Novel clinical phenotypes, drug categorization, and outcome prediction in drug-induced cholestasis: Analysis of a database of 432 patients developed by literature review and machine learning support.

BACKGROUND: Serum transaminases, alkaline phosphatase and bilirubin are common parameters used for DILI diagnosis, classification, and prognosis. However, the relevance of clinical examination, histopathology and drug chemical properties have not been fully investigated. As cholestasis is a frequent and complex DILI manifestation, our goal was to investigate the relevance of clinical features and drug properties to stratify drug-induced cholestasis (DIC) patients, and to develop a prognosis model to identify patients at risk and high-concern drugs. METHODS: DIC-related articles were searched by keywords and Boolean operators in seven databases. Relevant articles were uploaded onto Sysrev, a machine-learning based platform for article review and data extraction. Demographic, clinical, biochemical, and liver histopathological data were collected. Drug properties were obtained from databases or QSAR modelling. Statistical analyses and logistic regressions were performed. RESULTS: Data from 432 DIC patients associated with 52 drugs were collected. Fibrosis strongly associated with fatality, whereas canalicular paucity and ALP associated with chronicity. Drugs causing cholestasis clustered in three major groups. The pure cholestatic pattern divided into two subphenotypes with differences in prognosis, canalicular paucity, fibrosis, ALP and bilirubin. A predictive model of DIC outcome based on non-invasive parameters and drug properties was developed. Results demonstrate that physicochemical (pKa-a) and pharmacokinetic (bioavailability, CYP2C9) attributes impinged on the DIC phenotype and allowed the identification of high-concern drugs. CONCLUSIONS: We identified novel associations among DIC manifestations and disclosed novel DIC subphenotypes with specific clinical and chemical traits. The developed predictive DIC outcome model could facilitate DIC prognosis in clinical practice and drug categorization.

Difficulties Fulfilling Self-Care Needs Among Family Caregivers: An Observational Study.

IMPORTANCE: Assuming the care of a family member with a disability or chronic illness constitutes a health risk factor for caregivers, who frequently overlook their own self-care. OBJECTIVE: To analyze the self-care activities (SCAs) among caregivers of a family member with a disability or chronic illness and assess the impact on their satisfaction and quality of life (QoL). DESIGN: Descriptive, cross-sectional, analytic study. SETTING: Community. PARTICIPANTS: Five hundred caregivers of family members with a disability or chronic illness in the city of Zaragoza, Spain. OUTCOMES AND MEASURES: The family caregivers' occupational performance and satisfaction were assessed with the Canadian Occupational Performance Measure, and their QoL was assessed with the World Health Organization-Quality of Life. RESULTS: In total, 32.8% of family caregivers had difficulty in all activities related to self-care, 46.6% had difficulty sleeping and resting, 31.6% had difficulty receiving health-related treatments, and 31.2% had difficulty with physical exercise. Women and younger family caregivers showed greater impairment in self-care. Occupational performance, satisfaction, and QoL worsened as the number of affected activities increased. CONCLUSIONS AND RELEVANCE: Caring for a family member with a disability or chronic illness has a negative impact on the SCAs of caregivers, especially among female caregivers and those of younger age. Caregiving is also associated with lower occupational performance, satisfaction, and QoL. Plain-Language Summary: Caring for a family member with a disability or chronic illness can become a health risk for caregivers, who frequently ignore their own self-care. The study results found that women and younger family caregivers showed a greater decline in self-care. This study provides information to help occupational therapists to work with family caregivers to prevent a decline in their self-care and improve their quality of life.

Peripheral T-cell responses of EphB2- and EphB3-deficient mice in a model of collagen-induced arthritis.

