The aim of this study was to review the available literature concerning Madura foot (“mycetoma”) caused by Madurella mycetomatis in immunocompromised patients. With a systematic literature search,... Show moreThe aim of this study was to review the available literature concerning Madura foot (“mycetoma”) caused by Madurella mycetomatis in immunocompromised patients. With a systematic literature search, we identified only three papers, describing a total of three immunocompromised patients. Hence, the clinical presentation and prognosis of the disease in this patient population have not yet been well described. In addition, we present a case from our institution, illustrating the complexity of the treatment of this rare disease. Although very rare in non-endemic countries, we emphasize that mycetoma should be included in the differential diagnoses of (immunocompromised) patients who have been residing in a geographical area where the disease is endemic and presenting with soft tissue inflammation of one of the extremities. Show less
Introduction: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody ... Show moreIntroduction: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is equivalent for both therapies, but there is accumulating data that the long-term safety profile of RTX might outperform CYC. Combination of RTX with low-dose CYC (LD-CYC) has been investigated in only a few uncontrolled cohort studies, in which clinical remission and a favourable immunological state with low relapse rates was quickly achieved. In this randomised controlled trial, we aim to investigate whether the combination treatment (RTX+LD CYC) is superior in comparison to standard care with RTX only. Methods and analysis: This study is an open-label, multicentre, 1:1 randomised, prospective study for patients with AAV with generalised disease, defined as involvement of major organs, that is, kidneys, lungs, heart and nervous system. In total, 100 patients will be randomised 1:1 to receive either remission induction therapy with standard of care (RTX) or combination treatment (RTX+LD CYC) in addition to steroids and both arms are followed by maintenance with RTX retreatments (tailored to B-cell and ANCA status). Our primary outcome is the number of retreatments needed to maintain clinical remission over 2 years. Secondary outcomes are relevant clinical endpoints, safety, quality of life and immunological responses. Ethics and dissemination: This study has received approval of the Medical Ethics Committee of the Leiden University Medical Center (P18.216, NL67515.058.18, date: 7 March 2019). The results of this trial (positive and negative) will be submitted for publication in relevant peer-reviewed publications and the key findings presented at national and international conferences. Show less
Background. Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential... Show moreBackground. Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF).Methods. Reported is the long-term follow-up of a Phase 2 proof-of-concept study in 15 patients with SLE including 12 (80%) with lupus nephritis (LN).Results. In 10/15 (67%) patients, a clinical response was observed by achievement of lupus low disease activity state, of which 8 (53%) continued treatment (BLM + <= 7.5 mg prednisolone) for the complete 2 years of follow-up. Five patients (33%) were referred to as 'non-responders' due to persistent LN, major flare or repetitive minor flares. Out of 12 LN patients, 9 (75%) showed a renal response including 8 (67%) complete renal responders. All anti-dsDNA(+) patients converted to negative, and both anti-C1q and extractable nuclear antigen autoantibodies showed significant reductions. CD19(+) B cells showed a median decrease from baseline of 97% at 24 weeks, with a persistent reduction of 84% up to 104 weeks. When comparing responders with non-responders, CD20(+) B cells were depleted significantly less in non-responders and double-negative (DN) B cells repopulated significantly earlier.Conclusions. Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. The observed immunological and clinical benefits in a therapy-refractory SLE population prompt further studies on RTX + BLM. Show less
Background. The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase... Show moreBackground. The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI).Methods. This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19(+) B-cell status and relapses were assessed >2years.Results. Patients (31/110) relapsed within 2years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity (n=29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity (n=49) and reappearance of PR3-ANCAs (n=10) associated significantly with more relapses (37%, P=0.002 and 50%, P=0.002). Patients with incomplete B-cell depletion (n=11) had significantly more relapses (54%) as compared with patients with B-cell depletion [n=76 (26%), P=0.02]. Also, patients with repopulation of B cells (n=58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [n=27 (15%), P=0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation.Conclusions. Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX. Show less
