The diagnosis and management of CMV colitis in IBD patients shows high practice variation: a national survey among gastroenterologists.

BACKGROUND: Clinical guidelines on cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) are hampered by the low quality of evidence. In this study, we aim to explore the attitude and management of CMV colitis in IBD among gastroenterologists. METHODS: A web-based survey was distributed to adult and pediatric gastroenterologists and trainees in academic and general hospitals in the Netherlands. The survey comprised data collection on respondents' demographics, attitudes towards the importance of CMV infection in IBD on a visual analogue scale (from 0 to 100), and diagnostic and therapeutic strategies. RESULTS: A total of 73/131 invited respondents from 32 hospitals completed the survey (response rate of 56%). The importance of CMV infection was scored at a median 74/100. Respondents indicated CMV testing as appropriate in the clinical setting of steroid-refractory colitis (69% of respondents), hospitalized patients with active colitis (64%), immunomodulator or biological refractory colitis (55%) and active colitis irrespective of medication use (14%). CMV diagnostics include histology of colonic biopsies (88% of respondents), tissue CMV PCR (43%), serum CMV PCR (60%), CMV serology (25%) and fecal CMV PCR (4%). 82% of respondents start antiviral therapy after a positive CMV test on colonic biopsies (histology or PCR). CONCLUSIONS: Most Dutch gastroenterologists acknowledge the importance of CMV colitis in IBD. Strategies vary greatly with regard to the indication for testing and diagnostic method, as well as indication for the start of antiviral therapy. These findings underline the need for pragmatic clinical studies on different management strategies, in order to reduce practice variation and improve the quality of care. Summary of the established knowledge on this subject:The clinical significance of CMV-associated colitis in IBD remains a matter of debateRecommendations regarding CMV colitis in current international guidelines are based on low to moderate evidence levels and different diagnostic strategies are proposed What are the significant and/or new findings of this study?We show that there is a high practice variation of diagnosis and management of CMV colitis in IBD amongst adult and pediatric gastroenterologistsThis study underlined the need for pragmatic studies and guidelines on different management strategies including cut-off values to start therapy.

Support needs of Dutch young adult childhood cancer survivors.

BACKGROUND: Studies about support needs of young adult childhood cancer survivors (YACCS) previously focused mainly on information needs. This study assessed support needs and associated factors (sociodemographic, medical, and psychosocial functioning) in Dutch YACCS. METHODS: YACCS (aged 18-30, diagnosed ≤ 18 years, time since diagnosis ≥ 5 years) cross-sectionally filled out a questionnaire regarding their need for various types of support (concrete information, personal counseling, and peer contact) in eight domains (physical consequences of childhood cancer, social-emotional consequences, relationships and sexuality, fertility, lifestyle, school and work, future perspective, insurance and mortgage), and questionnaires assessing health-related quality of life (PedsQL-YA), anxiety and depression (HADS), and fatigue (CIS-20R). Descriptive statistics were used to describe support needs. Linear regression was used to identify characteristics associated with support needs. RESULTS: One hundred fifty-one YACCS participated (response = 40%). Most YACCS reported a need for support in one or more domains (88.0%, N = 133). More than half of the participants reported a need for concrete information in the domains lifestyle, fertility, and physical consequences of childhood cancer and 25-50% in the domains insurance and mortgages, future perspective, and social-emotional consequences of childhood cancer. In the domains lifestyle and physical as well as emotional consequences of childhood cancer, 25-50% reported a need for counseling. Overall need for support was positively associated with middle (ß = 0.26, p = 0.024) and high (ß = 0.35, p = 0.014) compared to low educational attainment and (sub)clinical anxiety (ß = 0.22, p = 0.017), and negatively associated with social functioning (ß = - 0.37, p = 0.002) in multivariate analyses. CONCLUSION: YACCS report the strongest need for support, for concrete information, in the domains lifestyle, fertility, and physical consequences of childhood cancer. Associated factors were mostly socioeconomic and psychosocial in nature. Psychosocial care should be an integral part of survivorship care for YACCS, with screening for psychosocial problems, information provision including associated emotional consequences and support if necessary (psycho-education) and tailored interventions, and adequate referrals to more specialized care if necessary.