Both EphB2- and EphB3-deficient mice exhibit profound histological alterations in the thymic epithelial network but few changes in T-cell differentiation, suggesting that this organization would be sufficient to produce functional T lymphocytes. Also, other antigen-presenting cells involved in immunological education could substitute the thymic epithelium. Accordingly, we found an increased frequency of plasmacytoid dendritic cells but not of conventional dendritic cells, medullary fibroblasts or intrathymic B lymphocytes. In addition, there are no lymphoid infiltrates in the organs of mutant mice nor do they contain circulating autoantibodies. Furthermore, attempts to induce arthritic lesions after chicken type II collagen administration fail totally in EphB2-deficient mice whereas all WT and half of the immunized EphB3-/- mice develop a typical collagen-induced arthritis. Our results point out that Th17 cells, IL4-producing Th2 cells and regulatory T cells are key for the induction of disease, but mutant mice appear to have deficits in T cell activation or cell migration properties. EphB2-/- T cells show reduced in vitro proliferative responses to anti-CD3/anti-CD28 antibodies, produce low levels of anti-type II collagen antibodies, and exhibit low proportions of T follicular helper cells. On the contrary, EphB3-/- lymph node cells respond accurately to the different immune stimuli although in lower levels than WT cells but show a significantly reduced migration in in vitro transwell assays, suggesting that no sufficient type II collagen-dependent activated lymphoid cells reached the joints, resulting in reduced arthritic lesions.

[Patient safety training for ward clerks of an Occupational Mutual Insurance Company collaborating with the Social Security, immediate impact and after six months]. / Formación en seguridad del paciente para el personal administrativo de una Mutua Colaboradora con la Seguridad Social, impacto inmediato y a los seis meses.

INTRODUCTION: Ward Clerks are an essential part of the healthcare team, as they provide administrative and organizational support in healthcare institutions. The aim of this study is to determine the training impact of a basic one-hour online course on patient safety for this staff. METHOD: A quasi-experimental before/after study carried out on a population of 170 administrative staff working in the centers of an Occupational Mutual Insurance Company (MC Mutual) who took the patient safety course. A convenience sample of 22 administrative professionals, who agreed to participate, was chosen from this population, which made it possible to reconstruct their knowledge before and after the course, by examination and interview, immediately after the course and at 6 months. RESULTS: Of the 170 professionals participating in the course, 167 (98.2%) completed the initial test and the post-test, with mean scores increasing from 5.7 (P1) to 7.3 (P2) (p<0.05). A total of 22 out of a sample of 42 (52.4%) agreed to participate in the interviews and all three interviews were achieved by 21 (E1), 22 (E2) and 19 (E3) professionals, whose mean scores increased from 5.9 (E1) to 7.2 (E2) and 7.5 (E3) (p<0.05). CONCLUSIONS: The results suggest that the training course was effective. The evaluation by interview 6 months after the course indicates a likely medium to long term effect. The involvement of administrative professionals in the the Company´s patients care is key. Evaluating the impact of an intervention is essential to inform its effectiveness and guide its planning.

Introducción: El personal administrativo es un colectivo esencial. El objetivo de este estudio es analizar el impacto formativo de un curso online básico sobre seguridad del paciente para administrativos.  Método: Estudio cuasi experimental antes/después en una población de 170 administrativos/as que prestaban sus servicios en los centros de la Mutua Colaboradora con la Seguridad Social MC Mutual y que realizaron un curso de seguridad del paciente. Se evaluaron los conocimientos adquiridos mediante una prueba al inicio (P1) y al final del curso (P2). Además, se eligió una muestra de conveniencia de 42 administrativos/as para evaluar sus conocimientos mediante entrevista, previos (E1) y posteriores (E2) al curso, y a los 6 meses (E3). Resultados: De los 170 administrativos/as participantes en el curso, 167 (98,2%) completaron la prueba al inicio y final, con puntuaciones medias que incrementaron de 5,7 (P1) a 7,3 (P2) (p<0,05). Aceptaron participar en las entrevistas 22 administrativos/as de una muestra de 42 (52,4%), y se consiguieron las tres entrevistas de 21 (E1), 22 (E2) y 19 (E3) administrativos/as, cuyas puntuaciones medias incrementaron desde 5,9 (E1) a 7,2 (E2) y 7,5 (E3) (p<0,05).  Conclusiones: Los resultados sugieren que el curso de formación fue efectivo. La evaluación mediante la entrevista a los seis meses del curso indica un probable efecto a medio-largo plazo. La implicación de los/as profesionales administrativos/as en la atención a los usuarios de la Mutua es clave. La evaluación del impacto de una intervención es esencial para informar sobre su efectividad y orientar su planificación.

The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

BACKGROUND: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. METHODS: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression. CONCLUSIONS: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Dual ß-lactam therapy to improve treatment outcome in Mycobacterium abscessus disease.

