Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA.

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

Higher serum prealbumin levels are associated with higher graft take and wound healing in adult burn patients: A prospective observational trial.

INTRODUCTION: Nutritional support is essential in burn care. There are few studies investigating the effect of nutrition on burn healing. The purpose of this study was to determine the relationship between perioperative serum prealbumin levels and the probability of autologous skin graft take in burned patients. MATERIALS AND METHODS: A prospective observational study was carried out with burned adults recruited consecutively from April 2019 until September 2021. Serum prealbumin was determined perioperatively. The percentage of graft take was evaluated over the first 5 postoperative dressing changes. Time until full epithelialization (absence of wounds) was also registered. RESULTS: A total of 60 patients were recruited, mostly middle-aged people with moderate flame burns. Serum prealbumin levels and graft take had a weak-moderate, nonlinear, statistically significant correlation. They were also an independent predictor of full epithelialization on the fifth dressing change, together with burn depth. Higher perioperative serum prealbumin levels were significantly associated with a reduction in time until full epithelialization. CONCLUSIONS: Perioperative serum prealbumin levels are significantly correlated with the probability of split-thickness skin autograft take in burned patients and with a reduced time to achieve complete epithelialization. They were an independent predictor of full graft take.

Influence of Pasteurisation (Conventional vs. Radiofrequency) and Chill Storage on Retention of Ascorbic Acid, Tocopherol and Carotenoids in Salmorejo.

Salmorejo, a Mediterranean tomato-oil puree, is considered a dietary source of antioxidant vitamins C and E and carotenoids lycopene and ß-carotene, the latter endowed with provitamin A activity. However, these antioxidants can be degraded in oxidation reactions catalysed or not by enzymes during pasteurisation and storage treatments used to stabilise the salmorejo before consumption. Due to its better penetration, the use of dielectric heating by radiofrequency (RF) may improve results of pasteurisation in this product. The objective was to assess the effects of pasteurisation temperature (70-100 °C, at 5 °C intervals) and storage time (0-5 months, at one-month intervals) on levels of ascorbic acid, α-tocopherol and carotenoids and antioxidant capacity (AC) in salmorejo pasteurised (over 10 s) by conventional (CH) or RF continuous heating. Two successive experiments were conducted to select an adequate pasteurisation temperature for use in the shelf-life study. Pasteurisation upon tested conditions allows a good retention of salmorejo antioxidants. Either CH or RF pasteurisers can be used with similar results. Vitamin C (L-ascorbic + dehydroascorbic acids) was more abundant (15-19 mg 100 g-1) than carotenoids (0.9-2.6 mg 100 g-1) (all-trans + cis lycopene and ß-carotene) and α-tocopherol (0.8-1.2 mg 100 g-1) in the pasteurised product. Using excessively low temperatures (70 °C) resulted in partial losses of the three antioxidants, possibly due to oxidase residual activities. Intensifying thermal treatment improved this issue with minor losses of the thermolabile vitamin C and increased carotenoid content. Using a suitable temperature (80 °C) did not prevent most vitamin C from being degraded by the first month, while α-tocopherol, and, to a lesser extent, carotenoids, showed good retention levels during shelf life under refrigeration. Vitamins C and E and carotenoids, either by degradation, regeneration or releasing, likely contribute to the AC in salmorejo. Phenolic antioxidant response, radical-scavenging activities and redox potential values confirmed this finding. The pasteurised-chilled salmorejo shows good antioxidant properties with potential health implications, a positive nutritional aspect for consumers of this tomato-oil homogenate. The losses of antioxidants and AC due to pasteurization would be of little relevance compared to the losses accumulated during shelf life.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry.

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

OBJECTIVES: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. DESIGN: Retrospective observational study. METHODS: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). RESULTS: Overall, 473 UC patients were included (330 IVi, 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4%, in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. CONCLUSION: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents. Data from the ENEIDA registry Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC), but little is known when it is used as the second anti-TNF.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Double-Blind Multicenter Randomized Clinical Trial Comparing Glucagon vs Placebo in the Resolution of Alimentary Esophageal Impaction.

