Application of a Computational Metabolomics Workflow for the Diagnosis of Inborn Errors of Metabolism in a Laboratory Setting.

Inborn errors of metabolism constitute a set of hereditary diseases that impose severe medical and physical challenges in the affected individual, in particular, for the pediatric patient population. Timely diagnosis is crucial for these patients, as any delay could result in irreversible health damage, underscoring the importance of early initiation of personalized treatment. Current routine diagnostic screening for inborn errors of metabolism relies on various targeted analyses of established biomarkers. However, this approach is time-consuming, focuses on a limited number of tests (based on clinical information) with a relatively small number of biomarkers, and does not facilitate the identification of new markers. In contrast, untargeted metabolomics-based screening offers a more efficient diagnostic solution, by assessing thousands of metabolites across multiple metabolic pathways in a single test. This not only saves time but also conserves resources for clinicians, the diagnostic laboratory, and for patients.This chapter describes the computational workflow of our "Next Generation Metabolic Screening" approach, which is a metabolomics-based method that is currently applied at the Translational Metabolic Laboratory of the Radboud University Medical Center (the Netherlands) for the diagnosis of inborn errors of metabolism.

Interrupções e distrações durante a preparação e administração de medicamentos de alto risco: Estudo transversal / Interruptions and distractions during the preparation and administration of high-risk medications: A cross-sectional study / Distracciones e interrupciones durante la preparación y administración de medicamentos de alto riesgo: Estudio transversal

Resumo Enquadramento: Estudos indicam que as interrupções contribuem para erros clínicos e falhas em procedimentos. Objetivo: Analisar as interrupções vivenciadas pelos enfermeiros durante a preparação e administração de medicamentos de alto risco. Metodologia: Foi realizado um estudo transversal numa unidade de cuidados intensivos e numa unidade de internamento. As interrupções vivenciadas pelos enfermeiros durante o processo de medicação foram observadas com a ajuda de duas checklists. A amostra foi selecionada por conveniência em abril e maio de 2019. Os dados quantitativos foram analisados através de estatística descritiva no programa IBM SPSS Statistics, versão 24.0, enquanto os dados qualitativos foram tratados por meio da análise de conteúdo. Resultados: Observaram-se 137 interrupções em 193 processos de medicação. A maioria das interrupções foi iniciada por outros membros da equipa de cuidados de saúde por meio de conversas. Estas interrupções foram maioritariamente prejudiciais e ocorreram durante a fase de preparação. A estratégia multitarefa foi utilizada para as gerir. Conclusão: As interrupções ocorridas durante o processo de medicação eram maioritariamente associadas com comunicações profissionais e sociais. A sua relevância diferiu consoante a fase do processo.

Abstract Background: Interruptions have been reported to contribute to clinical errors and procedural failures. Objective: To analyze the interruptions experienced by nurses during the preparation and administration of high-risk medications. Methodology: A cross-sectional study was conducted in an intensive care and inpatient unit. The interruptions experienced by nurses during the medication process were observed through two checklists. The sample was selected by convenience in April-May 2019. Descriptive statistics was used to analyze quantitative data in IBM SPSS Statistics software, version 24.0, while content analysis was used to analyze qualitative data. Results: In 193 medication processes, there were 137 interruptions. Other members of the healthcare team initiated most interruptions through conversations. These interruptions were mostly negative and occurred during the preparation phase. The multitasking strategy was used to manage them. Conclusion: Interruptions during the medication process were primarily associated with professional and social communications. The impact of these interruptions varied depending on the phase of the process.

