Spindle Cell Hemangioma of the Lung: A Case Report.

Spindle cell hemangioma (SCH) is an uncommon tumor that usually presents as a subcutaneous or deep dermal nodule affecting the extremities of young people. It is primarily a benign vascular neoplasm with a tendency to recur locally. Reports describing SCH diagnosed in muscles, retroperitoneum, mediastinum, and even in the spinal cord occasionally surface in the literature. We report a very rare case of SCH diagnosed in the lung.

End-Stage Renal Disease Patients on Chronic Hemodialysis Fare Better With COVID-19: A Retrospective Cohort Study From the New York Metropolitan Region.

Introduction Several comorbid conditions have been identified as risk factors in patients with coronavirus disease 2019 (COVID-19). However, there is a dearth of data describing the impact of COVID-19 infection in patients with end-stage renal disease on hemodialysis (ESRD-HD). Methods This retrospective case series analyzed 362 adult patients consecutively hospitalized with confirmed COVID-19 illness between March 12, 2020, and May 13, 2020, at a teaching hospital in the New York City metropolitan area. The primary outcome was severe pneumonia as defined by the World Health Organization. Secondary outcomes were the (1) the Combined Outcome of Acute respiratory distress syndrome or in-hospital Death (COAD), and (2) need for high levels of oxygen supplementation (HiO2). Results Patients with ESRD-HD had lower odds for poor outcomes including severe pneumonia [odds ratio (OR) 0.4, confidence interval (CI) 0.2-0.9, p=.04], HiO2 [OR 0.3, CI (0.1-0.8), p=.02] and COAD [OR 0.4, CI (0.2-1.05), p=.06], when compared to patients without ESRD. In contrast, higher odds for severe pneumonia, COAD and HiO2 were seen with advancing age. African Americans were over-represented in the hospitalized patient cohort, when compared to their representation in the community (35% vs 18%). Hispanics had higher odds for severe illness and HiO2 when compared to Caucasians. Conclusions Patients with ESRD-HD had a milder course of illness with a lower likelihood of severe pneumonia and a lesser need for aggressive oxygen supplementation when compared to patients not on chronic dialysis. The lower odds of severe illness in ESRD-HD patients might have a pathophysiologic basis and need to be further explored.

Incidence and Risk Factors for Acute Kidney Injury and Its Effect on Mortality in Patients Hospitalized From COVID-19.

OBJECTIVE: To determine the incidence of and risk factors for the development of acute kidney injury (AKI) and investigate the association between AKI and mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) infection. PATIENTS AND METHODS: This retrospective case series includes the first 370 patients consecutively hospitalized with confirmed COVID-19 illness between March 10, 2020, and May 13, 2020, at a 242-bed teaching hospital. To determine independent associations between demographic factors, comorbid conditions, and AKI incidence, multivariable logistic regression models were used to estimate odds ratios adjusted for clinical covariates. RESULTS: Median age of patients was 71 (interquartile range, 59-82) years and 44.3% (145 of 327) were women. Patients with AKI were significantly older with a higher comorbid condition burden and mortality rate (58.1% [104 0f 179] vs 19.6% [29 of 148]; P<.001) when compared with those without AKI. Increasing age, chronic kidney disease, hyperlipidemia, and being of African American descent showed higher odds of AKI. Patients with AKI had significantly higher odds of mortality when compared with patients without AKI, and this effect was proportional to the stage of AKI. Increasing age and acute respiratory distress syndrome also revealed higher adjusted odds of mortality. CONCLUSIONS: Acute kidney injury is a common complication among hospitalized patients with COVID-19 infection. We found significantly higher odds of AKI with increasing age and among patients with hyperlipidemia, those with chronic kidney disease, and among African Americans. We demonstrate an independent association between AKI and mortality with increasingly higher odds of mortality from progressively worsening renal failure in hospitalized patients with COVID-19 infection.

Confused or not Confused?: Disentangling Brain Activity from EEG Data Using Bidirectional LSTM Recurrent Neural Networks.

