Active smoking is associated with the development of adverse events of biological therapy in patients with inflammatory bowel disease.

INTRODUCTION: Smoking has been associated with lower levels of anti-TNF agents, higher antibodies and a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate the possible association between smoking and adverse events (AEs) of biologics in patients with IBD. MATERIAL AND METHODS: Consecutive IBD patients under biologics from a prospective, longitudinal registry of a tertiary center were included. A specially designed questionnaire including a wide range of AEs associated with biologics was also used. RESULTS: A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5-56) years, Crohn's disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] who had completed the questionnaire forms for AEs were included. There were 52 (35%) active smokers and 33 (22.5%) ex-smokers. The prevalence of all AEs was 88% in smokers, 87% in ex-smokers and 79% in nonsmokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes ( P = 0.01 and 0.002, respectively). These correlations were the same for the CD and ulcerative colitis (UC), except for arthralgias where there was a significant correlation only with CD ( P = 0.001). There were no significant associations between smoking and other AEs ( P > 0.05). CONCLUSION: Active smoking is associated with the development of dermatological manifestations (both in UC and CD) and arthralgias (in CD) in IBD patients under biologics.

Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease.

PURPOSE: The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. METHODS: Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. RESULTS: One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. CONCLUSIONS: In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.

Real-life utility and diagnostic accuracy of a home-performed fecal calprotectin test to predict endoscopic activity in patients with inflammatory bowel disease under maintenance treatment with adalimumab.

AIMS: The home-performed fecal calprotectin (FC) test has been proposed for the remote management of inflammatory bowel disease (IBD) patients. We present our real-world experience on the use of FC home testing in IBD patients under maintenance treatment with adalimumab. METHODS: Consecutive IBD patients on maintenance treatment with adalimumab were studied retrospectively on the basis of prospectively recorded data. FC calprotectin home test (IBDoc, Βühlmann Laboratories AG, Schönenbuch, Switzerland) was analyzed alongside sufficient information on baseline characteristics, follow-up data and treatment modifications, as well as serum biomarkers and endoscopic assessment data on the basis of validated endoscopic scores. RESULTS: From a total of 72 IBD patients under maintenance treatment with adalimumab, 65 (90%) showed compliance with performing the home FC test. FC values were significantly higher in patients who finally needed treatment modification (37%) compared with those who were maintained on stable treatment (63%) (761 µg/g [537-1000] vs. 108 [41-335], P < 0.0001). In the logistic regression analysis FC and erythrocyte sedimentation rate (ESR) were independently correlated with endoscopically active disease (odds ratio: 1.003; 95% confidence interval, 1.001-1.006, P < 0.01 and odds ratio: 1.058; 95% confidence interval, 1.013-1.105, P < 0.05). FC identified patients with endoscopically active disease more effectively than other biomarkers with an area under the receiver operating characteristic curve of 0.78. FC levels >413 µg/g had a sensitivity of 75% and a specificity of 76% in predicting active disease in endoscopy. CONCLUSIONS: These first real-life results indicate that in IBD patients under maintenance treatment with adalimumab FC home test is a valuable tool with high compliance rates that performs better than the other biomarkers in predicting disease endoscopic activity.

Immunoproliferative Small Intestinal Disease in a Liver Transplant Recipient: A Case Report and Literature Review.

Immunoproliferative small intestinal disease is an extranodal marginal zone B-cell lymphoma that arises from mucosa-associated lymphoid tissue and is associated with defective α heavy chain protein secretion. We present a case of an 18-year-old male patient admitted with diarrhea and weight loss who had previously received a liver transplant at the age of 19 months to treat biliary atresia. He underwent a thorough investigation and was diagnosed with immunoproliferative small intestinal disease lymphoma. The patient was switched from tacrolimus to everolimus and commenced on doxycycline treatment for 6 months and achieved long-term remission. Currently, 7 years after diagnosis, he is asymptomatic without evidence of histological relapse. This is the first case of immunoproliferative small intestinal disease described in a liver transplant recipient.

Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece.

BACKGROUND AND AIMS: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece. METHODS: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab. RESULTS: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period. CONCLUSIONS: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.