Resumen Marco contextual: Se ha reportado la participación de distracciones en errores clínicos y fallos de procedimiento. Objetivo: Analizar las distracciones del personal de enfermería durante la preparación y administración de fármacos de alto riesgo. Metodología: Estudio transversal desarrollado en una unidad de cuidados intensivos y una unidad de hospitalización. Se observaron distracciones del personal de enfermería durante el proceso de medicación a través de dos listas de control. La muestra fue seleccionada por conveniencia (abril-mayo 2019). Los datos cuantitativos se analizaron mediante estadística descriptiva (IBM SPSS Statistics, versión 24.0). Los datos cualitativos se analizaron mediante análisis de contenido. Resultados: Hubo 137 distracciones en 193 procesos de medicación. La mayoría de las distracciones fueron iniciadas por otros miembros del equipo sanitario a través de conversaciones. La mayoría se produjeron en la fase de preparación y fueron negativas y se gestionaron mediante la estrategia multitarea. Conclusión: Las distracciones durante el proceso de medicación se referían principalmente a las comunicaciones profesionales y sociales. La importancia de esas distracciones variaba en función de la fase del proceso.

Refractive errors in Tianjin youth aged 6-18 years: exploring urban-rural variations and contributing factors.

Purpose: Refractive errors, particularly myopia, constitute a significant global public health concern, contributing to morbidity and disability. A more comprehensive understanding of the determinants of refractive errors and the differences between urban and rural areas is essential to develop effective preventive measures for youth. This study aimed to compare the prevalence and risk factors of refractive errors among youth in urban and rural Tianjin, China. Methods: This school-based cross-sectional study was conducted in 2022. Elementary, middle, and high school students aged 6-18 years from both urban and rural areas of Tianjin were included. All participants underwent visual acuity testing and refractive measurement and completed comprehensive questionnaires. Results: A total of 346,146 participants (176,628 boys) were included in this investigation (50.36% for urban and 49.64% for rural, respectively). Myopia, hyperopia, astigmatism, and anisometropia were present in 56.8, 9.7, 56.64, and 21.3% of urban students, respectively. Similarly, rural students had a prevalence of 57.6, 11.5, 56.48, and 22.0% for the respective conditions. Compared to rural students, after adjusting for age, sex, and other significant variables, urban students were 1.05 times more likely to have myopia (95% CI: 1.03-1.07, p < 0.0001), 0.71 times less likely to have hyperopia (95% CI: 0.69-0.73, p < 0.0001), and 1.02 times more likely to have astigmatism (95% CI: 0.69-0.73, p < 0.0001). There was no significant association between anisometropia and residence (OR: 1.00, 95% CI: 0.98-1.02, p = 0.9850). Sociodemographic and physiological factors contribute to the disparities in the prevalence of refractive errors between urban and rural areas. Age, increased near-work activities, and Decreased outdoor time were identified as risk factors for myopia, astigmatism, and anisometropia. Conversely, the absence of a parental history of refractive errors emerged as a protective factor for myopia and astigmatism among students. Lower parental education levels were negatively correlated with the risk of myopia and anisometropia in their children. Specifically, the lower the parental education, the greater the risk of myopia in their offspring. For urban students only, lower parental education was associated with an increased risk of astigmatism. Conclusion: Crude prevalence estimates May not accurately reflect the true burden of refractive error due to confounding factors such as age and sex. Accounting for these factors revealed that urban students were more likely to have myopia and astigmatism but less likely to have hyperopia compared to their rural counterparts. These disparities highlight the importance of considering geographical variations when implementing strategies for myopia control and prevention.

Evidence That Long-Term Treatment Prevents Tissue Oxidative Damage in Patients With Inherited Disorders of the Propionate Pathway.