BACKGROUND: Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual ß-lactam and ß-lactam/ß-lactamase inhibitor combinations may be interesting leads to improve treatment outcomes. OBJECTIVES: To summarize the current preclinical studies on dual ß-lactam and ß-lactam/ß-lactamase inhibitor combinations against M. abscessus. SOURCES: We performed a literature search using the National Center for Biotechnology Information's PubMed interface with additional snowball sampling. CONTENT: Select combinations of ß-lactam antibiotics, as well as ß-lactam/ß-lactamase inhibitor combinations show promising in vitro activity and synergy against M. abscessus. ß-Lactam antibiotics differ in their ability to reach and interfere with their targets and their resistance to the M. abscessus ß-lactamase. The synergy is typically observed for combinations of ß-lactam antibiotics or a ß-lactam antibiotic with a ß-lactamase inhibitor. No additional killing capacity was demonstrated in three-drug combinations of synergistic ß-lactam antibiotics and a ß-lactamase inhibitor. The efficacy of select dual ß-lactam antibiotics and ß-lactam/ß-lactamase inhibitor combinations is retained in intracellular infection assays and mouse models, but no combination has a complete preclinical portfolio. IMPLICATIONS: Future clinical strategies should entail either dual ß-lactam or ß-lactam/ß-lactamase inhibitor combinations. Imipenem-ceftaroline and an all-oral tebipenem-avibactam combination are promising leads but still require a complete preclinical portfolio, target product profiles as well as clinical trial confirmation.

Exploring Individual Variability in Drug-Induced Liver Injury (DILI) Responses through Metabolomic Analysis.

Drug-induced liver injury (DILI) is a serious adverse hepatic event presenting diagnostic and prognostic challenges. The clinical categorization of DILI into hepatocellular, cholestatic, or mixed phenotype is based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values; however, this classification may not capture the full spectrum of DILI subtypes. With this aim, we explored the utility of assessing changes in the plasma metabolomic profiles of 79 DILI patients assessed by the RUCAM (Roussel Uclaf Causality Assessment Method) score to better characterize this condition and compare results obtained with the standard clinical characterization. Through the identification of various metabolites in the plasma (including free and conjugated bile acids and glycerophospholipids), and the integration of this information into predictive models, we were able to evaluate the extent of the hepatocellular or cholestatic phenotype and to assign a numeric value with the contribution of each specific DILI sub-phenotype into the patient's general condition. Additionally, our results showed that metabolomic analysis enabled the monitoring of DILI variability responses to the same drug, the transitions between sub-phenotypes during disease progression, and identified a spectrum of residual DILI metabolic features, which can be overlooked using standard clinical diagnosis during patient follow-up.

Hybrid hydrogels support neural cell culture development under magnetic actuation at high frequency.

The combination of hydrogels and magnetic nanoparticles, scarcely explored to date, offers a wide range of possibilities for innovative therapies. Herein, we have designed hybrid 3D matrices integrating natural polymers, such as collagen, chitosan (CHI) and hyaluronic acid (HA), to provide soft and flexible 3D networks mimicking the extracellular matrix of natural tissues, and iron oxide nanoparticles (IONPs) that deliver localized heat when exposed to an alternating magnetic field (AMF). First, colloidally stable nanoparticles with a hydrodynamic radius of ∼20 nm were synthesized and coated with either CHI (NPCHI) or HA (NPHA). Then, collagen hydrogels were homogeneously loaded with these coated-IONPs resulting in soft (E0 ∼ 2.6 kPa), biodegradable and magnetically responsive matrices. Polymer-coated IONPs in suspension preserved primary neural cell viability and neural differentiation even at the highest dose (0.1 mg Fe/mL), regardless of the coating, even boosting neuronal interconnectivity at lower doses. Magnetic hydrogels maintained high neural cell viability and sustained the formation of highly interconnected and differentiated neuronal networks. Interestingly, those hydrogels loaded with the highest dose of NPHA (0.25 mgFe/mg polymer) significantly impaired non-neuronal differentiation with respect to those with NPCHI. When evaluated under AMF, cell viability slightly diminished in comparison with control hydrogels magnetically stimulated, but not compared to their counterparts without stimulation. Neuronal differentiation under AMF was only affected on collagen hydrogels with the highest dose of NPHA, while non-neuronal differentiation regained control values. Taken together, NPCHI-loaded hydrogels displayed a superior performance, maybe benefited from their higher nanomechanical fluidity. STATEMENT OF SIGNIFICANCE: Hydrogels and magnetic nanoparticles are undoubtedly useful biomaterials for biomedical applications. Nonetheless, the combination of both has been scarcely explored to date. In this study, we have designed hybrid 3D matrices integrating both components as promising magnetically responsive platforms for neural therapeutics. The resulting collagen scaffolds were soft (E0 ∼ 2.6 kPa) and biodegradable hydrogels with capacity to respond to external magnetic stimuli. Primary neural cells proved to grow on these substrates, preserving high viability and neuronal differentiation percentages even under the application of a high-frequency alternating magnetic field. Importantly, those hydrogels loaded with chitosan-coated iron oxide nanoparticles displayed a superior performance, likely related to their higher nanomechanical fluidity.

Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score.

BACKGROUND AND AIMS: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.

Deciphering mechanisms affecting cefepime-taniborbactam in vitro activity in carbapenemase-producing Enterobacterales and carbapenem-resistant Pseudomonas spp. isolates recovered during a surveillance study in Spain.

PURPOSE: To characterize the resistance mechanisms affecting the cefepime-taniborbactam combination in a collection of carbapenemase-producing Enterobacterales (CPE) and carbapenem-resistant Pseudomonas spp. (predominantly P. aeruginosa; CRPA) clinical isolates. METHODS: CPE (n = 247) and CRPA (n = 170) isolates were prospectively collected from patients admitted to 8 Spanish hospitals. Susceptibility to cefepime-taniborbactam and comparators was determined by broth microdilution. Cefepime-taniborbactam was the most active agent, inhibiting 97.6% of CPE and 67.1% of CRPA (MICs ≤ 8/4 mg/L). All isolates with cefepime-taniborbactam MIC > 8/4 mg/L (5 CPE and 52 CRPA) and a subset with MIC ≤ 8/4 mg/L (23 CPE and 24 CRPA) were characterized by whole genome sequencing. RESULTS: A reduced cefepime-taniborbactam activity was found in two KPC-ST307-Klebsiella pneumoniae isolates with altered porins [KPC-62-K. pneumoniae (OmpA, OmpR/EnvZ), KPC-150-K. pneumoniae (OmpK35, OmpK36)] and one each ST133-VIM-1-Enterobacter hormaechei with altered OmpD, OmpR, and OmpC; IMP-8-ST24-Enterobacter asburiae; and NDM-5-Escherichia coli with an YRIN-inserted PBP3 and a mutated PBP2. Among the P. aeruginosa (68/76), elevated cefepime-taniborbactam MICs were mostly associated with GES-5-ST235, OXA-2+VIM-2-ST235, and OXA-2+VIM-20-ST175 isolates also carrying mutations in PBP3, efflux pump (mexR, mexZ) and AmpC (mpl) regulators, and non-carbapenemase-ST175 isolates with AmpD-T139M and PBP3-R504C mutations. Overall, accumulation of these mutations was frequently detected among non-carbapenemase producers. CONCLUSIONS: The reduced cefepime-taniborbactam activity among the minority of isolates with elevated cefepime-taniborbactam MICs is not only due to IMP carbapenemases but also to the accumulation of multiple resistance mechanisms, including PBP and porin mutations in CPE and chromosomal mutations leading to efflux pumps up-regulation, AmpC overexpression, and PBP modifications in P. aeruginosa.

Coaching leaders toward favorable trajectories of burnout and engagement.