Osteoclast: like giant cell undiferrentiated pancreatic tumor diagnosed by means of EUS guided FNA.

OBJECTIVE: Osteoclast-like giant cell tumours are rare abdominal malignant neoplasms mainly arising in the pancreas. Because of their rarity, clinical and cytopathology reports are very limited, and sonographic features have not been clearly specified ; these tumors are easily misdiagnosed by ultrasound as mucinous cystic tumors (MCTs)  or solid pseudopapillary neoplasms (SPNs). CASE STUDY: We report a case of osteoclast  like giant cell tumor arising in the pancreas of an 80 year old female patient offered by EUS-FNA cytology on direct and cell block slides. A biphasic pattern composed by a malignant mononuclear cell component and a giant cell component were hallmarks to the diagnosis. CONCLUSION: Our case highlights the performance of EUS-FNA in the diagnostic approach of  abdominal tumours and the significance of cell block method in the interpretation of osteoclast-like giant cell pancreatic tumour.

First case of Whipple's disease successfully treated with tigecycline.

INTRODUCTION: Whipple's disease is a rare chronic infectious disease caused by Tropheryma whipplei. The infection mainly affects the small intestine of middle-aged patients, approximately three times more often in males than in females causing malabsorption and excessive weight loss but other organs may be affected as well. CASE REPORT: We describe a case of a 42-year-old woman with a history of chronic diarrhea and weight loss evolving for at least the last 6 years. The diagnosis of Whipple's disease was confirmed by histopathological examination of duodenal biopsy samples with Periodic acid-Schiff positive macrophages and by polymerase chain reaction technique detecting the DNA of Tropheryma whipplei. The patient was commenced on several antimicrobials including beta-lactams and co-trimoxazole but she did not improve. Finally, after-long lasting i.v. tigecycline 100 mg BID she was commenced on p.o. doxycycline along with hydroxychloroquine 200 mg TID for one year and after by p.o. doxycycline alone. DISCUSSION: The intriguing thing with this case was not only the natural resistance to co-trimoxazole but that the infection was controlled empirically with long-lasting i.v. tigecycline since several failed attempts to discontinue i.v. treatment followed. This might be due to erratic absorption of oral drugs due to gut inflammation. CONCLUSIONS: To our knowledge, this is the first case of Whipple's disease successfully treated with long-lasting induction parenteral tigecycline followed by p.o. doxycycline along with hydroxychloroquine for one year and after by p.o. doxycycline alone.

Buried Bumper Syndrome: A common complication of levodopa intestinal infusion for Parkinson disease.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is required for Levodopa/Carbidopa Intestinal Gel (LCIG) delivery in patients with advanced Parkinson's disease (PD) as well as for enteral feeding in a variety of neurological disorders. Buried Bumper Syndrome (BBS) is a serious complication of PEG. The frequency of BBS in patients receiving LCIG treatment has never been reported. OBJECTIVES: To compare the frequency of BBS in patients on LCIG treatment or on enteral feeding over the past 12 years and identify possible risk factors. METHODS: We reviewed prospectively recorded data from 2009 to 2020 on two case-series: LCIG-treated PD patients and non-PD patients on enteral nutrition. We identified all BBS incidences. Patients' characteristics, clinical manifestations, BBS management, possible risk factors and outcomes were analyzed. RESULTS: During the 12 years, 35 PD patients underwent PEG insertion for LCIG infusion, and 123 non-PD patients for nutritional support. There were eight cases of BBS in six PD patients (17.1%). Six of them were effectively managed without treatment discontinuation. Of the enteral feeding patients, only one developed BBS (0.8%) (p < 0.001). We identified inappropriate PEG site aftercare, weight gain, early onset PD, longer survival, treatment duration, dementia and PEG system design as potential risk factors for BBS development. CONCLUSIONS: BBS occurs more frequently in LCIG patients than in patients receiving enteral feeding. If detected early, it can be successfully managed, and serious sequalae or treatment discontinuation can be avoided. Regular endoscopic follow-up visits of LCIG-treated patients and increased awareness in patients and clinicians are recommended.

Mucocutaneous manifestations in patients with inflammatory bowel disease: a decade study from a Greek cohort.