Brain fog, also known as confusion, is one of the main reasons for low performance in the learning process or any kind of daily task that involves and requires thinking. Detecting confusion in a human's mind in real time is a challenging and important task that can be applied to online education, driver fatigue detection and so on. In this paper, we apply Bidirectional LSTM Recurrent Neural Networks to classify students' confusion in watching online course videos from EEG data. The results show that Bidirectional LSTM model achieves the state-of-the-art performance compared with other machine learning approaches, and shows strong robustness as evaluated by cross-validation. We can predict whether or not a student is confused in the accuracy of 73.3%. Furthermore, we find the most important feature to detecting the brain confusion is the gamma 1 wave of EEG signal. Our results suggest that machine learning is a potentially powerful tool to model and understand brain activity.

Measuring time-frequency importance functions of speech with bubble noise.

Listeners can reliably perceive speech in noisy conditions, but it is not well understood what specific features of speech they use to do this. This paper introduces a data-driven framework to identify the time-frequency locations of these features. Using the same speech utterance mixed with many different noise instances, the framework is able to compute the importance of each time-frequency point in the utterance to its intelligibility. The mixtures have approximately the same global signal-to-noise ratio at each frequency, but very different recognition rates. The difference between these intelligible vs unintelligible mixtures is the alignment between the speech and spectro-temporally modulated noise, providing different combinations of "glimpses" of speech in each mixture. The current results reveal the locations of these important noise-robust phonetic features in a restricted set of syllables. Classification models trained to predict whether individual mixtures are intelligible based on the location of these glimpses can generalize to new conditions, successfully predicting the intelligibility of novel mixtures. They are able to generalize to novel noise instances, novel productions of the same word by the same talker, novel utterances of the same word spoken by different talkers, and, to some extent, novel consonants.

Acetaminophen overdose associated with double serum concentration peaks.

Acetaminophen is the most commonly used analgesic-antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy.

Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re-Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012).

BACKGROUND AND AIMS: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. METHODS: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. CONCLUSION: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe.

AIM: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). METHODS: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. RESULTS: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CONCLUSION: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.

Prevalence and predictors of hospitalization in Crohn's disease in a prospective population-based inception cohort from 2000-2012.

AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the population-based inception cohort from Veszprem province. METHODS: Data of 331 incident Crohn's disease (CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%, 53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures (37%), surgery or disease activity (27% and 21%). Non-inflammatory disease behavior at diagnosis (HR = 1.32, P = 0.001) and perianal disease (HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change (HR = 2.38, P = 0.002) and need for steroids (HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses. Early CD-related hospitalization (within the year of diagnosis) was independently associated with need for immunosuppressives (OR = 2.08, P = 0.001) and need for surgeries (OR = 7.25, P < 0.001) during the disease course. CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and re-hospitalization.

Decreasing trends in hospitalizations during anti-TNF therapy are associated with time to anti-TNF therapy: Results from two referral centres.

BACKGROUND: Hospitalization is an important outcome measure and a major driver of costs in patients with inflammatory bowel disease. We analysed medical and surgical hospitalization rates and predictors of hospitalization before and during anti-TNF therapy. METHODS: Data from 194 consecutive patients were analysed retrospectively (males, 45.4%, median age at diagnosis, 24.0 years, infliximab/adalimumab: 144/50) in whom anti-TNF therapy was started after January 1, 2008. Total follow-up was 1874 patient-years and 474 patient-years with anti-TNF exposure. RESULTS: Hospitalization rates hospitalization decreased only in Crohn's disease (odds ratio: 0.59, 95% confidence interval: 0.51-0.70, median 2-years' anti-TNF exposure) with a same trend for surgical interventions (p=0.07), but not in ulcerative colitis. Need for hospitalization decreased in Crohn's disease with early (within 3-years from diagnosis, p=0.016 by McNemar test), but not late anti-TNF exposure. At logistic regression analysis complicated disease behaviour (p=0.03), concomitant azathioprine (p=0.02) use, but not anti-TNF type, gender, perianal disease or previous surgeries were associated with the risk of hospitalization during anti-TNF therapy. CONCLUSION: Hospitalization rate decreased significantly in patients with Crohn's disease but not ulcerative colitis after the introduction of anti-TNF therapy and was associated with time to therapy. Complicated disease phenotype and concomitant azathioprine use were additional factors defining the risk of hospitalization.

Have biologics changed the natural history of Crohn's disease?

Crohn's disease (CD) is a progressive condition, with most patients developing a penetrating or stricturing phenotype over time. The introduction of anti-tumor necrosis factor (TNF) therapies over the past 10-15 years, which was supported by accumulating evidence both from trials and clinical practice, has led to a significant change in patient management, monitoring, and treatment algorithms. Anti-TNF therapy was demonstrated to be effective for both luminal and fistulizing disease. Regular therapy with both infliximab and adalimumab was shown to increase the likelihood of clinical remission and mucosal healing, as well as to reduce the need for surgery and hospitalization in both clinical trials and clinical practice, especially in patients with pediatric-onset CD, shorter disease duration, and when used in combination with immunosuppressives. This has led to new treatment goals and to the use of early aggressive medical therapy in a selected group of patients with a worse prognosis. Exploratory clinical trials are underway to determine if further optimization of therapies and treatment beyond clinical remission leads to superior disease outcomes. However, more long-term clinical data are needed to assess whether an early, aggressive therapeutic strategy employing anti-TNF, alone or in combination with biologicals, can further improve long-term disease outcomes in both pediatric patients and young adults.

Work disability and productivity loss in patients with inflammatory bowel diseases in Hungary in the era of biologics.

BACKGROUND AND AIMS: To assess work disability (WD) rates in an inflammatory bowel disease (IBD) cohort involving patients with Crohn's disease (CD) or ulcerative colitis (UC) cohort and to identify possible clinical or demographic factors associated with WD. To our knowledge, this is the first study from Eastern Europe that has estimated indirect costs in IBD. METHODS: Data from 443 (M/F: 202/241, CD/UC: 260/183, mean age: 35.5 (CD) and 40.5 (UC) years, biological drug exposure 31.2/11.5%) consecutive patients were included. WD data were collected by questionnaire and the work productivity and activity impairment instrument. Disability pension (DP) rates in the general population were retrieved from public databases. RESULTS: The overall DP rate in this IBD population was 32.3%, with partial disability in 24.2%. Of all DP events, 88.8% were directly related to IBD. Overall, full DP was more prevalent in IBD (RR: 1.51, p < 0.001) and CD (RR: 1.74, p < 0.001) but not in UC compared to the general population and also in CD compared to UC (OR 1.57, p = 0.03). RR for full DP was increased only in young CD patients (RR<35 year olds: 9.4; RR36-40 year olds: 9.4 and 5.6, p < 0.01 for both). In CD, age group, previous surgery, disease duration, frequent relapses, and the presence of arthritis/arthralgia were associated with an increased risk for DP. Among employed patients, absenteeism and presenteeism was reported in of 25.9 and 60.3% patients, respectively, leading to a 28% loss of work productivity and a 32% activity loss, and was associated with disease activity and age group. Average cost of productivity loss due to disability and sick leave with a human capital approach was 1,450 and 430 €/patient/year in IBD, respectively (total productivity loss 1,880 €/patient/year), the costs of presenteeism were 2,605 (SD = 2,770) and 2,410 (SD = 2,970) €/patient/year in CD and UC, respectively. CONCLUSION: Risk of DP was highly increased in young CD patients (sixfold to ninefold). Previous surgery and presence of arthritis/arthralgia was identified as risk factors for DP. Work productivity is significantly impaired in IBD and is associated with high productivity loss.

Inflammatory bowel disease course in Crohn's disease: is the natural history changing?

