Association of Implantation Biopsy Findings in Living Donor Kidneys With Donor and Recipient Outcomes.

RATIONALE & OBJECTIVE: Some living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Single center, living donor kidney transplants from January 2010 to July 2022. EXPOSURE: Chronic histological changes, glomerular disease in donor kidney implantation biopsies. OUTCOME: For donors, single-kidney estimated glomerular filtration rate (eGFR) increase, percent total eGFR loss, ≥40% eGFR decline from predonation baseline, and eGFR<60mL/min/1.73m2 at 6 months after donation; for recipients, death-censored allograft survival. ANALYTICAL APPROACH: Biopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes. RESULTS: Among 1,104 living donor kidneys, 155 (14%) had advanced chronic changes on implantation biopsy, and 12 (1%) had findings suggestive of possible donor glomerular disease. Adjusted logistic regression showed that age (odds ratio [OR], 2.44 per 10 years [95% CI, 1.98-3.01), Hispanic ethnicity (OR, 1.87 [95% CI, 1.15-3.05), and hypertension (OR, 1.92 [95% CI, 1.01-3.64), were associated with higher odds of chronic changes on implantation biopsy. Adjusted linear regression showed no association of advanced chronic changes with single-kidney eGFR increase or relative risk of eGFR<60mL/min/1.73m2. There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities. LIMITATIONS: Retrospective, absence of measured GFR. CONCLUSIONS: Approximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival. PLAIN-LANGUAGE SUMMARY: Kidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients.

Enlightening brain energy metabolism.

Brain tissue metabolism is distributed across several cell types and subcellular compartments, which activate at different times and with different temporal patterns. The introduction of genetically-encoded fluorescent indicators that are imaged using time-lapse microscopy has opened the possibility of studying brain metabolism at cellular and sub-cellular levels. There are indicators for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, and energy nucleotides, which inform about relative levels, concentrations and fluxes. This review offers a brief survey of the metabolic indicators that have been validated in brain cells, with some illustrative examples from the literature. Whereas only a small fraction of the metabolome is currently accessible to fluorescent probes, there are grounds to be optimistic about coming developments and the application of these tools to the study of brain disease.

Visualizing physiological parameters in cells and tissues using genetically encoded indicators for metabolites.

The study of metabolism is undergoing a renaissance. Since the year 2002, over 50 genetically-encoded fluorescent indicators (GEFIs) have been introduced, capable of monitoring metabolites with high spatial/temporal resolution using fluorescence microscopy. Indicators are fusion proteins that change their fluorescence upon binding a specific metabolite. There are indicators for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, and energy nucleotides. They permit monitoring relative levels, concentrations, and fluxes in living systems. At a minimum they report relative levels and, in some cases, absolute concentrations may be obtained by performing ad hoc calibration protocols. Proper data collection, processing, and interpretation are critical to take full advantage of these new tools. This review offers a survey of the metabolic indicators that have been validated in mammalian systems. Minimally invasive, these indicators have been instrumental for the purposes of confirmation, rebuttal and discovery. We envision that this powerful technology will foster metabolic physiology.

Conducta fumadora en estudiantes de kinesiología y su asociación con actitudes y conocimientos sobre tabaquismo: estudio de corte transversal / Smoking behavior in Chilean physical therapist students and their association with attitudes and knowledge on cigarette smoking: a cross sectional study