BACKGROUND: We sought to investigate the prevalence of mucocutaneous manifestations (MCM) and potential associations with clinical characteristics in Greek patients with IBD. METHODS: This was a retrospective observational single-center study. Patients with IBD diagnosis attending a tertiary referral hospital in Heraklion, Crete, from January 2010 to January 2020 were included. Data were extracted with relevant medical information from the IBD registry. Standard statistical tests, descriptive statistics tests, chi-square, Pearson correlation and multivariate analysis tests were performed, using IBM SPSS Statistics 25. RESULTS: A total of 806 IBD patients were included in the study: 463 (57.4%) males, 441 (54.7%) Crohn's Disease, 352 (43.7%) ulcerative colitis and 13 (1.6%) IBD unclassified (IBD-U). Mean age was 50.67 ± 17.67 years, mean age of IBD diagnosis 36.67 ± 16.53 years and mean disease duration 13.65 ± 9.89 years. The prevalence of MCM was 171/806 (21.2%), 9.65% in ulcerative colitis and 30.84% in CD. The presence of MCM was significantly correlated with younger age of IBD diagnosis, longer IBD duration, CD diagnosis, inflammatory behavior and ileal or ileocolonic location of CD, extensive colitis in ulcerative colitis, intestinal manifestations (EIMs) and treatment with immunosuppressant or anti-TNFa. The development of MCM was independently associated with the presence of other EIMs odds ratio (OR), 4.03 [95% confidence interval (CI), 2.60-6.24; P < 0.001] and treatment with immunosuppressant (OR, 1.87; 95% CI, 01.14-3.07; P = 0.013) or anti-TNFa (OR = 2.47; 95% CI, 1.59-3.84; P < 0.01). CONCLUSIONS: In our study, about one-fifth of IBD patients developed MCM that was more frequently present in CD than in ulcerative colitis.

The Effect of Early vs Delayed Initiation of Adalimumab on Remission Rates in Patients With Crohn's Disease With Poor Prognostic Factors: The MODIFY Study.

Background: Data on the effectiveness of anti-tumor necrosis factor medications in patients with Crohn's disease (CD) with poor prognostic factors (PPFs) are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) vs delayed (>24 months) initiation of adalimumab (ADL) on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. Methods: This multicentre, retrospective, chart review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe CD (Harvey-Bradshaw Index ≥8) with ≥3 PPFs who were initiated on ADL ≥12 months before enrollment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Results: Eligible patients (n = 171) were consecutively enrolled. In the early vs delayed cohorts, the 26-week remission rates (off-steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) vs 47.2% (50/106), respectively (Δ = 13.5%, P = .044). The respective remission rates were 61.2% vs 42.4% among anti-tumor necrosis factor-naive patients (P = .023) and 58.3% vs 53.2% among anti-tumor necrosis factor-experienced patients (P = .374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early vs delayed ADL cohorts, respectively. Conclusions: Patients with CD with PPFs who received early vs delayed treatment with ADL achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.

Comparative evaluation of ALBI, MELD, and Child-Pugh scores in prognosis of cirrhosis: is ALBI the new alternative?

BACKGROUND: The existence of reliable prognostic indices is of paramount importance in the management of cirrhosis. Both the model for end-stage liver disease (MELD) score and the older Child-Pugh (CP) scores are widely used. The albumin-bilirubin (ALBI) score, initially used in hepatocellular carcinoma, has not been thoroughly investigated in cirrhosis. The aim of this study was to compare the prognostic accuracy of ALBI, MELD, MELD with sodium (MELD-Na), CP, and the corrected for creatinine CP scores in a genetically homogeneous Cretan cirrhotic population. METHODS: One hundred ninety-five outpatients or hospitalized cirrhotics (127 male, median age 66 years) were studied over a period of 2 years and ALBI, platelet-albumin-bilirubin, MELD, MELD-Na, CP score, and 2 types of modified CP score (CP-I and CP-II) with serum creatinine were calculated and correlated with survival. RESULTS: ALBI had an optimum balance between sensitivity and specificity (area under the curve 0.704, 95% confidence interval [CI] 0.630-0.778) compared to the other scores. In the multivariate analysis, the only factors independently associated with death were the ALBI score (hazard ratio [HR] 2.51, 95%CI 1.69-3.73; P<0.001), the MELD-Na score (HR 1.04, 95%CI 1.00-1.09; P=0.045), and age (HR 1.05, 95%CI 1.03-1.07; P<0.001). When only decompensated cirrhosis was evaluated, the multivariate analysis showed that the ALBI score (HR 3.03; 95%CI 1.92-4.78; P<0.001), and age (HR 1.05, 95%CI 1.03-1.07; P<0.001) were independently associated with death. CONCLUSION: ALBI score might be a better prognostic indicator of mortality in cirrhosis and given its simplicity could substitute for the CP, MELD, and MELD-Na scores.

