Deep representation learning of tissue metabolome and computed tomography annotates NSCLC classification and prognosis.

The rich chemical information from tissue metabolomics provides a powerful means to elaborate tissue physiology or tumor characteristics at cellular and tumor microenvironment levels. However, the process of obtaining such information requires invasive biopsies, is costly, and can delay clinical patient management. Conversely, computed tomography (CT) is a clinical standard of care but does not intuitively harbor histological or prognostic information. Furthermore, the ability to embed metabolome information into CT to subsequently use the learned representation for classification or prognosis has yet to be described. This study develops a deep learning-based framework -- tissue-metabolomic-radiomic-CT (TMR-CT) by combining 48 paired CT images and tumor/normal tissue metabolite intensities to generate ten image embeddings to infer metabolite-derived representation from CT alone. In clinical NSCLC settings, we ascertain whether TMR-CT results in an enhanced feature generation model solving histology classification/prognosis tasks in an unseen international CT dataset of 742 patients. TMR-CT non-invasively determines histological classes - adenocarcinoma/squamous cell carcinoma with an F1-score = 0.78 and further asserts patients' prognosis with a c-index = 0.72, surpassing the performance of radiomics models and deep learning on single modality CT feature extraction. Additionally, our work shows the potential to generate informative biology-inspired CT-led features to explore connections between hard-to-obtain tissue metabolic profiles and routine lesion-derived image data.

Electronic Medication Reconciliation Tools Aimed at Healthcare Professionals to Support Medication Reconciliation: a Systematic Review.

The development of health information technology available and accessible to professionals is increasing in the last few years. However, a low number of electronic health tools included some kind of information about medication reconciliation. To identify all the electronic medication reconciliation tools aimed at healthcare professionals and summarize their main features, availability, and clinical impact on patient safety. A systematic review of studies that included a description of an electronic medication reconciliation tool (web-based or mobile app) aimed at healthcare professionals was conducted. The review protocol was registered with PROSPERO: registration number CRD42022366662, and followed PRISMA guidelines. The literature search was performed using four healthcare databases: PubMed, EMBASE, Cochrane Library, and Scopus with no language or publication date restrictions. We identified a total of 1227 articles, of which only 12 met the inclusion criteria.Through these articles,12 electronic tools were detected. Viewing and comparing different medication lists and grouping medications into multiple categories were some of the more recurring features of the tools. With respect to the clinical impact on patient safety, a reduction in adverse drug events or medication discrepancies was detected in up to four tools, but no significant differences in emergency room visits or hospital readmissions were found. 12 e-MedRec tools aimed at health professionals have been developed to date but none was designed as a mobile app. The main features that healthcare professionals requested to be included in e-MedRec tools were interoperability, "user-friendly" information, and integration with the ordering process.

Use of Ozone Therapy in Diabetic Foot Ulcers.

INTRODUCTION: ozone therapy is a therapy composed of ozone. This gas is in the atmosphere with various general effects: direct disinfectant and trophic effects and a systemic antibacterial and antiviral effect. This gas also improves blood circulation, makes glucose metabolism more effective, improves erythrocyte metabolism, and improves fatty acid metabolism. OBJECTIVE: Provide evidence of the effectiveness of ozone therapy in wounds of patients with diabetic foot. Analyze the effectiveness of ozone therapy compared to other treatments to achieve good wound healing in patients with diabetic foot. To study the benefits of the use of ozone therapy in ulcers of patients. Analyze the management of ozone therapy and other treatments to achieve healing of ulcers in patients. METHODOLOGY: A bibliographic review focused on articles published between November 2014 and June 2023 was carried out. The following databases were consulted: Pubmed (Medline), Dialnet, Google Scholar, Web of Science (WOS), Scielo, and Scopus. RESULTS: After applying the article selection criteria and evaluating the quality of the methodology, a total of 17 articles were obtained. The results affirm ozone therapy as promising for the treatment of wounds in patients with diabetic foot. CONCLUSIONS: the evidence has been able to determine that ozone therapy is adequate for the treatment of diabetic foot ulcers. In addition, the therapy has been shown to be effective, safe, and beneficial, with few adverse effects for the treatment of diabetic foot ulcers.

Influence of Donor Type-Donation After Brain Death Versus Donation After Circulatory Death-on Lung Transplant Outcomes.

BACKGROUND: We sought to analyze the influence of lung donor type (brain death [BD] vs controlled donation after cardiac death [DCD]) on lung graft viability and to compare short-term outcomes of lung transplantation using grafts from BD and DCD donors. METHODS: This was a retrospective study of the lung donor population and lung transplants performed at our Institution between January 2020 and December 2022. Demographic characteristics of the donors and donation type (BD vs DCD) were assessed. Lung graft viability rate and post-transplant outcomes were analyzed and compared between donor types. RESULTS: There were 203 donors; among them, 149 (73%) were viable. There were 176 BD donors (87%) and 27 DCD donors (13%), with viability rates of 75% and 59%, respectively, performing 81 single (40%) and 122 double-lung transplants (60%). Recipient PaO2/fraction of inspired oxygen and primary graft dysfunction at 24 and 72 hours did not differ between donor types. Thirty-day mortality did not differ between recipients from BD donors and recipients from DCD donors: n = 28 (21%) vs n = 3 (18%), respectively (P = .81). CONCLUSIONS: Donation after cardiac death donors is a safe source to increase the donor pool for lung transplantation, allowing similar short-term outcomes as lung transplants from BD donors regarding graft function and early survival.

Occurrence of Leishmania infantum in Wild Mammals Admitted to Recovery Centers in Spain.

Zoonotic leishmaniasis caused by Leishmania infantum is distributed worldwide and affects humans and domestic and wild mammals. In Europe, specifically in the Mediterranean basin, leishmaniasis is endemic due to the concurrence of the phlebotomine vectors and reservoir mammals, including carnivorous wildlife species and other less studied wild species. In this article, spleen, skin, and eye or oral swabs taken from 134 wild mammals admitted to five wildlife recovery centers in Spain were used. PCR employing fragments of the Repeat region, ITS1, and SSUrRNA were used for detection, and positive samples were processed for sequencing. L. infantum was detected in three out of the nine species analyzed, including European hedgehog, European badger, and red squirrel, with percentages ranging from 11.53 to 35.71%, depending on the species. Most of the species showed higher percentages of positivity in spleen samples than in skin samples. A small number of animals from the remaining six species tested negative, including Algerian hedgehog, stone marten, least weasel, garden dormouse, western polecat, and Egyptian mongoose. Hedgehogs and badgers are good candidates for consideration as epidemiological sentinels and pose a higher risk as potential reservoirs of leishmaniasis based on their percentage of infection and wide distribution.

Influence of De Novo Malignancies on Long-Term Survival after Lung Transplantation.

(1) Background: Malignancies are an important cause of mortality after solid organ transplantation. The purpose of this study was to analyze the incidence of malignancies in patients receiving lung transplants (LT) and their influence on patients' survival. (2) Methods: Review of consecutive LT from 1994 to 2021. Patients with and without malignancies were compared by univariable and multivariable analyses. Survival was compared with Kaplan-Meier and Cox regression analysis. (3) Results: There were 731 LT malignancies developed in 91 patients (12.4%) with related mortality of 47% (n = 43). Native lung cancer, digestive and hematological malignancies were associated with higher lethality. Malignancies were more frequent in males (81%; p = 0.005), transplanted for emphysema (55%; p = 0.003), with cyclosporine-based immunosuppression (58%; p < 0.001), and receiving single LT (65%; p = 0.011). Survival was worse in patients with malignancies (overall) and with native lung cancer. Risk factors for mortality were cyclosporine-based immunosuppression (OR 1.8; 95%CI: 1.3-2.4; p < 0.001) and de novo lung cancer (OR 2.6; 95%CI: 1.5-4.4; p < 0.001). (4) Conclusions: Malignancies are an important source of morbidity and mortality following lung transplantation that should not be neglected. Patients undergoing single LT for emphysema are especially at higher risk of mortality due to lung cancer in the native lung.

Model-Informed Precision Dosing Software Tools for Dosage Regimen Individualization: A Scoping Review.

BACKGROUND: Pharmacokinetic nomograms, equations, and software are considered the main tools available for Therapeutic Drug Monitoring (TDM). Model-informed precision dosing (MIPD) is an advanced discipline of TDM that allows dose individualization, and requires a software for knowledge integration and statistical calculations. Due to its precision and extensive applicability, the use of these software is widespread in clinical practice. However, the currently available evidence on these tools remains scarce. OBJECTIVES: To review and summarize the available evidence on MIPD software tools to facilitate its identification, evaluation, and selection by users. METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, OpenAIRE, and BASE before July 2022. The PRISMA-ScR was applied. The main inclusion criteria were studies focused on developing software for use in clinical practice, research, or modelling. RESULTS: Twenty-eight software were classified as MIPD software. Ten are currently unavailable. The remaining 18 software were described in depth. It is noteworthy that all MIPD software used Bayesian statistical methods to estimate drug exposure and all provided a population model by default, except NONMEN. CONCLUSIONS: Pharmacokinetic software have become relevant tools for TDM. MIPD software have been compared, facilitating its selection for use in clinical practice. However, it would be interesting to standardize the quality and validate the software tools.

Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency.

BACKGROUND: Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. METHODS: We conducted genetic, immunologic, and molecular assays in four patients from four unrelated families who presented with infections, early-onset severe immune dysregulation, normocytic anemia of variable severity associated with anisopoikilocytosis, and developmental delay. Functional assays were performed in patient-derived cells, as well as in mouse and zebrafish models. RESULTS: We identified rare, X-linked germline mutations in DOCK11 in the patients, leading to a loss of protein expression in two patients and impaired CDC42 activation in all four patients. Patient-derived T cells did not form filopodia and showed abnormal migration. In addition, the patient-derived T cells, as well as the T cells from Dock11-knockout mice, showed overt activation and production of proinflammatory cytokines that were associated with an increased degree of nuclear translocation of nuclear factor of activated T cell 1 (NFATc1). Anemia and aberrant erythrocyte morphologic features were recapitulated in a newly generated dock11-knockout zebrafish model, and anemia was amenable to rescue on ectopic expression of constitutively active CDC42. CONCLUSIONS: Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.).

One-Step Hydrothermal Synthesis of Cu2ZnSnS4 Nanoparticles as an Efficient Visible Light Photocatalyst for the Degradation of Congo Red Azo Dye.

A hydrothermal method was successfully employed to synthesize kesterite Cu2ZnSnS4 (CZTS) nanoparticles. X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and optical ultraviolet-visible (UV-vis) spectroscopy were used for characterization of structural, chemical, morphological, and optical properties. XRD results confirmed that a nanocrystalline CZTS phase corresponding to the kesterite structure was formed. Raman analysis confirmed the existence of single pure phase CZTS. XPS results revealed the oxidation states as Cu+, Zn2+, Sn4+, and S2-. FESEM and TEM micrograph images revealed the presence of nanoparticles with average sizes between 7 nm to 60 nm. The synthesized CZTS nanoparticles bandgap was found to be 1.5 eV which is optimal for solar photocatalytic degradation applications. The properties as a semiconductor material were evaluated through the Mott-Schottky analysis. The photocatalytic activity of CZTS has been investigated through photodegradation of Congo red azo dye solution under solar simulation light irradiation, proving to be an excellent photo-catalyst for CR where 90.2% degradation could be achieved in just 60 min. Furthermore, the prepared CZTS was reusable and can be repeatedly used to remove Congo red dye from aqueous solutions.

Estudio y manejo de casos y contactos en población general / Study and management of cases and contacts in general population

El 30 de enero de 2020 la enfermedad COVID-19 fue declarada emergencia de salud públicainternacional. El 31 de enero se confirmó el primer caso en España y casi un mes después, el28 de febrero, se detectó el primer caso positivo en la Comunidad Foral de Navarra.Desde el inicio de los primeros casos de COVID-19 se visualizó el rastreo de casos y contactoscomo herramienta esencial de Salud Pública para trazar el rastro de contagios y romper lacadena de transmisión de la COVID-19.En el contexto de responder a las necesidades de todo tipo que generó la pandemia, el Institutode Salud Pública y Laboral de Navarra (ISPLN) como responsable técnico y la Subdirecciónde Urgencias Extrahospitalarias a nivel operativo, emprendieron activamente la detección yrastreo de posibles casos y contactos por COVID-19 en mayo de 2020, dando inicio al rastreopoblacional.La evolución en olas de alta incidencia seguidas de periodos valle y la dificultad de disponerde profesionales de Enfermería complicaron el dimensionamiento y la composición del equi-po de rastreo.Los diferentes procedimientos específicos según colectivos y sus continuas actualizacionesfueron una dificultad añadida que se palió en gran medida con la formación continua en lasactualizaciones de la estrategia nacional de manejo de casos y contactos actualizada de ras-treo, la realización de reuniones informativas diarias y la especialización del equipo.La creación de nuevas herramientas informáticas con acceso desde la historia clínica deAtención Primaria, la automatización de procesos, la coordinación interdepartamental y contodos los intervinientes en el proceso, fueron clave para el adecuado desarrollo del equiporastreo.(AU)

Estudios de cribado en brotes poblacionales y situaciones especiales / Screening studies in population outbreaks and special situations

La pandemia SARS-CoV-19 se convirtió en un reto global para los sistemas sanitarios mundia-les. Una de las líneas estratégicas para el control de la trasmisión de esta enfermedad fue ladetección precoz de los casos de infección por COVID-19, a través de cribados poblacionales.En la Comunidad Foral de Navarra, a través de un engranaje de varios servicios, se realizaroncribados de detección precoz en diferentes ámbitos: penitenciario, laboral, sociosanitario,escolar, poblaciones con altas incidencias de casos y cualquier otra situación especial queimplicase un riesgo para la Salud Pública. La organización de los cribados en diferentes escenarios fue compleja y requirió una continuaadaptación de recursos materiales y personales.Los continuos cambios, debido a los picos de incidencia de la enfermedad, al aumento de lademanda asistencial y los cambios de protocolos dependiendo de la situación pandémica encada momento, dieron lugar a la incorporación de nuevos profesionales con diferentes perfilesy a la implantación de tareas que no existían. Podemos concluir, tras nuestra experiencia en estos años de pandemia, la importancia demantener un equipo especializado en organización y actuaciones en brotes epidémicos, quefacilitaría una gestión y actuación más eficaz para futuras situaciones, vistas las dificultadesque ha conllevado la escalada de medidas de control de los brotes epidémicos.(AU)

Airway Complications after Lung Transplantation-A Contemporary Series of 400 Bronchial Anastomoses from a Single Center.

(1) Objective: To determine whether recent advances in lung transplantation (LT) have reduced the incidence and changed the risk factors for airway complications (AC). (2) Methods: Retrospective analysis of patients receiving a lung transplant between January 2007 and January 2019. An AC was defined as a bronchoscopic abnormality in the airway, either requiring or not requiring an endoscopic or surgical intervention. Both univariable and multivariable analyses were performed to identify risk factors for AC. (3) Results: 285 lung transplants (170 single and 115 bilateral lung transplants) were analysed, comprising 400 anastomoses at risk. A total of 50 anastomoses resulted in AC (12%). There were 14 anastomotic and 11 non-anastomotic stenoses, 4 dehiscences, and 3 malacias. Independent predictors for AC were: gender male (OR: 4.18; p = 0.002), cardiac comorbidities (OR: 2.74; p = 0.009), prolonged postoperative mechanical ventilation (OR: 2.5; p = 0.02), PaO2/FiO2 < 300 mmHg at 24 h post-LT (OR: 2.48; p = 0.01), graft infection (OR: 2.16; p = 0.05), and post-LT isolation of Aspergillus spp. (OR: 2.63; p = 0.03). (4) Conclusions: In spite of advances in lung transplantation practice, the risk factors, incidence, and lethality of AC after LT remains unchanged. Graft dysfunction, an infected environment, and the need of prolonged mechanical ventilation remain an Achilles heel for AC.

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Infrared Clinical Thermography: Normal Foot Growth Parameters.

BACKGROUND: Clinical thermography is a relatively novel technique in wide use in different medical fields because of its versatility and ease of application. It inflicts no pain and entails no contact with the pediatric patient, which assuages anxiety and fear in patients when undergoing diagnostic exploration. The use of infrared clinical thermography being suggested herein is to establish normality patterns, which have not been described in the relevant literature. These patterns may be extrapolated to pathologic study by means of future research lines. METHODS: An observational, cross-sectional study (descriptive in nature) was performed with a sample population of 328 children divided into two age groups: 6 to 7 years and 13 to 16 years, all of them schooled in the province of Cáceres in Spain. The variables analyzed herein were age, sex, and temperature. A thermographic camera was used to study foot temperature. RESULTS: Results show that the temperature varies among the different study areas established for the foot, although they remain constant bilaterally. In addition, the highest temperature was found in the area of the first metatarsal head (29.8°C), and the lowest at the heel (28.8°C). CONCLUSIONS: It can be concluded that both feet have the same thermal behavior despite the variation in temperature among the different areas that were established in the foot for the purposes of this study.

An initial trial of OPT-In-Early: An online training program for caregivers of autistic children.

LAY ABSTRACT: Early intervention can help children learn language and improve social communication. However, many barriers, including the expense of services and an insufficient number of providers, prohibit families from accessing services when their children are young. We developed a comprehensive online program for caregivers of autistic children. The program, Online Parent Training in Early Behavioral Intervention (OPT-In-Early), uses text and video demonstrations to teach caregivers effective methods for improving their children's language, social, and adaptive skills (e.g. using utensils, toilet training), and reducing their children's disruptive behavior. Sixty-three parents from three states participated in the study. Half of the parents received access to the OPT-In-Early program. After 4 months, parents who had access to the OPT-In-Early program learned more effective intervention strategies, and started using these strategies during interactions with their children, than parents who did not receive access to the program. Parent participation in OPT-In-Early did not significantly influence children's social communication compared to children whose parents did not have access to OPT-In-Early. A longer duration of parents using learned intervention skills with their children may be needed for children's social communication skills to improve.

Afectaciones del miembro inferior en sujetos que realizan kick-boxing: estudio descriptivo / Affections of the lower limb in subjects that perform kick-boxing: descriptive study

Introducción: El kick-boxing es un deporte que se practica de pie, el cual consiste en aplicar golpes a un rival utilizando los brazos, las manos, los codos, las piernas y los pies, mediante puñetazos, patadas, empujes y barridos. Los objetivos son identificar las lesiones que se producen con mayor prevalencia en los sujetos en función del sexo y los años de práctica del kick-boxing. Pacientes y métodos: La muestra la componen 37 sujetos de diferentes centros de Extremadura (25 sujetos hombres y 12 mujeres, 67.7 % y 32.42 %, respectivamente), los cuales fueron explorados por un único explorador tres veces, donde se valoraría musculatura, ligamentos y patologías presentes. Resultados: Casi el 60 % de los sujetos han padecido alguna vez una lesión. Las lesiones más frecuentes son queratopatías, fracturas, esguinces y, en menor medida, tendinopatías. Los años de la práctica del kick-boxing tienen una asociación altamente significativa con la presencia de lesiones (p valor = 0.005). Conclusión: El comportamiento del pie en el kick-boxing es similar en ambos sexos (no existe diferencia entre hombres y mujeres). Además, es destacable según la estadística que cuanto mayor es el tiempo de práctica de kick-boxing, mayor es la probabilidad de presentar lesiones (AU)

Introduction: Kick-boxing is a sport that is practiced standing up, which consists of applying blows to an opponent using the arms, hands, elbows, legs and feet, through punches, kicks, pushes and sweeps. The objectives are to identify the injuries that occur with the highest prevalence in subjects based on sex and years of kick-boxing practice. Patients and methods: The sample is made up of 37 subjects from different centers in Extremadura (25 male subjects and 12 female subjects, 67.7 % and 32.42 %, respectively). Which were explored by a single explorer three times, where the musculature, ligaments and present pathologies would be evaluated. Results: Almost 60 % of the subjects have ever suffered an injury. The most frequent injuries are keratopathies, fractures, sprains and, to a lesser extent, tendinopathy. Years of kick-boxing practice has a highly significant association with the presence of injuries (p value = 0.005). Conclusion: The behavior of the foot in kick-boxing is the same for both men and women. And that the greater the number of years practicing kick-boxing, the greater the probability of presenting injuries (AU)

Estimación de la osificación de los huesos del pie sobre población extremeña. Estudio observacional / Estimation of the ossification of the bones of the foot about the population of Extremadura. Observational study

Objetivos: La estimación de la edad de un individuo es un tema de interés dentro del ámbito de la Medicina Legal y Forense. Una de las herramientas más utilizadas para este fin es la Radiología. Los objetivos son la cuantificación de las edades de osificación de cada hueso del pie y determinar si existe relación entre la osificación de los huesos y el sexo del individuo. Pacientes y métodos: La población de estudio se compuso de 2476 radiografías digitales, pertenecientes a un total de 816 sujetos en periodo de crecimiento. El análisis de las imágenes se realizó mediante la aplicación del método validado y diseñado para la estimación de la edad en meses sobre la radiografía del esqueleto del pie.Resultados: Sí existe diferencia en la osificación ósea de la población extremeña frente a la literatura (p valor < 0.05). Todos los huesos que forman el Tarso poseen significación estadística en la comparación por sexos a excepción del cuboides, el cuneiforme medial y el cuneiforme lateral. Conclusiones: Sí existe diferencia significativa en la osificación de hueso del pie entre sexos y entre poblaciones de diferente raza.(AU)

Objectives: The estimation of the age of an individual is a topic of interest within the field of Legal and Forensic Medicine. One of the most used tools for this purpose is Radiology. The objectives of the present work are the quantification of the ages of ossification of each bone of the foot and to determine if there is a relationship between the ossification of the bones and the sex of the individual.Patients and methods: The study population was made up of 2476 digital radiographs, belonging to a total of 816 subjects in the growth period. The analysis of the images was carried out by applying the method validated and designed for the estimation of age in months on the X-ray of the skeleton of the foot. Results: If there is a difference in the bone ossification of the population of Extremadura compared to the literature (p value < 0,05). All the bones that form the tarsus have statistical significance in the comparison by sex, except for the Cuboid, the Medial Cuneiform and the Lateral Cuneiform. Conclusions: If there is a significant difference in foot bone ossification between sexes and between populations of different races.(AU)