INTRODUCTION: The aim of this study was to compare the effectiveness of glucagon vs placebo in resolving esophageal foreign body impaction (EFBI), as well as the length of the procedure and adverse events. METHODS: This was a multicenter, randomized, double-blind trial involving consecutive patients diagnosed with alimentary EFBI. Participants were randomized to receive either 1 mg of intravenous glucagon or placebo. All patients underwent upper endoscopy, and adverse events were assessed through a protocolized telephonic interview 7 days later. RESULTS: The study included 72 subjects in the glucagon group and 68 in the placebo group. The foreign body was not identified in 23.6% of subjects in the glucagon group and 20.6% of subjects in the placebo group (difference 3%, 95% confidence interval -10.7% to 16.8%, P = 0.67). The median time required to remove the foreign body was similar in both groups 4 minutes (range 2-10) in the glucagon group and 3.5 minutes (range 2-7) in the placebo group (difference 0.5 minutes, 95% confidence interval -1.3 to 2.3; P = 0.59). The most common adverse event reported in both groups was mild pharyngeal pain. DISCUSSION: Glucagon is no more effective than placebo in resolving EFBI or shortening the time required to remove the foreign body (EUDRA-CT number 2019-004920-40).

Endoscopic ultrasound-guided gallbladder drainage with long-term lumen-apposing metal stent indwell: 1-year results from a prospective nationwide observational study.

BACKGROUND AND AIM: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with long-term indwell of lumen-apposing metal stents (LAMS). METHODS: This study is a multicenter prospective observational study on consecutive high surgical-risk patients requiring gallbladder drainage who underwent EUS-GBD with LAMS over 12 months. Centralized telephone follow-up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE-free survival was determined using log-rank tests. Cumulative risks were estimated using life-table analysis. RESULTS: Eighty-two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5-89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow-up; 45 patients (54.9%) completed 1-year follow-up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47-367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1-year cumulative risk of recurrent biliary events was 9.7% (4.1-21.8%). The 1-year risk of AEs and of severe AEs was 18.8% (11-31.2%) and 7.9% (3.3-18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs. CONCLUSIONS: Long-term LAMS indwell does not increase the risk of delayed AEs following EUS-GBD.

Impact of healthcare inequities on survival in Mexican patients with metastatic renal cell carcinoma.

Introduction: The survival of patients with metastatic renal cell carcinoma (mRCC) has improved dramatically due to novel systemic treatments. However, mRCC mortality continues to rise in Latin America. Methods: A retrospective, multicenter study of patients diagnosed with mRCC between 2010-2018 in Mexico City was conducted. The aim of the study was to evaluate the impact of healthcare insurance on access to treatment and survival in patients with mRCC. Results: Among 924 patients, 55.4%, 42.6%, and 1.9% had no insurance (NI), social security, (SS) and private insurance (PI), respectively. De novo metastatic disease was more common in NI patients (70.9%) compared to SS (47.2%) and PI (55.6%) patients (p<0.001). According to IMDC Prognostic Index, 20.2% were classified as favorable, 49% as intermediate, and 30.8% as poor-risk disease. Access to systemic treatment differed by healthcare insurance: 36.1%, 99.5%, and 100% for the NI, SS, and PI patients, respectively (p<0.001). NI patients received fewer lines of treatment, with 24.8% receiving only one line of treatment (p<0.001). Median overall survival (OS) was 13.9 months for NI, 98.9 months for SS, and 147.6 months for NI patients (p<0.001). In multivariate analysis, NI status, brain metastases, sarcomatoid features, bone metastases, no treatment were significantly associated with worse OS. Conclusion: OS in mRCC was affected by insurance availability in this resource-limited cohort of Mexican patients. These results underscore the need for effective strategies to achieve equitable healthcare access in an era of effective, yet costly systemic treatments.

Splanchnic Vein Thrombosis in Inflammatory Bowel Disease: An Observational Study from the ENEIDA Registry and Systematic Review.

BACKGROUND: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD. AIMS: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series. METHODS: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients. RESULTS: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn's disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients. CONCLUSIONS: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.

Risk factors determining adherence to tyrosine kinase inhibitors in chronic myeloid leukaemia.