A vulnerable age group: the impact of cancer on the psychosocial well-being of young adult childhood cancer survivors.

PURPOSE: This study aimed to increase our understanding of the psychosocial well-being of young adult childhood cancer survivors (YACCS) as well as the positive and negative impacts of cancer. METHODS: YACCS (aged 18-30, diagnosed ≤ 18, time since diagnosis ≥ 5 years) cross-sectionally filled out the "Pediatric Quality of Life Inventory Young Adults" (PedsQL-YA), "Hospital Anxiety and Depression Scale" (HADS), and "Checklist Individual Strengths" (CIS-20R) to measure fatigue and survivor-specific "Impact of Cancer - Childhood Survivors" (IOC-CS), which measures the long-term impact of childhood cancer in several domains. Descriptive statistics (IOC-CS), logistic regression (HADS, CIS-20R), and ANOVA (PedsQL-YA, HADS, CIS-20R) were performed. Associations between positive and negative impacts of childhood cancer and psychosocial outcomes were examined with linear regression analyses. RESULTS: YACCS (N = 151, 61.6% female, mean age 24.1 ± 3.6, mean time since diagnosis 13.6 ± 3.8) reported lower HRQOL (- .4 ≤ d ≤ - .5, p ≤ .001) and more anxiety (d = .4, p ≤ .001), depression (d = .4, p ≤ .01), and fatigue (.3 ≤ d ≤ .5, p ≤ .001) than young adults from the general Dutch population. They were at an increased risk of experiencing (sub)clinical anxiety (OR = 1.8, p = .017). YACCS reported more impact on scales representing a positive rather than negative impact of CC. Various domains of impact of childhood cancer were related to psychosocial outcomes, especially "Life Challenges" (HRQOL ß = - .18, anxiety ß = .36, depression ß = .29) and "Body & Health" (HRQOL ß = .27, anxiety ß = - .25, depression ß = - .26, fatigue ß = - .47). CONCLUSION: YACCS are vulnerable to psychosocial difficulties, but they also experience positive long-term impacts of childhood cancer. Positive and negative impacts of childhood cancer were associated with psychosocial outcomes in YACCS. Screening of psychosocial outcomes and offering targeted interventions are necessary to optimize psychosocial long-term follow-up care for YACCS.

Efficacy and safety of autologous adipose-derived stromal vascular fraction enriched with platelet-rich plasma in flap repair of transsphincteric cryptoglandular fistulas.

BACKGROUND: Transanal advancement flap repair of transsphincteric fistulas is a sphincter-preserving procedure, which frequently fails, probably due to ongoing inflammation in the remaining fistula tract. Adipose-derived stromal vascular fraction (SVF) has immunomodulatory properties promoting wound healing and suppressing inflammation. Platelet-rich plasma (PRP) reinforces this biological effect. The aim of this study was to evaluate the efficacy and safety of autologous adipose-derived SVF enriched with PRP in flap repair of transsphincteric cryptoglandular fistulas. METHODS: A prospective cohort study was conducted including consecutive patients with transsphincteric cryptoglandular fistula in a tertiary referral center. During flap repair, SVF was obtained by lipoharvesting and mechanical fractionation of adipose tissue and combined with PRP was injected around the internal opening and into the fistulous wall. Endpoints were fistula healing at clinical examination and fistula closure on postoperative magnetic resonance imaging (MRI). Adverse events were documented. RESULTS: Forty-five patients with transsphincteric cryptoglandular fistula were included (29 males, median age 44 years [range 36-53 years]). In the total study population, primary fistula healing was observed in 38 patients (84%). Among the 42 patients with intestinal continuity at time of surgery, primary fistula healing was observed in 35 patients (84%). In one patient, the fistula recurred, resulting in a long-term healing rate of 82%. MRI, performed in 37 patients, revealed complete closure of the fistula tract in 33 (89.2%). In the other patients, the tract was almost completely obliterated by scar tissue. During follow-up, none of these patients showed clinical signs of recurrence. The postoperative course was uneventful, except for three cases; venous thromboembolism in one patient and bleeding under the flap, necessitating intervention in two patients. CONCLUSIONS: Addition of autologous SVF enriched with PRP during flap repair is feasible, safe and might improve outcomes in patients with a transsphincteric cryptoglandular fistula. TRIAL REGISTRATION: Dutch Trial Register, Trial Number: NL8416, https://www.trialregister.nl/.

