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ImportanceIt has become common practice to offer immunocompromised patients with hematologic cancers a third COVID-19 vaccination dose, but data substantiating this are scarce.ObjectiveTo assess whether a third mRNA-1273 vaccination is associated with increased neutralizing antibody concentrations in immunocompromised patients with hematologic cancers comparable to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule.Design, Setting, and ParticipantsThis prospective observational cohort study was conducted at 4 university hospitals in the Netherlands and included 584 evaluable patients spanning the spectrum of hematologic cancers and 44 randomly selected age-matched adults without malignant or immunodeficient comorbidities.ExposuresOne additional mRNA-1273 vaccination 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule.Main Outcomes and MeasuresSerum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after a third mRNA-1273 vaccination, and antibody neutralization capacity of wild-type, Delta, and Omicron variants in a subgroup of patients.ResultsIn this cohort of 584 immunocompromised patients with hematologic cancers (mean [SD] age, 60 [11.2] years; 216 [37.0%] women), a third mRNA-1273 vaccination was associated with median S1-IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1-IgG concentration after the third vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid cancers or multiple myeloma and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1-IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients receiving or shortly after completing anti-CD20 therapy, CD19-directed chimeric antigen receptor T-cell therapy recipients, and patients with chronic lymphocytic leukemia receiving ibrutinib were less responsive or unresponsive to the third vaccination. In the 27 patients who received cell therapy between the second and third vaccination, S1 antibodies were preserved, but a third mRNA-1273 vaccination was not associated with significantly enhanced S1-IgG concentrations except for patients with multiple myeloma receiving autologous HCT. A third vaccination was associated with significantly improved neutralization capacity per antibody.Conclusions and RelevanceResults of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.Trial RegistrationEudraCT Identifier: 2021-001072-41

Immunosuppressive drugs are the cornerstone in the treatment of inflammatory bowel disease (IBD), however they are associated with an increased risk of extra-intestinal cancer. Whether the risk for female genital tract malignancies, including vulvar and vaginal cancer, is increased is less clear.Our aim was to investigate the risk of these malignancies in IBD-patients.Histopathological data of all IBD patients with a vulvar or vaginal (pre-)cancerous lesion were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology from 1991 to 2015. Medical history was retrieved from patient records. Data from the Central Office for Statistics, the Dutch comprehensive cancer organization, and the IBDSL cohort were obtained to calculate the standardized, and age-adjusted incidence rates.Fifty-five patients met the inclusion criteria. A standardized incidence rate of 1.2(95% CI:0.8-1.7) for vulvar and vaginal carcinoma among adult female IBD was calculated, which did not significantly differ from the general population. The use of immunosuppressive therapy did not increase the occurrence of vulvovaginal malignancy, nor did it influence the recurrence rate. However, immunosuppressive drugs ever-users were on average 11 years younger at the time of their gynaecological diagnosis.Overall, our data do not support intensified screening for vulvar or vaginal malignancies in female IBD patients. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background: Dialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities. Methods: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi-state model that attributed each hospitalisation to the current dialysis modality. Results: In total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 (± 5.0) and for HD 1.4 (± 3.2) hospitalisations per patient-year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02–1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1–1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient-year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access-related problems (33%). Conclusion: PD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future.

Human papillomavirus (HPV)-induced oropharyngeal squamous cell carcinoma (OPSCC) remains increasing worldwide. We aimed to investigate if the HPV-prevalence of OPSCC in the Netherlands is rising as well, also in female patients. In addition, we evaluated the association between HPV-positive OPSCC and suspicious Pap results of the cervix in these female patients. Patients with OPSCC treated in the period 2000–2015 at the VU University Medical Center Amsterdam, were included (n = 926). The presence of an oncogenic HPV infection was determined by p16-immunostaining, followed by a high-risk HPV general primer 5+/6+ DNA PCR on the p16-immunopositive cases. A review of pathology reports in all female patients (n = 305) was undertaken to identify cytological signs of HPV-related (pre)cancer of the cervix. In total 281 of 926 (30.3%) OPSCCs were HPV-positive. Moreover, a significant increase in the prevalence of HPV-positive OPSCCs was observed from 14.0% in 2000 to 48.1% in 2015 (p < 0.001). Among the female patients with an HPV-positive OPSSC (n = 70), the results of cervical smears were available in 56 of 70 patients (80.0%). Of the female patients with HPV-positive OPSCC, 9 of 56 (16.1%) patients had a vaginal cuff Papanicolaou (Pap) test ≥3b in their medical history compared to 7 of 168 (4.2%) in the HPV-negative group (p = 0.003). In conclusion, a continuous increase in the HPV-attributable fraction of OPSCC was demonstrated in the period 2000–2015 in the Amsterdam region. HPV-positive OPSCC has a significant association with a history of suspicious Pap results of the cervix in female patients.

Contains fulltext : 215386.pdf (Publisher’s version ) (Open Access) BACKGROUND: Autoimmune hepatitis requires long-term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse events but data from long-term studies are mainly derived from studies in rheumatic diseases. AIM: To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long-term maintenance treatment of patients with autoimmune hepatitis. METHODS: We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects. RESULTS: A total of 6634 years, with a median of 13 (range 1-40) per patient were recorded. The median age at diagnosis was 44 years (range 2-88). Adverse events were documented in 120 (25%) patients. Low-dose predniso(lo)ne (0.1-5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years. CONCLUSIONS: Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses.

BACKGROUND: Off-label prescribing is encountered across various fields of medicine and creates alternative treatment options, but is associated with unknown safety risks. The use of off-label drugs for the treatment of patients with inflammatory bowel diseases (IBD) has not been characterised before.AIM: To assess the proportion and characteristics of off-label prescribing for IBD in tertiary care centres in the Netherlands.METHODS: A prospective database of IBD patients from all Dutch university hospitals was used to collect data on drug prescriptions for IBD and demographics. Drugs were classified as off-label if they were unlicensed for Crohn's disease and/or ulcerative colitis by the Medicines Evaluation Board. Uni- and multivariable analyses were used to identify patient-specific characteristics predictive of increased off-label use.RESULTS: For the induction and/or maintenance treatment of 4583 IBD patients, 12 651 historical and current drug records were available in the database. Of these, 2374 (19%) were considered off-label prescriptions. Out of 4583 IBD patients, 1477 (32%) were exposed to off-label drugs. Commonly prescribed off-label IBD drugs were mercaptopurine (18%), beclomethasone (12%), thioguanine (4%) and allopurinol (3%). Non-thiopurine/methotrexate off-label drugs were prescribed in 243 patients (6%), including biological agents or tofacitinib in 47 IBD patients (1%). Off-label prescriptions were more common in ulcerative colitis than Crohn's disease (37% vs 29%, P < 0.001). Smokers and patients that received ≥5 drug types during their disease course were more likely to be exposed to off-label drugs (smoking 33% vs 27% and multiple drug use 66% vs 22%, both P < 0.001).CONCLUSION: About one-fifth of prescriptions for IBD were off-label and one-third of IBD patients, especially ulcerative colitis patients, were exposed to off-label drugs.

Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA