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.

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.

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.

Adverse diagnostic events in hospitalised patients: a single-centre, retrospective cohort study.

BACKGROUND: Adverse event surveillance approaches underestimate the prevalence of harmful diagnostic errors (DEs) related to hospital care. METHODS: We conducted a single-centre, retrospective cohort study of a stratified sample of patients hospitalised on general medicine using four criteria: transfer to intensive care unit (ICU), death within 90 days, complex clinical events, and none of the aforementioned high-risk criteria. Cases in higher-risk subgroups were over-sampled in predefined percentages. Each case was reviewed by two adjudicators trained to judge the likelihood of DE using the Safer Dx instrument; characterise harm, preventability and severity; and identify associated process failures using the Diagnostic Error Evaluation and Research Taxonomy modified for acute care. Cases with discrepancies or uncertainty about DE or impact were reviewed by an expert panel. We used descriptive statistics to report population estimates of harmful, preventable and severely harmful DEs by demographic variables based on the weighted sample, and characteristics of harmful DEs. Multivariable models were used to adjust association of process failures with harmful DEs. RESULTS: Of 9147 eligible cases, 675 were randomly sampled within each subgroup: 100% of ICU transfers, 38.5% of deaths within 90 days, 7% of cases with complex clinical events and 2.4% of cases without high-risk criteria. Based on the weighted sample, the population estimates of harmful, preventable and severely harmful DEs were 7.2% (95% CI 4.66 to 9.80), 6.1% (95% CI 3.79 to 8.50) and 1.1% (95% CI 0.55 to 1.68), respectively. Harmful DEs were frequently characterised as delays (61.9%). Severely harmful DEs were frequent in high-risk cases (55.1%). In multivariable models, process failures in assessment, diagnostic testing, subspecialty consultation, patient experience, and history were significantly associated with harmful DEs. CONCLUSIONS: We estimate that a harmful DE occurred in 1 of every 14 patients hospitalised on general medicine, the majority of which were preventable. Our findings underscore the need for novel approaches for adverse DE surveillance.

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.

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.

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.

[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.

Radiomic Analysis of Cohort-Specific Diagnostic Errors in Reading Dense Mammograms Using Artificial Intelligence.

OBJECTIVES: This study aims to investigate radiologists' interpretation errors when reading dense screening mammograms using a radiomics-based artificial intelligence approach. METHODS: Thirty-six radiologists from China and Australia read 60 dense mammograms. For each cohort, we identified normal areas that looked suspicious of cancer and the malignant areas containing cancers. Then radiomic features were extracted from these identified areas and random forest models were trained to recognize the areas that were most frequently linked to diagnostic errors within each cohort. The performance of the model and discriminatory power of significant radiomic features were assessed. RESULTS: We found that in the Chinese cohort, the AUC values for predicting false positives were 0.864 (CC) and 0.829 (MLO), while in the Australian cohort, they were 0.652 (CC) and 0.747 (MLO). For false negatives, the AUC values in the Chinese cohort were 0.677 (CC) and 0.673 (MLO), and in the Australian cohort, they were 0.600 (CC) and 0.505 (MLO). In both cohorts, regions with higher Gabor and maximum response filter outputs were more prone to false positives, while areas with significant intensity changes and coarse textures were more likely to yield false negatives. CONCLUSIONS: This cohort-based pipeline proves effective in identifying common errors for specific reader cohorts based on image-derived radiomic features. ADVANCES IN KNOWLEDGE: This study demonstrates that radiomics-based AI can effectively identify and predict radiologists' interpretation errors in dense mammograms, with distinct radiomic features linked to false positives and false negatives in Chinese and Australian cohorts.

High-risk pediatric medications: A listing proposal by interdisciplinary consensus technique. / Medicación pediátrica de alto riesgo: propuesta de listado a través de la técnica de consenso interdisciplinar.