INTRODUCCIÓN: El tabaquismo continúa siendo un problema sanitario en población universitaria y profesionales de la salud. Los kinesiólogos participan en la implementación de programas orientados a la prevención y cese del tabaquismo en la comunidad. El objetivo de este estudio fue explorar la prevalencia de tabaquismo y actitudes sobre consumo de tabaco en estudiantes de kinesiología. MÉTODOS: Estudio de corte transversal realizado en estudiantes de Kinesiología de Concepción (Chile), durante los años 2017 y 2018. Se determinó la conducta y actitudes sobre tabaquismo. Mediante regresión logística se determinó la asociación entre la conducta fumadora y las actitudes sobre tabaquismo. Se consideró un valor de p < 0,05 como estadísticamente significativo. RESULTADOS: Se contestaron 554 cuestionarios. El 57,8% de los estudiantes encuestados declaró no haber fumado nunca, 13 % no haber fumado los últimos 6 meses y 29,4% declaró ser fumador actual. Por su parte, el 99,5% expresó algún grado de acuerdo con que fumar es perjudicial para la salud, lo cual se relacionó con la conducta fumadora (p < 0,0002). En relación a actitudes sobre tabaquismo, comparado a los no fumadores, los fumadores actuales presentan mayor probabilidad de mostrar desacuerdo o indiferencia respecto a actitudes positivas sobre tabaquismo. Principalmente en aquellas acciones que restringen su consumo, venta y divulgación (OR ponderado = 2,43; 95%IC 2,02 - 2,92). CONCLUSIONES: La prevalencia de tabaquismo en estudiantes de Kinesiología de Concepción es del 29,2%. Los estudiantes fumadores expresan una menor aprobación relacionada a intervenciones, actitudes y consecuencias del tabaquismo para la salud comparada con los no fumadores.

INTRODUCTION: Notwithstanding control policies, smoking continues to be a health problem in university students and health professionals, who are responsible for implementing programs oriented to prevention and cessation of smoking in the community. The objective of this study was to explore the prevalence of smoking and attitudes about smoking in physical therapy students. METHODS: Cross-sectional study carried out in students of physical therapy from three universities of Concepción city (Chile), during the years 2017 and 2018. Behavior and attitudes about smoking were evaluated. Association between smoking behavior and attitudes about smoking was determined by logistic regression. A p value < 0.05 was considered statistically significant. RESULTS: 554 questionnaires were answered. 57.8% of respondents had never smoked, 13.0% had not smoked in the last 6 months and 29.4% were current smokers. Moreover 99.5% of respondents stated some degree of agreement that smoking is harmful to health, which was related to smoking behavior (p < 0.0002). In relation to attitudes about smoking, compared to non-smokers, current smokers have a greater chance of showing disagreement or indifference regarding positive attitudes about smoking. Mainly in those actions that restrict tobacco consumption, sale and disclosure (weighted OR = 2.43, 95% CI 2.02 - 2.92). CONCLUSIONS: The prevalence of current smoking in physical therapy students from Concepcion city is 29.2%. Smoking students express lower approval related to interventions, attitudes and consequences of smoking for health compared with non-smokers.

The clinical significance of receiving a kidney allograft from deceased donor with chronic histologic changes.

Allograft survival of deceased donor kidneys with suboptimal histology (DRTx/suboptimal histology: >10% glomerulosclerosis, >10% tubulointerstitial scarring, or >mild vascular sclerosis) is inferior to both DRTx with optimal histology (DRTx/optimal histology) and living donor kidneys irrespective of histologic changes (LRTx). In this report, we explored the reasons behind this guarded outcome with a special focus on the role of alloimmunity. We initially assessed gene expression in 39 time-zero allograft biopsies using the Nanostring 770 genes PanCancer Immune Profiling Panel. Subsequently, we studied 696 consecutive adult kidney allograft recipients that were grouped according to allograft type and histology at time-zero biopsy [DRTx/suboptimal histology (n = 194), DRTx/optimal histology (n = 166), and LRTx (n = 336)]. Part-1: Several immune pathways were upregulated in time-zero biopsies from DRTx/suboptimal histology (n = 11) compared to LRTx (n = 17) but not to DRTx/optimal histology (n = 11). Part-2: Amongst the three groups of recipients, DRTx/suboptimal histology had the highest incidence of acute rejection episodes, most of which occurred during the first year after transplantation (early rejection). This increase was mainly attributed to T cell mediated rejection, while the incidence of antibody-mediated rejection was similar amongst the three groups. Importantly, early acute T cell mediated rejection was a strong independent predictor for allograft failure in DRTx/suboptimal histology (adjusted HR: 2.13, P = 0.005) but not in DRTx/optimal histology nor in LRTx. Our data highlight an increased baseline immunogenicity in DRTx/suboptimal histology compared to LRTx but not to DRTx/optimal histology. However, our results suggest that donor chronic histologic changes in DRTx may help transfer such increased baseline immunogenicity into clinically relevant acute rejection episodes that have detrimental effects on allograft survival. These findings may provide a rationale for enhanced immunosuppression in recipients of DRTx with baseline chronic histologic changes to minimize subsequent acute rejection and to prolong allograft survival.

Impact of Deceased Donor Kidney Procurement Biopsy Technique on Histologic Accuracy.

INTRODUCTION: The factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy. METHODS: We retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying "suboptimal" histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification. RESULTS: A total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge (r 2 = 0.11) and core (r 2 = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04-1.22). CONCLUSIONS: Biopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices.

COVID-19 in pancreas transplant recipients.

Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients.

Origen intraorbitario de las arterias etmoidales: estudio anatómico / Intraorbital origin of the ethmoidal arteries: anatomical study

RESUMEN Introducción: Ramas de la arteria oftálmica contribuyen a la irrigación de diversos territorios de la fosa nasal y de los senos paranasales. Objetivo: El objetivo de nuestro estudio es describir las arterias etmoidales desde su origen intraorbitario, y su relación con las estructuras musculares y nerviosas. Material y Método: Se realizó un estudio anatómico endoscópico en 20 fosas nasales y órbitas de diez cadáveres. Resultados: La disección del plano muscular permitió definir dos espacios de entrada a la órbita. Un primer espacio entre el músculo recto inferior y músculo recto medial (área 1) y otro entre el músculo recto medial y músculo oblicuo superior (área 2). En el área 1, la arteria oftálmica discurrió superior al nervio óptico en el 90%. La arteria etmoidal anterior se observó en todos los casos inferior al músculo oblicuo superior. En el área 2, la arteria etmoidal posterior, se localizó en todos los casos superior al músculo oblicuo superior. No se identificó la arteria etmoidal media en ningún caso. El origen de la arteria supraorbitaria se identificó entre las dos arterias etmoidales. Conclusión: La comprensión anatómica del origen intraorbitario de la arteria oftálmica permite el abordaje de determinada patología intraorbitaria compleja a través de la pared medial de la órbita.

ABSTRACT Introduction: Branches of the ophthalmic artery contribute to the irrigation of various territories of the nasal cavity and paranasal sinuses. Aim: The aim of our study is to describe the intraorbital course of the ethmoidal arteries and their relationship with the muscular and nervous structures. Material and method: We performed twenty nasal cavities and orbital dissections in ten adults cadaveric heads. Results: The dissection of the muscular orbital wall allowed defining two surgical orbital corridors, between the inferior rectus and the medial rectus muscles (area 1) and between the medial rectus and the superior oblique muscles (area 2). In area 1, the ophthalmic artery crosses over the optic nerve in 90% of the cases. The anterior ethmoidal artery was observed inferior to the superior oblique muscle. In area 2, the posterior ethmoidal artery was located superior to the superior oblique muscle in all cavities. No middle ethmoidal artery was identified. The origin of the supraorbital artery was found between the two ethmoidal arteries. Conclusions: The anatomical understanding of the intraorbital origin of the arteries of the ophthalmic artery allows perform two surgical approaches through the media orbital wall.

Procurement Biopsies in the Evaluation of Deceased Donor Kidneys.

BACKGROUND AND OBJECTIVES: Biopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys). RESULTS: For kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (κ=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (κ=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (κ=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (κ=0.13) and 80% (κ=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure. CONCLUSIONS: We found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.

