Steroid avoidance or withdrawal for pancreas and pancreas with kidney transplant recipients

Background Pancreas or kidney‐pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after transplantation is associated with complications. Steroids have adverse effects on cardiovascular risk factors such as hypertension, hyperglycaemia or hyperlipidaemia, increase risk of infection, obesity, cataracts, myopathy, bone metabolism alterations, dermatologic problems and cushingoid appearance. Whether avoiding steroids changes outcomes is unclear. Objectives We aimed to assess the safety and efficacy of steroid early withdrawal (treatment for less than 14 days after transplantation), late withdrawal (after 14 days after transplantation) or steroid avoidance in patients receiving a pancreas (including a vascularized organ) alone (PTA), simultaneous with a kidney (SPK) or after kidney transplantation (PAK). Search methods We searched the Cochrane Renal Group's Specialised Register (to 18 June 2014) through contact with the Trials' Search Co‐ordinator. We handsearched: reference lists of nephrology textbooks, relevant studies, recent publications and clinical practice guidelines; abstracts from international transplantation society scientific meetings; and sent emails and letters seeking information about unpublished or incomplete studies to known investigators. Selection criteria We included randomised controlled trials (RCTs) or cohort studies of steroid avoidance (including early withdrawal) versus steroid maintenance or versus late withdrawal in pancreas or pancreas with kidney transplant recipients. We defined steroid avoidance as complete avoidance of steroid immunosuppression, early steroid withdrawal as steroid treatment for less than 14 days after transplantation and late withdrawal as steroid withdrawal after 14 days after transplantation. Data collection and analysis Two authors independently assessed the retrieved titles and abstracts, and where necessary the full text reports to determine which studies satisfied the inclusion criteria. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Cohort studies were not meta‐analysed, but their findings summarised descriptively. Main results Three RCTs enrolling 144 participants met our inclusion criteria. Two compared steroid avoidance versus late steroid withdrawal and one compared late steroid withdrawal versus steroid maintenance. All studies included SPK and only one also included PTA. All studies had an overall moderate risk of bias and presented only short‐term results (six to 12 months). Two studies (89 participants) compared steroid avoidance or early steroid withdrawal versus late steroid withdrawal. There was no clear evidence of an impact on mortality (2 studies, 89 participants: RR 1.64, 95% CI 0.21 to 12.75), risk of kidney loss censored for death (2 studies, 89 participants: RR 0.35, 95% CI 0.04 to 3.09), risk of pancreas loss censored for death (2 studies, 89 participants: RR 1.05, 95% CI 0.36 to 3.04), or acute kidney rejection (1 study, 49 participants: RR 2.08, 95% CI 0.20 to 21.50), however results were uncertain and consistent with no difference or important benefit or harm of steroid avoidance/early steroid withdrawal. The study that compared late steroid withdrawal versus steroid maintenance observed no deaths, no graft loss or acute kidney rejection at six months in either group and reported uncertain effects on acute pancreas rejection (RR 0.88, 95% CI 0.06 to 13.35). Of the possible adverse effects only infection was reported by one study. There were significantly more UTIs reported in the late withdrawal group compared to the steroid avoidance group (1 study, 25 patients: RR 0.41, 95% CI 0.26 to 0.66). We also identified 13 cohort studies and one RCT which randomised tacrolimus versus cyclosporin. These studies in general showed that steroid‐sparing and withdrawal strategies had benefits in lowering HbAc1 and risk of infections (BK virus and CMV disease) and improved blood pressure control without increasing the risk of rejection. However, two studies found an increased incidence of acute pancreas rejection (HR 2.8, 95% CI 0.89 to 8.81, P = 0.066 in one study and 43.3% in the steroid withdrawal group versus 9.3% in the steroid maintenance, P < 0.05 at three years in the other) and one study found an increased incidence of acute kidney rejection (18.7% in the steroid withdrawal group versus 2.8% in the steroid maintenance, P < 0.05) at three years. Authors' conclusions There is currently insufficient evidence for the benefits and harms of steroid withdrawal in pancreas transplantation in the three RCTs (144 patients) identified. The results showed uncertain results for short‐term risk of rejection, mortality, or graft survival in steroid‐sparing strategies in a very small number of patients over a short period of follow‐up. Overall the data was sparse, so no firm conclusions are possible. Moreover, the 13 observational studies findings generally concur with the evidence found in the RCTs

