Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Consequences of the spilled gallstones during laparoscopic cholecystectomy: a systematic review.

INTRODUCTION: Complications secondary to spilled gallstones can be classified in the category of disease of medical progress because prior to advent of laparoscopic cholecystectomy very few reports published on the topic. The aim of the present study was to investigate the predisposing factors and the complication rate of spilled gallstones during laparoscopic cholecystectomy over the past 21 years. METHODS: Embase, Pubmed, Medline, Google scholar and Cochrane library were systematically searched for pertinent literature. RESULTS: Seventy five out of 181 articles were selected including 85 patients; of those 38% were men and 62% women. The median age of the cohort was 64 years old and ranged between 33 and 87 years. Only 23(27%) of the authors reported the incident of spillage of the gallstones during the operation. Time of onset of symptoms varied widely from the second postoperative day to 15 years later. Ten of 85 patients were asymptomatic and diagnosed with spilled gallstones incidentally. The rest of the patients presented with complications of severe morbidity and almost, 87% of the patients needed to be treated with surgical intervention and 12% with US ± CT scan guidance drainage. Only one perioperative death reported. CONCLUSIONS: Symptomatic patients with lost gallstones present with severe morbidity complications and required mostly major surgical procedures. Therefore, standardisation of the management of spilled gallstones is needed urgently. Hospitals need to review their policy with audits and recommendations and clinical guidelines are needed urgently.

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Anorectal emergencies: WSES-AAST guidelines.

Anorectal emergencies comprise a wide variety of diseases that share common symptoms, i.e., anorectal pain or bleeding and might require immediate management. While most of the underlying conditions do not need inpatient management, some of them could be life-threatening and need prompt recognition and treatment. It is well known that an incorrect diagnosis is frequent for anorectal diseases and that a delayed diagnosis is related to an impaired outcome. This paper aims to improve the knowledge and the awareness on this specific topic and to provide a useful tool for every physician dealing with anorectal emergencies.The present guidelines have been developed according to the GRADE methodology. To create these guidelines, a panel of experts was designed and charged by the boards of the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) to perform a systematic review of the available literature and to provide evidence-based statements with immediate practical application. All the statements were presented and discussed during the WSES-AAST-WJES Consensus Conference on Anorectal Emergencies, and for each statement, a consensus among the WSES-AAST panel of experts was reached. We structured our work into seven main topics to cover the entire management of patients with anorectal emergencies and to provide an up-to-date, easy-to-use tool that can help physicians and surgeons during the decision-making process.

The New Test for Monitoring Infliximab Therapy: From Laboratory to Clinical Practice.

BACKGROUND: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation. OBJECTIVES: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies. METHODS: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies. RESULTS: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006). CONCLUSIONS: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Working Towards an Appropriate Use of Ibuprofen in Children: An Evidence-Based Appraisal.

Ibuprofen is the most widely used non-steroidal anti-inflammatory drug (NSAID) for the treatment of inflammation, mild-to-moderate pain and fever in children, and is the only NSAID approved for use in children aged ≥3 months. Its efficacy and safety profile have led to its increasing use in paediatric care, even without medical prescription. However, an increase of suspected adverse reactions to ibuprofen has been noted in concomitance with the raised, often medically unsupervised, consumption of the drug. The purpose of this work was a critical review of the paediatric literature over the last 15 years on side effects and adverse events associated with ibuprofen, in order to highlight circumstances associated with higher risks and to promote safe and appropriate use of this drug. The literature from 2000 to date demonstrates that gastrointestinal events are rare, but (when they occur) include both upper and lower digestive tract lesions. Dehydration plays an important role in triggering renal damage, so ibuprofen should not be given to patients with diarrhoea and vomiting, with or without fever. Likewise, ibuprofen should never be administered to patients who are sensitive to it or to other NSAIDs. It is contraindicated in neonates and in children with wheezing and persistent asthma and/or during varicella. Most of the analysed studies reported adverse events when ibuprofen was being used for fever symptoms or flu-like syndrome. Ibuprofen should not be used as an antipyretic, except in rare cases. Ibuprofen remains the drug of first choice in the treatment of inflammatory pain in children.

Eosinophilic disorders of the gastro-intestinal tract: an update.

Eosinophilic diseases of the gastrointestinal tract, including eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), are rare chronic pathologies of the digestive system, with an immuno-mediated pathogenesis. Recent data suggest that, together with the "classic" IgE-response to allergens, also a delayed hypersensitivity mechanism could be involved in the development of eosinophilic disorders. EoE and EGE were studied only in the latest decades and as a consequence accurate data are not yet available, concerning not only pathogenesis, but also epidemiology, treatment and outcomes. The diagnosis of EoE is centered on endoscopic findings but the certainty is obtained by histological examination from biopsy samples, that has a sensitivity of 100% when based on five samples. The currently available treatments include topical corticosteroids, specific diets and endoscopic treatment. Concerning EGE, three subtypes (mucosal, muscular, and serosal) were identified. The diagnosis is based, as for EoE, on endoscopic and histological assessment, and the treatment includes pharmacological and dietetic approaches. Further studies are warranted in order to better define the etiology and pathogenesis of eosinophilic diseases of the gastrointestinal tract, and thus to develop more appropriate and specific therapies.