Existing literature on executive coaching has shown beneficial outcomes for leaders. Indeed, executive coaching can positively affect an individual's psychological well-being and quality of work life. However, while burnout among leaders is on the rise, to our knowledge no prior study has investigated the influence of executive coaching on the dimensions of burnout and engagement concurrently. Therefore, the aim of the current study is to examine if an executive coaching intervention has positive effects on managerial burnout and engagement. We implemented a ten-week coaching intervention for leaders, where questionnaire data were collected at two time points. Participants (N = 92; Mage = 42; 64% male) were randomly assigned to an intervention or a wait-list control group. Self-reported levels of engagement and burnout were collected at the start of the study protocol (T1) and at the end (T2). Coaching sessions for the intervention group were one hour once per week. The control group did not receive coaching. Repeated measures ANOVAs examined the extent to which the intervention influences the leader's engagement and burnout. Analyses revealed that all three dimensions of burnout significantly decreased for the intervention group over time while vigor increased. Findings did not reveal an increase in dedication and absorption. Consistent with prior literature, this study supports that executive coaching can improve a leader's well-being. Specifically, this study shows that an executive coaching intervention can decrease burnout symptoms and increase vigor in leaders. Adding a follow-up survey to the design would allow for further exploration of the intervention on engagement.

Endothelial progenitor cells as biomarkers of diabetes-related cardiovascular complications.

Diabetes mellitus (DM) constitutes a chronic metabolic disease characterized by elevated levels of blood glucose which can also lead to the so-called diabetic vascular complications (DVCs), responsible for most of the morbidity, hospitalizations and death registered in these patients. Currently, different approaches to prevent or reduce DM and its DVCs have focused on reducing blood sugar levels, cholesterol management or even changes in lifestyle habits. However, even the strictest glycaemic control strategies are not always sufficient to prevent the development of DVCs, which reflects the need to identify reliable biomarkers capable of predicting further vascular complications in diabetic patients. Endothelial progenitor cells (EPCs), widely known for their potential applications in cell therapy due to their regenerative properties, may be used as differential markers in DVCs, considering that the number and functionality of these cells are affected under the pathological environments related to DM. Besides, drugs commonly used with DM patients may influence the level or behaviour of EPCs as a pleiotropic effect that could finally be decisive in the prognosis of the disease. In the current review, we have analysed the relationship between diabetes and DVCs, focusing on the potential use of EPCs as biomarkers of diabetes progression towards the development of major vascular complications. Moreover, the effects of different drugs on the number and function of EPCs have been also addressed.

Consensus on post COVID in the Spanish national health system: Results of the CIBERPOSTCOVID eDelphi study.

BACKGROUND: In 2021, the Spanish Ministry of Health launched the CIBERPOSTCOVID project to establish what post COVID was. The present study reports the level of agreement among stakeholders on post COVID and its clinical and diagnostic characteristics in the Spanish health system. METHODS: The agreement on post COVID among clinicians, public health managers, researchers and patients' representatives was explored in a real-time, asynchronous online Delphi. In a two-wave consensus, respondents rated from 1 (total disagreement) to 6 (total agreement) 67 statements related to terminology, duration, etiology, symptoms, impact on quality of life, severity, elements to facilitate diagnosis, applicability in the pediatric population, and risk factors. Consensus was reached when 70 % of ratings for a statement were 5 or 6, with an interquartile range equal or less than 1. FINDINGS: A total of 333 professionals and patients participated in this eDelphi study. There was agreement that post COVID was "a set of multi-organic symptoms that persist or fluctuate after acute COVID-19 infection and are not attributable to other causes" with a minimum duration of 3 months. The highest levels of agreement were found in the most frequent symptoms and its impacts on everyday activities. Aspects related to the diagnostic process and the measurement of its severity reached a lower level of consensus. There was agreement on the need to rule out previous health problems and assess severity using validated functional scales. However, no agreement was reached on the risk factors or specific features in the pediatric population. INTERPRETATION: This policy-based consensus study has allowed the characterization of post COVID generating collective intelligence and has contributed to an operational definition applicable in clinical practice, health services management and useful for research purposes in Spain and abroad. Agreements are consistent with existing evidence and reference institutions at European and international level.

Influence of Clinical and Sociodemographic Variables on Health-Related Quality of Life in the Adult Population with Long COVID.