Crohn's disease (CD) is a multifactorial potentially debilitating disease. It has a variable disease course, but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability. Studies on the natural history of CD provide invaluable data on its course and clinical predictors, and may help to identify patient subsets based on clinical phenotype. Most data are available from referral centers, however these outcomes may be different from those in population-based cohorts. New data suggest the possibility of a change in the natural history in Crohn's disease, with an increasing percentage of patients diagnosed with inflammatory disease behavior. Hospitalization rates remain high, while surgery rates seem to have decreased in the last decade. In addition, mortality rates still exceed that of the general population. The impact of changes in treatment strategy, including increased, earlier use of immunosuppressives, biological therapy, and patient monitoring on the natural history of the disease are still conflictive. In this review article, the authors summarize the available evidence on the natural history, current trends, and predictive factors for evaluating the disease course of CD.

Incidence rates and disease course of paediatric inflammatory bowel diseases in Western Hungary between 1977 and 2011.

BACKGROUND: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011. METHODS: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort. RESULTS: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%). CONCLUSIONS: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low.

Is early limited surgery associated with a more benign disease course in Crohn's disease?

AIM: To analyze the difference in disease course and need for surgery in patients with Crohn's disease (CD). METHODS: Data of 506 patients with incident CD were analyzed (age at diagnosis: 31.5 ± 13.8 years). Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which includes incident CD patients diagnosed between January 1, 1977 and December 31, 2008. Follow-up data were collected until December 31, 2009. All patients included had at least 1 year of follow-up available. Patients with indeterminate colitis at diagnosis were excluded from the analysis. RESULTS: Overall, 73 patients (14.4%) required resective surgery within 1 year of diagnosis. Steroid exposure and need for biological therapy were lower in patients with early limited surgery (P < 0.001 and P = 0.09). In addition, surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores (P < 0.001, HR = 0.23). The need for reoperation was also lower in patients with early limited resective surgery (P = 0.038, HR = 0.42) in a Kaplan-Meier and multivariate Cox regression (P = 0.04) analysis. However, this advantage was not observed after matching on propensity scores (P(Logrank) = 0.656, P(Breslow) = 0.498). CONCLUSION: Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery, but reoperation rates did not differ.

Risk of colorectal cancer in Crohn's disease patients with colonic involvement and stenosing disease in a population-based cohort from Hungary.

BACKGROUND & AIMS: Since data is limited regarding the risk of colorectal cancer (CRC) in Crohn's disease (CD) patients who present with stenosing disease in the colon, this study was undertaken to assess CRC risk in such patients, using a population-based, Veszprem province database, which includes incidental patients diagnosed between January 1, 1977 and December 31, 2011. METHODS: Data from 640 incidental CD patients were analyzed (M/F ratio: 321/319, age-at-diagnosis: 28 years (IQR: 22-38)). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: CRC was diagnosed in six CD patients during a follow-up of 7759 person-years. Sixty-two patients presented with colonic/ileocolonic disease and a stenotic lesion in the colon with a follow-up of 702 person-years (median: 10.5, IQR: 5-16years). Colorectal cancer developed in 6.5% (equalling 0.57/100 person-years), the SIR (6.53, 95% CI: 2.45-17.4) was increased with four patients observed versus 0.61 expected. In a Kaplan-Meier analysis, the probability of developing CRC was 5.5% and 7.5% after 5- and 10 years, respectively, versus 0.4% in patients with other phenotypes (HR: 18.8, p<0.001). A sensitivity analysis included patients with stenosing colonic lesion at diagnosis or during follow-up (n=91, follow-up: 1180 person-years, median: 12, IQR: 6-17years). The probability of developing CRC was 3.6% and 4.9% after 5- and 10 years, respectively. CONCLUSIONS: The risk of CRC in CD patients presenting with or developing a stenotic lesion in the colon is high even after a short disease duration, suggesting the need for careful surveillance.

Clinical aspects of mucosal healing in inflammatory bowel diseases: what is it and what is the real value for the everyday practice?