Diarrea por Clostridium difficile en pacientes hospitalizados / Diarrhea due to Clostridium difficile in hospitalized patients

Resumen ANTECEDENTES: La infección por Clostridium difficile es la causa más importante de enfermedad gastrointestinal relacionada con el sistema hospitalario que conlleva alta morbilidad y mortalidad y costos estimados en 3.2 mil millones de dólares anualmente. OBJETIVO: Conocer el comportamiento de la diarrea intrahospitalaria por C. difficile, así como las características de la enfermedad y de los pacientes. MATERIAL Y MÉTODO: Estudio longitudinal, efectuado del 1 de julio de 2015 al 30 de abril de 2016, en el que se incluyeron los casos de diarrea intrahospitalaria atendidos en todos los servicios del Hospital Regional Lic. Adolfo López Mateos, Ciudad de México. Con el apoyo del Laboratorio de Vigilancia Epidemiológica del ISSSTE, ubicado en el Centro Médico Nacional 20 de Noviembre, a todos los casos se les realizó prueba de inmunoensayo para la identificación de toxinas A, B o ambas. RESULTADOS: Se identificaron 220 casos de diarrea intrahospitalaria en el periodo de estudio, de los que 106 (48.2%) resultaron positivos a la prueba de inmunoensayo para toxinas A, B (o ambas) de C. difficile y correspondieron a los servicios de Medicina Interna, Cirugía General y Unidad de Cuidados Intensivos. Se realizó seguimiento a 100 pacientes de los que 75 fueron dados de alta y 25 fallecieron (tasa de mortalidad de 25%). El servicio en el que se identificaron más casos fue Medicina Interna con 58 (54.7%), seguido de Cirugía General con 14 (13.2%) y de Ortopedia con 10 (10.6%). Los 106 pacientes incluidos que resultaron positivos habían recibido durante su estancia hospitalaria y antes de manifestar el cuadro diarreico al menos un antimicrobiano, 41.4% monoterapia y 58.6% dos o más antibióticos. El antibiótico más frecuente en los casos de monoterapia fue ceftriaxona (50%), seguido de meropenem (20.6%) y en los casos de combinaciones se observó una variedad de ellas. La mediana de días de estancia hospitalaria en los pacientes que fallecieron fue de 24 días (intervalo: 5-112) y en los que fueron dados de alta la mediana fue de 20 días (intervalo: 2-85). CONCLUSIONES: Este estudio aporta información muy similar a la reportada en las escasas publicaciones mexicanas referidas en este trabajo en cuanto a los factores de riesgo, variabilidad de las manifestaciones clínicas, oportunidad del tratamiento, evidencia, consecuencias de la administración indiscriminada de antibióticos con fines profilácticos, terapéuticos o ambos y necesidad del tratamiento multidisciplinario de los pacientes con enfermedad grave o severa. Destaca también la participación de los bloqueadores H2 como un importante factor de riesgo encontrado en más de 70% de los casos y la administración de mesalazina y probióticos como coadyuvantes en el tratamiento.

Abstract BACKGROUND: Infection due to Clostridium difficile is the most important cause of gastrointestinal disease related to the hospitality system leading to high morbidity and mortality and costs estimated in 3.2 billion dollars each year. OBJECTIVE: To know the behavior of intrahospitalary diarrhea due to C. difficile, as well as the characteristics of the disease and patients. MATERIAL AND METHOD: A longitudinal study done from July 1st 2015 to April 30 2016, in which cases of intrahospitalary diarrhea attended in all services of the Reginal Hospital Lic. Adolfo López Mateos, Mexico City, were included. With the support of the Laboratory of Epidemiological Surveillance of ISSSTE, at Centro Médico Nacional 20 de Noviembre, Mexico City, all cases were submitted to immunoassay test to the identification of toxins A, B or both. RESULTS: There were identified 220 cases of intrahospitalary diarrhea in the study period, from which 106 (48.2%) were positive to immunoassay test for toxins A, B (or both) of C. difficile and corresponded to services of Internal Medicine, General Surgery and Intensive Care Unit. One hundred patients were followed, from which 75 were discharged and 25 died (mortality rate of 25%). Service in which most cases were identified was Internal Medicine with 58 (54.7%), followed by General Surgery with 14 (13.2%) and Orthopedics with 10 (10.6%). The 106 patients included that resulted positive had received during their hospitalization and before presenting diarrhea at least one antimicrobial, 41.4% monotherapy and 58.6% two or more antimicrobials. The most frequently prescribed antibiotic in cases of monotherapy was ceftriaxone (50%), followed by meropenem (20.6%) and in all cases of combinations it was observed a variety of them. The mean days of hospitalization of patients who died was of 24 days (range: 5-112) and of discharged patients was of 20 days (range: 2-85). CONCLUSIONS: This study gives information very similar to that reported in the little Mexican publications referred in this paper about risk factors, variability of clinical manifestations, opportunity of treatment, evidence, consequences of the indiscriminate administration of antibiotics with prophylactic and/or therapeutic objectives and the need of multidisciplinary treatment of patients with severe disease. It is also highlighted the participation of H2 blockers as an important risk factor found in more than 70% of cases and the administration of mesalazine and probiotics as adjuvant in the treatment.