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) have successfully changed the natural course of chronic myeloid leukaemia (CML). Although they are highly effective drugs, their clinical benefit is conditioned by adherence. This study aims to analyse the adherence of CML patients treated with TKIs and to identify the main factors influencing their adherence to TKIs treatment. MATERIAL AND METHODS: An 8-month prospective, observational, multicentre study which included patients diagnosed with CML on treatment with TKIs attending the outpatient departments (OPD) of the Pharmacy Services of the participating hospitals. Adherence was assessed using two methods: the Simplified Medication Adherence Questionnaire (SMAQ) and the register of treatment dispensations from the OPDs. To analyse the predictors of adherence, a questionnaire was developed to report demographic and socio-economic information on the patients. RESULTS: A total of 130 patients enrolled in this study. Adherence rate was 56.9% (n = 74) among individuals, not conditioned by the type of drug used: imatinib (54.8%), nilotinib (63.6%) or dasatinib (54.3%) (p = 0.67). The patient educational level (p = 0.047) and employment status (p = 0.028) were predictors of non-adherence to treatment. CONCLUSIONS: Adherence is one of the most relevant parameters affecting the effectiveness of highly effective chronic treatments. Approximately half of our patients showed inadequate adherence to treatment with TKIs, with employment status and the individual's level of education emerging as the determining factors.

Erdafitinib in the Treatment of Metastatic Urothelial Carcinoma.

A Hispanic man, aged 42 years, was diagnosed with stage IV metastatic urothelial bladder cancer (MUBC) with nonregional lymphadenopathies and lung, bone, and skin involvement. He received first-line treatment with gemcitabine and cisplatin for 6 cycles, achieving a partial response (PR). Next, he received immunotherapy maintenance with avelumab for 4 months until disease progression. A next-generation sequencing test of paraffin-embedded tumor tissue identified a fibroblast growth factor receptor 3 (FGFR3) S249C missense mutation.

Electrochemical monitoring of enzymatic cleavage in nanochannels with nanoparticle-based enhancement: determination of MMP-9 biomarker.

For the first time the use of nanoparticles as carriers of an enzymatic substrate immobilized inside nanoporous alumina membranes is proposed with the aim of amplifying the nanochannel blocking produced and, consequently, improving the efficiency of an enzyme determination through enzymatic cleavage. Streptavidin-modified polystyrene nanoparticles (PSNPs) are proposed as carrier agents, contributing to the steric and the electrostatic blockage due to the charge they present at different pH values. Electrostatic blockage is the predominant effect that governs the blockage in the interior of the nanochannel and is dependent not just in the charge inside the channel, but also in the polarity of the redox indicator used. Hence, the effect of using negatively charged ([Fe(CN)6]4-) and positively charged ([Ru(NH3)6]3+) redox indicator ions is studied for the first time. Under the optimum conditions, matrix-metalloproteinase 9 (MMP-9) is detected at clinically relevant levels (100-1200 ng/mL) showing a detection limit of 75 ng/mL and a quantification limit of 251 ng/mL with good reproducibility (RSD: 8%) and selectivity, also showing an excellent performance in real samples with acceptable recovery percentages (in the range around 80-110%). Overall, our approach represents a cheap and fast sensing methodology of great potential in point-of-care diagnostics.

Endoscopic removal of lumen-apposing metal stents - risk factors for stent embedment, complex removals, and adverse events: analysis from a multicenter prospective case series.