A method for measuring individual research productivity in hospitals: development and feasibility.

BACKGROUND: Research capacity is a prerequisite for any health care institution intending to provide high-quality care, yet, few clinicians engage in research, and their work is rarely recognized. To make research an institutional activity, it could be helpful to measure health care professionals' research performance. However, a comprehensive approach to do this is lacking. METHODS: We conducted a literature analysis to determine how best to assess research performance. Our method was not restricted to bibliometric and citation parameters, as is usually the case, but also including "hidden" activities, generally not considered in research performance evaluations. RESULTS: A set of 12 easily retrievable indicators was used and corresponding points assigned according to a weighting system intended to reflect the effort estimated to perform each activity. We observed a highly skewed score distribution, with a minority of health care professionals performing well across the indicators. The highest score was recorded for scientific papers (768/1098 points, 70%). Twenty percent of researchers at our institution generated 50% of points. CONCLUSIONS: We develop a simple method for measuring research performance, which could be rapidly implemented in health care institutions. It is hoped that the proposed method might be useful for promoting research and guiding resource allocation, although further evaluations are needed to confirm the method's utility.

The HAC trial (harmonic for acute cholecystitis): a randomized, double-blind, controlled trial comparing the use of harmonic scalpel to monopolar diathermy for laparoscopic cholecystectomy in cases of acute cholecystitis.

BACKGROUND: The HARMONIC SCALPEL (H) is an advanced ultrasonic cutting and coagulating surgical device with important clinical advantages, such as: reduced ligature demand; greater precision due to minimal lateral thermal tissue damage; minimal smoke production; absence of electric corrents running through the patient. However, there are no prospective RCTs demonstrating the advantages of H compared to the conventional monopolar diathermy (MD) during laparoscopic cholecystectomy (LC) in cases of acute cholecystitis (AC). METHODS: This study was a prospective, single-center, randomized trial (Trial Registration Number: NCT00746850) designed to investigate whether the use of H can reduce the incidence of intra-operative conversion during LC in cases of AC, compared to the use of MD. Patients were divided into two groups: both groups underwent early LC, within 72 hours of diagnosis, using H and MD respectively (H = experimental/study group, MD = control group). The study was designed and conducted in accordance with the regulations of Good Clinical Practice. RESULTS: 42 patients were randomly assigned the use of H (21 patients) or MD (21 patients) during LC. The two groups were comparable in terms of basic patient characteristics. Mean operating time in the H group was 101.3 minutes compared to 106.4 minutes in the control group (p=ns); overall blood loss was significantly lower in the H group. Conversion rate was 4.7% for the H group, which was significantly lower than the 33% conversion rate for the control group (p<0.05). Post-operative morbidity rates differed slightly: 19% and 23% in the H and control groups, respectively (p=ns). Average post-operative hospitalization lasted 5.2 days in the H group compared to 5.4 days in the control group (p=ns). CONCLUSIONS: The use of H appears to correlate with reduced rates of laparoscopic-open conversion. Given this evidence, H may be more suitable than MD for technically demanding cases of AC.

Subtypes of irritable bowel syndrome in children: prevalence at diagnosis and at follow-up.

OBJECTIVES: To assess the prevalence of irritable bowel syndrome (IBS) subtypes in childhood at diagnosis and their changes over 1 year. STUDY DESIGN: This is an observational, prospective, multicenter study. Consecutive pediatric patients with IBS, according to Rome III criteria, were enrolled over a 1-year period. Parents recorded weekly stool frequency and consistency and gastrointestinal and extraintestinal symptoms in a diary. Stool consistency was scored according to the Bristol Stool Form Scale. Children were evaluated after 2, 3, 6, and 12 months. RESULTS: We enrolled 100 children with IBS (median age 9.9 years, range 4.2-16.7 years, 52 girls and 48 boys). At time of enrollment, constipation-IBS was the prevalent subtype (45%), with a prevalence of girls at 62% (P < .005); diarrhea-IBS was reported in 26% of children, with a prevalence of boys at 69% (P < .005); and alternating-IBS was described in 29% of children, without a difference between sexes. During the follow-up, 10% of patients changed their IBS subtypes at 2 months, 9% at 3 months, 7% at 6 months, and 6.3% at 12 months. Twenty-four percent of patients changed IBS subtype between the time of enrollment and 12 months. CONCLUSIONS: Constipation-IBS is the prevalent subtype in children, with a higher frequency in girls. In boys, diarrhea-IBS is the most common subtype. It is important to acquire knowledge about IBS subtypes to design clinical trials that may eventually shed new light on suptype-specific approaches to this condition.