INTRODUCTION: Pediatric patients are more likely to experience medication-related errors and serious associated harms. The identification of high-risk medications (HRM) and their study in special populations, such as children with excess body weight, is a part of safety improvement strategies. OBJECTIVE: To generate, through a consensus technique structured by an interdisciplinary group of pediatricians and hospital pharmacists, an operational and updated list of HRM for hospital use in children over 2 years of age. The document was part of a collaboration project between the Spanish Society of Hospital Pharmacists and the Spanish Society of Pediatric Hospital Medicine. METHODS: The study was carried out in two sequential phases: a) preparation of a preliminary list of HRM through bibliographic review and b) subsequent application of the double-round Delphi method to agree on a definitive list of HRM. The results obtained were validated by calculating the probability of chance agreement and the modified Kappa statistic for each drug. RESULTS: The original list obtained by bibliographic review included 26 pharmacological classes and 96 drugs. Of the total of 37 experts, 32 (86.4%) completed both rounds of the Delphi. The final consensus list of HRM incorporated 24 pharmacological classes and 100 drugs. The modified Kappa statistic reflected a high percent agreement (94.9%) in the consensus reached by the participants. CONCLUSION: This list can establish a tool for future studies and interventions to improve the safety of medications in general pediatric population, as well as in high-risk subgroups, such as pediatric patients with excess body weight.

The Association Between Plasma Amyloid-ß 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment.

Background: Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-ß (Aß) burden in older adults with amnestic mild cognitive impairment (aMCI). Objective: Plasma Aß biomarkers including the Aß42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). Methods: This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aß42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aß positivity (Aß+), while 50 aMCI participants scored above this cut-off indicating Aß negative status (Aß-). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aß-). Results: The aMCI plasma Aß+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aß-. The CU Aß- group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aß+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aß-group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aß- participants evidenced deficits, compared to 37.8% of aMCI Aß-, and 74.0% of aMCI Aß+. Conclusions: SIEs reflecting frPSI were associated with aMCI Aß+ status based on the Aß42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood.

Significance of early diagnosis and treatment of adult late-onset Pompe disease on the effectiveness of enzyme replacement therapy in improving muscle strength and respiratory function: a case report.

BACKGROUND: Pompe disease, a rare autosomal recessive disorder, is caused by mutations in the acid α-glucosidase gene. Pompe disease is a congenital metabolic disorder that affects all organs, particularly the striated muscle and nerve cells. Diagnosis is typically confirmed through enzyme assays that reveal reduced acid α-glucosidase activity. Enzyme replacement therapy utilizing human α-glucosidase is an available treatment option. Timely diagnosis and treatment in the early stages of the disease significantly impact the effectiveness of enzyme replacement therapy in enhancing patient condition. Here, we present a case of a patient with Pompe disease diagnosed 20 years after the onset of clinical symptoms. CASE PRESENTATION: A 38-year-old Iranian Baloch woman referred to our rheumatology clinic with progressive muscle weakness presents with a complex medical history. On mechanical ventilation for 12 years, she has endured fatigue and limb weakness since the age of 16, exacerbated following an abortion at 19. Despite undergoing corticosteroid and azathioprine therapies, the suspected diagnosis of inflammatory myopathy did not yield improvement. Hospitalization at 23 due to respiratory failure post-pregnancy led to her continued reliance on a ventilator. A dried blood spot test indicated reduced GAA enzyme activity, confirming a diagnosis of Pompe disease through genetic testing. Treatment with myozyme for 2 years demonstrated limited efficacy, as the patient experienced improved breathing but no significant overall improvement in limb-girdle muscular weakness. This case underscores the challenges and complexities involved in diagnosing and managing rare neuromuscular disorders like Pompe disease. CONCLUSION: Early intervention with enzyme replacement therapy plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients. It is important to note that treatment during advanced stages of the disease may not yield substantial benefits. Nevertheless, enzyme instability and denaturation due to temperature and neutral pH levels, along with limited delivery to disease-relevant tissues, can pose challenges in treatment. However, timely diagnosis of Pompe disease is paramount for its effective management and improved outcomes.

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.

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.