Exploring Renal Changes after Bariatric Surgery in Patients with Severe Obesity

Obesity-related hyperfiltration leads to an increased glomerular filtration rate (GFR) and hyperalbuminuria. These changes are reversible after bariatric surgery (BS). We aimed to explore obesity-related renal changes post-BS and to seek potential mechanisms. Sixty-two individuals with severe obesity were prospectively examined before and 3, 6 and 12 months post-BS. Anthropometric and laboratory data, 24 h-blood pressure, renin-angiotensin-aldosterone system (RAS) components, adipokines and inflammatory markers were determined. Both estimated GFR (eGFR) and albuminuria decreased from the baseline at all follow-up times (p -for-trend <0.001 for both). There was a median (IQR) of 30.5% (26.2-34.4) reduction in body weight. Plasma glucose, glycosylated hemoglobin, fasting insulin and HOMA-index decreased at 3, 6 and 12 months of follow-up (p -for-trend <0.001 for all). The plasma aldosterone concentration (median (IQR)) also decreased at 12 months (from 87.8 ng/dL (56.8; 154) to 65.4 (56.8; 84.6), p = 0.003). Both leptin and hs-CRP decreased (p < 0.001) and adiponectine levels increased at 12 months post-BS (p = 0.017). Linear mixed-models showed that body weight (coef. 0.62, 95% CI: 0.32 to 0.93, p < 0.001) and plasma aldosterone (coef. −0.07, 95% CI: −0.13 to −0.02, p = 0.005) were the independent variables for changes in eGFR. Conversely, glycosylated hemoglobin was the only independent variable for changes in albuminuria (coef. 0.24, 95% CI: 0.06 to 0.42, p = 0.009). In conclusion, body weight and aldosterone are the main factors that mediate eGFR changes in obesity and BS, while albuminuria is associated with glucose homeostasis

Assessment of glial activation response in the progress of natural scrapie after chronic dexamethasone treatment

Neuroinflammation has been correlated with the progress of neurodegeneration in many neuropathologies. Although glial cells have traditionally been considered to be protective, the concept of them as neurotoxic cells has recently emerged. Thus, a major unsolved question is the exact role of astroglia and microglia in neurodegenerative disorders. On the other hand, it is well known that glucocorticoids are the first choice to regulate inflammation and, consequently, neuroglial inflammatory activity. The objective of this study was to determine how chronic dexamethasone treatment influences the host immune response and to characterize the beneficial or detrimental role of glial cells. To date, this has not been examined using a natural neurodegenerative model of scrapie. With this aim, immunohistochemical expression of glial markers, prion protein accumulation, histopathological lesions and clinical evolution were compared with those in a control group. The results demonstrated how the complex interaction between glial populations failed to compensate for brain damage in natural conditions, emphasizing the need for using natural models. Additionally, the data showed that modulation of neuroinflammation by anti-inflammatory drugs might become a research focus as a potential therapeutic target for prion diseases, similar to that considered previously for other neurodegenerative disorders classified as prion-like diseases

Outcomes of Frail Patients While Waiting for Kidney Transplantation : Differences between Physical Frailty Phenotype and FRAIL Scale

Frailty is associated with poorer outcomes among patients waiting for kidney transplantation (KT). Several different tools to measure frailty have been used; however, their predictive value is unknown. This is a prospective longitudinal study of 449 KT candidates evaluated for frailty by the Physical Frailty Phenotype (PFP) and the FRAIL scale. During the study period, 296 patients received a KT, while 153 remained listed. Patients who did not get receive a transplant were more frequently frail according to PFP (16.3 vs. 7.4%, p = 0.013). Robust patients had fewer hospital admissions during the 1st year after listing (20.8% if PFP = 0 vs. 43.4% if ≥1, and 27.1% if FRAIL = 0 vs. 48.9% if ≥1) and fewer cardiovascular events (than FRAIL ≥ 1) or major infectious events (than PFP ≥ 1). According to PFP, scoring 1 point had an impact on patient survival and chance of transplantation in the univariate analysis. The multivariable analysis corroborated the result, as candidates with PFP ≥ 3 had less likelihood of transplantation (HR 0.45 [0.26-0.77]). The FRAIL scale did not associate with any of these outcomes. In KT candidates, pre-frailty and frailty according to both the PFP and the FRAIL scale were associated with poorer results while listed. The PFP detected that frail patients were less likely to receive a KT, while the FRAIL scale did not

Increased mortality after kidney transplantation in mildly frail recipients

Physical Frailty Phenotype (PFP) is the most used frailty instrument among kidney transplant recipients, classifying patients as pre-frail if they have 1-2 criteria and as frail if they have ≥3. However, different definitions of robustness have been used among renal patients, including only those who have 0 criteria, or those with 0-1 criteria. Our aim was to determine the impact of one PFP criterion on transplant outcomes. We undertook a retrospective study of 296 kidney transplant recipients who had been evaluated for frailty by PFP at the time of evaluating for transplantation. Only 30.4% of patients had 0 criteria, and an additional 42.9% showed one PFP criterion. As PFP score increased, a higher percentage of women and cerebrovascular disease were found. Recipients with 0-1 criteria had lower 1-year mortality after transplant than those with ≥2 (1.8% vs 10.1%), but this difference was already present when we only considered those who scored 0 (mortality 1.1%) and 1 (mortality 2.4%) separately. The multivariable analysis confirmed that one PFP criterion was associated to a higher risk of patient death after kidney transplantation [hazard ratio 3.52 (95% confidence interval 1.03-15.9)]. Listed kidney transplant candidates frequently show only one PFP frailty criterion. This has an independent impact on patient survival after transplantation

Validation of a survival benefit estimator tool in a cohort of European kidney transplant recipients