BACKGROUND: Removing lumen-apposing metal stents (LAMSs) may be difficult and even harmful, but these features have seldom been analyzed. We aimed to generate a comprehensive assessment of the feasibility and safety of LAMS retrieval procedures. METHODS: A prospective multicenter case series including all technically successfully deployed LAMSs between January 2019 and January 2020 that underwent endoscopic stent removal. All retrieval-related data were prospectively recorded using standardized telephone questionnaires as part of centralized follow-up that ended after stent removal had been performed. Multivariable logistic regression models assessed the potential risk factors for complex removal. RESULTS: For the 407 LAMSs included, removal was attempted in 158 (38.8 %) after an indwell time of 46.5 days (interquartile range [IQR] 31-70). The median (IQR) removal time was 2 (1-4) minutes. Removal was labelled as complex in 13 procedures (8.2 %), although advanced endoscopic maneuvers were required in only two (1.3 %). Complex removal risk factors were stent embedment (relative risk [RR] 5.84, 95 %CI 2.14-15.89; P = 0.001), over-the-wire deployment (RR 4.66, 95 %CI 1.60-13.56; P = 0.01), and longer indwell times (RR 1.14, 95 %CI 1.03-1.27; P = 0.01). Partial and complete embedment were observed in 14 (8.9 %) and five cases (3.2 %), respectively. The embedment rate during the first 6 weeks was 3.1 % (2/65), reaching 15.9 % (10/63) during the following 6 weeks (P = 0.02). The adverse event rate was 5.1 %, including seven gastrointestinal bleeds (5 mild, 2 moderate). CONCLUSIONS: LAMS removal is a safe procedure, mostly requiring basic endoscopic techniques attainable in conventional endoscopy rooms. Referral to advanced endoscopy units should be considered for stents with known embedment or long indwell times, which may require more technically demanding procedures.

Prospective multicenter assessment of the impact of EUS-guided gastroenterostomy on patient quality of life in unresectable malignant gastric outlet obstruction.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used for malignant gastric outlet obstruction (GOO) in inoperable patients. However, the impact of EUS-GE on patient quality of life (QoL) has not been evaluated prospectively. METHODS: Consecutive patients with unresectable malignant GOO who underwent EUS-GE between August 2019 and May 2021 at 4 Spanish centers were prospectively assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 at baseline and 1 month after the procedure. Centralized follow-up by telephone calls was undertaken. The Gastric Outlet Obstruction Scoring System (GOOSS) was used to assess oral intake, defining clinical success as a GOOSS ≥2. Differences between baseline and 30-day QoL scores were assessed using a linear mixed model. RESULTS: Sixty-four patients were enrolled, 33 (51.6%) men, with a median age of 77.3 years (interquartile range, 65.5-86.5). The most common diagnoses were pancreatic (35.9%) and gastric (31.3%) adenocarcinoma. Thirty-seven patients (57.9%) presented a 2/3 baseline Eastern Cooperative Oncology Group performance status score. Oral intake was restarted within 48 hours in 61 patients (95.3%), and the median postprocedure hospital stay was 3.5 days (interquartile range, 2-5). The 30-day clinical success rate was 83.3%. A clinically significant increase of 21.6 points (95% confidence interval, 11.5-31.7) in the global health status scale was documented, with significant improvements in nausea and vomiting, pain, constipation, and appetite loss. CONCLUSIONS: EUS-GE relieves GOO symptoms in patients with unresectable malignancy, allowing rapid oral intake and hospital discharge. It also provides a clinically relevant increase in QoL scores at 30 days from baseline. (Clinical trial registration number: NCT04660695.).

Influence of HLADQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring: A Retrospective Cohort Study.

BACKGROUND: Carriers of the human leucocyte antigen variant HLADQA1*05 (rs2097432) are at risk of developing antibodies against infliximab and adalimumab with reduced tumor necrosis factor (TNF) antagonist persistence. The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed. METHODS: We conducted a retrospective single-center cohort study including patients with inflammatory bowel disease starting anti-TNF therapy between January 2017 and March 2021. Proactive therapeutic drug monitoring was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, followed by dose optimization. Variables associated with treatment persistence were assessed with multivariable Cox regression analysis. RESULTS: A total of 112 patients were included, 52 (46.4%) HLA-DQA1*05 carriers, with a median follow-up of 73.9 (interquartile range, 35.4-133.1) weeks. Combination therapy with thiopurines was more frequent among HLA-DQA1*05 noncarriers (28 [46.7%] vs 12 [23.1%]; P = .01). Clinical remission rates at week 14 (77.9% vs 73.9%; P = .69) and 56 (73.2% vs 68.4%; P = .64) were similar between HLA-DQA1*05 noncarriers and carriers. Drug persistence was higher among HLA-DQA1*05 carriers (hazard ratio [HR], 0.32; 95% confidence interval, 0.14-0.71; P = .01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (HR, 4; 95% confidence interval, 1.7-9.7) as a risk factor and HLA-DQA1*05 carriers (HR, 0.31; 95% confidence interval, 0.12-0.81) as a protective factor of treatment cessation. CONCLUSION: In adult patients with PTDM, a positive HLA-DQA1*05 genotype does not associate a higher risk of treatment cessation nor worse clinical outcomes.