Propionic and methylmalonic acidemias (PAcidemia and MMAcidemia, respectively) are genetic disorders clinically characterized by metabolic decompensation associated with life-threatening encephalopathic episodes in the neonatal period. Adequate and rapid therapeutic management is essential for patients' survival and prognosis. In this study, a restricted protein diet associated with L-carnitine (LC) supplementation was shown to decrease mortality and morbidity in patients affected by these disorders probably by decreasing the accumulation of the major metabolites and therefore their toxicity. Since oxidative stress was proposed as a contributing mechanism of tissue damage in PAcidemia and MMAcidemia and LC has potent antioxidant properties, our objective in this work was to investigate the effects of a long-term therapy consisting of reduced protein intake associated with LC supplementation on oxidative damage markers in patients affected by these diseases. We measured urinary isoprostanes, di-tyrosine, and oxidized guanine species, which reflect oxidative damage to lipids, proteins, and DNA/RNA, respectively, as well as the concentrations of NO products (nitrate plus nitrite) in patients untreated or submitted to short-term or a long-term treatment. Results revealed significant increases of isoprostanes, di-tyrosine, and oxidized guanine species, as well as a moderate nonsignificant increase of NO levels in the untreated patients, relatively to controls. Furthermore, these altered markers were attenuated after short-term treatment and normalized after prolonged treatment. In conclusion, data from this work show for the first time that long-standing treatment of patients with disorders of the propionate pathway can protect against oxidative damage. However, it remains to be elucidated whether oxidative stress identified in this study directly correlates with the clinical conditions of the affected patients.

Decreased trabecular bone score in patients affected by Fabry disease.

BACKGROUND: Fabry disease (FD) is an inherited X-linked lysosomal storage disease characterized by increased risk of osteoporosis and fractures. The impact of FD on clinical measures of bone quality is unknown. This considered, aim of our study was to evaluate whether trabecular bone microarchitecture, measured by trabecular bone score (TBS), is altered in patients with FD compared to control subjects. METHODS: This retrospective monocentric study enrolled 14 patients (M/F 1/1, median age 46 [37-63] years, range 31-72 years) newly diagnosed with FD between January 2016 and July 2023 who underwent dual-energy X-ray absorptiometry (DXA) image at the time of diagnosis and 42 matched controls. In all subjects, data about bone mineral density (BMD) and lumbar spine TBS were collected and total calcium, parathyroid hormone (PTH), 25(OH) vitamin D, alkaline phosphatase (ALP), creatinine and estimated glomerular filtration rate (eGFR) were evaluated. In subjects with FD, globotriaosylsphingosine (lyso-Gb3), 24-hour proteinuria and albumin-creatinine ratio were also assessed. RESULTS: Patients with FD presented significantly lower lumbar spine TBS (1.29 [1.22-1.38] vs. 1.42 [1.39-1.47], p < 0.001) and lower lumbar spine BMD (0.916 ± 0.166 vs. 1.031 ± 0.125 g/cm2, p = 0.008) compared to controls; moreover, FD was shown to be an independent risk factor for both low lumbar spine TBS (ß = -0.118, p < 0.001) and BMD (ß = -0.115, p = 0.009). No differences were found in serum calcium, ALP, 25(OH) vitamin D and eGFR in both groups, but FD patients had significantly higher PTH levels compared to controls (p = 0.016). Finally, 8 patients with FD presented either moderately or severely increased albuminuria and only 2 patients presented normal lyso-Gb3 levels. CONCLUSION: Patients affected by FD present significantly lower lumbar spine TBS and BMD compared to controls. Our findings strongly support the importance of carrying out a thorough evaluation of bone status in all patients affected by FD at baseline.

Investigating Concomitant RAG-2 and LRBA Mutations in SCID and Autoimmunity.