Clinical and endoscopic complications of Epstein-Barr virus in inflammatory bowel disease: an illustrative case series.

BACKGROUND AND AIM: Epstein-Barr virus (EBV) is a proposed trigger in the etiopathogenesis of inflammatory bowel disease (IBD) and is associated with lymphoproliferative diseases. Nevertheless, testing for EBV DNA in the intestinal mucosa and screening for EBV infection before initiation of a drug therapy are not routinely performed. The aim of this article is to increase awareness of the relevance of EBV infection in specific clinical situations. METHODS: In this short communication, we describe the disease course of three IBD patients with EBV infection, varying from EBV reactivation during disease flare up to a trigger of EBV-related mucocutaneous ulcer (EBV-MCU) and haemophagocytic lymphohistiocytosis (HLH). RESULTS: Our first patient was diagnosed with EBV reactivation-associated severe colitis and showed a rapid clinical improvement after induction therapy with infliximab and azathioprine. Without antiviral treatment, the patient remained in complete remission and no complications of EBV were seen. After diagnosing EBV-MCU in the second patient, immunosuppressive medication was discontinued and four infusions of rituximab resulted in a rapid clinical recovery and eventually complete response. After discontinuation of the immunosuppression in our last patient with haemophagocytic lymphohistiocytosis, treatment with a combination of corticosteroid and antiviral therapy resulted in a complete recovery over a time span of several weeks. CONCLUSION: EBV infection has a wide variety of potentially life-threatening clinical manifestations in IBD patients. Testing for EBV in case of a flare up and screening for EBV before the start of immunosuppressive therapy will create awareness for EBV-related symptoms or complications during follow-up.

A prospective randomized controlled trial comparing infliximab and etanercept in patients with moderate-to-severe chronic plaque-type psoriasis: the Psoriasis Infliximab vs. Etanercept Comparison Evaluation (PIECE) study.

BACKGROUND: There are currently no independent data available comparing infliximab and etanercept for the treatment of psoriasis. OBJECTIVES: To compare these biologics without funding from pharmaceutical companies. METHODS: Overall, 50 patients were randomized to etanercept (n = 23) 50 mg subcutaneously twice weekly or infliximab (n = 25) 5 mg kg-1 intravenously at week 0, 2, 6, 14 and 22. After 24 weeks, 19 patients stopped and 22 continued treatment and were followed up to week 48. The primary outcome was ≥ 75% improvement of Psoriasis Area and Severity Index (PASI 75) at week 24. The secondary outcomes included PASI 75 at week 6 (onset of action) and week 12, Investigator's Global Assessment (IGA), Patient Global Assessment, impact on quality of life (Skindex-17 and SF-36), Treatment Satisfaction Questionnaire of Medication, duration of remission, maintenance treatment and safety. RESULTS: At week 24, PASI 75 was achieved in 72% (infliximab) vs. 35% (etanercept) (P = 0·01). The onset of action was achieved in 52% (infliximab) and 4% (etanercept). At week 12, 76% (infliximab) and 22% (etanercept) achieved PASI 75 (P < 0·001). At week 24, IGA 'clear or almost clear' was observed in 76% (infliximab) and 30% (etanercept) (P = 0·01). Skindex-17 symptom score was significantly better for infliximab. Maintenance treatment achieved PASI 75 for 67% (n = 6) infliximab vs. 50% (n = 5) etanercept, at week 48 (P = 0·65). Mild adverse events were reported in 76% (infliximab) vs. 66% (etanercept). CONCLUSIONS: Infliximab showed a rapid and significant higher level of efficacy until week 24 compared with etanercept. Long-term data showed no significant differences between both groups at week 48. Safety parameters were comparable.

