48,723 research outputs found

    Effectiveness of amniotic membrane allograft dressing in diabetic foot neuropathic ulcers

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    RESUMEN: El presente protocolo de investigación pretende determinar aspectos concretos de las úlceras de pie diabético. Objetivos: El objetivo principal es evaluar la efectividad, en términos de cicatrización en 12 semanas y calidad de vida, del apósito de aloinjerto de membrana amniótica deshidratado (AMAD) en el tratamiento de la úlcera neuropática del pie diabético junto con descargas específicas con fieltro. Metodología: Se realizará un estudio experimental unicéntrico tipo ensayo clínico aleatorizado. Se comparará el novedoso tratamiento con un apósito AMAD frente a la terapia estándar que frecuentemente se usa de forma habitual en la clínica diaria de las consultad de enfermería. Se realizará de forma longitudinal y prospectiva. Se trabajará con dos grupos, un grupo control y un grupo experimental. Un total de al menos 30 úlceras no isquémicas de pie diabético. El protocolo se realizará sobre la población con úlceras de pie diabético no isquémica del departamento de salud 20 en Elche (Alicante). Bajo el amparo de la Universidad Miguel Hernández y el Hospital General Universitario de Elche. Plan de trabajo: Curas programadas serán realizadas durante 12 semanas de duración del estudio. Una vez incluidos en el estudio, los sujetos serán atendidos por enfermeras/podólogas entrenadas en el tratamiento pautado según pertenencia a grupo experimental o grupo control. Todas las curas serán registradas según protocolo. Los pacientes se seguirán durante 12 semanas para observar la cicatrización completa de la úlcera. Un panel de expertos determinará si ha cicatrizado completamente o no la úlcera. El investigador principal gestionará y supervisará todo el proceso y solucionará los diferentes asuntos que puedan surgir. Se realizará estadística descriptiva para el perfil de la población. Estadística inferencial para extrapolarlo a la población general. Test de K-S, t de student, Kaplan-Meier y técnicas de análisis multivariante podrán ser usados. Se aseguran todos los aspectos éticos conforme a la Declaración de Helsinki, la aprobación por parte del comité de ética y las normas de buena práctica clínica. Se procederá a la difusión de los resultados en congresos y revistas especializadas de heridas y en las diferentes unidades de heridas crónicas de España.ABSTRACT: The current research protocol aims to determine specific aspects of diabetic foot ulcers. OBJECTIVE: The main purpose is to evaluate the effectiveness, in terms of healing at 12 weeks and quality of life, of the dehydrated amniotic membrane allograft dressing (DAMA) in the treatment of neuropathic ulcer of the diabetic foot together with specific felt discharges. DESIGN AND METHODS: A randomized experimental unicentre clinical trial has been designed. A novel treatment will be sized up with a DAMA dressing compared to the standard therapy that is frequently used in the daily clinic of nursing consultants. Longitunal and prospective study has been designed. We will work with two groups, a control group and an experimental group. A total of at least 30 non-ischemic ulcers of diabetic foot. The protocol will be carried out on the population with non-ischemic diabetic foot ulcers of the health department 20 in Elche (Alicante). Under the protection of the Miguel Hernández University and the Hospital General Univeristario of Elche. WORK SCHEDULE: Scheduled cures will be performed during 12 weeks of study duration. Once included in the study, the subjects will be attended by nurses / podiatrists trained in the treatment prescribed according to the experimental group or control group. All cures will be registered according to protocol. Patients will be followed for 12 weeks to observe complete healing of the ulcer. A panel of experts will determine the complete healing of the ulcer. The principal investigator will manage and supervise the entire process and will solve the different issues that may arise. Descriptive statistics for the profile of the population. Inferential statistics to extrapolate it to the general population. K-S test, student t-test, Kaplan-Meier and multivariate analysis techniques may be used All ethical aspects are ensured in accordance with the Declaration of Helsinki, approval by the ethics committee and standards of good clinical practice. The results will be disseminated in congresses and specialized journals of wounds and in the different units of chronic wounds in SpainMáster en Gestión Integral e Investigación de las Heridas Crónica

