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.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Hidratación con Ringer Lactato combinado con diclofenaco rectal en la prevención de pancreatitis poscolangiopancreatografía retrógrada endoscópica / Hydration with Lactated Ringer's solution combined with rectal diclofenac in the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography

OBJETIVO: Se aconsejan diferentes medidas para disminuir la pancreatitis poscolangiopancreatografía retrógrada endoscópica (PPCPRE). Efectuamos un estudio en pacientes con CPRE tratados con diclofenaco rectal o Ringer Lactato o bien ambas intervenciones para valorar si existe una disminución en el número de PPCPRE. MATERIAL Y MÉTODOS: Estudio de cohortes mixto con 1.896 pacientes desde 2009 hasta 2018. Hasta junio de 2012 sin tratamiento (grupo i). Posteriormente 100mg de diclofenaco rectal (grupo ii). Desde 2016 Ringer Lactato 200ml/h durante el procedimiento y 4h después del mismo, además 500ml en 30min cuando se canuló el páncreas (grupo iii). Desde 2017 Ringer Lactato más diclofenaco (grupo iv). Hubo 725 pacientes en el grupo i, 530, 227 y 414 pacientes en grupos ii,iii y IV. Se han recogido factores predisponentes a PPCPRE y los casos de PPCPRE que fue definida por criterios de consenso. RESULTADOS: Hubo 65 PPCPRE (3,4%); 2,9; 3,4; 3,1 y 4,3% en los grupos i, ii,iii y IV respectivamente (p = 0,640). En el grupo I hubo un 4,2% de PPCPRE en papilas naïve y un 4; 4,9% y 6,3% en los grupos ii,iii y IV respectivamente (p = 0,585). La gravedad de PPCPRE y los efectos adversos fueron similares en los grupos. El 38,4% eran pacientes de alto riesgo. Tampoco hubo diferencias de PPCPRE en este grupo (p = 0,501). CONCLUSIÓN: En este trabajo no se ha obtenido beneficio con diclofenaco más hidratación en la disminución del número y gravedad de la PPCPRE. Tampoco con las otras medidas profilácticas

OBJECTIVE: Different measures are recommended to reduce pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We conducted a study in patients with ERCP treated with rectal diclofenac or lactated Ringer's solution, or both interventions, to assess whether there is a decrease in the number of cases of post-ERCP pancreatitis. MATERIAL AND METHODS: A mixed cohort study involving 1,896 patients from 2009 to 2018. Up to June 2012 without treatment (Group I). Subsequently, 100mg of rectal diclofenac (Group II). Since 2016, lactated Ringer's solution 200ml/hour during the procedure and 4hours after it, in addition to 500ml over 30minutes when the pancreas was cannulated (Group III). Since 2017, lactated Ringer's solution plus Diclofenac (Group IV). There were 725 patients in group I, and 530, 227 and 414 patients in groups II, III and IV, respectively. Factors predisposing to post-ERCP pancreatitis and post-ERCP pancreatitis cases that were defined by consensus criteria have been collected. RESULTS: There were 65 cases of post-ERCP pancreatitis (3.4%); 2.9%, 3.4%, 3.1% and 4.3% in groups I, II, III and IV, respectively (P=.640). In group I, there was 4.2% of post-ERCP pancreatitis in naïve papillae and 4%, 4.9% and 6.3% in groups II, III and IV, respectively (P=.585). The severity of post-ERCP pancreatitis and adverse effects were similar in all groups. 38.4% were high-risk patients. There were also no differences in post-ERCP pancreatitis in this group (P=.501). CONCLUSION: In this work, no benefit was obtained with diclofenac plus hydration in reducing the number and severity of cases of post-ERCP pancreatitis nor with the other prophylactic measures

Hydration with Lactated Ringer's solution combined with rectal diclofenac in the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography. / Hidratación con Ringer Lactato combinado con diclofenaco rectal en la prevención de pancreatitis poscolangiopancreatografía retrógrada endoscópica.

OBJECTIVE: Different measures are recommended to reduce pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We conducted a study in patients with ERCP treated with rectal diclofenac or lactated Ringer's solution, or both interventions, to assess whether there is a decrease in the number of cases of post-ERCP pancreatitis. MATERIAL AND METHODS: A mixed cohort study involving 1,896 patients from 2009 to 2018. Up to June 2012 without treatment (Group I). Subsequently, 100mg of rectal diclofenac (Group II). Since 2016, lactated Ringer's solution 200ml/hour during the procedure and 4hours after it, in addition to 500ml over 30minutes when the pancreas was cannulated (Group III). Since 2017, lactated Ringer's solution plus Diclofenac (Group IV). There were 725 patients in group I, and 530, 227 and 414 patients in groups II, III and IV, respectively. Factors predisposing to post-ERCP pancreatitis and post-ERCP pancreatitis cases that were defined by consensus criteria have been collected. RESULTS: There were 65 cases of post-ERCP pancreatitis (3.4%); 2.9%, 3.4%, 3.1% and 4.3% in groups I, II, III and IV, respectively (P=.640). In group I, there was 4.2% of post-ERCP pancreatitis in naïve papillae and 4%, 4.9% and 6.3% in groups II, III and IV, respectively (P=.585). The severity of post-ERCP pancreatitis and adverse effects were similar in all groups. 38.4% were high-risk patients. There were also no differences in post-ERCP pancreatitis in this group (P=.501). CONCLUSION: In this work, no benefit was obtained with diclofenac plus hydration in reducing the number and severity of cases of post-ERCP pancreatitis nor with the other prophylactic measures.

Assessment of radiation doses received by patients during endoscopic retrograde cholangiopancreatography according to disease location.

OBJECTIVE: patients are exposed to ionizing radiation during endoscopic retrograde cholangiopancreatography (ERCP). Radiation dose depends on multiple factors. The goal of this study was to assess fluoroscopy time (FT), radiation doses and effective dose (ED) during ERCP according to the condition being treated. MATERIALS AND METHODS: a descriptive study was performed of 369 consecutive ERCPs from January 2017 to June 2019. Patient demographic and procedure data were collected. FT, cumulative dose area product (DAP), fluoroscopy DAP, DA fluoroscopy, air kerma, and number of radiographs were assessed. ED was estimated using specific conversion factors. RESULTS: the mean age was 73.34 years and 193 subjects were male. Mean FT was 4.56 ± 0.17 min, cumulative DAP was 2,056.73 ± 188.83 cGycm2, fluoroscopy DAP was 1,722.90 ± 82.26 cGycm2 and air kerma was 85.84 ± 4.93 mGy. The number of radiographs was 2.10 ± 0.07 and the mean ED was 5.34 ± 0.49 mSv. FT was significantly longer for choledocholithiasis (CL), proximal malignant biliary stricture (PMBS) and distal malignant biliary stricture (DMBS) versus others (OT). Cumulative DAP was higher for PMBS (p < 0.002). FT, cumulative DAP, fluoroscopy DAP and air kerma values were significantly higher for complicated CL as compared to simple CL. ED was higher for CL, DMBS and PMBS, but only significantly (p < 0.002) for PMBS. CONCLUSIONS: FT for ERCP is variable and increases with exploration difficulty. Thus, it is longer in the case of PMBS, as well as with the amount of radiation received by the patients and ED.

Prevalence and factors associated with poor sleep quality in inflammatory bowel disease outpatients.

INTRODUCTION: sleep disorders are common in the general population and have obvious repercussions on quality of life. Poor sleep quality is associated to inflammatory activity and fatigue in inflammatory bowel disease (IBD) patients. This study aimed to analyze the prevalence of poor sleep quality and the factors associated with it, in IBD outpatients. METHODS: an observational and prospective study was performed in which epidemiological, clinical and laboratory data were collected from clinical records and patients who consecutively attended an outpatient clinic. Pittsburgh Sleep Quality index (PSQI), Hospital Anxiety and Depression Scale (HADS) and International Physical Activity Questionnaire (IPAQ) were used to measure sleep quality, anxiety, depression and physical activity, respectively. Treatment optimizations, hospital admissions or surgery were prospectively verified three months after the baseline visit. RESULTS: one hundred and two patients were included and 54.9 % had poor sleep quality (PSQI score > 5). No association was found between poor sleep quality and IBD-related variables such as type of disease, ulcerative colitis (UC) extent, Crohn's disease (CD) location or behavior, time from diagnosis, treatment, prior admissions or surgery and laboratory values. Rotating night shift job (OR 6.116, 95 % CI: 1.312-28.514), HAD score for depression (OR 1.125, 95 % CI: 1.062-1.490) and frequency (days per week) of vigorous physical activity (OR 0.783, 95 % CI: 0.619-0.991) were independent predictors of poor sleep quality. A Pittsburgh questionnaire score higher than 5 was not significantly associated to treatment optimization in the total patient cohort (15.2 % vs 18.2 %, p = 0.451), in UC patients (18.2 % vs 10.7 %, p = 0.362) or CD patients (12.5 % vs 25.9 %, p = 0.198). CONCLUSIONS: poor sleep quality is present in more than half of IBD patients. Aspects not directly related to IBD are associated to poor sleep quality.

Púrpura trombocitopénica inmune asociada a colitis ulcerosa inactiva en tratamiento crónico con adalimumab / Immune thrombocytopenic purpura associated with inactive ulcerative colitis in chronic treatment with adalimumab

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El diclofenaco rectal no previene la pancreatitis post-CPRE en pacientes consecutivos de alto y bajo riesgo / Rectal diclofenac does not prevent post-ERCP pancreatitis in consecutive high-risk and low-risk patients

Objetivo: el diclofenaco rectal, un antiinflamatorio no esteroideo (AINE), se utiliza para prevenir la pancreatitis en pacientes de alto riesgo en la colangiopancreatografía retrógrada endoscópica (CPRE). La Sociedad Europea de Endoscopia Digestiva (ESGE) recomienda profilaxis con indometacina o diclofenaco a todos los pacientes a los que se les realice una CPRE, incluso en aquellos de riesgo medio-bajo de pancreatitis. Hemos realizado un estudio para investigar la eficacia de esta recomendación. Métodos: estudio de cohortes mixto. Se incluyeron 1.512 CPRE efectuadas en nuestro centro entre enero de 2009 y julio de 2016. Hasta junio de 2012, 718 pacientes no recibieron diclofenaco. Posteriormente, 794 pacientes sin contraindicaciones recibieron 100 mg rectales de diclofenaco al inicio del procedimiento. Se registraron los factores de riesgo para pancreatitis aguda post-CPRE (PAPC) y los casos de PAPC que se definieron por criterios de consenso. Resultados: hubo 47 PAPC (3,1%), un 3,4% de las cuales correspondió al grupo con diclofenaco y un 2,8%, al grupo no tratado (p = 0,554). El 26,1% de todos los pacientes presentaba factores de riesgo para PAPC. En el grupo con diclofenaco hubo un 4,4%, 0,5% y 2,6% de PAPC en papilas intactas, con esfinterotomía previa y con ampliación de la misma, respectivamente, similar al grupo no tratado (4% papila intacta, 0,9% esfinterotomía previa y 2,5% ampliación). La gravedad de la PAPC fue similar en los dos grupos. Conclusiones: en nuestro estudio, el diclofenaco rectal antes de la CPRE en pacientes consecutivos no seleccionados no previene la aparición de pancreatitis aguda post-CPRE

Objective: rectal diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that is used to prevent pancreatitis in high-risk patients during endoscopic retrograde cholangiopancreatography (ERCP). The European Society of Gastrointestinal Endoscopy (ESGE) recommends the use of prophylaxis with indomethacin or diclofenac in all patients undergoing ERCP, including those at low or intermediate risk of pancreatitis. A study to investigate the efficacy of this recommendation was performed. Methods: this was a mixed cohort study. A total of 1,512 ERCP procedures performed in our institution from January 2009 to July 2016 were included in the study. Until June 2012, 718 patients did not receive diclofenac. Subsequently, 794 patients without contraindications received 100 mg of rectal diclofenac at the onset of the procedure. Risk factors for post-ERCP pancreatitis (PEAP) and PEAP cases defined using consensus criteria were recorded. Results: a total of 47 PEAP events (3.1%) were reported, 3.4% in the diclofenac group and 2.8% in the non-diclofenac group (p = 0.554); 26.1% of patients had risk factors for PEAP. In the diclofenac group, PEAP developed in 4.4%, 0.5% and 2.6% of subjects with intact papillae, prior sphincterotomy and extended sphincterotomy, respectively. The results were similar for the non-diclofenac group: 4% with intact papillae, 0.9% with prior sphincterotomy, and 2.5% with extended sphincterotomy, respectively. PEAP severity was similar in both groups. Conclusions: rectal diclofenac before ERCP did not prevent the development of post-ERCP acute pancreatitis in non-selected consecutive patients

Rectal diclofenac does not prevent post-ERCP pancreatitis in consecutive high-risk and low-risk patients.

OBJECTIVE: rectal diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that is used to prevent pancreatitis in high-risk patients during endoscopic retrograde cholangiopancreatography (ERCP). The European Society of Gastrointestinal Endoscopy (ESGE) recommends the use of prophylaxis with indomethacin or diclofenac in all patients undergoing ERCP, including those at low or intermediate risk of pancreatitis. A study to investigate the efficacy of this recommendation was performed. METHODS: this was a mixed cohort study. A total of 1,512 ERCP procedures performed in our institution from January 2009 to July 2016 were included in the study. Until June 2012, 718 patients did not receive diclofenac. Subsequently, 794 patients without contraindications received 100 mg of rectal diclofenac at the onset of the procedure. Risk factors for post-ERCP pancreatitis (PEAP) and PEAP cases defined using consensus criteria were recorded. RESULTS: a total of 47 PEAP events (3.1%) were reported, 3.4% in the diclofenac group and 2.8% in the non-diclofenac group (p = 0.554); 26.1% of patients had risk factors for PEAP. In the diclofenac group, PEAP developed in 4.4%, 0.5% and 2.6% of subjects with intact papillae, prior sphincterotomy and extended sphincterotomy, respectively. The results were similar for the non-diclofenac group: 4% with intact papillae, 0.9% with prior sphincterotomy, and 2.5% with extended sphincterotomy, respectively. PEAP severity was similar in both groups. CONCLUSIONS: rectal diclofenac before ERCP did not prevent the development of post-ERCP acute pancreatitis in non-selected consecutive patients.

Tuberculosis, un diagnóstico más a tener en cuenta ante una masa pancreática / Tuberculosis, one more consideration in the differential diagnosis of a pancreatic mass

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Fístula hepatocólica tratada con el nuevo dispositivo de cierre endoscópico Padlock(R) / Hepatocolic fistula managed with a novel Padlock(R) device for endoscopic closure

El avance de la terapéutica endoscópica está permitiendo abordar patologías que hasta hace poco quedaban reservadas al tratamiento quirúrgico, como las fístulas digestivas. El sistema Padlock(R) consiste en un clip de nitinol introducido recientemente para terapéutica endoscópica. Hasta el momento, son pocas las comunicaciones sobre su utilización en la práctica diaria. Presentamos un caso de fístula colónica tratada mediante este nuevo sistema de clip endoscópico de nitinol (AU)

Recent advances in endoscopic therapeutics allow conditions such as fistulas of the digestive system to be treated endoscopically. These cases were recently managed with surgery. The Padlock(R) system includes a nitinol clip that was recently introduced for endoscopic therapy. There are few reports with regard to its use in the daily clinical practice. We report a case of a colonic fistula that was endoscopically managed with this novel over-the-scope nitinol clip system (AU)

Hepatocolic fistula managed with a novel Padlock® device for endoscopic closure.

Recent advances in endoscopic therapeutics allow conditions such as fistulas of the digestive system to be treated endoscopically. These cases were recently managed with surgery. The Padlock® system includes a nitinol clip that was recently introduced for endoscopic therapy. There are few reports with regard to its use in the daily clinical practice. We report a case of a colonic fistula that was endoscopically managed with this novel over-the-scope nitinol clip system.

Influencia de la experiencia acumulada del explorador en el valor predictivo negativo de la cápsula endoscópica / Impact of the endoscopist's experience on the negative predictive value of capsule endoscopy

INTRODUCCIÓN: La influencia de la experiencia acumulada del médico que interpreta cápsulas endoscópicas sobre su capacidad diagnóstica es discutida. OBJETIVO: Determinar si existen diferencias en el valor predictivo negativo de las cápsulas endoscópicas informadas por los mismos endoscopistas a lo largo del tiempo. MÉTODOS: Revisamos las 900 primeras cápsulas endoscópicas realizadas por tres gastroenterólogos expertos en endoscopia durante 8 años. Se dividieron en 3 grupos de 300 cápsulas cada uno. El grupo 1 fue la suma de las tres primeras centenas informadas por cada uno, el grupo 2 la suma de las tres segundas centenas y el grupo 3 la suma de las tres terceras centenas. Se hizo un seguimiento mínimo de 28 meses a los casos con exploración normal. RESULTADOS: Aunque se consideraron normales el 18% de las cápsulas del grupo 1, el 19,3% de las del grupo 2 y el 15,6% de las del grupo 3, solo fue posible seguir y finalmente analizar a 34 enfermos en el grupo 1, a 38 en el 2 y a 36 en el 3. Sobre estos casos, el valor predictivo negativo fue del 88,2% en el grupo 1, del 89,5% en el grupo 2 y del 97% en el grupo 3 (p > 0,05). CONCLUSIÓN: El valor predictivo negativo de la cápsula endoscópica, aunque con tendencia a aumentar, se mantiene alto y sin diferencias significativas desde las 100 primeras exploraciones si los médicos que la interpretan son expertos en endoscopia convencional y tienen formación específica previa

INTRODUCTION: The impact of the accumulated experience of the capsule endoscopy (CE) reader on the accuracy of this test is discussed. AIM: To determine whether the negative predictive value of CE findings changes along the learning curve. METHODS: We reviewed the first 900 CE read by 3 gastroenterologists experienced in endoscopy over 8 years. These 900 CE were divided into 3 groups (300 CE each): group 1 consisted of the sum of the first 100 CE read by each of the 3 endoscopists; group 2, the sum of the second 100 and groups 3, the sum of the third 100. Patients with normal CE were monitored for at least 28 months to estimate the negative predictive value. RESULTS: A total of 54 (18%) CE in group 1, 58 (19.3%) in group 2 and 47 (15.6%) in group 3 were normal, although only 34 patients in group 1, 38 in group 2 and 36 in group 3 with normal CE completed follow up and were eventually studied. The negative predictive value was 88.2% in group 1, 89.5% in group 2 and 97% in group 3 (P > .05). CONCLUSION: The negative predictive value tended to increase, but remained high and did not change significantly after the first 100 when readers are experienced in conventional endoscopy and have preliminary specific training

Impact of the endoscopist's experience on the negative predictive value of capsule endoscopy. / Influencia de la experiencia acumulada del explorador en el valor predictivo negativo de la cápsula endoscópica.

INTRODUCTION: The impact of the accumulated experience of the capsule endoscopy (CE) reader on the accuracy of this test is discussed. AIM: To determine whether the negative predictive value of CE findings changes along the learning curve. METHODS: We reviewed the first 900 CE read by 3 gastroenterologists experienced in endoscopy over 8 years. These 900 CE were divided into 3 groups (300 CE each): group 1 consisted of the sum of the first 100 CE read by each of the 3 endoscopists; group 2, the sum of the second 100 and groups 3, the sum of the third 100. Patients with normal CE were monitored for at least 28 months to estimate the negative predictive value. RESULTS: A total of 54 (18%) CE in group 1, 58 (19.3%) in group 2 and 47 (15.6%) in group 3 were normal, although only 34 patients in group 1, 38 in group 2 and 36 in group 3 with normal CE completed follow up and were eventually studied. The negative predictive value was 88.2% in group 1, 89.5% in group 2 and 97% in group 3 (P>.05). CONCLUSION: The negative predictive value tended to increase, but remained high and did not change significantly after the first 100 when readers are experienced in conventional endoscopy and have preliminary specific training.