Producción CientíficaPre-transplant prognostic scores help to optimize donor/recipient allocation and to minimize organ discard rates. Since most of these scores come from the US, direct application in non-US populations is not advisable. The Survival Benefit Estimator (SBE), built upon the Estimated Post-Transplant Survival (EPTS) and the Kidney Donor Profile Index (KDPI), has not been externally validated. We aimed to examine SBE in a cohort of Spanish kidney transplant recipients. We designed a retrospective cohortbased study of deceased-donor kidney transplants carried out in two different Spanish hospitals. Unadjusted and adjusted Cox models were applied for patient survival. Predictive models were compared using Harrell’s C statistics. SBE, EPTS and KDPI were independently associated with patient survival (p ≤ 0.01 in all models). Model discrimination measured with Harrell’s C statistics ranged from 0.57 (KDPI) to 0.69 (SBE) and 0.71 (EPTS). After adjustment, SBE presented similar calibration and discrimination power to that of EPTS. SBE tended to underestimate actual survival, mainly among high EPTS recipients/high KDPI donors. SBE performed acceptably well at discriminating posttransplant survival in a cohort of Spanish deceased-donor kidney transplant recipients, although its use as the main allocation guide, especially for high KDPI donors or high EPTS recipients requires further testing.Rio Hortega contract (ISCIII-11453)Fondo de Investigaciones Sanitarias - Fondo Europeo de Desarrollo Regional (project PI16/0617)Redinren (project RD16/0009/001

Zoonotic "Enterocytozoon bieneusi" genotypes in free-ranging and farmed wild ungulates in Spain

Microsporidia comprises a diverse group of obligate, intracellular, and spore-forming parasites that infect a wide range of animals. Among them, Enterocytozoon bieneusi is the most frequently reported species in humans and other mammals and birds. Data on the epidemiology of E. bieneusi in wildlife are limited. Hence, E. bieneusi was investigated in eight wild ungulate species present in Spain (genera Ammotragus, Capra, Capreolus, Cervus, Dama, Ovis, Rupicapra, and Sus) by molecular methods. Faecal samples were collected from free-ranging (n = 1058) and farmed (n = 324) wild ungulates from five Spanish bioregions. The parasite was detected only in red deer (10.4%, 68/653) and wild boar (0.8%, 3/359). Enterocytozoon bieneusi infections were more common in farmed (19.4%, 63/324) than in wild (1.5%, 5/329) red deer. A total of 11 genotypes were identified in red deer, eight known (BEB6, BEB17, EbCar2, HLJD-V, MWC_d1, S5, Type IV, and Wildboar3) and three novel (DeerSpEb1, DeerSpEb2, and DeerSpEb3) genotypes. Mixed genotype infections were detected in 15.9% of farmed red deer. Two genotypes were identified in wild boar, a known (Wildboar3) and a novel (WildboarSpEb1) genotypes. All genotypes identified belonged to E. bieneusi zoonotic Groups 1 and 2. This study provides the most comprehensive epidemiological study of E. bieneusi in Spanish ungulates to date, representing the first evidence of the parasite in wild red deer populations worldwide. Spanish wild boars and red deer are reservoir of zoonotic genotypes of E. bieneusi and might play an underestimated role in the transmission of this microsporidian species to humans and other animal

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

The sustainable materials roadmap

Over the past 150 years, our ability to produce and transform engineered materials has been responsible for our current high standards of living, especially in developed economies. However, we must carefully think of the effects our addiction to creating and using materials at this fast rate will have on the future generations. The way we currently make and use materials detrimentally affects the planet Earth, creating many severe environmental problems. It affects the next generations by putting in danger the future of the economy, energy, and climate. We are at the point where something must drastically change, and it must change now. We must create more sustainable materials alternatives using natural raw materials and inspiration from nature while making sure not to deplete important resources, i.e. in competition with the food chain supply. We must use less materials, eliminate the use of toxic materials and create a circular materials economy where reuse and recycle are priorities. We must develop sustainable methods for materials recycling and encourage design for disassembly. We must look across the whole materials life cycle from raw resources till end of life and apply thorough life cycle assessments (LCAs) based on reliable and relevant data to quantify sustainability. We need to seriously start thinking of where our future materials will come from and how could we track them, given that we are confronted with resource scarcity and geographical constrains. This is particularly important for the development of new and sustainable energy technologies, key to our transition to net zero. Currently 'critical materials' are central components of sustainable energy systems because they are the best performing. A few examples include the permanent magnets based on rare earth metals (Dy, Nd, Pr) used in wind turbines, Li and Co in Li-ion batteries, Pt and Ir in fuel cells and electrolysers, Si in solar cells just to mention a few. These materials are classified as 'critical' by the European Union and Department of Energy. Except in sustainable energy, materials are also key components in packaging, construction, and textile industry along with many other industrial sectors. This roadmap authored by prominent researchers working across disciplines in the very important field of sustainable materials is intended to highlight the outstanding issues that must be addressed and provide an insight into the pathways towards solving them adopted by the sustainable materials community. In compiling this roadmap, we hope to aid the development of the wider sustainable materials research community, providing a guide for academia, industry, government, and funding agencies in this critically important and rapidly developing research space which is key to future sustainability.journal articl

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] 15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activityS