Worldwide, about 10 percent of patients affected by long COVID require appropriate follow-up and intervention. The main objective of this study was to analyze the long-term impact of mild long COVID in the adult population, and to determine the effect of clinical and sociodemographic variables on health-related quality of life in those affected. Methods: A cross-sectional descriptive study of a sample of Spanish adult patients with persistent COVID-19 symptoms at least three months after diagnosis. Data collection took place between April and July 2021. The health-related quality of life of the sample was low, with worse results in the physical component summary (PCS) 24.66 (SD = 4.45) compared to the mental component summary (MCS) 45.95 (SD = 8.65). The multi-regression analysis showed significant differences by sex in the dimensions of physical functioning (p = 0.040); bodily pain (p = 0.036); and health transition (p = 0.018). Additionally, a longer time since infection had a significant effect on physical functioning (p = 0.039); general health (p = 0.037); vitality (p = 0.034); and general health transition (p = 0.002). The effect of occupational imbalance was significant for all dimensions. Conclusions: people with long COVID have a reduced quality of life. Sex, time since infection, and occupational imbalance are predictors of a worse quality of life.

Enhancing the accuracy of mid-infrared spectroscopy-based liver steatosis quantification using digital image analysis as a reference.

The assessment of liver steatosis is crucial in both hepatology and liver transplantation (LT) surgery. Steatosis can negatively impact the success of LT. Steatosis is a factor for excluding donated organs for LT, but the increasing demand for transplantable organs has led to the use of organs from marginal donors. The current standard for evaluating steatosis is a semi-quantitative grading based on the visual examination of a hematoxylin and eosin (H&E)-stained liver biopsy, but this method is time-consuming, subjective, and lacks reproducibility. Recent research has shown that infrared (IR) spectroscopy could be used as a real-time quantitative tool to assess steatosis during abdominal surgery. However, the development of IR-based methods has been hindered by the lack of appropriate quantitative reference values. In this study, we developed and validated digital image analysis methods for the quantitation of steatosis in H&E-stained liver sections using univariate and multivariate strategies including linear discriminant analysis (LDA), quadratic DA, logistic regression, partial least squares-DA (PLS-DA), and support vector machines. The analysis of 37 tissue samples with varying grades of steatosis demonstrates that digital image analysis provides accurate and reproducible reference values that improve the performance of IR spectroscopic models for steatosis quantification. A PLS model in the 1810-1052 cm-1 region using first derivative ATR-FTIR spectra provided RMSECV = 0.99%. The gained improvement in accuracy critically enhances the applicability of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) to support an objective graft evaluation at the operation room, which might be especially relevant in cases of marginal liver donors to avoid unnecessary graft explantation.

Spanish Cultural Adaptation and Inter-Rater Reliability of the Revised Knox Preschool Play Scale.

BACKGROUND: The Revised Knox Preschool Play Scale (RKPPS) is a comprehensive assessment test that observes the level of play development; however, there is no culturally adapted version available with stable psychometric values that would allow its widespread use and provide objective information during clinical evaluations. METHODS: Cross-cultural adaptation included direct and retrospective translations, along with cognitive interviews with pediatric occupational therapists to analyze the comprehensibility of the translation. In addition, a final phase of linguistic revision was carried out to determine the grammatical and semantic fit of the adapted version. Finally, inter-rater reliability was analyzed in a sample of typically developing children aged four to six years old. RESULTS: The processes of translation and back-translation, cognitive interview, and linguistic review determined an adequate grammatical and semantic equivalence to the Spanish cultural context. Almost perfect agreement, with values between 0.82 and 0.94, was obtained for items and play dimensions, indicating that the precision of the measurements between both evaluators was excellent. CONCLUSIONS: The cross-culturally adapted version of the RKPPS meets the necessary adjustments for the sociocultural context and can be used in the clinical practice of occupational therapy.

Prospective One-Year Follow-Up of Sensory Processing in Phelan-McDermid Syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by the loss (deletion) of a small portion of chromosome 22 in a region designated q13.3 (22q13.3 deletion). PMS is one of the most common genetic forms of autism spectrum disorder (ASD) in which sensory reactivity difficulties have been described on limited occasions. METHODS: The objective of this study is to identify whether changes in sensory reactivity skills occur after one year of follow-up in a group of 44 participants diagnosed with PMS. All participants completed the Short Sensory Profile (SSP). Two-factor ANOVA tests were performed with repeated measures for the study of the evolution of the scores. RESULTS: Participants with PMS showed significant changes after one year of follow-up in sensory reactivity skills associated with tactile hyperreactivity (p = 0.003). The rest of the study variables did not show significant differences compared to the baseline assessment, showing definite differences associated with patterns of hypo-responsiveness and sensory seeking, low/weak energy, and difficulties in auditory filtering. CONCLUSIONS: Understanding the evolution of sensory reactivity skills can facilitate the adjustment to behavioral changes in people with PMS and design-targeted interventions to address sensory reactivity challenges.

