data from open surgery extrapolated to enhanced recovery after surgery or fast-track programmes ranging between 24 and 48 h. The aim of this study is to provide a rationale for reducing catheterization time while at the same time avoiding acute urine retention (AUR), in patients undergoing scheduled laparoscopic colon surgery. METHOD: This is a multicentre, prospective, controlled, randomized non-inferiority study of bladder catheter management in patients undergoing scheduled laparoscopic colon surgery, randomized into two groups: experimental (with catheter removal immediately after surgery) and control (with catheter removal 24 h post-surgery). The main outcome will be the development of AUR, and secondary outcomes the development of urinary infection within the first 30 days and hospital stay. Demographic, surgical and pathological variables will also be evaluated, especially the development of adverse effects assessed according to the Clavien scale and the Comprehensive Complication Index. Following the literature, we assume an incidence of AUR of 11% and a margin of non-inferiority (delta) of 8% and estimate that a sample size of 208 patients per group will be required (with an estimated 10% of losses per group). CONCLUSIONS: In this study we try to demonstrate that the bladder catheter can be removed immediately after scheduled laparoscopic colon surgery, without increasing acute urine retention. This measure would offers the benefits of earlier mobilization and reduces catheter-related morbidity.

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

BACKGROUND: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. METHODS/DESIGN: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. DISCUSSION: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home.

ECCO Topical Review: Roadmap to Optimal Peri-Operative Care in IBD.

BACKGROUND AND AIMS: Despite the advances in medical therapies, a significant proportion of patients with inflammatory bowel diseases [IBD] require surgical intervention. This Topical Review aims to offer expert consensus practice recommendations for peri-operative care to optimize outcomes of IBD patients who undergo surgery. METHODS: A multidisciplinary panel of IBD healthcare providers systematically reviewed aspects relevant to peri-operative care in IBD. Consensus statements were developed using Delphi methodology. RESULTS: A total of 20 current practice positions were developed following systematic review of the current literature covering use of medication in the peri-operative period, nutritional assessment and intervention, physical and psychological rehabilitation and prehabilitation, and immediate postoperative care. CONCLUSION: Peri-operative planning and optimization of the patient are imperative to ensure favourable outcomes and reduced morbidity. This Topical Review provides practice recommendations applicable in the peri-operative period in IBD patients undergoing surgery.

Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn's Disease.

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn's disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.

Accreditation of specialized surgical units in general and digestive surgery: A step forward by the AEC for quality improvement and subspecialized Fellowship training.

At present, in daily practice, the Departments of Surgery in most hospitals in Spain are organized into "Specialized Surgical Units", including specific structure, human resources, organization, teaching and research in the different subspecialties included in General and Digestive Surgery (GDS). Furthermore, there are also several specialized "fellowship-like", training programs in the different subspecialties already working in some of these "Specialized Surgical Units", although not officially financed. However, until now there was no model for accreditation or recognition of these Units or fellowship programs. The AEC has designed a regulation for the accreditation of Specialized Surgical Units in GDS, that will also serve as a model to define subspecialty training in these areas. The accreditation process, and with it, the process of quality improvement, includes different quality indicators, including unit structure, process quality, and result indicators.

Inflammatory Bowel Diseases Benefit from Enhanced Recovery After Surgery [ERAS] Protocol: A Systematic Review with Practical Implications.

BACKGROUND: Enhanced Recovery After Surgery [ERAS] is widely adopted in patients undergoing colorectal surgery, with demonstrated benefits. Few studies have assessed the feasibility, safety, and effectiveness of ERAS in patients with inflammatory bowel diseases [IBD]. The aim of this study was to investigate the current adoption and outcomes of ERAS in IBD. METHODS: This PRISMA-compliant systematic review of the literature included all articles reporting on adult patients with IBD who underwent colorectal surgery within an ERAS pathway. PubMed/MEDLINE, Cochrane Library, and Web of Science were searched. Endpoints included ERAS adoption, perioperative outcomes, and ERAS items more consistently reported, with associated evidence levels [EL] [PROSPERO CRD42021238653]. RESULTS: Out of 217 studies, 16 totalling 2347 patients were included. The median number of patients treated was 50.5. Malnutrition and anaemia optimisation were only included as ERAS items in six and four articles, respectively. Most of the studies included the following items: drinking clear fluids until 2 h before the surgery, fluid restriction, nausea prophylaxis, early feeding, and early mobilisation. Only two studies included postoperative stoma-team and IBD-team evaluation before discharge. Highest EL were observed for ileocaecal Crohn's disease resection [EL2]. Median in-hospital stay was 5.2 [2.9-10.7] days. Surgical site infections and anastomotic leaks ranged between 3.1-23.5% and 0-3.4%, respectively. Complications occurred in 5.7-48%, and mortality did not exceed 1%. CONCLUSIONS: Evidence on ERAS in IBD is lacking, but this group of patients might benefit from consistent adoption of the pathway. Future studies should define if IBD-specific ERAS pathways and selection criteria are needed.

Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial.

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40-60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40-60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50-58% of the 40-60 mg/Kg/day DFO-treated patients.

Accreditation of specialized surgical units in general and digestive surgery: A step forward by the AEC for quality improvement and subspecialized Fellowship training. / Acreditación de unidades quirúrgicas especializadas en cirugía general y aparato digestivo: un paso de la Asociación Española de Cirujanos para mejorar la calidad asistencial y la formación subespecializada tipo fellowship.

At present, in daily practice, the Departments of Surgery in most hospitals in Spain are organized into "Specialized Surgical Units", including specific structure, human resources, organization, teaching and research in the different subspecialties included in General and Digestive Surgery (GDS). Furthermore, there are also several specialized "fellowship-like", training programs in the different subspecialties already working in some of these "Specialized Surgical Units", although not officially financed. However, until now there was no model for accreditation or recognition of these Units or fellowship programs. The AEC has designed a regulation for the accreditation of Specialized Surgical Units in GDS, that will also serve as a model to define subspecialty training in these areas. The accreditation process, and with it, the process of quality improvement, includes different quality indicators, including unit structure, process quality, and result indicators.

Crohn's Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat.

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn's disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn's disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms' tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn's disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen-DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn's disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn's disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn's disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

Patient-Reported Outcome Measures in Colorectal Surgery: Construction of Core Measures Using Open-Source Research Method.

Purpose. The primary aim of the study was to review the existing literature about patient-reported outcome measures (PROMs) in colorectal cancer and IBD. The secondary aim was to present a road map to develop a core outcome set via opinion gathering using social media. Method. This study is the first step of a three-step project aimed at constructing simple, applicable PROMs in colorectal surgery. This article was written in a collaborative manner with authors invited both through Twitter via the #OpenSourceResearch hashtag. The 5 most used PROMs were presented and discussed as slides/images on Twitter. Inputs from a wide spectrum of participants including researchers, surgeons, physicians, nurses, patients, and patients' organizations were collected and analyzed. The final draft was emailed to all contributors and 6 patients' representatives for proofreading and approval. Results. Five PROM sets were identified and discussed: EORTC QLQ-CR29, IBDQ short health questionnaire, EORTC QLQ-C30, ED-Q5-5L, and Short Form-36. There were 315 tweets posted by 50 tweeters with 1458 retweets. Awareness about PROMs was generally limited. The general psycho-physical well-being score (GPP) was suggested and discussed, and then a survey was conducted in which more than 2/3 of voters agreed that GPP covers the most important aspects in PROMs. Conclusion. Despite the limitations of this exploratory study, it offered a new method to conduct clinical research with opportunity to engage patients. The general psycho-physical well-being score suggested as simple, applicable PROMs to be eventually combined procedure-specific, disease-specific, or symptom-specific PROMs if needed.

Postoperative Complications in Hemorrhoidal Disease and Special Conditions.

BACKGROUND: Hemorrhoidal disease is still one of the most prevalent proctological diseases. Pain is the most common complication after surgery but bleeding, urinary retention and perianal infection are also frequent. There is also an important group of patients, such as those with inflammatory bowel disease, pregnancy or immunosuppression, who can present an increased rate or more severe complications. OBJECTIVE: To describe the complications following different surgical and instrumental techniques for hemorrhoids in a literature review. Special situations were reviewed to determine how they affect the management of the disease. METHODS: During August 2019, a narrative review of hemorrhoid surgery complications and special situations was performed using the Pubmed MESH DATABASE. CONCLUSION: Pain, urinary retention and bleeding remain the most frequent complications after surgery for hemorrhoids; however, special situations must be taken into account in order to choose the best technique to prevent more severe complications.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. AIM: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. METHODS: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). RESULTS: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. CONCLUSIONS: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Adipose stem cells from patients with Crohn's disease show a distinctive DNA methylation pattern.