    Secondary endothelial keratoplasty: a narrative review of the outcomes of secondary corneal endothelial allografts

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    Background: We review the literature on the efficacy and safety outcomes of secondary Descemet stripping endothelial keratoplasty (DSEK) and Descemet membrane endothelial keratoplasty (DMEK). Methods: Literature search of English-written publications up to 27th September 2020 in PubMed database, using the terms "endothelial keratoplasty" in combination with keywords "secondary" or "repeat". In addition, we manually searched the references of the primary articles. Results: 27 studies (n = 651 eyes) were retained and reviewed, including 10 studies on repeat DSEK, 8 studies on repeat DMEK, 6 studies of DMEK following DSEK, and 3 studies of DSEK after failed DMEK. All studies reported significant improvement in visual acuity after secondary EK. Twelve studies compared visual outcomes between primary and secondary EK, reporting conflicting findings. Sixteen studies reported endothelial cell loss rates (%ECL) after secondary EK, and only one study reported significantly increased %ECL compared with primary EK. Allograft rejection episodes occurred in 1.8% of eyes (range 0-50%). Six studies compared complication rates between primary and secondary EK eyes, and only one study found a higher median number of complications. However, two studies reported higher regraft failure rates compared with primary EK eyes. Conclusions: Secondary EK is surgically feasible and renders significant visual improvement after failed primary EK, although it is not clear whether visual outcomes and allograft survival are comparable with primary EK, raising the question of whether secondary EK eyes are "low-risk" as primary EK eyes. Further larger, prospective studies are encouraged to obtain additional quality data on secondary corneal endothelial allotransplantation.info:eu-repo/semantics/acceptedVersio

    PREDICTORS OF EARLY AND DELAYED GRAFT FUNCTION IN LIVE AND CADAVERIC RENAL TRANSPLANTATION

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    Background: Kidney transplantation gives the best quality of life to chronic kidney disease patients and also increases longevity. Aim: Analysis of factors responsible for the early and delayed graft functioning in live and cadaver renal transplants Methods: It was a retrospective observational study. Donor and recipient age, sex, BMI, comorbid illness, and functioning status of the donor kidney, duration and severity of chronic kidney disease and associated bladder disorders were collected. Operative factors like perfusion time, cold ischemia time, blood pressure fall, need for blood transfusion, vasopressor support was recorded. Patients were divided into two groups based on early versus delayed graft function. Results: 27 cases of Live donor renal transplant and 23 cadaver transplants were included. The average age in live donor and cadaveric transplants was 43.5 ±7.6 years and 38.3 ±10.5 years, respectively. 24 Live Transplant Recipients had Early Graft function (89%). Seven Cadaveric Transplant Recipients had Early Graft function (31%) and 16 of them had Delayed Graft Function (69%). HLA Mismatch, Perioperative Hypotension and BMI of recipient had statistically significant relationship to Early Graft Function with p values of 0.02, 0.004 and 0.007, respectively. With p-value of 0.021 and of 0.046, respectively, perioperative hypotension and cold ischemic time in Cadaveric renal transplantation had statistically significant relationship to Early Graft Function. Conclusion: Live donor transplants have better early graft function. HLA Mismatch, Perioperative Hypotension, BMI of recipient and cold ischemic time in Cadaveric renal transplantation are the predictors of early graft function. Keywords Cadaveric,, ,،,؛Kidney transplantation,, ,،,

    Urinary excretion of N-Acetyl Glucosaminidase (NAG) as a marker of tubular injury in cyclosporin A associated nephrotoxicity in rat and human