Oesophageal mucosal intercellular space diameter and reflux pattern in childhood erosive and non-erosive reflux disease.

BACKGROUND AND AIMS: We sought to compare intercellular space diameter in children with non-erosive and erosive reflux disease, and a control group. We also aimed to characterize the reflux pattern in erosive and non-erosive reflux disease patients, and to explore the relationship between intercellular space diameter values and reflux parameters. METHODS: Twenty-four children with non-erosive reflux disease, 20 with erosive reflux disease, and 10 controls were prospectively studied. All patients and controls underwent upper endoscopy. Biopsies were taken at 2-3 cm above the Z-line, and intercellular space diameter was measured using transmission electron microscopy. Non-erosive and erosive reflux disease patients underwent impedance-pH monitoring. RESULTS: Mean intercellular space diameter values were significantly higher in both non-erosive (0.9 ± 0.2 µm) and erosive reflux disease (1 ± 0.2 µm) compared to controls (0.5 ± 0.2 µm, p<0.01). No difference was found between the two patient groups. Acid exposure time, the number of acid, weakly acidic and weakly alkaline reflux events did not differ between the two patient groups. No difference was found in the mean intercellular space diameter between non-erosive reflux disease children with and without abnormal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 µm). No correlation was found between any reflux parameter and intercellular space diameter values. CONCLUSIONS: Dilated intercellular space diameter seems to be a useful and objective marker of oesophageal damage in paediatric gastro-oesophageal reflux disease, regardless of acid exposure. In childhood, different gastro-oesophageal reflux disease phenotypes cannot be discriminated on the basis of reflux pattern.

Effects of disease activity on anti-Saccharomyces cerevisiae antibodies: implications for diagnosis and follow-up of children with Crohn's disease.

BACKGROUND: To determine diagnostic accuracy of anti-Saccharomyces cerevisiae antibodies (ASCA) in identifying children with inflammatory bowel disease (IBD) and to differentiate Crohn's disease (CD) from other IBD forms; and to determine the effect of medical or surgical treatment and of disease location and activity on ASCA titers. METHODS: Serum samples were obtained from 196 IBD children and 142 controls. ASCA IgA and IgG titers were measured by ELISA. Measurements were repeated during the follow up of CD children. RESULTS: ASCA titers were significantly higher in CD than in other IBD and in control patients. Combination of IgA and IgG ASCA positivity was highly specific for CD. Medical treatment and disease location did not influence assay results. Significantly lower ASCA titers were obtained in CD children with intestinal resection compared to CD-affected children who did not undergo surgical resection. ASCA titers correlated significantly with disease activity, and children with severe active disease showed higher ASCA values compared to those in remission. A significant reduction of ASCA was observed during the follow-up of CD children when clinical remission was achieved. CONCLUSIONS: The diagnostic accuracy of ASCA is influenced by disease activity and this suggests an additional use for the follow-up of CD children of this assay.

Relationships between serum IGF-1, IGFBP-2, interleukin-1beta and interleukin-6 in inflammatory bowel disease.

AIMS: To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and interleukin (IL)-1beta and IL-6 in inflammatory bowel disease (IBD). METHODS: Thirty-seven patients (18 males, 19 females, aged 8.8-26.1 years) with IBD (Crohn's disease, CD, n = 17, and ulcerative colitis, UC, n = 20) were studied. Patients were in relapse or remission according to established criteria. Serum IGF-1, IGFBP-3, IGFBP-2, IL-1beta and IL-6 levels were determined in patients and 15 healthy controls (aged 8.2-19.0 years). RESULTS: IGF-1 levels were lower in patients with CD in relapse compared with controls (p < 0.05). IGFBP-2 levels were higher in CD in relapse compared with other groups (all p < 0.05). In CD and UC patients (n = 37), IGF-1 levels were inversely correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). IGFBP-2 levels correlated positively with ESR and IL-1beta. IL-6 levels correlated positively with ESR and CRP. IL-1beta levels were elevated in CD in relapse compared to controls (p < 0.05) and were higher in UC in relapse than in other groups (all p < 0.05). In combined CD/UC patients in relapse (n = 20), IL-1beta levels were higher (p < 0.05) in patients with recto-sigmoiditis (n = 5) than in other patients. CONCLUSIONS: IGF-1, IGFBP-2 levels were related to IL levels, disease activity and anatomical distribution, consistent with active inflammation modifying the IGF-IGFBP system, possibly relevant to disturbance of growth.