This is a retrospective cohort study including 112 inflammatory bowel disease patients starting anti-TNF therapy under proactive therapeutic drug monitoring (PTDM). The HLA-DQA1*05 carriers did not present lower drug persistence or remission rates, suggesting PTDM overcomes the reduced treatment survival expected in HLA-DQA1*05 carriers.

Prospective cohort study to evaluate premedication with simethicone and n-acetilcysteine for upper diagnostic gastrointestinal endoscopy.

INTRODUCTION: The use of premedication for upper gastrointestinal endoscopy (UGE) is not widely established in western countries. The primary aim of the study was to compare gastric visibility according to the total visibility score (TVS). The secondary aim was to assess complications, diagnostic yield, endoscopic procedure time, sedation dose and patient satisfaction. METHODS: A single center prospective cohort study was performed of consecutive adults undergoing an UGE in the afternoon working shift. After completing enrolment in the control group, patients were administered 200 mg simethicone and 500 mg N-acetylcysteine diluted in 100 ml of water >15 minutes before the procedure. All procedures were recorded and a single, blinded endoscopist evaluated the TVS after recruitment of both cohorts. Patient satisfaction was evaluated using the Spanish translation of the American Society of Gastrointestinal Endoscopy satisfaction questionnaire. RESULTS: 205 patients were included in the study, 103 females (50.2%) with a median age of 54.8-years (IQR: 41.2-65.2). 104 were enrolled to the control group and 101 to the intervention group. Patients receiving premedication presented a higher rate of adequate (74.3% vs 45.2; difference 95% CI: 16,3-41,9%, p<0.001) and excellent gastric visibility (23.8% vs 7.7%; difference 95% CI: 6,3-25,8%, p=0.002). Propofol dose was similar, although the median procedure time was lower in the group of no intervention [5 (IQR: 4-7) vs 6 minutes (IQR: 5-7); p=0.03]. Procedure related adverse events were similar, except that patient without premedication experienced more nausea episodes. Major and minor endoscopic findings and the satisfaction questionnaire showed no differences between both groups. CONCLUSION: Patients receiving premedication with simethicone and N-acetylcysteine had a better gastric visibility score, without any increase in adverse events or affecting the patients' satisfaction.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage in malignant distal bile duct obstruction using a self-expanding metal stent: Study protocol for a prospective European multicenter trial (PUMa trial).

BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) was associated with better clinical success and a lower rate of adverse events (AEs) than fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD) in recent single center studies with mainly retrospective design and small case numbers (< 50). The aim of this prospective European multicenter study is to compare both drainage procedures using ultrasound-guidance and primary metal stent implantation in patients with malignant distal bile duct obstruction (PUMa Trial). METHODS: The study is designed as a non-randomized, controlled, parallel group, non-inferiority trial. Each of the 16 study centers performs the procedure with the best local expertise (PTBD or EUS-BD). In PTBD, bile duct access is performed by ultrasound guidance. EUS-BD is performed as an endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS), EUS-guided choledochoduodenostomy (EUS-CDS) or EUS-guided antegrade stenting (EUS-AGS). Insertion of a metal stent is intended in both procedures in the first session. Primary end point is technical success. Secondary end points are clinical success, duration pf procedure, AEs graded by severity, length of hospital stay, re-intervention rate and survival within 6 months. The target case number is 212 patients (12 calculated dropouts included). DISCUSSION: This study might help to clarify whether PTBD is non-inferior to EUS-BD concerning technical success, and whether one of both interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization is not provided as both procedures are rarely used after failed endoscopic biliary drainage and study centers usually prefer one of both procedures that they can perform best. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03546049 (22.05.2018).

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.