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    The possible role of NAG in the diagnosis of early reversible renal tubular damage caused by cyclosporin A (CyA) was examined. A trial was also done to elucidate any possible cmrelation in chronic CyA nephrotoxicity. We first tested the effects of different doses of Cy A (10,20,40, and 80 mg/kg) on urinary NAG level, serum creatinine (Cr), sodium (Na), potassium (K), creatinine clearance (CC), FENa, FEK, and histopathology of the rat kidney. Secondly, we determined blood CyA trough level in rat and human renal allograft recipient and was correlated to NAG. We found that oral 10 and 20 mg/kg/day Cy A produced no tubular toxicity nor drop in CC while 40 mg/kg doses resulted in a significant increase in Cr. with tubular vacuolation of low score in 33% of rats. On the other hand, higher doses of 80 mg/kg/day of Cy A produced tubular vacuolation of higher score in 83% of rats. A positive correlation was found between plasma K and Cy A doses. NAG was found to be elevated significantly before the appearance of definite pathogenic changes starting from 20 mg/kg/day. A strong positive correlation was observed between NAG and different doses of Cy A. Cy A trough level was found neither to be correlated to tubular toxicity nor to urinary NAG level. NAG was found to be increased in vast majority of renal allograft recipient on Cy A therapy with no correlation to either Cy A trough level or CyA dose. We can conclude that urinary NAG is superior to conventional methods used to diagnose acute Cy A toxicity as they appear in the urine before any pathological changes become evident. It is of no diagnostic value in chronic Cy A nephrotoxicity

    Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

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    Abstract Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short- or long-term MPA treatment. Variants in genes related to T cell activation (CD28, CTL4, ICOS, PDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNF, IFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation

    Hyperparathyroidism Is an Independent Risk Factor for Allograft Dysfunction in Pediatric Kidney Transplantation

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    Allograft outcome; Hyperparathyroidism; Kidney transplantationResultado del aloinjerto; Hiperparatiroidismo; Trasplante de riñónResultat de l'aloempelt; Hiperparatiroïdisme; Trasplantament de ronyóIntroduction Little is known about the consequences of deranged chronic kidney disease–mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome. Methods This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m2 or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates. Results We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82–4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28–2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71–4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87–2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR. Conclusion Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children.This study was supported by a research grant from the European Society for Paediatric Nephrology to AP. The authors gratefully acknowledge the funding of the Cooperative European Paediatric Renal Transplant Initiative Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology, and the German Society for Paediatric Nephrology and by grants from the pharmaceutical companies Astellas and Novartis

    Determination of serum KIM-1 in patients with chronic kidney injury

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    Background: Chronic kidney disease (CKD) affects more than 800 million people worldwide and is one of the leading non-communicable causes of death. Despite being a latent issue, once renal damage has started, the disease can rapidly progress to an advanced stage. Aims and Objectives: Currently, the most commonly used markers for the diagnosis of renal disease are non-specific and insensitive. As a result, the goal of the current study is to investigate whether KIM-1 could be a precise and sensitive biomarker for identifying early kidney injury in CKD patients. Materials and Methods: This case–control study recruited 155 participants from the Index Medical College Hospital v Research Centre, Indore, Madhya Pradesh, based on inclusion and exclusion criteria. 150 non-CKD subjects matched for age and sex were also taken from the hospital. The levels of KIM-1 were compared between CKD and non-CKD participants. Serum creatinine, urea, and creatinine clearance were also measured. Results: The levels of KIM-1 were substantially higher in CKD patients than in non-CKD participants. In addition, a negative relationship between KIM-1 and creatinine clearance was observed with a P<0.05. Conclusion: KIM-1 is a precise and sensitive kidney injury biomarker that can identify early kidney injury in CKD and contribute to the progression of interstitial fibrosis in kidney disease

    Human granzyme B regulatory B cells prevent effector CD4+CD25- T cell proliferation through a mechanism dependent from lymphotoxin alpha