BACKGROUND: Crohn's disease (CD) is characterized by persistent inflammation and ulceration of the small or large bowel, and expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-derived stem cells (hASCs) from CF of patients with CD exhibit dysfunctional phenotypes, including a pro-inflammatory profile, high phagocytic capacity, and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission and are found in all adipose depots explored including subcutaneous fat. We hypothesized that changes in hASCs are a consequence of epigenetic modifications. METHODS: We applied epigenome-wide profiling with a methylation array (Illumina EPIC/850k array) and gene expression analysis to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat of patients with CD and healthy controls (n = 7 and 5, respectively; cohort I). Differentially methylated positions (p value cutoff < 1 × 10-4 and ten or more DMPs per gene) and regions (inclusion threshold 0.2, p value cutoff < 1 × 10-2 and more than 2 DMRs per gene) were identified using dmpfinder and Bumphunter (minfi), respectively. Changes in the expression of differentially methylated genes in hASCs were validated in a second cohort (n = 10/10 inactive and active CD and 10 controls; including patients from cohort I) and also in peripheral blood mononuclear cells (PBMCs) of patients with active/inactive CD and of healthy controls (cohort III; n = 30 independent subjects). RESULTS: We found a distinct DNA methylation landscape in hASCs from patients with CD, leading to changes in the expression of differentially methylated genes involved in immune response, metabolic, cell differentiation, and development processes. Notably, the expression of several of these genes in hASCs and PBMCs such as tumor necrosis factor alpha (TNFA) and PR domain zinc finger protein 16 (PRDM16) were not restored to normal (healthy) levels after disease remission. CONCLUSIONS: hASCs of patients with CD exhibit a unique DNA methylation and gene expression profile, but the expression of several genes are only partially restored in patients with inactive CD, both in hASCs and PBMCs. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies. Human adipose-stem cells isolated from subcutaneous fat of patients with Crohn's disease exhibit an altered DNA methylation pattern and gene expression profile compared with those isolated from healthy individuals, with immune system, cell differentiation, metabolic and development processes identified as the main pathways affected. Interestingly, the gene expression of several genes involved in these pathways is only partially restored to control levels in patients with inactive Crohn's disease, both in human adipose-stem cells and peripheral blood mononuclear cells. Understanding how Crohn's disease shapes the functionality of human adipose-stem cells is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.

A video guide of five access methods to the splenic flexure: the concept of the splenic flexure box.

AIM: The aim of this study was to describe all the possible approaches for laparoscopic splenic flexure mobilization (SFM), each suitable for specific situations, and create an illustrated system to show SFM approaches in an easy and practical way to make it easy to learn and teach. METHODS: Two different phases. First part: Cadaver-based study of the colonic splenic flexure anatomy. In order to demonstrate the different approaches, a balloon was placed through the colonic hepatic flexure in the lesser sac without sectioning any of the fixing ligaments of the splenic flexure. Second part: A real case series of laparoscopic SFM. RESULTS: First part: 11 cadavers were dissected. Five potential approaches to SFM were found: anterior, trans-omentum, lateral, medial infra-mesocolic, and medial trans-mesocolic. The illustrative system developed was named: Splenic Flexure "Box"(SFBox). Second part: One of the types of SFM described in first part was used in five patients with colorectal cancer. Each laparoscopic approach to the splenic flexure was illustrated in a video accompanied by illustration aids delineating the access. CONCLUSION: With the cadaver dissection and subsequent demonstration in real-life laparoscopic surgery, we have shown five types of laparoscopic splenic flexure mobilization. The Splenic Flexure "Box" is a useful way to learn and teach this surgical maneuver.

Minimizing the impact of colorectal surgery in the older patient: The role of enhanced recovery programs in older patients.