In Vivo Evaluation of Customized Aortic Repair Using a Novel Survival Model.

OBJECTIVE: The aim of the study was to evaluate the feasibility and mid-term biological behavior of the novel customized aortic repair (CAR) method for endovascular aneurysm treatment. METHODS: CAR consists of exclusion of an aneurysm from the circulation using a custom-designed dog bone-shaped balloon, followed by aneurysm sac filling with an in situ curing polymer. After curing and balloon deflation, the circulation is restored through a patent cast neolumen. A liquid two-component polymer was injected via a small bore catheter under X-ray control into a surgically created aneurysm. In 50% of the procedures, a self expanding bare metal stent was placed in the polymer cast lumen. A novel animal model was established involving creation of an aneurysm by anastomosing a venous interposition graft into the common carotid artery of eight adult sheep. Two animals were excluded because of non-device related complications. The remaining six animals were monitored for 20 weeks with duplex sonograms performed monthly to assess blood flow and polymer cast lumen patency. After the animals were sacrificed the polymer cast, common carotid artery, and the brain in the carotid outflow tract were removed for histological assessment. RESULTS: In four of the six animals, the aneurysm was successfully excluded using CAR with uneventful follow up. The aneurysm sac was filled incompletely in two animals, resulting in a stent malpositioning and cast lumen occlusion after 12 weeks in one case, and a type 1 endoleak in the other. All six animals survived for 20 weeks. Neither migration nor expansion of the polymer cast was observed and the polymer was demonstrated to be biocompatible and non-thrombogenic. Polymer emboli were not detected in the brain or meninges after sacrifice. CONCLUSIONS: The feasibility and mid-term biological safety of the CAR method for minimally invasive aneurysm repair was demonstrated using a simulated aneurysm survival model.

Efficacy of tenofovir and efavirenz in combination with lamivudine or emtricitabine in antiretroviral-naive patients in Europe.

BACKGROUND: The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice. METHODS: A multicentre cohort study was performed in therapy-naive patients initiating ART with TELE before July 2009. Efficacy was studied using ITT (missing or switch = failure) and on-treatment (OT) analyses. Genotypic susceptibility scores (GSSs) were determined using the Stanford HIVdb algorithm. RESULTS: Efficacy analysis of 1608 patients showed virological suppression to <50 copies/mL at 48 weeks in 91.5% (OT) and 70.6% (ITT). Almost a quarter of all patients (22.9%) had discontinued TELE at week 48, mainly due to CNS toxicity. Virological failure within 48 weeks was rarely observed (3.3%, n = 53). In multilevel, multivariate analysis, infection with subtype B (P = 0.011), baseline CD4 count <200 cells/mm³ (P < 0.001), GSS <3 (P = 0.002) and use of lamivudine (P < 0.001) were associated with a higher risk of virological failure. After exclusion of patients using co-formulated compounds, virological failure was still more often observed with lamivudine. Following virological failure, three-quarters of patients switched to a PI-based regimen with GSS <3. After 1 year of second-line therapy, viral load was suppressed to <50 copies/mL in 73.5% (OT). CONCLUSIONS: In clinical practice, treatment failure on TELE regimens is relatively frequent due to toxicity. Virological failure is rare and more often observed with lamivudine than with emtricitabine. Following virological failure on TELE, PI-based second-line therapy was often successful despite GSS <3.

Decreased serum anti-Müllerian hormone levels in girls with newly diagnosed cancer.