Problem:Effective clinical workplace learning depends on interprofessional and multidisciplinary learning. However, traditional patient wards are centered around patient care and not so much around... Show moreProblem:Effective clinical workplace learning depends on interprofessional and multidisciplinary learning. However, traditional patient wards are centered around patient care and not so much around education. Other barriers such as time constraints also contribute to suboptimal interprofessional and multidisciplinary learning.Intervention:Six formal and informal learning activities that aimed at stimulation of interprofessional and multidisciplinary learning were designed and introduced in our patient ward to enable optimal integration of clinical practice and learning.Context:The study took place in an internal medicine inpatient ward where daily patient care is performed by specialized teams consisting of different healthcare professionals from the departments of Endocrinology, Nephrology, and Infectious Diseases. In the traditional ward setting, interprofessional and multidisciplinary learning mostly takes place during shared clinical activities. In this article, we describe the development and implementation of a Clinical Teaching Unit to support learning between different healthcare professionals.Impact:The intervention was evaluated with an online questionnaire among 108 nurses, student nurses, clerks, residents, supervising clinicians, and managers. Open-ended questions (response rate 65%) were used to determine the changes in the workplace experienced by the participants since the introduction of the Clinical Teaching Unit and what influenced their learning process and motivation to learn. Closed questions (response rate 46%) aimed to measure the effect of our intervention on collaboration, learning, and the quality of care and education. The results of the open-ended questions showed that participants experienced more interprofessional collaboration and learning. This took place in a less hierarchical, safer work climate which also resulted in perceptions of a better quality of patient care and education. The closed-ended questions showed that the intervention resulted in perceptions of improved collaboration, work culture, quality of care, education, and learning conditions.Lessons Learned:The findings imply that implementation of a Clinical Teaching Unit not only facilitates the integration of patient care and education but also the integration of different professions working together. From the intervention, we also learned that a successful Clinical Teaching Unit requires investment of time and staff, clear communication between healthcare professionals, and dedication of teachers within all professions. Show less
Background: Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential... Show moreBackground: Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF).Methods: Reported is the long-term follow-up of a Phase 2 proof-of-concept study in 15 patients with SLE including 12 (80%) with lupus nephritis (LN).Results: In 10/15 (67%) patients, a clinical response was observed by achievement of lupus low disease activity state, of which 8 (53%) continued treatment (BLM + ≤7.5 mg prednisolone) for the complete 2 years of follow-up. Five patients (33%) were referred to as 'non-responders' due to persistent LN, major flare or repetitive minor flares. Out of 12 LN patients, 9 (75%) showed a renal response including 8 (67%) complete renal responders. All anti-dsDNA+ patients converted to negative, and both anti-C1q and extractable nuclear antigen autoantibodies showed significant reductions. CD19+ B cells showed a median decrease from baseline of 97% at 24 weeks, with a persistent reduction of 84% up to 104 weeks. When comparing responders with non-responders, CD20+ B cells were depleted significantly less in non-responders and double-negative (DN) B cells repopulated significantly earlier.Conclusions: Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. The observed immunological and clinical benefits in a therapy-refractory SLE population prompt further studies on RTX + BLM. Show less
Atherosclerotic changes of the carotid artery are associated with elevated cardiovascular risk. Non-invasive imaging studies of the artery can provide information on the presence or absence of... Show moreAtherosclerotic changes of the carotid artery are associated with elevated cardiovascular risk. Non-invasive imaging studies of the artery can provide information on the presence or absence of abnormalities. Although the techniques are extensively used in clinical research their implementation in common practice is not widespread. In this thesis the potential benefits and challenges of carotid imaging in clinical practice are studied. Ultrasound and magnetic resonance imaging are the two modalities of interest. The findings suggest that ultrasound can be performed by the clinician in a routine outpatient setting. Clinicians are able to detect atherosclerotic plaques but not intima-media thickness. Plaques are highly prevalent in asymptomatic primary prevention patients. Magnetic resonance imaging is a new highly reproducible modality but requires further clinical validation. Its utility in individual patient risk assessment is unclear and ultrasound validity cannot be extrapolated to magnetic resonance. The use of a combination of the two imaging modalities may allow for estimation of the lamina adventitia in vivo. Finally, interpretation of the imaging parameters must be done in conjunction with all cardiovascular risk factors and treatment decision should not be based on imaging results alone. Show less
Kallianidis, A.F.; Ray, A.; Goudkade, D.; Fijter, J.W. de 2016
Background: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima... Show moreBackground: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima-media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima-media thickness by trained internists in a routine outpatient setting. Methods and results: Carotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3 min (range 4.5 to 16.7 min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively. Conclusions: In conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory. (C) 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. Show less