Infliximab trough levels are decreasing over time in patients with inflammatory bowel disease on maintenance treatment with infliximab.

BACKGROUND: Infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATIs) have been suggested as useful markers for the optimization of treatment in inflammatory bowel disease (IBD). We aimed to estimate the patterns over time of IFX-TLs and ATIs in IBD patients on maintenance treatment with IFX. METHODS: Two different measurements of IFX-TLs and ATIs were performed (ELISA; Eagle BioSciences) at a 10-month interval using serum samples of consecutive patients on maintenance treatment with IFX. Certain biomarkers [hemoglobin, erythrocyte sedimentation rate, C-reactive protein (CRP), platelets, albumin] measured at the same time as well as clinical disease activity and quality of life were assessed. RESULTS: Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 Crohn's disease, 15 ulcerative colitis (UC), 42 men, mean age 44.2±15.2 years, 41 in combination therapy with immunomodulator, six in intensified dose], with two available measurements of IFX-TLs and ATIs (A and B), were included in the study. The median levels of IF-TLs were 5.07 (interquartiles range: 1.60-12.73) µg/ml in measurement A and 4.68 (1.19-7.83) µg/ml in measurement B (P<0.0001). Patients whose dose was intensified after the first measurement showed an increase in their median IFX-TLs from 1.47 to 8.5 µg/ml, whereas patients with stable IFX dose showed a significant reduction in the median IFX-TLs from 5.65 to 3.8 µg/ml (P<0.0001). In the logistic regression analysis, the decrease in IFX-TL was correlated significantly and independently with the increase in CRP [odds ratio 5.2 (1.4-19.0), P=0.01]. CONCLUSION: IBD patients on maintenance treatment with IFX show decreasing patterns of IFX-TLs over time associated with increasing patterns of CRP levels.

Hysteroscopy in women with implantation failures after in vitro fertilization: findings and effect on subsequent pregnancy rates.

OBJECTIVE: To evaluate hysteroscopic findings and estimate the effect of hysteroscopy on achieving a pregnancy in women with a history of 2 implantation failures after in vitro fertilization (IVF). DESIGN: Prospective observational and matched case control study. DESIGN CLASSIFICATION: II-2. SETTING: Private assisted reproduction units. PATIENTS: A total of 1475 patients with a history of 2 consecutive implantation failures after IVF who had a hysteroscopy were studied; there were 414 matched pairs of women with a similar history who either had or did not have a hysteroscopy. INTERVENTIONS: Hysteroscopy (diagnostic or operative), IVF/intracytoplasmic sperm injection cycle. MEASUREMENTS AND MAIN RESULTS: Hysteroscopic findings, clinical pregnancy rate (CPR), and ongoing pregnancy rate (OPR) were measured. In all, 36.6% of the study population had abnormal hysteroscopic findings and 22.2% had unsuspected findings; women with abnormal hysteroscopic findings showed significantly increased CPR and increased OPR in a new IVF cycle compared with those with a normal hysteroscopy result. Women who had a hysteroscopy showed significantly increased CPR and OPR compared with matched control subjects who did not have the procedure. Hysteroscopy and appropriate therapy significantly increased the chances of achieving a subsequent clinical and ongoing pregnancy. CONCLUSION: Women with 2 implantation failures after IVF had a remarkably high possibility for unsuspected abnormalities seen at hysteroscopy. Hysteroscopy could serve as a positive prognostic factor for achieving a subsequent pregnancy.