STUDY QUESTION: Are anti-Müllerian hormone (AMH) levels reduced in girls with newly diagnosed cancer before the start of treatment? SUMMARY ANSWER: AMH levels are already compromised in girls at the time of cancer diagnosis compared with healthy girls. WHAT IS KNOWN ALREADY: In women diagnosed with cancer, evidence of reduced ovarian function has been described even before treatment has started. In girls with newly diagnosed cancer, no data are available. STUDY DESIGN, SIZE, DURATION: We performed an age-matched case-control study in girls with newly diagnosed cancer. PARTICIPANTS/MATERIALS, SETTING, METHODS: We determined serum AMH levels in a cohort of 208 girls with newly diagnosed cancer, up to 18 years of age at diagnosis, and compared them with AMH levels of 250 age-matched healthy girls. The diagnoses included were acute lymphoblastic leukaemia, acute myeloid leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, nephroblastoma, sarcoma and neuroblastoma. MAIN RESULTS AND THE ROLE OF CHANCE: The median age was 6.6 years (range 0.0-17.4), comparable with that in the control group (median 6.3 years, range 0.3-18.0). Girls with childhood cancer presented with significantly lower serum AMH levels compared with healthy age-matched controls (standard deviation scores (SDS) -0.8, P < 0.001). Median AMH level in patients was 1.4 µg/l (0.1-10.2) versus 3.0 µg/l (0.1-18.3) in controls. Specifically, 84% of all patients had AMH levels below the 50th percentile of normal AMH levels, and 19% below the 10th percentile. Surrogate markers of general health status (temperature, C-reactive protein and haemoglobin levels at diagnosis) were significantly correlated with AMH SDS. LIMITATIONS, REASONS FOR CAUTION: Some caution is warranted because AMH levels increase with age in healthy children but the cases and controls were age-matched in our study. Although our sample size was large, additional studies are still required in an independent cohort. WIDER IMPLICATIONS OF THE FINDINGS: Our study shows that AMH levels are reduced in girls with newly diagnosed cancer even before the cancer treatment has started. AMH levels correlate with impairment of general health status in girls. Therefore, besides (pre) antral follicle number, other factors may influence serum AMH levels. Longitudinal studies during and after childhood cancer are currently being performed in order to evaluate possible ovarian recovery after discontinuation of treatment. STUDY FUNDING/COMPETING INTEREST(S): W.v.D. is supported by the Paediatric Oncology Centre Society for Research (KOCR), Rotterdam, The Netherlands. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Genovum, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. All other authors have nothing to disclose.

Preoperative risk information and patient involvement in surgical treatment for rectal and sigmoid cancer.

AIM: Surgery for rectal and sigmoid cancer is a model setting for investigating preoperative information provision and shared decision making (SDM), as the decision consists of a trade-off between the pros and cons of different treatment options. The aim of this study was to explore surgeons' opinion on the preoperative information that should be given to rectal and sigmoid cancer patients and to evaluate what is actually communicated. In addition, we assessed surgeons' attitudes towards SDM and compared these with patient involvement. METHOD: A questionnaire was sent to Dutch surgeons with an interest in gastroenterology. Preoperative consultations were recorded. A checklist was used to code the information that surgeons communicated to the patients. The OPTION-scale was used to measure patient involvement. RESULTS: Questionnaires were sent to 240 surgeons, and 103 (43%) responded. They stated that information on anastomotic leakage and its consequences, the benefits and risks of a defunctioning stoma and the impact of a stoma on quality of life were necessary preoperative information. In practice, patients were inconsistently informed of these items. Most participants agreed to using SDM in their consultations. However, in practice, most patients were offered only one treatment option and little SDM was seen. The mean OPTION-score was low (7/100). CONCLUSION: Insufficient information is given to patients with rectal and sigmoid cancer to guide them on their preferred surgical option. Information should be given on all treatment options, together with their complications and outcome, before any decision is made.

Summary of the Dutch S3-guidelines on the treatment of psoriasis 2011. Dutch Society of Dermatology and Venereology.

This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.

Follow-up of premalignant lesions in patients at risk for progression to gastric cancer.