The course of inflammatory bowel diseases is heterogeneous and varies over time. Therefore, the search for predictive factors has increasingly become the focus of research. Mucosal healing has emerged as an important objective, as evidence indicates that it is associated with improved disease outcome. Nevertheless, many unsolved questions remain, including the definition of complete or partial healing as well as the best assessment method using endoscopic or imaging techniques, most of which are relatively invasive and expensive procedures, which therefore are not ideal for frequent monitoring and it is not clear. This review summarizes the available evidence in order to assist clinicians when assessing the mucosal status in the everyday practice.

Levels of anti-double-strained DNA but not antinuclear antibodies are associated with treatment efficacy and adverse outcomes in Crohn's disease patients treated with anti-TNFα.

BACKGROUND & AIMS: Treatment of Crohn's disease (CD) by infliximab (IFX) has been associated with the induction of antinuclear (ANA) and anti-double strand DNA (dsDNA) autoantibodies and in some studies the formation of dsDNA antibodies was associated with lupus-like syndromes. The aims of this study were to analyse the relationship between the development of ANA and dsDNA antibodies during anti-tumor necrosis factor (TNF)α therapy and the clinical efficacy or adverse outcome in patients with inflammatory bowel disease (IBD). METHODS: Data of 96 CD patients (age at presentation: 25.1 years, folow-up: 5 years, males/females 43/53) treated with anti-TNFα for at least one-year were analyzed. Records of a total of 198 one-year treatment cycles were collected and levels of autoantibodies were determined at induction and after one-year treatment periods. RESULTS: The majority of CD patients had ileocolonic (67.4%) and complicated disease (B2-B3: 72.6%) with perianal lesions (63.2%). At any time ANA or dsDNA positivity was 28.6% and 18%. Elevated level of ANA at induction or during anti-TNFα therapy was not associated with treatment efficacy or development of adverse outcomes. In contrast, treatment efficacy (dsDNA positivity no/partial response vs. remission: 68.5% vs. 31.5%, P=0.003) was inferior and adverse outcomes were more frequent in patients with dsDNA positivity during the anti-TNFα therapy in both univariate analysis and in logistic regression models (OR efficacy: 4.91, 95%CI: 1.15-20.8; OR adverse outcome: 3.81,95%CI 1.04-13.9). CONCLUSIONS: Our data suggest that development of dsDNA during biological therapy may be associated with suboptimal treatment efficacy and adverse outcomes in CD patients.

Methotrexate: should we start using it in clinical practice?

Therapeutic approaches in inflammatory bowel disease have changed significantly in the past decade. Early aggressive immunosuppression has become the mainstay of therapy for patients at risk for complicated disease. Azathioprine is the most widely used immunosuppressant; however, a subgroup of patients is intolerant or refractory. Since the late 1990s, methotrexate (MTX) has become more widely used as an immunomodulator in patients with chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. Yet according to recent clinical data, methotrexate remained the second most commonly used immunosuppressive in inflammatory bowel diseases. Two landmark trials and subsequent studies provided evidence for the use of methotrexate in Crohn's disease, both for induction and maintenance of remission. The evidence is less solid in ulcerative colitis, for which results of further randomized controlled trials are pending (e.g. Meteor, Merit). A potential new indication of MTX could be combination therapy with biologicals. While this is state of the art therapy in rheumatoid arthritis, data in inflammatory bowel diseases are less clear. Some studies suggest that combination with immunosuppressants could prevent the development of anti-drug antibodies, while others suggested anti- TNF induced autoimmune disorders as a potential indication. In contrast, improved efficacy was not reported by one study (COMMIT). Limitations include frequent side effects, route of administration, pregnancy and concerns about long-term safety. This review summarizes current knowledge on the efficacy and side effects of methotrexate, and tries to reevaluate the drug in the current IBD armamentarium.

Evolution of disease phenotype in adult and pediatric onset Crohn's disease in a population-based cohort.

AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn's disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long-term evolution of disease behavior was not different in pediatric- and adult-onset CD patients in this population-based cohort but was associated to location, perianal disease and smoking status.