Primary immunodeficiencies, mycobacterial infections, and cytokines

Dit proefschrift onderzoekt de invloed van pro-inflammatoire cytokinen op de gevoeligheid van de mens voor mycobacteri_le infecties. Infecties met niet-tuberculeuze mycobacteri_n (NTM) komen zelden voor. Omdat NTM sommige mensen ernstig en ook bij herhaling ziek maken, hebben wetenschappers zich lang afgevraagd of genetische afwijkingen daarbij een rol spelen. In de laatste vijftien jaar is dit vermoeden bevestigd. Wereldwijd zijn ruim 360 pati_nten met Mendelian Susceptibility to Mycobacterial Disease (MSMD) bekend. In dit proefschrift wordt NEMO defici_ntie voor het eerst aangemerkt als MSMD. Vervolgens legden wij het verband tussen het v__rkomen van mycobacteri_le infecties in jonge kinderen en variaties in IFNG en IL10. Ook onderzochten wij Cryopyrin Associated Periodic Syndrome (CAPS) waarbij een te hoge cytokine productie tot ontsteking leidt. Deze pati_nten bleken hun cytokine productie onvoldoende te kunnen verhogen na activatie van hun cellen. Dit bleek onafhankelijk van de IL-1_ antagonist Anakinra, een zeer effectief medicijn tegen deze ziekte, en daarom van IL-1_. Een zich steeds verder ontwikkelende medische wetenschap en toenemende hygi_ne zorgen ervoor dat immuundefici_nties slechts in gematigde vorm tot uiting komen. Tegelijkertijd blijven de meest ernstig zieke pati_nten nu veelal wel in leven. Deze pati_nten zijn een belangrijke bron van informatie over de werking van ons immuunsysteem.- Fulbright/Netherland America Foundation - the intramural Research Program of the NIH - Netherlands Organisation for Scientific Research (NWO) - Stichting Doctor Catharine van Tussenbroek Fonds - the Prins Bernard Cultuurfonds - the Leids Universiteits Fonds - the Stichting Dr Hendrik Muller's Vaderlandsch Fonds - the Stichting Fundatie Vrijvrouwe van Renswoude - the Stichting Algemeen StudiefondsUBL - phd migration 201

Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease

Introduction: Langerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as “Histiocytosis X”, “Type II Histiocytosis” or “Langerhans Cell Granulomatosis”. Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described. Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis. Methods and material: Eight closely cooperating centres collected patients’ data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined. Results: A total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9–134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen. Radiation treatment was carried out with a median total dose of 15 Gy (range 3–50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy). Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed. Conclusion: In the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.<br

Recurrent respiratory tract infections (RRTI) in the elderly: A late onset mild immunodeficiency?

Transplantation and immunomodulatio

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Reply to: Nontuberculous mycobacterial cervicofacial lymphadenitis in children from the multicenter, randomized, controlled trial in the Netherlands: Relevance of polymorphisms in candidate host immunity genes

Immunogenetics and cellular immunology of bacterial infectious disease

Choosing Wisely should bring the cost of unnecessary care back into the discussion

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Nontuberculous mycobacterial infections in children with inborn errors of the immune system

Immunogenetics and cellular immunology of bacterial infectious disease

Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS)

Immunogenetics and cellular immunology of bacterial infectious disease