Effectiveness and safety of ustekinumab dose escalation in Crohn's disease: a multicenter observational study.

BACKGROUND: ustekinumab has proven effective in Crohn's disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. AIM: to evaluate the effectiveness of ustekinumab dose escalation in CD. METHODS: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. RESULTS: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. CONCLUSION: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Efficacy and safety of tofacitinib in the treatment of ulcerative colitis: real-life experience in Andalusia.

BACKGROUND: tofacitinib is a Janus kinase inhibitor approved for the treatment of moderate-severe ulcerative colitis (UC). This study aimed to evaluate its efficacy in a real-life setting. METHODS: a retrospective and multicenter observational study was performed with UC patients treated with tofacitinib. Short and long-term treatment effectiveness, treatment survival, need for dose escalation and safety were analyzed. Clinical response and remission were defined in accordance with the partial Mayo score. RESULTS: seventy-four patients were included, 98.3 % had received prior biological treatment, 55.4 % with three or more biologicals and up to 64.9% with two or three different mechanisms of action. Clinical remission and response rates were 37.8 % and 77 % at eight weeks, and 41.8 % and 70.1 % at 16 weeks. With regard to non-responders at eight weeks, 37.5 % achieved a delayed clinical response at 16 weeks. Mean treatment duration was 19 months (95 % CI: 16-22), with a treatment survival of 56 % at 28 months, and remission and response rates at 24 months of 53.8 % and 61.5 %. Twenty-three treatments were withdrawn, most of them (18) during the induction period. There were adverse events in a quarter of the patients; only four were severe and led to treatment discontinuation. CONCLUSION: tofacitinib has a demonstrated efficacy in clinical practice to induce and maintain clinical response in treatment-refractory UC patients, with an acceptable safety profile.

A Gastroenterologist' clinical experience in COVID 19 and in-hospital mortality and length of stay analysis.

OBJECTIVES: COVID19 pandemic has forced physicians from different specialties to assist cases overload. Our aim is to assess gastroenterologist's assistance in COVID-19 by assessing mortality, ICU admission, and length of stay, and seek for risk factors for in-hospital mortality and longer hospital stay. METHODS: A total of 41 COVID-19 patients assisted by gastroenterologist (GI cohort) and 137 assisted by pulmonologist, internal medicine practitioners, and infectious disease specialists (COVID expert cohort) during October-November 2020 were prospectively collected. Clinical, demographic, imaging, and laboratory markers were collected and compared between both cohorts. Bivariate analysis and logistic regression were performed to search for risk factors of mortality and longer hospital stays. RESULTS: A total of 27 patients died (15.1%), 11 were admitted to ICU (6.1%). There were no differences between cohorts in mortality (14.6% vs 15.4%;p = 0.90), ICU admission (12.1% vs 4%;p = 0.13), and length of stay (6.67 ± 4 vs 7.15 ± 4.5 days; p = 0.58). PaO2/FiO2 on admission (OR 0.991;CI95% 0.984-0.998) and age > 70 (OR 17.54;CI95% 3.93-78.22) were independently related to mortality. Age > 70, history of malignancy, diabetes, and cardiovascular disease were related to longer hospital stays (p < 0.001, p = 0.03, p = 0.04, p = 0.02 respectively). CONCLUSIONS: COVID-19 assistance was similar between gastroenterologist and COVID experts when assessing mortality, ICU admission, and length of stay. Age>70 and decreased PaO2/FiO2 on admission were independent risk factors of mortality. Age and several comorbidities were related to longer hospital stay.

Clinical outcome after anti-tumour necrosis factor therapy discontinuation in 1000 patients with inflammatory bowel disease: the EVODIS long-term study.

BACKGROUND: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. AIMS: To assess the risk of relapse in the long-term after anti-TNF discontinuation. METHODS: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. RESULTS: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. CONCLUSIONS: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Hemophagocytic syndrome, a diagnostic challenge in Gastroenterology.

Hemophagocytic lymphohistiocytosis is a syndrome of severe immune activation with macrophage and T- cell infiltration resulting in multi organ damage. We report the case of a patient successfully treated for a haemophagocytic syndrome triggered by a metastatic neoplasm of the rectum. A 57 years old man is initially presented with fever without focus. Despite of wide spectrum antibiotics he developed a multi-organ dysfunction. A bone marrow aspirate showed histiocytes that had phagocytosed hematic cells. Hemophagocytic syndrome was suspected and specific treatment was administered. The patient's condition improved remarkably and he was discharged. Nevertheles, finally, the patient died due to a bad response to chemotherapy. Malignancies are a well known triggering of hemophagocytic lymphohistiocytosis being hematological the most commun malignancy associated. However, solid tumors are anecdotic and, to our knowledge, this case is the first one documented due only to rectal carcinoma.

[Effect of influenza vaccination in Primary Healthcare workers and the general population in Gran Canaria: A cross-sectional study]. / Efecto de la vacunación antigripal en trabajadores de atención primaria y población general de Gran Canaria: estudio transversal.

OBJECTIVE: To estimate the effect of the influenza vaccination in Primary Healthcare workers and the general population vaccinated during the 2015/2016 campaign. DESIGN: Cross-sectional study. SETTING: All the Primary Healthcare centres within the Gran Canaria healthcare region. PARTICIPANTS: A total of 1,868 Primary Healthcare workers (33.5% men; 66.5% women) and 795,605 individuals from the general population (49.4% men; 50.6% women). PRINCIPAL MEASUREMENTS: The outcome variables in Primary Healthcare workers were: influenza cases reported to the Epidemiological Surveillance System, and the sick leave days due to illness. In the general population: reported flu cases and vaccination coverage in connection with the vaccination status of the healthcare professional. The magnitude of association between vaccination and morbidity was estimated applying logistic regression models. RESULTS: Although not statistically significant, healthcare professionals that were not vaccinated had 1.7-fold increase in the risk of having influenza than those vaccinated. In the general population the association was significant in the female population (OR: 1.3; 95%CI: 1.1-1.5). Population coverage was significantly higher when both the doctor and nurse were vaccinated (OR: 1.3; 95%CI: 1.3-1.3), and reported flu cases decreased when the nurse was vaccinated (OR: 0.9; 95%CI: 0.9-0.9). CONCLUSION: A possible protective effect of influenza vaccination was observed in the general population, as well as an influence of Primary Healthcare workers on the patients regarding this. Even so, the low coverages registered point to a need to implement measures that may lead to a more favourable attitude towards influenza vaccination.

Consistent association between hypnotics/sedatives and non-traffic injuries. Results from a national household survey.

AIM: To quantify the relationship between patterns of psychostimulants, hypnotics/sedatives and alcohol consumption and the frequency of unintentional non-traffic injuries (UNTIs) requiring medical assistant in Spain. METHODS: We carried out a cross sectional study using a randomized pooled sample from two household surveys on psychoactive drugs use (n=51,649 subjects aged 15-64 years). We estimated the magnitude of the association between the use of psychostimulants and hypnotics/sedatives in the last 12 months as well as alcohol consumption in the last 30days with the occurrence of UNTIs in the last 12 months (falls, knocks/bumps and cuts) by building several logistic regression models, which took into account the effect of sociodemographic characteristics and the use of other psychoactive drugs (including cannabis). The presence of interactions between age or gender with drug use was also assessed. RESULTS: Psychostimulants use was associated with a higher frequency of UNTIs (aOR=1.24; 95%CI:1.03-1.49). The strongest association was found with cuts (aOR=1.64; 95%CI:1.10-2.43). An association between hypnotics/sedatives and UNTIs was also found in each type of injury and was higher with regular use (>=30days) than with non-regular use (<30days). The age modified the association between hypnotic/sedatives and knocks/bumps, being higher in the 35-64 years group (aOR=2.34; 95%CI:1.78-3.06) than in the 15-34 years group (aOR=1.59; 95%CI:1.14-2.21). Regarding alcohol, an increased risk of UNTIs was also observed in all types of UNTIs, even with moderate use, being the association higher for cuts in heavy drinkers (aOR=2.41; 95%CI:1.63-3.57). CONCLUSIONS: Our results reveal a consistent relationship between hypnotics/sedatives and UNTIs, especially in regular users. Additional research should apply longitudinal designs to establish causal relationships and to gain an in-depth knowledge in this area in order to specific public health interventions.

The role of exposure on differences in driver death rates by gender and age: Results of a quasi-induced method on crash data in Spain.

AIM: Part of the differences by age and gender in driver death rates from traffic injuries depends on the amount of exposure (km/year travelled). Unfortunately, direct indicators of exposure are not available in many countries. Our aim was to compare the age and gender differences in death rates with and without adjustment by exposure using a quasi-induced exposure approach in Spain, during 2004-2012. METHODS: Crude and adjusted death rate ratios (CDRR and ADRR, respectively) were calculated for each age and gender group. To obtain the latter estimates, in accordance with quasi-exposure reasoning, the number of registered drivers was replaced by the number of non-infractor drivers, passively involved in collisions with another vehicle whose driver committed an infraction. 18-29 years and female drivers were chosen as the reference categories for age and gender. RESULTS: Striking differences were found between CDRR and ADRR estimates. When CDRR were estimated, we found the highest traffic mortality among the youngest drivers, except for females in non-urban roads. ADRR however showed the highest mortality among the oldest groups, especially in females, peaking among drivers >74 years in all types of roads. Regarding differences by gender, both estimates revealed higher traffic mortality in males, although the differences were much smaller when using ADRR. CDRR and ADRR for males tended to converge as age increased. CONCLUSIONS: Death risk from traffic injuries among drivers is clearly influenced by the amount of exposure. These findings further emphasize the need to obtain direct traffic exposure estimates by subgroups of drivers.

Duodenal duplication cyst and pancreas divisum causing acute pancreatitis in an adult male.

Duodenal duplication cysts are rare congenital abnormalities which are more commonly diagnosed in infancy and childhood. However, in rare cases, these lesions can remain asymptomatic until adulthood. The combination of duplication cyst and pancreas divisum is extremely rare and both conditions have been linked with acute recurrent pancreatitis. We present the case of a 37 years-old patient who presented with repeated episodes of acute pancreatitis. By means of magnetic resonance imaging and endoscopic ultrasonography we discovered a duplication cyst whose cavity received drainage from the dorsal pancreas. After opening the cyst cavity to the duodenal lumen with a needle knife the patient presented no further episodes in the clinical follow-up. Comparable literature findings and therapeutic options for these abnormalities are discussed with regard to the presented case.