Search

Background: Mastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric mastocytosis cases persist after puberty. In particular, monomorphic maculopapular cutaneous mastocytosis (mMPCM) is often persistent and associated with systemic mastocytosis. However, clinical differentiation of MPCM from polymorphic (p)MPCM can be difficult. Aim: To identify histopathological features that can help to distinguish mMPCM from other subtypes of paediatric mastocytosis. Methods: This was a retrospective study using skin biopsies from patients with any subtype of mastocytosis. The localization and density of the MC infiltrate, MC morphology and expression of aberrant markers were evaluated and correlated with clinical characteristics. Results: In total, 33 biopsies were available for evaluation from 26 children [(10 with mMPCM, 5 with mastocytoma, 3 with diffuse cutaneous mastocytosis (DCM), 8 with pMPCM)] and 7 adults with MPCM. The MC number was increased in all patients, but was higher in children than adults (P < 0.01). The presence of mMPCM was associated with sparing of the papillary dermis from MC infiltration, whereas MC density in the papillary dermis was highest in pMPCM and DCM (P < 0.01). The positive predictive value of the presence of a reticular MC infiltrate for mMPCM was 72.7% (95% CI 51.4–87.0), and the negative predictive value was 83.3% (95% CI 42.2–97.2). There were no relevant differences in the expression of CD2, CD25 or CD30 between the different subtypes. Conclusion: Skin histopathology might enhance the phenotypical differentiation of mMPCM from other subtypes in children, thereby increasing the accuracy of one's prognosis.

Contains fulltext : 291409.pdf (Publisher’s version ) (Open Access) AIM: To outline the International Learning Collaborative (ILC) Oxford Statement, explicating our commitment to ensuring health and care systems are equipped to meet patients' fundamental care needs during times of unprecedented crisis. DESIGN/METHOD: Discussion paper. The content was developed via a co-design process with participants during the ILC's international conference. KEY ARGUMENTS: We, the ILC, outline what we do and do not want to see within our health and care systems when faced with the challenges of caring for patients during global pandemics and other crises. Specifically, we want fundamental care delivery to be seen as the minimum standard rather than the exception across our health and care systems. We want nursing leaders to call out and stand up for the importance of building fundamental care into systems, processes and funding priorities. We do not want to see the voices of nursing leaders quashed or minimized in favour of other agendas. In turn, what we want to see is greater recognition of fundamental care work and greater respect for the people who do it. We expect nurses to have a 'seat at the table' where the key health and care decisions that impact patients and staff are made. CONCLUSION: To achieve our goals we must (1) ensure that fundamental care is embedded in all health and care systems, at all levels; (2) build on and strengthen the leadership skills of the nursing workforce by clearly advocating for person-centred fundamental care; (3) co-design systems that care for and support our staff's well-being and which foster collective resilience rather than overly rely on individual resilience; (4) improve the science and methodologies around reporting and measuring fundamental care to show the positive impact of this care delivery and (5) leverage the COVID pandemic crisis as an opportunity for transformational change in fundamental care delivery.

Contains fulltext : 293211.pdf (Publisher’s version ) (Open Access) BACKGROUND: Nurse engagement, perceived need and usefulness affect healthcare technology use, acceptance and improvements in quality, safety and accessibility of healthcare. Nurses' opinions regarding continuous monitoring appear to be positive. However, facilitators and barriers were little studied. This study explored nurses' post-implementation experiences of the facilitators and barriers to continuously monitoring patients' vital signs using a wireless device on general hospital wards. METHODS: This study employed a cross-sectional survey. Vocational and registered nurses from three general wards in a Dutch tertiary university hospital participated in a survey comprising open and closed questions. The data were analysed using thematic analysis and descriptive statistics. RESULTS: Fifty-eight nurses (51.3%) completed the survey. Barriers and facilitators were identified under four key themes: (1) timely signalling and early action, (2) time savings and time consumption, (3) patient comfort and satisfaction and (4) preconditions. CONCLUSIONS: According to nurses, early detection and intervention for deteriorating patients facilitate the use and acceptance of continuously monitoring vital signs. Barriers primarily concern difficulties connecting patients correctly to the devices and system.

Background: Treatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an integrated interdisciplinary national research program. Objectives: The SYMPHONY consortium strives to orchestrate personalized treatment in patients with an inborn bleeding disorder, by unraveling the mechanisms behind interindividual variations of bleeding phenotype. Patients: The SYMPHONY consortium will investigate patients with an inborn bleeding disorder, both diagnosed and not yet diagnosed. Results: Research questions are categorized under the themes: (1) diagnosis, (2) treatment, and (3) fundamental research, and consist of work packages addressing specific domains. Importantly, collaborations between patients and talented researchers from different areas of expertise promise to augment the impact of the SYMPHONY consortium, leading to unique interactions and intellectual property. Conclusions: SYMPHONY will perform research on all aspects of care, treatment individualization in patients with inborn bleeding disorders, as well as diagnostic innovations and results of molecular genetics and cellular model technology with regard to the hemostatic process. We believe that these research investments will lead to health-care innovations with long-term clinical and societal impact. This consortium has been made possible by a governmental, competitive grant from the Netherlands Organization for Scientific Research (NWO) within the framework of the NWA-ORC Call grant agreement NWA.1160.18.038.