Inborn errors of immunity (IEI) are a large heterogenous group of diseases characterized by immunodeficiency, immune dysregulation, allergy, auto-inflammation and predisposition for malignancies. Most are inherited in an autosomal recessive trait. We studied a patient with severe combined immunodeficiency (SCID) and immune dysregulation who harbored two distinct bi-allelic IEI-associated genetic mutations. Clinical, immunological and genetic data were collected. Genetic investigation included whole exome sequencing on DNA extracted from skin fibroblasts. Family segregation was performed by Sanger sequencing. Immunological evaluation included absolute and functional evaluation of lymphocytes and chimerism analysis post hematopoietic stem cell transplantation (HSCT). Treg subsets, LRBA and CTLA4 expression levels were measured by flow-cytometric analysis. A nineteen-year-old female patient from a consanguine background underwent unconditioned matched sibling related HSCT during infancy due to clinical presentation of SCID with an Omenn phenotype. At that time her underlying genetic defect was not defined. Years after HSCT, severe auto-immune phenomena were noted, including a systemic lupus erythematosus-like syndrome and ophthalmic manifestations. Genetic evaluation revealed bi-allelic homozygous mutations in RAG-2 (c.685C>T, p.Arg229Trp) and a previously undescribed mutation in LRBA (c.3325G>T, p.Asp1109Tyr). LRBA and CTLA4 expression levels were normal, suggesting that the LRBA variant identified in these kindred is unlikely to be pathogenic. Multiple genetic defects causing complex IEIs may be identified in the same individual in highly consanguineous populations. Functional immunological testing is essential for evaluation of novel genetic variants.

Mental Health and Medical Error among Nursing Staffs at Korean Medicine Clinics: a first survey in South Korea.

Objectives: Nurses face mental health issues like emotional labor, stress, and depression, increasing the risk of medical errors. This study assesses the mental health and medical errors among nurses in Korean medicine clinics in South Korea. Methods: The cross-sectional analysis involved 83 nurses, examining relationships between emotional labor, stress, depression, cognitive failure, Hwa-byung (HB) (a syndrome of suppressed anger in Korean culture), and medical errors. It identified factors associated with HB and medical errors using multiple regression analysis, presenting their odds ratios (ORs) with 95% confidence intervals (CIs). Results: The findings revealed a current HB prevalence of 19.28% and a 6-month medical error prevalence of 16.87% among participants. The regression analysis showed that higher levels of depression (OR = 1.368, 95% CI = 1.098 to 1.703, p = 0.005), cognitive failure (OR = 1.072, 95% CI = 1.011 to 1.136, p = 0.020), and HB trait (OR = 1.136, 95% CI = 1.005 to 1.284, p = 0.041) significantly correlated with HB presence. Conclusion: This groundbreaking study on this previously under-researched nurse workforce highlights the critical need for comprehensive mental health care, with the objective of significantly enhancing their mental well-being and improving their overall work environment.

[Events and errors in radiation oncology: Conciliating perspectives to support care]. / Survenue d'un évènement ou d'une erreur en oncologie radiothérapie : concilier les perspectives pour préserver le soin.

The term "event" covers a wide range of concrete situations in radiation oncology, from particularly intense radiation-related side effects to the possibility of technical or human error. Although quality procedures are an integral part of radiotherapy oncology department operations ensuring the analysis and prevention of such events, their occurrence during radiation treatment still has a significant impact on patients and their experience of the treatment process, as well as on health professionals. These practical, emotional and symbolic impacts are all the greater when the event occurs in the aftermath of an error. The ethical approach therefore comprises three essential stages: recognizing the event as such, informing those involved of the event and, finally, creating conditions for the continuation of care. Each of these stages is marked by specific issues and questions, requiring a complex ethical approach that constantly involves reconciling the possible divergent perceptions of patients and health professionals. The occurrence of an event can also lead to a genuine crisis of confidence with multiple dimensions, which health professionals will also have to face and to support. Finally, the occurrence of an event calls into question not only our responsibility towards patients, but also our ideal of control. We need to criticize our culture of performance, rethink our approach to events and errors, and see them also as opportunities for positive change.

First Brazilian Case Report of Unrelated Patients with Identical ISG15 Mutation.

BACKGROUND: ISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy. OBJECTIVE: To characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant. METHODS: We began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families. RESULTS: A mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls. CONCLUSION: This study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine. CLINICAL IMPLICATIONS: Reporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.

Type and Frequency of Misdiagnosis and Time Lag to Diagnosis in Patients with Chronic Progressive External Ophthalmoplegia.