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    IntroductionHuman Granzyme B (GZMB) regulatory B cells (Bregs) have suppressive properties on CD4+ effector T cells by a mechanism partially dependent on GZMB. Moreover, these cells may be easily induced in vitro making them interesting for cell therapy.MethodsWe characterized this population of in vitro induced GZMB+Bregs using single cell transcriptomics. To investigate their regulatory properties, Bregs or total B cells were also co-cultured with T cells and scRNAseq was used to identify receptor ligand interactions and to reveal gene expression changes in the T cells.ResultsWe find that Bregs exhibit a unique set of 149 genes differentially expressed and which are implicated in proliferation, apoptosis, metabolism, and altered antigen presentation capacity consistent with their differentiated B cells profile. Notably, Bregs induced a strong inhibition of T cell genes associated to proliferation, activation, inflammation and apoptosis compared to total B cells. We identified and validated 5 receptor/ligand interactions between Bregs and T cells. Functional analysis using specific inhibitors was used to test their suppressive properties and we identified Lymphotoxin alpha (LTA) as a new and potent Breg ligand implicated in Breg suppressive properties.DiscussionWe report for the first time for a role of LTA in GZMB+Bregs as an enhancer of GZMB expression, and involved in the suppressive properties of GZMB+Bregs in human. The exact mechanism of LTA/GZMB function in this specific subset of Bregs remains to be determined

    Bilateral lung transplantation for pediatric pulmonary arterial hypertension: perioperative management and one-year follow-up

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    BackgroundBilateral lung transplantation (LuTx) remains the only established treatment for children with end-stage pulmonary arterial hypertension (PAH). Although PAH is the second most common indication for LuTx, little is known about optimal perioperative management and midterm clinical outcomes.MethodsProspective observational study on consecutive children with PAH who underwent LuTx with scheduled postoperative VA-ECMO support at Hannover Medical School from December 2013 to June 2020.ResultsTwelve patients with PAH underwent LuTx (mean age 11.9 years; age range 1.9–17.8). Underlying diagnoses included idiopathic (n = 4) or heritable PAH (n = 4), PAH associated with congenital heart disease (n = 2), pulmonary veno-occlusive disease (n = 1), and pulmonary capillary hemangiomatosis (n = 1). The mean waiting time was 58.5 days (range 1–220d). Three patients were bridged to LuTx on VA-ECMO. Intraoperative VA-ECMO/cardiopulmonary bypass was applied and VA-ECMO was continued postoperatively in all patients (mean ECMO-duration 185 h; range 73–363 h; early extubation). The median postoperative ventilation time was 28 h (range 17–145 h). Echocardiographic conventional and strain analysis showed that 12 months after LuTx, all patients had normal biventricular systolic function. All PAH patients are alive 2 years after LuTx (median follow-up 53 months, range 26–104 months).ConclusionLuTx in children with end-stage PAH resulted in excellent midterm outcomes (100% survival 2 years post-LuTx). Postoperative VA-ECMO facilitates early extubation with rapid gain of allograft function and sustained biventricular reverse-remodeling and systolic function after RV pressure unloading and LV volume loading

    Improving Mechanical Properties of Tendon Allograft through Rehydration Strategies: An In Vitro Study

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    Allogenic tendons grafts sourced from intrasynovial tendons are often used for tendon reconstruction. Processing is achieved through repetitive freeze–thaw cycles followed by lyophilization. Soaking the lyophilized tendon in saline (0.9%) for 24 h is the standard practice for rehydration. However, data supporting saline rehydration over the use of other hydrating solutions are scant. The purpose of the current study was to compare the effects of different rehydration solutions on biomechanical properties of lyophilized tendon allograft. A total of 36 canine flexor digitorum profundus tendons were collected, five freeze–thaw cycles followed by lyophilization were performed for processing, and then divided into three groups rehydrated with either saline solution (0.9%), phosphate-buffered saline (PBS), or minimum essential medium (MEM). Flexural stiffness, tensile stiffness, and gliding friction were evaluated before and after allograft processing. The flexural moduli in both fibrous and fibrocartilaginous regions of the tendons were measured. After lyophilization and reconstitution, the flexural moduli of both the fibrocartilaginous and non-fibrocartilaginous regions of the tendons increase significantly in the saline and MEM groups (p p p p < 0.05). There is no significant difference in either tensile moduli or gliding friction between tendons treated with different rehydration solutions. These results demonstrate that allograft reconstitution can be optimized through careful selection of hydrating solution and that PBS could be a better choice as the impact on flexural properties is lower
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