Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.

BACKGROUND: Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools. METHODS: EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform. RESULTS: Different-sized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p, miR-28-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-429, were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT. CONCLUSIONS: These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT.

Operational tolerance research in liver transplantation: a bibliometric analysis using a new web resource.

Background: Operational tolerance in liver transplantation (OT-LT), defined as the graft survival with normal function in absence of immunosuppression, has been a field of intense research since the 1980s. Thereafter, tens of clinical trials and hundreds of articles have been published, making it challenging for researchers to assimilate all the information, more so outside of their disciplines. The aim of the present study was to analyze the research in OT-LT through a new web tool (https://tolerance.imib.es). Methods: We have developed a web resource that allowed the identification of the present trends and potential research avenues in OL-LT, an overview biomedical terms that were most often cited, including which journals published the most articles, and an advanced search engine that exploited all the information in these publications. Results: A total of 734 studies were analyzed until November 2023, with a mean of 15 articles published per year, a total sum of 3,751 impact factor points and a total of 26,542 citations. The analysis of citations allowed us to establish a ranking of the most prolific countries, authors, journals and institutions, in addition to the most influential publications in OT-LT. Likewise, keyword and co-occurrence analyses answered which themes involving OT-LT are the most popular, whereas cooperation analysis showed that principal authors in OT-LT form a network, although the lack of international cooperation, especially with regard to clinical trials, appears to be one of the main challenges. Conclusion: Despite its limitations, our web tool will allow both OT-LT expert and novel researchers to be able to draw a comprehensive picture of the past, present and future of OT-LT research.

Telemedicine screening program for diabetic retinopathy in patients with type 1 diabetes mellitus.

PURPOSE: To analyze the results of the telemedicine screening program for diabetic retinopathy (DR) in patients with type 1 diabetes conducted by the Endocrinology and Nutrition Management Unit of Virgen del Rocío University Hospital. METHODS: This cross-sectional study comprised patients with type 1 diabetes mellitus (DM) in our DR screening program from January 2018 to November 2020. Fundus photographs are performed by trained nurses and reviewed by a trained endocrinologist. Those suggestive of pathology are sent to ophthalmology through a telematic program for review. RESULTS: Of the 995 fundus photographs evaluated, 646 (65.3%) showed no evidence of DR, 327 (33.1%) presented possible DR, and 16 (1.6%) were not gradable. The diagnosis was confirmed in 254 patients after reviewing by ophthalmology, and the screening program achieved a positive predictive value for DR of 77.7%. Seventy-three were excluded by ophthalmology due to the absence of DR (false positive rate - 22.3%). In 92.5% of the cases classified by the ophthalmologist, the degree of DR was mild or very mild. CONCLUSION: Our telemedicine screening program for DR in patients with type 1 DM is consistent with the literature. Effective screening for DR is performed, with patients diagnosed in the early stages. Telemedicine programs facilitate efficient communication among healthcare personnel.

Keratograph 5M As A Useful And Objective Tool For Evaluating The Ocular Surface In Limbal Stem Cell Deficiency.

PURPOSE: In limbal stem cell deficiency, both the Ocular Surface Disease Index (OSDI) questionnaire and tear break-up time (BUT) are comparable between traditional methods and the Keratograph 5M. In this study, we aimed to correlate OSDI with Keratograph 5M interviewed OSDI, as well as slit-lamp tear BUT with Keratograph 5M noninvasive tear break-up time (NIKBUT) in limbal stem cell deficiency. PATIENTS AND METHODS: Thirty-eight limbal stem cell-deficiency patients (76 eyes) from Virgen Macarena-Rocio Hospital (Seville, Spain) underwent this diagnostic test study. All patients completed the traditional OSDI. We measured the BUT, performed a Keratograph 5M analysis of NIKBUT first (employed for the analysis) followed by the average NIKBUT, the level of dryness, and conducted the OSDI questionnaire through an interview. For each pair of tests, we analyzed the means and applied an intraclass correlation coefficient (r), creating a Bland-Altman plot for data dispersion. RESULTS: Average values were 47.5 points (±25.8), and 47.3 points (±27.5) for traditional OSDI and Keratograph OSDI, respectively (P =0.87); the r value indicates good agreement (0.72). The Bland-Altman plot followed a linear pattern, and the results were similarly distributed. The NIKBUT mean was shorter than the BUT mean (P = 0.007); the r value indicates moderate agreement (0.574). The Bland-Altman plot formed an almost horizontal line, with almost all values between the mean and two standard deviations. CONCLUSION: Keratograph 5M is useful for the evaluation of the ocular surface in limbal stem cell deficiency. NIKBUT can substitute BUT based on its advantages of being noninvasive, objective, with intraobserver and interobserver repeatability and reliability. The Keratograph 5M OSDI is comparable to the traditional questionnaire.

In vivo confocal microscopy indicates an inverse relationship between the sub-basal corneal plexus and the conjunctivalisation in patients with limbal stem cell deficiency.

BACKGROUND/AIMS: Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification. METHODS: We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity. RESULTS: The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm2) was less (p<0.001) than in controls (20911±4142 µm/mm2). The SND, but not basal cell density, played a protective role against conjunctivalisation (OR, 0.069; 95% CI 0.008-0.619; p=0.01). An SND cut-off value of 17 215 µm/mm2 yielded a sensitivity and specificity of 95.5% and 90.6%, respectively, for LSCD diagnosis. CONCLUSION: The density of the corneal sub-basal nerve plexus was inversely related to conjunctivalisation in LSCD. Further studies are needed to verify this and to elucidate the directionality between these factors.

FOVEAL HYPOPLASIA: DIAGNOSIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the clinical presentations and image findings of a patient with foveal hypoplasia. METHODS: Observational case report of one patient. The clinical presentation of the patient was documented by fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 55-year-old healthy white female with bilateral foveal hypoplasia without nystagmus was presented. There were no signs suggestive of ocular albinism. Absence of foveal depression was noted on both clinical examination and optical coherence tomography. Lack of foveal avascular zone was confirmed on fluorescein angiography and optical coherence tomography angiography. CONCLUSION: To the best of our knowledge this is the first report of findings in foveal hypoplasia examined by angio-optical coherence tomography. Optical coherence tomography angiography is an easy, rapid, and noninvasive tool that allows imaging of the retinal microvasculature without intravenous dye injection.

Combined Hamartoma of the Retina and Retinal Pigment Epithelium in a Patient with Gorlin Syndrome: Spontaneous Partial Resolution of Traction Caused by Epiretinal Membrane.

Purpose. To describe the case of spontaneous resolution of epiretinal membrane in a patient with Combined Hamartoma of the Retina and Retinal Pigment Epithelium (CHR-RPE), in the clinical context of Gorlin Syndrome (GS). Methods. Observational case report of a 12-year-old female patient is presented. The diagnosis of CHRRPE was made by OCT and fundus examination, which showed a mound of disorganized tissue originating from retina and retinal pigment epithelium. Epiretinal membrane (EM) was also detected. Genetic study was performed to confirm the diagnosis of GS. Results. The patient was observed for 39 months, showing spontaneous resolution of the traction caused by the EM and improvement in visual acuity (VA), which was 20/80 at initial presentation, rising to 20/40 after follow-up period. Conclusions. The presence of EM in CHR-REP is a cause of reduction of visual acuity. Management of this condition is controversial; however, we would like to highlight that spontaneous resolution of the traction caused by EM is possible, resulting in recovery of VA.

Terapia metabólica con yodo 131 en paciente con insuficiencia renal crónica. Caso clínico / Metabolic therapy with iodine 131 in patients with chronic renal failure. clinical case

OBSERVACIÓN CLÍNICA: Varón de 62 años con insuficiencia renal crónica en estadio 5 en programa de diálisis desde el 2012 que es intervenido de carcinoma papilar de tiroides con metástasis ganglionares. Posteriormente el paciente ingresa en la Unidad de Terapia Metabólica de su hospital de referencia donde se le administran 80 milicurios de yodo-131 como tratamiento asociado al quirúrgico. Ante la imposibilidad de practicarle su sesión de diálisis convencional, se le realizan las intervenciones de enfermería requeridas en las distintas etapas de aplicación de las técnicas continuas de depuración extrarrenal (TCDE). PLAN DE CUIDADOS: Se abordan los cuidados orientados a pacientes sometidos a TCDE en tratamiento con I131: material específico, medidas de protección personal y los principales diagnósticos e intervenciones enfermeras. DISCUSIÓN: Las TCDE a pesar de ser propias de pacientes críticos, en un momento dado se pueden extrapolar a otro tipo de pacientes. Las TCDE permiten dializar a este tipo de pacientes en un entorno seguro para el personal, garantizándose la adecuada eliminación de líquidos contaminados. CONCLUSIONES: Las TCDE resultaron ser un tratamiento eficaz para la eliminación del I131, siendo necesaria una única sesión para normalizar los niveles de radiactividad. La coordinación entre servicios permitió garantizar un tratamiento adecuado y eficaz para el paciente

CASE REPORT: 62 year-old male with CKD stage 5 in dialysis program since 2012 who underwent surgery for papillary thyroid carcinoma with lymph node metastasis. Subsequently, the patient was admitted to the Unit of Metabolic Therapy at his reference hospital, where he is administered 80 mill curies of iodine-131 as a treatment associated with the surgery, unable to have his conventional dialysis, nursing interventions required in various stages of implementation of the continuous extrarenal clearance techniques (TCDE) were performed. CARE PLAN: The following care values were addressed targeted to patients undergoing treatment with I131: specific equipment, personal protective measures and major diagnoses and nursing INTERVENTIONS: PROGRESS: TCDE, despite being attributed to very critical patients, they can be extrapolated to other patients in a given time. TCDE allowed these patients to undergo dialysis in a safe environment for staff, ensuring proper disposal of contaminated liquids. CONCLUSIONS: TCDE were an effective treatment for the removal of I131, a single session being necessary to normalize the levels of radioactivity. Coordination between services allowed ensure proper and effective treatment for the patient

[Metabolic therapy with iodine 131 in patients with chronic renal failure. Clinical case]. / Terapia metabólica con yodo 131 en paciente con insuficiencia renal crónica. Caso clínico.

CASE REPORT: 62 year-old male with CKD stage 5 in dialysis program since 2012 who underwent surgery for papillary thyroid carcinoma with lymph node metastasis. Subsequently, the patient was admitted to the Unit of Metabolic Therapy at his reference hospital, where he is administered 80 millicuries of iodine-131 as a treatment associated with the surgery, unable to have his conventional dialysis, nursing interventions required in various stages of implementation of the continuous extrarenal clearance techniques (TCDE) were performed. CARE PLAN: The following care values were addressed targeted to patients undergoing treatment with I(131): specific equipment, personal protective measures and major diagnoses and nursing interventions. PROGRESS: TCDE, despite being attributed to very critical patients, they can be extrapolated to other patients in a given time. TCDE allowed these patients to undergo dialysis in a safe environment for staff, ensuring proper disposal of contaminated liquids. CONCLUSIONS: TCDE were an effective treatment for the removal of I131, a single ssesion being necessary to normalize the levels of radioactivity. Coordination between services allewed ensure proper and effective treatment for the patient.