Biological stratification of clinical disease courses in childhood immune thrombocytopenia

Background In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. Objective To predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. Methods Children aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. Results In the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 × 109/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc‐receptor (FcγR) IIc; (4) the presence of immunoglobulin G (IgG) anti‐platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80‐1.00) and specificity was 0.67 (95% confidence interval, 0.53‐0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow‐up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. Conclusions The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification

Albumin/asparaginase capsules prepared by ultrasound to retain ammonia

"Published online: 17 June 2016"Asparaginase reduces the levels of asparagine in blood, which is an essential amino acid for the proliferation of lymphoblastic malign cells. Asparaginase converts asparagine into aspartic acid and ammonia. The accumulation of ammonia in the bloodstream leads to hyperammonemia, described as one of the most significant side effects of asparaginase therapy. Therefore, there is a need for asparaginase formulations with the potential to reduce hyperammonemia. We incorporated 2 % of therapeutic enzyme in albumin-based capsules. The presence of asparaginase in the interface of bovine serum albumin (BSA) capsules showed the ability to hydrolyze the asparagine and retain the forming ammonia at the surface of the capsules. The incorporation of Poloxamer 407 in the capsule formulation further increased the ratio aspartic acid/ammonia from 1.92 to 2.46 (and 1.10 from the free enzyme), decreasing the levels of free ammonia. This capacity to retain ammonia can be due to electrostatic interactions and retention of ammonia at the surface of the capsules. The developed BSA/asparaginase capsules did not cause significant cytotoxic effect on mouse leukemic macrophage cell line RAW 264.7. The new BSA/asparaginase capsules could potentially be used in the treatment of acute lymphoblastic leukemia preventing hyperammonemia associated with acute lymphoblastic leukemia (ALL) treatment with asparaginase.Fundação para a Ciência e a Tecnologia - SFRH\BPD\98388\2013 ; UID/BIO/04469/2013 ; UID/BIA/04050/2013COMPETE 2020 (POCI-01-0145-FEDER-006684

Scoliosis in patients with Prader Willi Syndrome – comparisons of conservative and surgical treatment

In children with Prader Willi syndrome (PWS), besides growth hormone (GH) therapy, control of the food environment and regular exercise, surgical treatment of scoliosis deformities seems the treatment of choice, even though the risks of spinal surgery in this specific population is very high. Therefore the question arises as to whether the risks of spinal surgery outweigh the benefits in a condition, which bears significant risks per se. The purpose of this systematic review of the Pub Med literature was to find mid or long-term results of spinal fusion surgery in patients with PWS, and to present the conservative treatment in a case study of nine patients with this condition

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Assessments Related to the Physical, Affective and Cognitive Domains of Physical Literacy Amongst Children Aged 7–11.9 Years: A Systematic Review

Background Over the past decade, there has been increased interest amongst researchers, practitioners and policymakers in physical literacy for children and young people and the assessment of the concept within physical education (PE). This systematic review aimed to identify tools to assess physical literacy and its physical, cognitive and affective domains within children aged 7–11.9 years, and to examine the measurement properties, feasibility and elements of physical literacy assessed within each tool. Methods Six databases (EBSCO host platform, MEDLINE, PsycINFO, Scopus, Education Research Complete, SPORTDiscus) were searched up to 10th September 2020. Studies were included if they sampled children aged between 7 and 11.9 years, employed field-based assessments of physical literacy and/or related affective, physical or cognitive domains, reported measurement properties (quantitative) or theoretical development (qualitative), and were published in English in peer-reviewed journals. The methodological quality and measurement properties of studies and assessment tools were appraised using the COnsensus-based Standards for the selection of health Measurement INstruments risk of bias checklist. The feasibility of each assessment was considered using a utility matrix and elements of physical literacy element were recorded using a descriptive checklist. Results The search strategy resulted in a total of 11467 initial results. After full text screening, 11 studies (3 assessments) related to explicit physical literacy assessments. Forty-four studies (32 assessments) were relevant to the affective domain, 31 studies (15 assessments) were relevant to the physical domain and 2 studies (2 assessments) were included within the cognitive domain. Methodological quality and reporting of measurement properties within the included studies were mixed. The Canadian Assessment of Physical Literacy-2 and the Passport For Life had evidence of acceptable measurement properties from studies of very good methodological quality and assessed a wide range of physical literacy elements. Feasibility results indicated that many tools would be suitable for a primary PE setting, though some require a level of expertise to administer and score that would require training. Conclusions This review has identified a number of existing assessments that could be useful in a physical literacy assessment approach within PE and provides further information to empower researchers and practitioners to make informed decisions when selecting the most appropriate assessment for their needs, purpose and context. The review indicates that researchers and tool developers should aim to improve the methodological quality and reporting of measurement properties of assessments to better inform the field. Trial registration PROSPERO: CRD4201706221