Consideraciones bioéticas en el manejo de la esclerosis lateral amiotrófica: Una aproximación al quehacer fonoaudiológico

Introducción: La esclerosis lateral amiotrófica (ELA) es la forma más común de enfermedad degenerativa de motoneurona en la edad adulta y es considerada una enfermedad terminal. Por lo mismo, el accionar del fonoaudiólogo debe considerar el respeto a los principios bioéticos básicos para garantizar una asistencia adecuada. Objetivo: Conocer aquellas consideraciones bioéticas relacionadas al manejo y estudio de personas con ELA para luego brindar una aproximación hacia el quehacer fonoaudiológico. Método: Se efectuó una búsqueda bibliográfica en las bases de datos PubMed, Scopus y SciELO. Se filtraron artículos publicados desde 2000 hasta junio de 2023 y fueron seleccionados aquellos que abordaban algún componente bioético en población con ELA. Resultados: Aspectos relacionados al uso del consentimiento informado y a la toma de decisiones compartidas destacaron como elementos esenciales para apoyar la autonomía de las personas. Conclusión: Una correcta comunicación y una toma de decisiones compartida son claves para respetar la autonomía de las personas. A su vez, la estandarización de procedimientos mediante la investigación clínica permitirá aportar al cumplimiento de los principios bioéticos de beneficencia y no maleficencia, indispensables para la práctica profesional.

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood and is considered a terminal disease. For this reason, the actions of the speech therapist must consider respect for basic bioethical principles to guarantee adequate assistance. Objective: To know those bioethical considerations related to the management and study of people with ALS to then provide an approach to speech therapy. Methodology: A bibliographic search was carried out in the PubMed, Scopus, and SciELO databases. Articles published from 2000 to June 2023 were filtered and those that addressed a bioethical component in the population with ALS were selected. Results: Aspects related to the use of informed consent and shared decision-making stood out as essential elements to support people's autonomy. Conclusion: Proper communication and shared decision-making are key to respecting people's autonomy. In turn, the standardization of procedures through clinical research will contribute to compliance with the bioethical principles of beneficence and non-maleficence, essential for professional practice.

Outcomes of a Community of Practice on Quebec Speech Language Pathologists' Voice Assessment Practices and Professional Identity

In a context where different protocols for recommended practices in clinical voice assessment exist, while there are gaps in the literature regarding the evidence base supporting assessment procedures and measures, clinicians from regions where a strong community holding expertise in clinical and scientific voice practices lack can struggle to confidently develop their voice assessment practices. In an effort to improve voice assessment practices and strengthen professional identity among speech-language pathologists in Quebec, Canada, a community of practice (CoP) was established, with the aim of promoting knowledge sharing, implementing change in clinical practice, and improving professional identity. Thirty-nine participants took part in the CoP activities conducted over a four-month period, including virtual meetings and in-person workshops. Participants had a high rate of attendance (> 74% participation rate in virtual meetings), and were highly satisfied with their participation and intended to remain involved after the project's end. Statistically significant changes in voice assessment practices were observed post-CoP, regarding probability of performing assessments (p < .001), and perceived importance of assessment for evaluative purposes (p <.001), as well as improvements in assessment specific confidence, specifically for procedure of auditory-perceptual assessment (p < .001) and purpose of aerodynamic assessment (p = .05). Moreover, there was an increase in professional identity post-CoP (p < .001) and participants felt they made significant learnings. The present study highlighted the need to involve SLPs in future research to identify assessments that are relevant to the specific evaluative objectives of SLPs working with voice, and suggests CoPs are an efficient tool for that purpose.

En un contexto en el que existen diferentes protocolos para las prácticas recomendadas en la evaluación vocal clínica, y en el que se presentan vacíos en la literatura respecto a la base de evidencia que respalda los procedimientos y medidas de evaluación, los profesionales de regiones donde no hay una comunidad sólida con experiencia en prácticas vocales clínicas y científicas pueden enfrentar dificultades para desarrollar con confianza sus prácticas de evaluación vocal. Con el propósito de mejorar las prácticas de evaluación vocal y fortalecer la identidad profesional entre los logopedas de Quebec, Canadá, se estableció una comunidad de práctica (CdP). Esta tenía como objetivo fomentar el intercambio de conocimientos, implementar cambios en la práctica clínica y mejorar la identidad profesional. Un total de treinta y nueve participantes se involucraron en las actividades de la CdP, llevadas a cabo durante un período de cuatro meses, que incluyeron reuniones virtuales y talleres presenciales. Los participantes tuvieron una alta tasa de asistencia (> 74% de participación en las reuniones virtuales) y expresaron un alto grado de satisfacción con su participación, manifestando su intención de continuar involucrados después de la finalización del proyecto. Se observaron cambios estadísticamente significativos en las prácticas de evaluación vocal posterior a la CdP, en lo que respecta a la probabilidad de llevar a cabo evaluaciones (p < .001) y la percepción de la importancia de la evaluación con fines evaluativos (p < .001), así como mejoras en la confianza específica en la evaluación, particularmente en el procedimiento de evaluación auditivo-perceptual (p < .001) y el propósito de la evaluación aerodinámica (p = .05). Además, se registró un aumento en la identidad profesional posterior a la CdP (p < .001) y los participantes sintieron que obtuvieron aprendizajes significativos. El presente estudio destacó la necesidad de involucrar a los logopedas en investigaciones futuras, para identificar evaluaciones pertinentes a los objetivos evaluativos específicos de los logopedas que trabajan con la voz, y sugiere que las CdP son una herramienta eficiente con ese propósito.

ChatGPT es un estudiante por encima de la media en la Facultad de Medicina de la Universidad de Zaragoza y un colaborador excelente en la elaboración de material docente / ChatGPT is an above-average student at the Faculty of Medicine of the University of Zaragoza and an excellent collaborator in the development of teaching materials

Introducción y objetivo: La inteligencia artificial se halla plenamente presente en nuestras vidas. En educación las posibilidades de su uso son infinitas, tanto para alumnos como para docentes. Material y métodos: Se ha explorado la capacidad de ChatGPT a la hora de resolver preguntas tipo test a partir del examen de la asignatura Procedimientos Diagnósticos y Terapéuticos Anatomopatológicos de la primera convocatoria del curso 2022-2023. Además de comparar su resultado con el del resto de alumnos presentados, se han evaluado las posibles causas de las respuestas incorrectas. Finalmente, se ha evaluado su capacidad para realizar preguntas de test nuevas a partir de instrucciones específicas. Resultados: ChatGPT ha acertado 47 de las 68 preguntas planteadas, obteniendo una nota superior a la de la media y mediana del curso. La mayor parte de preguntas falladas presentan enunciados negativos, utilizando las palabras «no», «falsa» o «incorrecta» en su enunciado. Tras interactuar con él, el programa es capaz de darse cuenta de su error y cambiar su respuesta inicial por la correcta. Finalmente, ChatGPT sabe elaborar nuevas preguntas a partir de un supuesto teórico o bien de una simulación clínica determinada. Conclusiones: Como docentes estamos obligados a explorar las utilidades de la inteligencia artificial, e intentar usarla en nuestro beneficio. La realización de tareas que suponen un consumo de tipo importante, como puede ser la elaboración de preguntas tipo test para evaluación de contenidos, es un buen ejemplo. (AU)

Introduction and objective: Artificial intelligence is fully present in our lives. In education, the possibilities of its use are endless, both for students and teachers. Material and methods: The capacity of ChatGPT has been explored when solving multiple choice questions based on the exam of the subject «Anatomopathological Diagnostic and Therapeutic Procedures» of the first call of the 2022-23 academic year. In addition, to comparing their results with those of the rest of the students presented the probable causes of incorrect answers have been evaluated. Finally, its ability to formulate new test questions based on specific instructions has been evaluated. Results: ChatGPT correctly answered 47 out of 68 questions, achieving a grade higher than the course average and median. Most failed questions present negative statements, using the words «no», «false» or «incorrect» in their statement. After interacting with it, the program can realize its mistake and change its initial response to the correct answer. Finally, ChatGPT can develop new questions based on a theoretical assumption or a specific clinical simulation. Conclusions: As teachers we are obliged to explore the uses of artificial intelligence and try to use it to our benefit. Carrying out tasks that involve significant consumption, such as preparing multiple-choice questions for content evaluation, is a good example. (AU)

The eye in forensic practice: In the dead.

Post-mortem examination of the eye provides valuable forensic information yet is often overlooked. This brief review focuses on determining the cause/manner of death and post-mortem interval. External eye findings like corneal haziness and tache noire, combined with post-mortem changes in the iris, lens, retina and vitreous humour, can help estimate time since death. Ocular biometrics (iris/retinal scans) may facilitate identification. Age-related ocular changes can provide insights. The eye offers clues into personality (corneal tattooing, trichotillomania) and cause of death (petechiae in strangulation, retinal haemorrhages in abusive head trauma). Ocular trauma and underlying eye disease may be evident. Toxicology of vitreous humour can detect drugs/poisons. As a window into systemic disease and age-related changes, the eye aids pathology interpretations and, accordingly, post-mortem examinations have value. Ocular findings should not be overlooked in forensic examinations as they provide distinct information in determining cause/manner of death and post-mortem interval.

Differences in imaging biomarkers between patients with intermediate and advanced non-neovascular age-related macular degeneration (AMD) in the University of Colorado AMD registry.

PURPOSE: To quantify and compare the different prevalence rates of specific retinal imaging biomarkers in patients with intermediate AMD (iAMD) and advanced non-neovascular AMD (nnAMD). METHODS: Cross-sectional study of patients with iAMD and advanced nnAMD. Imaging studies were reviewed for qualitative imaging biomarkers. Choroidal thickness measurements were obtained subfoveally and in 1000 um and 2000 um intervals away from the fovea. The Chi-squared test and Fisher's exact test were used to compare rates of imaging biomarkers among the two cohorts. P-value of <0.05 was considered significant. RESULTS: 376 eyes of 197 patients with iAMD and 187 eyes of 97 patients with advanced nnAMD were recruited. There were significantly lower rates of the following imaging biomarkers in the iAMD compared with the advanced nnAMD cohorts: soft drusen (66.0% vs. 84.2%, p = 0.001), calcified drusen (4.3% vs. 40.0%, p < 0.0001), RPD (26.2% vs. 53.3%, p < 0.0001), ORT (0.5% vs. 46.9%, p < 0.0001), RP (1.1% vs. 46.3%, p < 0.0001), pigment migration (53.2% vs. 100%, p < 0.0001), and iRORA (17.9% vs. 80.2%, p < 0.0001). In the iAMD cohort, choroidal thickness was significantly greater at 188 µm (SD: 60) and 194 µm (SD: 69), compared to the advanced nnAMD with measurements of 153 µm (SD: 68), and 161 µm (SD: 76). This difference was statistically significant (p < 0.0001 and p = 0.0002). CONCLUSIONS: Our results highlight significant differences in imaging biomarkers between both cohorts. Key biomarkers, such as iRORA, RPD, pigment migration, and thinner choroidal thickness, were associated with advanced nnAMD. Identifying these biomarkers early may help target patients who could benefit from new treatments, potentially delaying vision loss.

Phenotypes of maternal vascular malperfusion placental pathology and adverse pregnancy outcomes: A retrospective cohort study.

OBJECTIVE: To identify which components of maternal vascular malperfusion (MVM) pathology are associated with adverse pregnancy outcomes and to investigate the morphological phenotypes of MVM placental pathology and their relationship with distinct clinical presentations of pre-eclampsia and/or fetal growth restriction (FGR). DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in Toronto, Canada. POPULATION: Pregnant individuals with low circulating maternal placental growth factor (PlGF) levels (<100 pg/mL) and placental pathology analysis between March 2017 and December 2019. METHODS: Association between each pathological finding and the outcomes of interest were calculated using the chi-square test. Cluster analysis and logistic regression was used to identify phenotypic clusters, and their association with adverse pregnancy outcomes. Cluster analysis was performed using the K-modes unsupervised clustering algorithm. MAIN OUTCOME MEASURES: Preterm delivery <34+0 weeks of gestation, early onset pre-eclampsia with delivery <34+0 weeks of gestation, birthweight <10th percentile (small for gestational age, SGA) and stillbirth. RESULTS: The diagnostic features of MVM most strongly associated with delivery <34+0 weeks of gestation were: infarction, accelerated villous maturation, distal villous hypoplasia and decidual vasculopathy. Two dominant phenotypic clusters of MVM pathology were identified. The largest cluster (n = 104) was characterised by both reduced placental mass and hypoxic ischaemic injury (infarction and accelerated villous maturation), and was associated with combined pre-eclampsia and SGA. The second dominant cluster (n = 59) was characterised by infarction and accelerated villous maturation alone, and was associated with pre-eclampsia and average birthweight for gestational age. CONCLUSIONS: Patients with placental MVM disease are at high risk of pre-eclampsia and FGR, and distinct pathological findings correlate with different clinical phenotypes, suggestive of distinct subtypes of MVM disease.

Integrated Case-Based Learning Session for Breast and Upper Limb Anatomy.

Introduction: Medical students are frequently introduced to medical school curricula through anatomy coursework, which often includes histology and embryology content. As medical education has increasingly emphasized integration of content areas, use of activities such as case-based learning (CBL) sessions has grown. Little published work has demonstrated the effectiveness of CBL sessions in integrating anatomy, embryology, and histology on first-year medical students' ability to improve content mastery and adapt their study techniques. Methods: We developed a CBL session that included anatomy, embryology, and histology content covering the upper extremity and breast pathology that was taught to incoming first-year medical students (N = 51) during a prematriculation program in the summers of 2022 and 2023. The session involved completion of an individual pre- and postsession quiz; group completion of clinical cases involving image interpretation, matching exercises, and construction of diagrams, flowcharts, or tables; and a postsession survey with Likert-style and free-response questions about preparation and session effectiveness. Results: Postsession quiz scores significantly improved (p < .001). On the postsession survey (response rate: 59%), students commented that they enjoyed the real-life application and integration of the cases and that the sessions improved their understanding of the connections between content areas. Other comments demonstrated that students were evaluating and adapting their study approach in preparation for the sessions, often using techniques introduced and practiced in the sessions. Discussion: CBL sessions can provide opportunities to incoming first-year medical students to practice, adapt, and evaluate study techniques while delivering integrated content.

Understanding the financial aspects of digital pathology: A dynamic customizable return on investment calculator for informed decision-making.

Background: The adoption of digital pathology has transformed the field of pathology, however, the economic impact and cost analysis of implementing digital pathology solutions remain a critical consideration for institutions to justify. Digital pathology implementation requires a thorough evaluation of associated costs and should identify and optimize resource allocation to facilitate informed decision-making. A dynamic cost calculator to estimate the financial implications of deploying digital pathology systems was needed to estimate the financial effects on transitioning to a digital workflow. Methods: A systematic approach was used to comprehensively assess the various components involved in implementing and maintaining a digital pathology system. This consisted of: (1) identification of key cost categories associated with digital pathology implementation; (2) data collection and analysis of cost estimation; (3) cost categorization and quantification of direct and indirect costs associated with different use cases, allowing customization of each factor based on specific intended uses and market rates, industry standards, and regional variations; (4) opportunities for savings realized by digitization of glass slides and (5) integration of the cost calculator into a unified framework for a holistic view of the financial implications associated with digital pathology implementation. The online tool enables the user to test various scenarios specific to their institution and provides adjustable parameters to assure organization specific relatability. Results: The Digital Pathology Association has developed a web-based calculator as a companion tool to provide an exhaustive list of the necessary concepts needed when assessing the financial implications of transitioning to a digital pathology system. The dynamic return on investment (ROI) calculator successfully integrated relevant cost and cost-saving components associated with digital pathology implementation and maintenance. Considerations include factors such as digital pathology infrastructure, clinical operations, staffing, hardware and software, information technology, archive and retrieval, medical-legal, and potential reimbursements. The ROI calculator developed for digital pathology workflows offers a comprehensive, customizable tool for institutions to assess their anticipated upfront and ongoing annual costs as they start or expand their digital pathology journey. It also offers cost-savings analysis based on specific user case volume, institutional geographic considerations, and actual costs. In addition, the calculator also serves as a tool to estimate number of required whole slide scanners, scanner throughput, and data storage (TB). This tool is intended to estimate the potential costs and cost savings resulting from the transition to digital pathology for business plan justifications and return on investment calculations. Conclusions: The digital pathology online cost calculator provides a comprehensive and reliable means of estimating the financial implications associated with implementing and maintaining a digital pathology system. By considering various cost factors and allowing customization based on institution-specific variables, the calculator empowers pathology laboratories, healthcare institutions, and administrators to make informed decisions and optimize resource allocation when adopting or expanding digital pathology technologies. The ROI calculator will enable healthcare institutions to assess the financial feasibility and potential return on investment on adopting digital pathology, facilitating informed decision-making and resource allocation.

Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

PURPOSE: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. MATERIALS AND METHODS: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. RESULTS: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). CONCLUSIONS: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. CLINICALTRIALS.GOV IDENTIFIER: NCT04936334.

Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival.

PURPOSE: In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. METHODS: Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. RESULTS: Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2- to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2- (5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). CONCLUSION: Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.

Multifocal Extramedullary Plasmacytoma of the Thyroid With Cervical and Paratracheal Lymph Node Involvement and Progression to Multiple Myeloma.

Extramedullary plasmacytomas without evidence of systemic illness make up less than 5% of all plasma cell neoplasms. The incidence of extramedullary plasmacytoma of the thyroid region is exceedingly rare. This report discusses the case of a 72-year-old male with extramedullary plasmacytoma of the thyroid. The patient underwent a total thyroidectomy for an enlarging right-sided thyroid nodule, and intraoperatively, the plasmacytoma was found to have an extracapsular component with adherence to the regional soft tissue as well as involvement of the right laryngeal nerve and regional lymph nodes. Despite a comprehensive negative workup for multiple myeloma initially, including a bone marrow biopsy and hematologic workup, the disease progressed to multiple myeloma following definitive radiation therapy, as evidenced by the development of hypermetabolic lytic lesions and further pathological examination. The patient's treatment course included systemic chemotherapy and an autologous stem cell transplant, resulting in a favorable treatment response. The progression to multiple myeloma despite established guidelines highlights the need for close observation and the potential for innovative therapeutic strategies to manage this rare entity.

Applications of Artificial Intelligence in Lung Pathology.

Artificial intelligence/machine learning tools are being created for use in pathology. Some examples related to lung pathology include acid-fast stain evaluation, programmed death ligand-1 (PDL-1) interpretation, evaluating histologic patterns of non-small-cell lung carcinoma, evaluating histologic features in mesothelioma associated with adverse outcomes, predicting response to anti-PDL-1 therapy from hematoxylin and eosin-stained slides, evaluation of tumor microenvironment, evaluating patterns of interstitial lung disease, nondestructive methods for tissue evaluation, and others. There are still some frameworks (regulatory, workflow, and payment) that need to be established for these tools to be integrated into pathology.

High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

Intrahepatic cholangiocarcinoma with FGFR alterations: A series of Chinese cases with an emphasis on their clinicopathologic and genetic features.

Intrahepatic Cholangiocarcinoma (iCCA) with FGFR alterations is relatively rare, and its identification is important in the era of targeted therapy. We collected a large series of FGFR-altered cases in the Chinese population and characterized their clinicopathological and genetic features. Among the 18 FGFR-altered cases out of 260 iCCAs, 10 were males and 8 were females, ranging in age from 35 to 74 years (mean, 57.3 years; median, 58 years). Pathologically, they include 9 cases of large duct (LD, 50 %) and small duct (SD, 50 %) types each. All of them (100 %, 18/18) showed microsatellite stable (MSS) and low tumor mutation burden (TMB). Genetically, FGFR alterations involved FGFR1 (20 %), FGFR2 (70 %), and FGFR3 (10 %), with FGFR2 rearrangement accounting for the most (11/18). The most frequently altered genes/biological processes were development/proliferation-related pathways (44 %), chromatin organization (20 %), and tumor suppressors (32 %). Our study further revealed the clinicopathological and genetic features of FGFR-altered iCCA and demonstrated that its occurrence may show regional or ethnic variability and is less common in the Chinese population. A significant number of LD-type iCCA cases also have FGFR alterations rather than the SD type.

Proarrhythmic drugs, drug levels, and polypharmacy in victims of sudden arrhythmic death syndrome: An autopsy-based study from Denmark.

BACKGROUND: Sudden arrhythmic death syndrome (SADS), characterized by an unknown or inconclusive cause of death at autopsy, together with a negative or non-lethal toxicology screening, is the most common cause of sudden cardiac death (SCD) in victims under the age of 35. The complete causality of SADS remains unclear, with drugs being a potential risk factor. OBJECTIVE: To describe the toxicological profiles of SADS victims, focusing on proarrhythmic drugs, drug levels, and polypharmacy. METHODS: All deaths in Denmark from 2000-2019 aged 1-35 years and 2007-2019 aged 36-49 years were examined through death certificates, national registries, and autopsy reports with toxicology screenings. We investigated all sudden unexpected death victims with an autopsy performed, and where cause of death was unknown or inconclusive, including negative or non-lethal drug findings (SADS). RESULTS: We identified 477 SADS victims; 313 (66%) had a positive toxicology screening (adjudicated non-lethal), with an average of 2.8 drugs/case. More than half of the SADS victims with a positive toxicology screening had QT-prolonging or brugadogenic drugs present. Polypharmacy was present in 66%, psychotropic polypharmacy in 37%, and QT-prolonging polypharmacy in 22%, with the most frequent overall and QT-prolonging drug combination being an antipsychotic and a psychoanaleptic drug. QT-prolonging drugs were more often present at suprapharmacological levels than non-QT-prolonging drugs. CONCLUSION: A majority of the SADS population had a positive toxicology, with a notably large proportion having proarrhythmic drugs and polypharmacy. This highlights the need for future focus on drugs as a risk factor for SADS.

CSChighE-cadherinlow immunohistochemistry panel predicts poor prognosis in oral squamous cell carcinoma.

Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.

COS-PPA: protocol to develop a core outcome set for primary progressive aphasia.

INTRODUCTION: The term primary progressive aphasia (PPA) describes a group of language-led dementias. Disease-modifying treatments that delay, slow or reverse progression of PPA are currently lacking, though a number of interventions to manage the symptoms of PPA have been developed in recent years. Unfortunately, studies exploring the effectiveness of these interventions have used a variety of different outcome measures, limiting comparability. There are more constructs, apart from word retrieval, that are important for people with PPA that have not received much attention in the research literature. Existing core outcome sets (COS) for dementia and non-progressive aphasia do not meet the needs of people with PPA, highlighting a need to develop a specific COS for PPA. METHODS AND ANALYSIS: This protocol describes a three-stage study to identify a COS for PPA interventions in research and clinical practice. The stage 1 systematic review will identify existing speech, language and communication measures used to examine the effectiveness of interventions for PPA in the research literature. Employing a nominal group technique, stage 2 will identify the most important outcomes for people with PPA and their families. The data collected in stages 1 and 2 will be jointly analysed with the project PPI group and will inform the stage 2 modified Delphi consensus study to identify a core outcome measurement set for PPA among a range of research disciplines undertaking intervention studies for people with PPA. ETHICS AND DISSEMINATION: Ethical approval for stage 2 of the study has been sought individually in each country at collaborating institutions and is stated in detail in the manuscript. Stage 3 has been granted ethical approval by the Chairs of UCL Language and Cognition Department Ethics, Project ID LCD-2023-06. Work undertaken at stages 1, 2 and 3 will be published in open-access peer-reviewed journal articles and presented at international scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022367565.

The role of machine learning in advancing diabetic foot: a review.

Background: Diabetic foot complications impose a significant strain on healthcare systems worldwide, acting as a principal cause of morbidity and mortality in individuals with diabetes mellitus. While traditional methods in diagnosing and treating these conditions have faced limitations, the emergence of Machine Learning (ML) technologies heralds a new era, offering the promise of revolutionizing diabetic foot care through enhanced precision and tailored treatment strategies. Objective: This review aims to explore the transformative impact of ML on managing diabetic foot complications, highlighting its potential to advance diagnostic accuracy and therapeutic approaches by leveraging developments in medical imaging, biomarker detection, and clinical biomechanics. Methods: A meticulous literature search was executed across PubMed, Scopus, and Google Scholar databases to identify pertinent articles published up to March 2024. The search strategy was carefully crafted, employing a combination of keywords such as "Machine Learning," "Diabetic Foot," "Diabetic Foot Ulcers," "Diabetic Foot Care," "Artificial Intelligence," and "Predictive Modeling." This review offers an in-depth analysis of the foundational principles and algorithms that constitute ML, placing a special emphasis on their relevance to the medical sciences, particularly within the specialized domain of diabetic foot pathology. Through the incorporation of illustrative case studies and schematic diagrams, the review endeavors to elucidate the intricate computational methodologies involved. Results: ML has proven to be invaluable in deriving critical insights from complex datasets, enhancing both the diagnostic precision and therapeutic planning for diabetic foot management. This review highlights the efficacy of ML in clinical decision-making, underscored by comparative analyses of ML algorithms in prognostic assessments and diagnostic applications within diabetic foot care. Conclusion: The review culminates in a prospective assessment of the trajectory of ML applications in the realm of diabetic foot care. We believe that despite challenges such as computational limitations and ethical considerations, ML remains at the forefront of revolutionizing treatment paradigms for the management of diabetic foot complications that are globally applicable and precision-oriented. This technological evolution heralds unprecedented possibilities for treatment and opportunities for enhancing patient care.