[Neuromyelitis optica spectrum disorders: profile of a cohort according to the 2015 diagnostic criteria]. / Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.

INTRODUCTION: The new 2015 criteria for neuromyelitis optica spectrum disorders (NMOSD) have been recently incorporated in the study of different international cohorts. AIM: To describe clinical-radiological characteristics and prognostic factors in patients with NMOSD according to the 2015 criteria. PATIENTS AND METHODS: Retrospective analysis of 36 patients diagnosed with NMOSD according to serologic AQP4 status (positive, negative, unknown and negative + unknown). Clinical and radiological characteristics were compared and possible disability prognostic factors were evaluated. RESULTS: AQP4 were positive in 7 patients, negative in 12 and unknown in 17. Age of presentation was 36.6 ± 16 years, with higher female proportion (4:1). Mean disease duration was 7.4 ± 7.6 years. Most frequent presenting symptoms were acute myelitis (61%), optic neuritis (33%) and area postrema syndrome (11%). Most frequent MRI lesion was longitudinally extensive transverse myelitis (75%). All patients received acute treatment during attacks, and preventive treatment was used in 81% (azathioprine and rituximab mostly prescribed). Median EDSS was 2.0 at the end of follow-up. No differences were observed in any of the variables comparing serologic status. Age of first attack was prognostic, with direct correlation with EDSS. First attack in < 30 years was protective, meanwhile > 50 years old patients had increased risk of disability. CONCLUSIONS: The 2015 criteria allow the description and classification of NMOSD patients within different cohorts. Age of first attack seems to be a prognostic factor for developing disability.

TITLE: Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.Introduccion. Los nuevos criterios diagnosticos de 2015 del espectro de neuromielitis optica (NMO) estan comenzando a utilizarse en diferentes poblaciones en el mundo. Objetivo. Describir las caracteristicas clinicorradiologicas y pronosticas de pacientes diagnosticados de NMO con los criterios de 2015. Pacientes y metodos. Analizamos retrospectivamente 36 pacientes diagnosticados de NMO con los actuales criterios. Se generaron cuatro grupos segun la serologia de antiacuaporina 4 (positivos, negativos, desconocidos y negativos mas desconocidos agrupados). Se compararon sus caracteristicas clinicorradiologicas y se evaluaron posibles variables pronosticas de discapacidad. Resultados. Encontramos siete pacientes seropositivos, 12 negativos y 17 desconocidos. La edad de inicio fue de 36 ± 16 años, con mayor proporcion de mujeres (4 a 1). La duracion de la enfermedad fue de 7,4 ± 7,6 años. Los sintomas iniciales mas frecuentes fueron mielitis (61%), neuritis optica (33%) y sindrome del area postrema (11%). La lesion mas frecuente en la resonancia magnetica fue la mielitis longitudinalmente extensa (75%). Todos los pacientes recibieron tratamiento agudo, y el preventivo se utilizo en el 81%; la azatioprina y el rituximab fueron los que mas se usaron. La mediana de la Expanded Disability Status Scale (EDSS) fue de 2 al final del seguimiento. No hubo diferencias significativas en las variables clinicorradiologicas entre los distintos grupos de pacientes. La edad de inicio fue pronostica y presenta correlacion directa con la EDSS. El inicio antes de los 30 años fue protector y, despues de los 50 años, un factor de riesgo para mayor discapacidad. Conclusiones. Los actuales criterios permiten describir diferentes cohortes. La edad de inicio parece ser un factor pronostico para desarrollar discapacidad.