Disorders of the long arm of chromosome 11 (11q) are rare and involve various chromosomal regions. Patients with 11q disorders, including Jacobsen syndrome, often present with a susceptibility for bacterial and prolonged viral and fungal infections partially explained by hypogammaglobulinemia. Additional T lymphocyte or granular neutrophil dysfunction may also be present. In order to evaluate infectious burden and immunological function in patients with 11q disorders, we studied a cohort of 14 patients with 11q deletions and duplications. Clinically, 12 patients exhibited prolonged and repetitive respiratory tract infections, frequently requiring (prophylactic) antibiotic treatment (n = 7), ear-tube placement (n = 9), or use of inhalers (n = 5). Complicated varicella infections (n = 5), chronic eczema (n = 6), warts (n = 2), and chronic fungal infections (n = 4) were reported. Six patients were on immunoglobulin replacement therapy. We observed a high prevalence of low B lymphocyte counts (n = 8), decreased T lymphocyte counts (n = 5) and abnormal T lymphocyte function (n = 12). Granulocyte function was abnormal in 29% without a clinical phenotype. Immunodeficiency was found in patients with terminal and interstitial 11q deletions and in one patient with terminal 11q duplication. Genetically, FLI1 and ETS1 are seen as causative for the immunodeficiency, but these genes were deleted nor duplicated in 4 of our 14 patients. Alternative candidate genes on 11q may have a role in immune dysregulation. In conclusion, we present evidence that inborn errors of immunity are present in patients with 11q disorders leading to clinically relevant infections. Therefore, broad immunological screening and necessary treatment is of importance in this patient group.

Contains fulltext : 232917.pdf (Publisher’s version ) (Open Access) Multi-parametric prostate MRI (mpMRI) is a powerful tool to diagnose prostate cancer, though difficult to interpret even for experienced radiologists. A common radiological procedure is to compare a magnetic resonance image with similarly diagnosed cases. To assist the radiological image interpretation process, computerized Content-Based Image Retrieval systems (CBIRs) can therefore be employed to improve the reporting workflow and increase its accuracy. In this article, we propose a new, supervised siamese deep learning architecture able to handle multi-modal and multi-view MR images with similar PIRADS score. An experimental comparison with well-established deep learning-based CBIRs (namely standard siamese networks and autoencoders) showed significantly improved performance with respect to both diagnostic (ROC-AUC), and information retrieval metrics (Precision-Recall, Discounted Cumulative Gain and Mean Average Precision). Finally, the new proposed multi-view siamese network is general in design, facilitating a broad use in diagnostic medical imaging retrieval.

Abstract Artificial intelligence developments are essential to the successful deployment of community-wide, MRI-driven prostate cancer diagnosis. AI systems should ensure that the main benefits of biopsy avoidance are delivered while maintaining consistent high specificities, at a range of disease prevalences. Since all current artificial intelligence / computer-aided detection systems for prostate cancer detection are experimental, multiple developmental efforts are still needed to bring the vision to fruition. Initial work needs to focus on developing systems as diagnostic supporting aids so their results can be integrated into the radiologists’ workflow including gland and target outlining tasks for fusion biopsies. Developing AI systems as clinical decision-making tools will require greater efforts. The latter encompass larger multicentric, multivendor datasets where the different needs of patients stratified by diagnostic settings, disease prevalence, patient preference, and clinical setting are considered. AI-based, robust, standard operating procedures will increase the confidence of patients and payers, thus enabling the wider adoption of the MRI-directed approach for prostate cancer diagnosis. Key Points • AI systems need to ensure that the benefits of biopsy avoidance are delivered with consistent high specificities, at a range of disease prevalence. • Initial work has focused on developing systems as diagnostic supporting aids for outlining tasks, so they can be integrated into the radiologists’ workflow to support MRI-directed biopsies. • Decision support tools require a larger body of work including multicentric, multivendor studies where the clinical needs, disease prevalence, patient preferences, and clinical setting are additionally defined.

Introduction: Diagnostic evaluation of patients with a bleeding tendency remains challenging, as no disorder is identified in approximately 50% of patients. An impaired interplay of several haemostatic factors might explain bleeding phenotype in these patients. Objective: To investigate whether global haemostasis assays are able to identify haemostatic abnormalities in patients with a bleeding tendency unexplained by current diagnostic laboratory tests. Materials and methods: Patients of ≥12 years with a bleeding tendency were included from a tertiary outpatient clinic. Bleeding phenotype was assessed with the ISTH-BAT. Patients were classified as having bleeding of unknown cause (BUC) or a mild bleeding disorder (MBD) based on abnormalities assessed by routine haemostatic tests. Global haemostasis tests (rotational thromboelastometry (ROTEM), thrombin generation test (TG) and plasma clot lysis time (CLT)) were measured in all patients. The results were compared with 76 controls. Results: One hundred and eighty-one patients were included, and 60% (109/181) was classified as having BUC. BUC patients demonstrated a significantly prolonged lag time in TG (median 7.7 minutes, IQR 6.7-8.7) and a significantly prolonged CLT (median 60.5 minutes, IQR 54.7-66.1) compared to controls. No differences in ROTEM variables were found. Patients with MBD showed an impaired thrombin generation with a significantly decreased ETP (median 1024 nmol/L*min, IQR 776-1355) and peak height (median 95 nmol/L, IQR 76-138), compared to BUC patients and controls. Conclusion: No major differences were found in ROTEM and TG variables in BUC patients compared to controls. BUC patients did have a significantly prolonged clot lysis time. The underlying mechanism for this finding is unknown.

The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25 × 109/L compared with 50 × 109/L for major bleeding and/or mortality in preterm neonates (7% absolute-risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25 × 109/L threshold. We wanted to assess this heterogeneity of treatment effect in the PlaNet-2 trial, to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariate logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into 4 risk quartiles. Within these quartiles, we assessed absolute-risk difference between the 50 × 109/L- and 25 × 109/L-threshold groups. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval, 0.58-0.68). The 25 × 109/L threshold was associated with absolute-risk reduction in all risk groups, varying from 4.9% in the lowest risk group to 12.3% in the highest risk group. These results suggest that a 25 × 109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. This trial was registered at www.isrctn.com as #ISRCTN87736839.