BACKGROUND AND STUDY AIMS: A recent international guideline recommends surveillance of premalignant gastric lesions for patients at risk of progression to gastric cancer. The aim of this study was to identify the role of the distribution and severity of premalignant lesions in risk categorization. PATIENTS AND METHODS: Patients with a previous diagnosis of atrophic gastritis, intestinal metaplasia, or low grade dysplasia were invited for surveillance endoscopy with non-targeted biopsy sampling. Biopsy specimens were evaluated by pathologists (four general and one expert) using the Sydney and the operative link for gastric intestinal metaplasia (OLGIM) systems, and scores were compared using kappa statistics. RESULTS: 140 patients were included. In 37 % (95 % confidence interval [CI] 29 % - 45 %) the severity of premalignant lesions was less than at baseline, while 6 % (95 %CI 2 % - 10 %) showed progression to more severe lesions. Intestinal metaplasia in the corpus was most likely to progress to more than one location (57 %; 95 %CI 36 % - 76 %). The proportion of patients with multilocated premalignant lesions increased from 24 % at baseline to 31 % at surveillance (P = 0.014). Intestinal metaplasia was the premalignant lesion most frequently identified in subsequent endoscopies. Intestinal metaplasia regressed in 27 % compared with 44 % for atrophic gastritis and 100 % for low grade dysplasia. Interobserver agreement was excellent for intestinal metaplasia (k = 0.81), moderate for dysplasia (k = 0.42), and poor for atrophic gastritis (k < 0). CONCLUSIONS: Premalignant gastric lesions found in the corpus have the highest risk of progression, especially intestinal metaplasia, which has excellent interobserver agreement. This supports the importance of intestinal metaplasia as marker for follow-up in patients with premalignant gastric lesions.

Platelet-Rich stroma from Crohn's disease patients for treatment of perianal fistula shows a higher myeloid cell profile compared to non-IBD controls.

BACKGROUND: New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls. METHODS: Consecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis. RESULTS: Twenty-three patients (37.8 [IQR 30.7-45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.62*105 cells/mL versus non-IBD 12.20 ± 3.39*105). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples. CONCLUSIONS: The composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn's disease does not appear to alter the immunological composition of adipose-derived products.

Cumulative exposure to immunomodulators increases risk of cervical neoplasia in women with inflammatory bowel disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) are at increased risk of high-grade cervical intraepithelial neoplasia and cervical cancer (CIN2+). AIM: To assess the association between cumulative exposure to immunomodulators (IM) and biologic agents (BIO) for IBD and CIN2+ METHODS: Adult women diagnosed with IBD before December 31st 2016 in the Dutch IBD biobank with available cervical records in the nationwide cytopathology database were identified. CIN2+ incidence rates in IM- (i.e., thiopurines, methotrexate, tacrolimus and cyclosporine) and BIO- (anti-tumour necrosis factor, vedolizumab and ustekinumab) exposed patients were compared to unexposed patients and risk factors were assessed. Cumulative exposure to immunosuppressive drugs was evaluated in extended time-dependent Cox-regression models. RESULTS: The study cohort comprised 1981 women with IBD: 99 (5%) developed CIN2+ during median follow-up of 17.2 years [IQR 14.6]. In total, 1305 (66%) women were exposed to immunosuppressive drugs (IM 58%, BIO 40%, IM and BIO 33%). CIN2+ risk increased per year of exposure to IM (HR 1.16, 95% CI 1.08-1.25). No association was observed between cumulative exposure to BIO or both BIO and IM and CIN2+. In multivariate analysis, smoking (HR 2.73, 95%CI 1.77-4.37) and 5-yearly screening frequency (HR 1.74, 95% CI 1.33-2.27) were also risk factors for CIN2+ detection. CONCLUSION: Cumulative exposure to IM is associated with increased risk of CIN2+ in women with IBD. In addition to active counselling of women with IBD to participate in cervical screening programs, further assessment of the benefit of intensified screening of women with IBD on long-term IM exposure is warranted.

Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma.

PURPOSE: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. METHODS: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. RESULTS: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [ 95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. CONCLUSION: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

Chronic fatigue in childhood cancer survivors is associated with lifestyle and psychosocial factors; a DCCSS LATER study.

BACKGROUND: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). PATIENTS AND METHODS: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. RESULTS: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37). CONCLUSION: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS.

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).

Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter Study Group (EHSG), the European Society of Pathology (ESP) and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach (termed MAPS). A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia, and the need for adequate staging in the case of high grade dysplasia, and they focus on treatment and surveillance indications and methods.

Hepatitis E infection with a benign course during vedolizumab treatment for Crohn's disease: A case report.

We present a 49 year old female patient with Crohn's disease (CD) in remission on vedolizumab therapy who experienced a symptomatic, though benign, course of acute hepatitis E. Routine blood tests showed substantial elevation of liver enzymes and polymerase chain reaction (PCR) testing confirmed hepatitis E virus (HEV) infection. Vedolizumab therapy was paused, liver enzymes improved three weeks after infection and normalized after six months. The patient recovered completely from mild symptoms. This case shows that hepatitis E is a potential cause of acute hepatitis during vedolizumab therapy, and in this case the infection has run a benign course.

Bovine antibody-based oral immunotherapy for reduction of intragastric Helicobacter pylori colonization: a randomized clinical trial.

BACKGROUND: Antibiotic-based regimens are frequently used for the treatment of Helicobacter pylori infection. These regimens fail to eradicate H pylori in 15% to 40% of patients, primarily due to antimicrobial resistance and insufficient patient compliance. Effective prevention and eradication of H pylori by passive immunization with orally administered bovine antibodies has been demonstrated in animal studies, and may serve as an alternative therapy in humans. OBJECTIVE: To study the efficacy and safety of orally administered bovine anti-H pylori antibodies for the reduction of intragastric bacterial load and eradication of H pylori in humans. METHODS: Dairy cows were immunized against H pylori. After confirmation of the presence of anti-H pylori antibodies in the milk, the milk was subsequently processed into a whey protein concentrate (WPC). In a prospective, double-blind, placebo-controlled randomized clinical trial, H pylori-infected subjects were randomly assigned to treatment with the WPC preparation or placebo. Study medication was continued for 28 days; subjects were followed-up for 56 days. RESULTS: Of the 30 subjects included, 27 completed the protocol. Of these 27 evaluable subjects, 14 were treated with WPC and 13 with placebo. There was no significant difference in urea breath test decrease between the WPC- and placebo-treated group (P=0.75). H pylori-associated gastritis and density were not significantly reduced in either group after treatment (P>0.05 for all). CONCLUSION: Bovine antibody-based oral immunotherapy appears to be safe, but does not significantly reduce intragastric density in humans. Further studies are needed to determine whether WPC treatment has additional value to conventional antibiotic treatment for H pylori.

Increased Risk of High-grade Cervical Neoplasia in Women with Inflammatory Bowel Disease: A Case-controlled Cohort Study.

BACKGROUND AND AIMS: Women with inflammatory bowel disease [IBD] may be at higher risk for cervical intraepithelial neoplasia [CIN]. However, data are conflicting. The aim of this study was to assess the risk of high-grade dysplasia and cancer [CIN2+] in IBD women and identify risk factors. METHODS: Clinical data from adult IBD women in a multicentre Dutch IBD prospective cohort [PSI] from 2007 onwards were linked to cervical cytology and histology records from the Dutch nationwide cytology and pathology database [PALGA], from 2000 to 2016. Patients were frequency-matched 1:4 to a general population cohort. Standardised detection rates [SDR] were calculated for CIN2+. Longitudinal data were assessed to calculate CIN2+ risk during follow-up using incidence rate ratios [IRR] and risk factors were identified in multivariable analysis. RESULTS: Cervical records were available from 2098 IBD women [77%] and 8379 in the matched cohort; median follow-up was 13 years. CIN2+ detection rate was higher in the IBD cohort than in the matched cohort (SDR 1.27, 95% confidence interval [CI] 1.05-1.52). Women with IBD had an increased risk of CIN2+ [IRR 1.66, 95% CI 1.21-2.25] and persistent or recurrent CIN during follow-up (odds ratio [OR] 1.89, 95% CI 1.06-3.38). Risk factors for CIN2+ in IBD women were smoking and disease location (ileocolonic [L3] or upper gastrointestinal [GI] [L4]). CIN2+ risk was not associated with exposure to immunosuppressants. CONCLUSIONS: Women with IBD are at increased risk for CIN2+ lesions. These results underline the importance of human papillomavirus [HPV] vaccination and adherence to cervical cancer screening guidelines in IBD women, regardless of exposure to immunosuppressants.