Association between Reperfusion Renal Allograft Biopsy Findings and Transplant Outcomes.

Biopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0-3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation-related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.

Análisis cuantitativo y cualitativo de las ecografías del segundo y tercer trimestres en mujeres gestantes mexicanas / Quantitative and qualitative analysis of the ultrasound of the second and third trimester in Mexican pregnant women

Resumen OBJETIVO: cuantificar el número de ecografías durante la gestación y evaluar la calidad de los estudios del segundo y tercer trimestres en pacientes de bajo riesgo del área metropolitana de la Ciudad de México. MATERIALES Y MÉTODOS: estudio prospectivo, observacional y descriptivo de mujeres con control prenatal fuera de nuestra unidad que acudieron a la Clínica Perinatal de Embarazo de Alto riesgo, Hospital de la Mujer de la Ciudad de México, para la finalización del embarazo. Cuantificación de las ecografías tomadas durante la gestación, identificación del profesional encargado del estudio y evaluación de la calidad de los estudios del segundo y tercer trimestres mediante una lista de cotejo basada en guías internacionales; obtención del porcentaje de apego a las mismas. RESULTADOS: se estudiaron 199 pacientes a quienes se tomaron, en promedio, 3.7 ecografías; al 80% tres o más ultrasonidos. El análisis de las ecografías del segundo trimestre arrojó un promedio de 13.8 parámetros evaluados, con 43% de apego a las normas. En las ecografías del tercer trimestre, el promedio de parámetros evaluados fue de 10 con un porcentaje de apego de 66.7%. Los médicos ultrasonografistas fueron quienes realizaron el mayor número de estudios en ambos trimestres. CONCLUSIONES: la ecografía es un recurso accesible a la población del área metropolitana; sin embargo, debe insistirse en la calidad de los estudios.

Abstract OBJECTIVE: To quantify the number of ultrasound scans during pregnancy and evaluate the quality of ultrasound in the second and third trimester of gestation in the low risk obstetric population in the metropolitan area. MATERIAL AND METHODS: we conducted a prospective, observational and descriptive study in 199 women that arrived to the hospital for delivery without prenatal care in our unit, quantified the number of ultrasound scans performed during pregnancy, and evaluate the quality of the second and third trimester echographies with a check list based on international guidelines. The percentage of adherence was obtained and analyzed by the professional in health responsible of the study. RESULTS: The average scan per patient was 3.37, 80% had three or more. Analysis of ultrasound for the second trimester showed an average of 13.8 parameters evaluated with 43% of adherence to standards; in the ultrasounds of the third trimester, the evaluated parameters averaged 10 with a percentage of attachment of 66.7%. The largest number of studies was performed by sonographists. CONCLUSIONS: The ultrasound is a tool accessible to the population of the metropolitan area; however, it should be emphasized in the quality of studies.

Evidence of ß-Cell Dedifferentiation in Human Type 2 Diabetes.

CONTEXT: Diabetes is associated with a deficit of insulin-producing ß-cells. Animal studies show that ß-cells become dedifferentiated in diabetes, reverting to a progenitor-like stage, and partly converting to other endocrine cell types. OBJECTIVE: To determine whether similar processes occur in human type 2 diabetes, we surveyed pancreatic islets from 15 diabetic and 15 nondiabetic organ donors. DESIGN: We scored dedifferentiation using markers of endocrine lineage, ß-cell-specific transcription factors, and a newly identified endocrine progenitor cell marker, aldehyde dehydrogenase 1A3. RESULTS: By these criteria, dedifferentiated cells accounted for 31.9% of ß-cells in type 2 diabetics vs 8.7% in controls, and for 16.8% vs 6.5% of all endocrine cells (P < .001). The number of aldehyde dehydrogenase 1A3-positive/hormone-negative cells was 3-fold higher in diabetics compared with controls. Moreover, ß-cell-specific transcription factors were ectopically found in glucagon- and somatostatin-producing cells of diabetic subjects. CONCLUSIONS: The data support the view that pancreatic ß-cells become dedifferentiated and convert to α- and δ-"like" cells in human type 2 diabetes. The findings should prompt a reassessment of goals in the prevention and treatment of ß-cell dysfunction.

Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome.

Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-ß (TGF-ß)- and angiotensin II-dependent pathways, alterations in the vascular extracellular matrix (ECM) may also play a role in the onset and progression of the aortic disease. Lysyl oxidases (LOX) are extracellular enzymes, which initiates the formation of covalent cross-linking of collagens and elastin, thereby contributing to the maturation of the ECM. Here we have explored the role of LOX in the formation of aortic aneurysms in MFS. We show that aortic tissue from MFS patients and MFS mouse model (Fbn1(C1039G/+)) displayed enhanced expression of the members of the LOX family, LOX and LOX-like 1 (LOXL1), and this is associated with the formation of mature collagen fibers. Administration of a LOX inhibitor for 8weeks blocked collagen accumulation and aggravated elastic fiber impairment, and these effects correlated with the induction of a strong and rapidly progressing aortic dilatation, and with premature death in the more severe MFS mouse model, Fbn1(mgR/mgR), without any significant effect on wild type animals. This detrimental effect occurred preferentially in the ascending portion of the aorta, with little or no involvement of the aortic root, and was associated to an overactivation of both canonical and non-canonical TGF-ß signaling pathways. The blockade of angiotensin II type I receptor with losartan restored TGF-ß signaling activation, normalized elastic fiber impairment and prevented the aortic dilatation induced by LOX inhibition in Fbn1(C1039G/+) mice. Our data indicate that LOX enzymes and LOX-mediated collagen accumulation play a critical protective role in aneurysm formation in MFS.

Validity and reliability of the T-Scan(®) III for measuring force under laboratory conditions.

Although measuring bite force is an important indicator of the health of the masticatory system, few commercially available transducers have been validated for routine clinical use. T-Scan(®) III Occlusal Analysis System allows to record the bite force distribution, indicating its relative intensity and occlusal timing. Nevertheless, even fewer studies have evaluated the validity and reliability of the latest generation of the T-Scan(®) occlusal analysis system. To determine the validity and reliability of the T-Scan(®) III system when measuring total absolute bite force under laboratory conditions. Known forces were applied to 18 T-Scan(®) III sensors, which were classified into two groups differentiated by their production series. Both Lin's concordance correlation coefficient (CCC) and the intra-class correlation coefficient (ICC) were used to assess the system's reliability and validity. Considering all the sensors studied, a substantial level (Lin's CCC 0·969) and a very good level of reliability (CCI 0·994) were obtained. When evaluating the validity of the system, a poor (Lin's CCC 0·530) and moderate (ICC 0·693) agreement were also obtained. The main factor that negatively influenced the validity of the T-Scan(®) III under these study conditions was the significant difference in the behaviour of the two sensor groups. The T-Scan(®) III showed a high degree of reliability when used to perform consecutive measurements. However, the system showed an insufficient degree of validity for measuring absolute force when estimating total occlusal force under laboratory conditions.

FOXO1 inhibition yields functional insulin-producing cells in human gut organoid cultures.

Generation of surrogate sources of insulin-producing ß-cells remains a goal of diabetes therapy. While most efforts have been directed at differentiating embryonic or induced pluripotent stem (iPS) cells into ß-like-cells through endodermal progenitors, we have shown that gut endocrine progenitor cells of mice can be differentiated into glucose-responsive, insulin-producing cells by ablation of transcription factor Foxo1. Here we show that FOXO1 is present in human gut endocrine progenitor and serotonin-producing cells. Using gut organoids derived from human iPS cells, we show that FOXO1 inhibition using a dominant-negative mutant or lentivirus-encoded small hairpin RNA promotes generation of insulin-positive cells that express all markers of mature pancreatic ß-cells, release C-peptide in response to secretagogues and survive in vivo following transplantation into mice. The findings raise the possibility of using gut-targeted FOXO1 inhibition or gut organoids as a source of insulin-producing cells to treat human diabetes.

Kidneys at higher risk of discard: expanding the role of dual kidney transplantation.

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI)>85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80-90% and >90%). Kidneys with KDPI>90% were associated with increased odds of discard (OR=1.99, 95% CI 1.74-2.29) compared to ones with KDPI<80%. DKTs of KDPI>90% were associated with lower overall allograft failure (HR=0.74, 95% CI 0.62-0.89) and better patient survival (HR=0.79, 95% CI 0.64-0.98) compared to single ECD kidneys with KDPI>90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile.

Tratamiento mediante aloinjertos óseos estructurales en resecciones por tumores óseos de huesos largos. Revisión de 37 casos / Treatment using structural bone allografts in long bone tumour resections. A review of 37 cases

Los aloinjertos óseos estructurales han supuesto una alternativa al tratamiento de los tumores óseos de miembros, con posibilidad de cirugía de conservación del mismo. Presentamos un estudio retrospectivo observacional del manejo de los aloinjertos óseos estructurales en tumores óseos de huesos largos en nuestro hospital, durante los años 1993 a 2010, en el que obtenemos una muestra de 37 pacientes subsidiarios de esta técnica quirúrgica. Mediante la obtención de datos clínicos de la muestra aplicamos las escalas de funcionalidad de Mankin y EVACOM HUVA con resultados excelentes, muy buenos o buenos del 84%, y con los datos radiológicos aplicamos la escala de osteointegración ISOLS con un 95,6% de resultados excelentes a los 24 meses. Estos resultados nos muestran que los aloinjertos óseos estructurales constituyen una técnica válida y reproducible en pacientes con tumores óseos destructivos de huesos largos (AU)

Structural bone allografts have become an alternative in the treatment of limb bone tumours with a chance of limb-saving surgery. We present an observational retrospective study on the use of structural bone allografts in bone tumours of the long bones in our hospital between January 1993 and January 2010, with a sample of 37 patients subjected to this surgical technique. After obtaining clinical information from our sample we applied the Mankin and EVACOM HUVA functional scales with excellent, very good and good results in 84%, and with the radiological information we applied the ISOLS osseointegration scale, with 95.6% of excellent results after 24 months. These results demonstrate that structural bone allografts are a valid and reproducible technique in patients with destructive long bone tumours (AU)

Impact of small variations in the delivered dose of rabbit antithymocyte induction therapy in kidney transplantation with early corticosteroid withdrawal.

BACKGROUND: Optimal dosing of rabbit antithymocyte globulin (rATG) induction therapy in kidney transplantation is not well defined. The impact of dosing from variations in dose rounding or single dose limits has not been studied. METHODS: This retrospective study of 242 adult renal transplant recipients receiving rATG induction and steroid-sparing maintenance therapy evaluates the effect of small changes in rATG induction dosing. The local protocol calls for four doses of rATG 1.5 mg/kg, approximated to the nearest 25 mg and limited to a max of 150 mg. Patients were stratified by total rATG dose received 5 to 6 mg/kg (n=151) and 6 mg/kg (n=91) or more. Incidence of biopsy-proven acute rejection, patient and graft survival, and allograft function were examined. RESULTS: Baseline and transplantation characteristics were similar between groups except for differences in mean weight (SD) (81 [17.3] vs. 76.3 [15.6]) and cumulative rATG dose received (451.8 [96.2] vs. 481.1 [93]) for patients in the 5- to 6-mg/kg group and 6-mg/kg or more group, respectively. Patients who received more rATG showed a significantly lower incidence of biopsy-proven acute rejection at last follow-up 11% (32/151) vs. 21.2% (10/91) among those who received only 5 to 6 mg/kg (P<0.042). Renal function (mean serum creatinine level) was similar at both 90 days and time of last follow-up. Safety review of leukopenia or thrombocytopenia did not differ. CONCLUSION: Small changes in total rATG induction administered seem to significantly impact the incidence of rejection. Adequate rATG dosing is associated with improved rejection-free graft survival and should be achieved for all patients; doses should be rounded up when appropriate or additional doses should be administered if necessary.