Enhanced recovery after surgery (ERAS) programs are multimodal treatment bundles designed with the aim to decrease the perioperative stress response to surgical trauma and reduce complication rates with elective surgery. They include different items in the preoperative, intra-operative, and postoperative phases that are based on prospective randomized trials with different grades of evidence. Their use is widespread in colorectal surgery and they have been proven to improve outcomes. Older patients are a specific group of patients with particular needs, due to age-related decline in physiological reserve and functional capacity, and frequent co-morbidity. There has been some hesitation to apply ERAS pathways in the older population, because of a lower compliance with the ERAS measures and a higher postoperative morbidity in these patients. However, recent studies have shown that most elements of the ERAS programs can be applied safely in older patients with the same benefits in reducing general complications and perioperative mortality as in younger patients.

Correlation of blood biomarkers with early-onset seizures after an acute stroke event.

INTRODUCTION: Blood biomarkers have not been widely studied in stroke-related seizures. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and to analyze their association with early-onset seizures. METHODS: We retrospectively evaluated a panel of 14 blood biomarkers in 1115 patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z scores. We also recorded stroke and epilepsy-related variables, including stroke severity (National Institute of Health Stroke Scale [NIHSS] scores), type, and causes, time from onset of stroke to occurrence of early seizures, and type of seizure. Adjusted logistic regression models were built to identify clinical variables and biomarkers independently associated with early seizures. RESULTS: Mean ±â€¯standard deviation (SD) age was 72.3 ±â€¯13.2 years, and 56.8% of the patients were men. Thirty-eight patients (3.9%) developed early seizures with a median time to onset of 1 day (interquartile range (IQR), 0-4). A higher NIHSS score (odds ratio [OR] = 1.046; 95% confidence interval (CI): 1.001-1.094; p = 0.044) and hemorrhagic stroke (OR = 2.133; 95% CI: 1.010-4.504; p = 0.047) were independently associated with a greater risk of early seizures. Independent blood biomarkers predictive of early seizures were lower levels of tumor necrosis factor receptor 1 (TNF-R1) (<0.013) (p = 0.006; OR = 3.334; 95% CI: 1.414-7.864) and higher levels of neural cell adhesion molecule (NCAM) (>0.326) (p = 0.009; OR = 2.625; 95% CI: 1.271-5.420). The predictive power of the regression model was greater when clinical variables were combined with blood biomarkers (73.5%; 95% CI: 65.1%-81.9%) than when used alone (64%; 95% CI: 55%-72.9%). CONCLUSION: Higher NCAM and lower TNF-R1 levels may help predict the occurrence of early seizures. The combined use of these biomarkers and clinical variables could be useful for identifying patients at risk of seizures. This article is part of the Special Issue "Seizures & Stroke".

Revalidation of the RACE scale after its regional implementation in Catalonia: a triage tool for large vessel occlusion.

BACKGROUND AND PURPOSE: Our aim was to revalidate the RACE scale, a prehospital tool that aims to identify patients with large vessel occlusion (LVO), after its region-wide implementation in Catalonia, and to analyze geographical differences in access to endovascular treatment (EVT). METHODS: We used data from the prospective CICAT registry (Stroke Code Catalan registry) that includes all stroke code activations. The RACE score evaluated by emergency medical services, time metrics, final diagnosis, presence of LVO, and type of revascularization treatment were registered. Sensitivity, specificity, and area under the curve (AUC) for the RACE cut-off value ≥5 for identification of both LVO and eligibility for EVT were calculated. We compared the rate of EVT and time to EVT of patients transferred from referral centers compared with those directly presenting to comprehensive stroke centers (CSC). RESULTS: The RACE scale was evaluated in the field in 1822 patients, showing a strong correlation with the subsequent in-hospital evaluation of the National Institute of Health Stroke Scale evaluated at hospital (r=0.74, P<0.001). A RACE score ≥5 detected LVO with a sensitivity 0.84 and specificity 0.60 (AUC 0.77). Patients with RACE ≥5 harbored a LVO and received EVT more frequently than RACE <5 patients (LVO 35% vs 6%; EVT 20% vs 6%; all P<0.001). Direct admission at a CSC was independently associated with higher odds of receiving EVT compared with admission at a referral center (OR 2.40; 95% CI 1.66 to 3.46), and symtoms onset to groin puncture was 133 min shorter. CONCLUSIONS: This large validation study confirms RACE accuracy to identify stroke patients eligible for EVT, and provides evidence of geographical imbalances in the access to EVT to the detriment of patients located in remote areas.

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer.

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.