The Impact of Social Distancing Due to COVID-19 on Activities of Daily Living in Parkinson's Disease.

INTRODUCTION: To explore the impact of the lockdown and social distancing measures, applied for one year, due to the COVID-19 pandemic on Activities of Daily Living in patients with Parkinson's disease, as well as to determine the association between daily performance and tasks requiring more manipulative dexterity. METHODS: Data collection was carried out between 18 January and 22 March 2021 through telephone interviews. Patients were recruited from associations of patients with Parkinson's disease in Spain. A questionnaire was designed including items from standardized tools of the Activities of Daily Living Questionnaire to measure the level of independence and from the Dexterity Questionnaire for manipulative dexterity. RESULTS: There were 126 participants aged 36-89 years, 58% of whom were male. The results of our study reveal a significant decline in almost all the ADLs assessed. There is a moderate correlation between the degree of dependence in ADLs and the difficulty in performing activities requiring manipulative dexterity. CONCLUSIONS: Social isolation related to the COVID-19 pandemic and its consequences may have contributed to an increase in the deterioration of manipulative ability, leading to a loss of ability to perform ADLs. These results show specific needs to be considered in the rehabilitation treatment of these patients.

The assessment of the potential hepatotoxicity of new drugs by in vitro metabolomics.

Drug hepatotoxicity assessment is a relevant issue both in the course of drug development as well as in the post marketing phase. The use of human relevant in vitro models in combination with powerful analytical methods (metabolomic analysis) is a promising approach to anticipate, as well as to understand and investigate the effects and mechanisms of drug hepatotoxicity in man. The metabolic profile analysis of biological liver models treated with hepatotoxins, as compared to that of those treated with non-hepatotoxic compounds, provides useful information for identifying disturbed cellular metabolic reactions, pathways, and networks. This can later be used to anticipate, as well to assess, the potential hepatotoxicity of new compounds. However, the applicability of the metabolomic analysis to assess the hepatotoxicity of drugs is complex and requires careful and systematic work, precise controls, wise data preprocessing and appropriate biological interpretation to make meaningful interpretations and/or predictions of drug hepatotoxicity. This review provides an updated look at recent in vitro studies which used principally mass spectrometry-based metabolomics to evaluate the hepatotoxicity of drugs. It also analyzes the principal drawbacks that still limit its general applicability in safety assessment screenings. We discuss the analytical workflow, essential factors that need to be considered and suggestions to overcome these drawbacks, as well as recent advancements made in this rapidly growing field of research.

Adverse events in the global healthcare practice of an Occupational Mutual Insurance Company in Spain.

BACKGROUND: Patient safety is currently a main issue in healthcare practice. Adverse events (AEs) management is a key instrument for the application of strategies to prevent harm to patients. OBJECTIVE: To analyze the type, severity and preventability, according to validated scales, of AEs occurring annually in the healthcare practice of an Occupational Mutual Insurance Company in order to implement action plans to improve patient safety. METHODS: We analyzed the reported AEs in an Incident Reporting System and AEs detected in the Audit program of clinical records as a result of treating injured or ill workers in our 88 ambulatory care centers. RESULTS: We detected 28 AEs in the clinical records (CR), representing 0.05 AE/CR, with maximum values in the COM sample (26 AEs, 0.11) and much lower in INT (1 AEs, 0.02) and MIN (1 AE, 0.02). The most frequent AE type was procedure-related, followed by infection and care. AEs of severity level D (11 cases) and E (9 cases) predominated, while level F was also detected (6 cases). Intermediate values in preventability (3 and 4) predominated, 61.5% were preventable. With the Incident Reporting System, 27 AEs were identified, predominated by procedural type. Most reported AE severities was in levels E (10 cases) and C (8 cases), 89% were preventable. CONCLUSION: Our company detects AEs via the Incident Reporting System and annual Audit program of clinical records, both of which are complementary, and may result in the implementation of more effective Patient Safety measures.