Purpose: Since ptosis is an early feature of chronic progressive external ophthalmoplegia (CPEO), patients are commonly misdiagnosed with other causes of ptosis. This study aims to report the type and frequency of misdiagnosis and time lag to diagnosis and the palpebral fissure transfer (PFT) procedure in patients with CPEO. Methods: This is a retrospective analysis of consecutive patients with CPEO who underwent PFT between 2006 and 2017. The data on previous diagnoses and treatments, age at definitive diagnosis of CPEO, and clinical manifestations were recorded. While the diagnosis of CPEO was based on clinical examination, 75% (24/32) of patients had undergone a confirmatory muscle biopsy and genetic tests. Results: There were 32 patients (19 females) with a mean age of 24.8 years (range, 13-36) at the final diagnosis and 34.1 years (range, 15-56) at the time of PFT. Also, 78% (25/32) of patients had been initially misdiagnosed with congenital ptosis (60%; 15/25) and ocular myasthenia gravis (OMG) (40%; 10/25). The majority of patients (20/32) had one to three previous eyelid surgical procedures, of which 90% (18/20) were performed before the definitive diagnosis of CPEO. The mean time lag from the first surgical procedure to CPEO diagnosis and PFT was 6.2 and 14.7 years, respectively. Conclusion: In a referral center, 78% of the patients with CPEO were initially misdiagnosed with congenital ptosis and OMG, and 56% of them underwent ptosis repair before the diagnosis. While the onset of the disease was in the first or second decades of life, diagnosis was delayed up to a mean age of 25 years. Reviewing early family photos and paying attention to other signs of CPEO could prevent misdiagnosis.

Walking the Talk: "Reflexivity" to Advance Integration of Patient Reported Outcomes for Cancer Care Screening.

In this commentary, we propose the use of video-reflexive ethnography (VRE) as a means to support integration of patient-reported outcomes (PROs) in cancer care screening. As for any policy or intervention, the optimization of PROs depends on moving beyond their mere formal introduction, and depends on the integration of PROs in the everyday practice contexts of health care professionals (HPEs). The use of VRE allows for video-playback sessions among oncology professionals to support team-based learning and practice-change grounded in "reflexivity." Through a review of previous methods used to support organizational change in healthcare settings (e.g., policies, quality improvement initiatives, simulation sessions), we present some unsung advantages of VRE that can be applied to a complex integrated setting, such as cancer care. As opposed to other methods to create change, VRE does not dictate new measures, but rather supports "bottom-up" provider-initiated changes to health care practices and contexts, grounded in collaborative day-to-day practice. We argue that VRE optimizes PROs in cancer care by facilitating their effective and sustainable integration, to promote improved patient care.

Development of an Emergency Department Safety Checklist through a global consensus process.

Emergency departments (EDs) are at high risk for medical errors. Checklist implementation programs have been associated with improved patient outcomes in other high-risk clinical settings and when used to address specific aspects of ED care. The aim of this study was to develop an ED Safety Checklist with broad applicability across different international ED settings. A three-round modified Delphi consensus process was conducted with a multidisciplinary and multinational panel of experts in emergency medicine and patient safety. Initial checklist items were identified through a systematic review of the literature. Each item was evaluated for inclusion in the final checklist during two rounds of web-based surveys and an online consensus meeting. Agreement for inclusion was defined a priori with a threshold of 80% combined agreement. Eighty panel members from 34 countries across all seven world regions participated in the study, with comparable representation from low- and middle-income and high-income countries. The final checklist contains 86 items divided into: (1) a general ED Safety Checklist focused on diagnostic evaluation, patient reassessment, and disposition and (2) five domain-specific ED Safety Checklists focused on handoff, invasive procedures, triage, treatment prescription, and treatment administration. The checklist includes key clinical tasks to prevent medical errors, as well as items to improve communication among ED team members and with patients and their families. This novel ED Safety Checklist defines the essential elements of high-quality ED care and has the potential to ensure their consistent implementation worldwide.

Keeping Patients Safe Online: A Study of Refractive Surgery Advertisements on Social Media.

Introduction Refractive error is the leading cause of visual impairment and blindness globally. Increasingly, patients are exposed to information about refractive surgery through social media advertisements. While national guidelines specify how refractive surgery should be advertised in traditional media, it is unclear to what extent these standards are adhered to in the emerging commercial arena of social media. The adherence of refractive surgery advertisements on social media to professional standards is poorly studied. Method We retrospectively analyzed the content of refractive surgery advertisements on the social media platform "TikTok," shown in the United Kingdom (UK) from October 2022 to October 2023, and compared them to the guidelines set out by The Royal College of Ophthalmologists (RCOphth) and the Advertising Standards Authority (ASA). Results We found that 39/51 (76%) of advertisements did not state the specific pathology to be corrected, and 41/51 (80%) did not specify a surgical procedure. Additionally, 33/51 (65%) of advertisements included at least one financial inducement, 44/51 (86%) contained misleading claims. None of the analyzed advertisements provided specific prices, offered refractive surgery as a competition prize, or featured celebrity endorsements. No medical jargon was found in any of the advertisements. The most viewed advertisement was seen by over 1.2 million unique users, with the median number of views for all advertisements being 34,000. Conclusion In conclusion, our analysis revealed that none of the refractive surgery advertisements on a popular social media platform met the standards set by RCOphth or ASA. This study presents the first qualitative analysis of social media refractive surgery advertisements, offering insights into what users can expect and providing recommendations for patients, doctors, social media platforms, and regulators to enhance refractive surgery advertising in the future.

Optimizing mammography interpretation education: leveraging deep learning for cohort-specific error detection to enhance radiologist training.

Purpose: Accurate interpretation of mammograms presents challenges. Tailoring mammography training to reader profiles holds the promise of an effective strategy to reduce these errors. This proof-of-concept study investigated the feasibility of employing convolutional neural networks (CNNs) with transfer learning to categorize regions associated with false-positive (FP) errors within screening mammograms into categories of "low" or "high" likelihood of being a false-positive detection for radiologists sharing similar geographic characteristics. Approach: Mammography test sets assessed by two geographically distant cohorts of radiologists (cohorts A and B) were collected. FP patches within these mammograms were segmented and categorized as "difficult" or "easy" based on the number of readers committing FP errors. Patches outside 1.5 times the interquartile range above the upper quartile were labeled as difficult, whereas the remaining patches were labeled as easy. Using transfer learning, a patch-wise CNN model for binary patch classification was developed utilizing ResNet as the feature extractor, with modified fully connected layers for the target task. Model performance was assessed using 10-fold cross-validation. Results: Compared with other architectures, the transferred ResNet-50 achieved the highest performance, obtaining receiver operating characteristics area under the curve values of 0.933 ( ± 0.012 ) and 0.975 ( ± 0.011 ) on the validation sets for cohorts A and B, respectively. Conclusions: The findings highlight the feasibility of employing CNN-based transfer learning to predict the difficulty levels of local FP patches in screening mammograms for specific radiologist cohort with similar geographic characteristics.

Isokinetic assessment of the female's soccer player's knee. A systematic review of outcomes measures.

BACKGROUND: Isokinetic normative data in females' soccer players is scarce in comparison to males. Furthermore, evaluation protocols employed to obtain those data in female's studies, strongly differ from each other, using different ranges of speeds and movement patterns, thus producing different output data. Thus, it is difficult for the researcher and the clinician to choose a correct protocol for knee isokinetic test in female soccer players. Aim of this paper is to review the literature to provide updated information on how to interpret a knee isokinetic testing in healthy females. METHODS: Google Scholar, PubMed, Sport Discus, and Psych info databases were queried, and 17 papers were selected. Following PRISMA methodology and PEDro scale, we classified the retrieved papers and assessed the quality. RESULTS: In this review some common features of isokinetic testing in female soccer players of various levels of qualification are highlighted. The isokinetic performance indexes widely accepted are the hamstring/quadriceps (H/Q) ratio and dominant/non-dominant (D/ND) ratio. It also emerges that, 3 reps at the speed of 60°/sec in knee flexion/extension are preferable due to the higher reliability and that the optimal H/Q ratio in healthy female soccer players of different level of qualification and age is 50%, while the interlimb differences (D/ND) should be below 10%. CONCLUSIONS: Normative data and methodologies reviewed can be useful for the isokinetic test of female soccer players. It emerges that simplifying test procedures limiting at few testing speed and considering selected H/Q and D/ND gives all the necessary relevant informations.

Infusion parameters, safety, and practical guidance for the manual administration of subcutaneous immunoglobulin 20% (Ig20Gly).

Primary immunodeficiency diseases (PIDs), also referred to as inborn errors of immunity, constitute a group of genetic conditions that affect the immune system. The current standard of care for patients with PIDs is lifelong immunoglobulin replacement therapy, delivered by intravenous (IVIG) or subcutaneous (SCIG) infusion. Immune globulin subcutaneous (human) 20% solution stabilized with glycine (Ig20Gly) is indicated as a replacement therapy for PIDs in adults and children of any age in Europe and in patients aged 2 years and above in the USA. Typically, Ig20Gly is administered using an infusion pump; however, delivery of Ig20Gly by manual administration has recently been approved in Europe. Practical recommendations on the use of Ig20Gly manual administration are lacking; this review therefore aims to provide guidance for use of this method of administration. Additionally, we summarize the infusion parameters, safety, patient-reported outcomes, and economic benefits associated with Ig20Gly manual administration. Manual administration of Ig20Gly was shown to permit faster rates of infusion than administration via infusion pump. Patients typically infused at two or fewer infusion sites with manual administration of Ig20Gly. Safety and tolerability profiles were similar for Ig20Gly manual administration and administration by infusion pump. Overall, there were comparable levels of patient satisfaction with manual administration and infusion pump, with patient preference deemed to be a key determinator of success for either method of administration. Economic studies identified cost savings for the healthcare system through manual administration compared with IVIG or SCIG infusion by infusion pump because of the reduced equipment costs and nurse support. For infusion of Ig20Gly by manual administration, a syringe and butterfly needle are used; patients are advised to start infusion at 1-2 mL/min to prevent discomfort. Overall, manual administration of Ig20Gly offers an effective and well-tolerated alternative to administration by infusion pump.

Inborn errors of immunity and somatic variant phenocopies disrupting human JAK-STAT signaling.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling cascade is an evolutionarily conserved signal transduction pathway that regulates many vital cellular processes, including immune function and hematopoiesis. Human genetic variants that disrupt JAK-STAT signaling are being found to cause a rapidly increasing number of diseases, including both germline-encoded inborn errors of immunity (IEI) and acquired somatic variants causing a 'phenocopy' of the IEI. Multiple genetic mechanisms are responsible for this growing group of JAK-STAT diseases including loss-of-function (LOF), gain-of-function (GOF), and dominant negative (DN) effects. In this review, we discuss the clinical presentation and pathogenesis of all currently described JAK/STAT defects, as well as providing an overview of the guiding principles to consider in diagnosing and treating these conditions.

Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis.

While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8 %. Through systematic reanalysis, we identified variants of interest in 5.2 % of undiagnosed patients, with 76.7 % being (candidate) disease-causing, providing a (candidate) diagnosis in 15.2 % of our cohort. We find a 1.7 percentage point increase in conclusive molecular diagnoses. We find a high degree of actionability in patients with a genetic diagnosis (76.4 %). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in IEI patients, conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated.