Effectiveness and safety of a simple catheter securement device aimed at preventing catheter-associated urinary tract infection in intensive care unit patients: A randomized controlled trial.

BACKGROUND: Clinical practice guidelines for the prevention of catheter associated urinary tract infection (CAUTI) recommend urinary catheter securement in critical patients although there is scant research on its effectiveness. AIM: To analyse whether securement of an indwelling urinary catheter (IUC) reduces the risk of CAUTI and meatal pressure injury among intensive care unit (ICU) patients and assess medical adhesive-related skin injury (MARSI) associated with the securement device. STUDY DESIGN: Open randomized controlled trial involving patients admitted to two ICUs in Spain. In the intervention group (n = 169 patients), the IUC was secured to the thigh using an in-house device piloted as part of this trial. Controls (n = 181) received standard care, including non-securement of the IUC. Barrier film spray was applied to the securement site with the aim of preventing MARSI. The definitions of the main outcomes were: CAUTI was diagnosed according to the criteria of the European Centre for Disease Prevention and Control, meatal pressure injury was categorized into four grades and MARSI was classified as either erythema or skin tears. Bivariate analysis and multivariate logistic regression were performed. Log-rank and Cox regressions were used to compare risk over time to CAUTI and meatal pressure injury in the two groups. RESULTS: Data from 350 patients were analysed, 169 (48.29%) from IG and 181 (51.71%) from CG. In the multiple logistic regression analysis, IUC securement was an independent protective factor against both CAUTI (RR = 0.2, 95% CI [0.05, 0.67]) and meatal pressure injury (RR = 0.31, 95% CI [0.15, 0.58]). The incidence of MARSI was 7.1%. CONCLUSION: Effective IUC securement significantly reduces the risk of CAUTI and meatal pressure injury among ICU patients. The in-house device piloted in the present trial is simple for nurses to use, and the incidence of MARSI was low. These results underline the benefits of IUC securement. RELEVANCE TO CLINICAL PRACTICE: Indwelling urinary catheter (IUC) securement reduces the risk of urinary tract infection. IUC securement helps prevent meatal pressure injury. IUC securement with in-house devices is safe and effective.

How virtual and mechanical coupling impact bimanual tracking.

Bilateral training systems look to promote the paretic hand's use in individuals with hemiplegia. Although this is normally achieved using mechanical coupling (i.e., a physical connection between the hands), a virtual reality system relying on virtual coupling (i.e., through a shared virtual object) would be simpler to use and prevent slacking. However, it is not clear whether different coupling modes differently impact task performance and effort distribution between the hands. We explored how 18 healthy right-handed participants changed their motor behaviors in response to the uninstructed addition of mechanical coupling, and virtual coupling using a shared cursor mapped to the average hands' position. In a second experiment, we then studied the impact of connection stiffness on performance, perception, and effort imbalance. The results indicated that both coupling types can induce the hands to actively contribute to the task. However, the task asymmetry introduced by using a cursor mapped to either the left or right hand only modulated the hands' contribution when not mechanically coupled. The tracking performance was similar for all coupling types, independent of the connection stiffness, although the mechanical coupling was preferred and induced the hands to move with greater correlation. These findings suggest that virtual coupling can induce the hands to actively contribute to a task in healthy participants without hindering their performance. Further investigation on the coupling types' impact on the performance and hands' effort distribution in patients with hemiplegia could allow for the design of simpler training systems that promote the affected hand's use.NEW & NOTEWORTHY We showed that the uninstructed addition of a virtual and/or a mechanical coupling can induce both hands to actively contribute in a continuous redundant bimanual tracking task without impacting performance. In addition, we showed that the task asymmetry can only alter the effort distribution when the hands are not connected, independent of the connection stiffness. Our findings suggest that virtual coupling could be used in the development of simpler VR-based training devices.

Magnetic resonance detection of advanced atrial cardiomyopathy increases the risk for atypical atrial flutter occurrence following atrial fibrillation ablation.

AIMS: Recurrence of arrhythmia after catheter ablation of atrial fibrillation (AF) in the form of atypical atrial flutter (AFL) is common among a significant number of patients and often requires redo ablation with limited success rates. Identifying patients at high risk of AFL after AF ablation could aid in patient selection and personalized ablation approach. The study aims to assess the relationship between pre-existing atrial cardiomyopathy and the occurrence of AFL following AF ablation. METHODS AND RESULTS: We analysed a cohort of 1007 consecutive AF patients who underwent catheter ablation and were included in a prospective registry. Patients who did not have baseline cardiac magnetic resonance imaging and late gadolinium enhancement (LGE-CMR) or did not experience any recurrences were excluded. A total of 166 patients were included gathering 56 patients who underwent re-ablation due to AFL recurrences and 110 patients who underwent re-ablation due to AF recurrences (P = 0.11). A multiparametric assessment of atrial cardiomyopathy was based on basal LGE-CMR, including left atrial (LA) volume, LA sphericity, and global and segmental LA fibrosis using semiautomated post-processing software. Out of the initial cohort of 1007 patients, AFL and AF occurred in 56 and 110 patients, respectively. An age higher than 65 [odds ratio (OR) = 5.6, 95% confidence interval (CI): 2.2-14.4], the number of previous ablations (OR = 3.0, 95% CI: 1.2-7.8), and the management of ablation lines in the index procedure (OR = 2.5, 95% CI: 1.0-6.3) were independently associated with AFL occurrence. Furthermore, several characteristics assessed by LGE-CMR were identified as independent predictors of AFL recurrence after the index ablation for AF, such as enhanced LA sphericity (OR = 1.3, 95% CI: 1.1-1.6), LA global fibrosis (OR = 1.03, 95% CI: 1.01-1.07), and increased fibrosis in the lateral wall (OR = 1.03, 95% CI: 1.01-1.04). CONCLUSION: Advanced atrial cardiomyopathy assessed by LGE-CMR, such as increased LA sphericity, global LA fibrosis, and fibrosis in the lateral wall, is independently associated with arrhythmia recurrence in the form of AFL following AF ablation.

Mechano-responsiveness of fibrillar adhesions on stiffness-gradient gels.

Fibrillar adhesions are important structural and adhesive components in fibroblasts, and are required for fibronectin fibrillogenesis. While nascent and focal adhesions are known to respond to mechanical cues, the mechanoresponsive nature of fibrillar adhesions remains unclear. Here, we used ratiometric analysis of paired adhesion components to determine an appropriate fibrillar adhesion marker. We found that active α5ß1-integrin exhibits the most definitive fibrillar adhesion localization compared to other proteins, such as tensin-1, reported to be in fibrillar adhesions. To elucidate the mechanoresponsiveness of fibrillar adhesions, we designed a cost-effective and reproducible technique to fabricate physiologically relevant stiffness gradients on thin polyacrylamide (PA) hydrogels, embedded with fluorescently labelled beads. We generated a correlation curve between bead density and hydrogel stiffness, thus enabling a readout of stiffness without the need for specialized knowhow, such as atomic force microscopy (AFM). We find that stiffness promotes growth of fibrillar adhesions in a tensin-1-dependent manner. Thus, the formation of these extracellular matrix-depositing structures is coupled to the mechanical parameters of the cell environment and may enable cells to fine-tune their matrix environment in response to changing physical conditions.

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study.

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group. Patients in the LCPT group exhibited higher relative bioavailability (Cmin /total daily dose [TDD]) vs. PR-Tac (61% increase; P < .001) with similar Cmin and 30% lower TDD levels (P < .0001). The incidence of treatment failure was 3.9% in the LCPT group and 9.0% in the PR-Tac group (P = .117). Study discontinuation rates were 6.2% in the LCPT group and 12.4% in the PR-Tac group (P = .113). Adverse events, renal function and other complications were comparable between groups. The median accumulated dose of tacrolimus in the LCPT group from day 14 to month 6 was 889 mg. Compared to PR-Tac, LCPT showed higher relative bioavailability, similar effectiveness at preventing allograft rejection, comparable effect on renal function, safety, adherence, treatment failure and premature discontinuation rates.

Development and validation of a new model for predicting hypocalcaemia after total thyroidectomy: the NuGra model.

BACKGROUND: Hypocalcaemia is the most frequent complication after total thyroidectomy. Finding a method for its early detection has become a priority. A single-center prospective cohort study was conducted to identify risk factors for postoperative hypocalcaemia, develop an early detection model, and test its validity in a different group of patients. METHODS: The sample was composed of patients who underwent a total thyroidectomy between May 2012 and September 2015. Demographic, clinical, laboratory, and surgical data were collected. The incidence of hypocalcaemia and permanent hypoparathyroidism was calculated. Bivariate and multivariate analysis identified several independent predictors of hypocalcaemia, which were used to design a predictive model. The validity of the model was subsequently tested in a different cohort. Area under the ROC curve (AUROC) was calculated to determine its predictive power. RESULTS: The study and validation groups included 352 and 118 patients, respectively. Seventy-three patients developed laboratory-confirmed hypocalcaemia (20.7%), and symptomatic in 43 (12.2%). Multivariate analysis confirmed as independent predictors of hypocalcaemia the higher number of parathyroid glands identified [OR 1.41(0.98, 2.02); p = 0.063] and pre-to-postoperative gradient of parathormone decline [OR 1.06(1.04, 1.08); p < 0.001]. Based on these variables, the NuGra (Number of parathyroid glands identified-Gradient of decline) model was developed for predicting laboratory-confirmed hypocalcaemia. Its predictive power was high (AUROC 0.902, CI 0.857-0.947) for the study and the validation group (AUROC 0.956, CI 0.919-0.993). CONCLUSIONS: A higher number of parathyroid glands identified and a higher gradient of parathormone decline are risk factors for post-thyroidectomy hypocalcaemia. The NuGra model is useful for early prediction of individual risk for hypocalcaemia.

Infectious stress triggers a POLG-related mitochondrial disease.

A 3-year-old girl presented with severe epilepsy in the context of Borrelia infection. After ceftriaxone/lidocaine administration, she showed secondarily generalized focal crises that led to neurological and motor sequelae. Genetic studies identified in the patient two heterozygous POLG mutations (c.2591A>G; p.Asn864Ser and c.3649G>C; p.Ala1217Pro). Through analysis of POLG activity in cultured fibroblasts, we confirmed that the mutations altered the mtDNA turnover. Moreover, patient fibroblasts were more sensitive than controls in the presence of a mitochondrial replication-affecting drug, the antiretroviral azidothymidine. To test if ceftriaxone treatment could worsen the deleterious effect of the patient mutations, toxicity assays were performed. Cell toxicity, without direct effect on mitochondrial respiratory function, was detected at different antibiotic concentrations. The clinical outcome, together with the different in vitro sensitivity to ceftriaxone among patient and control cells, suggested that the mitochondrial disease symptoms were hastened by the infection and were possibly worsened by the pharmacological treatment. This study underscores the benefit of early genetic diagnosis of the patients with mitochondrial diseases, since they may be a target group of patients especially vulnerable to environmental factors.

Genetic and phenotypic associations between root architecture, arbuscular mycorrhizal fungi colonisation and low phosphate tolerance in strawberry (Fragaria × ananassa).

BACKGROUND: Phosphate is an essential plant macronutrient required to achieve maximum crop yield. Roots are able to uptake soil phosphate from the immediate root area, thus creating a nutrient depletion zone. Many plants are able to exploit phosphate from beyond this root nutrient depletion zone through symbiotic association with Arbuscular Mycorrhizal Fungi (AMF). Here we characterise the relationship between root architecture, AMF association and low phosphate tolerance in strawberries. The contrasting root architecture in the parental strawberry cultivars 'Redgauntlet' and 'Hapil' was studied through a mapping population of 168 progeny. Low phosphate tolerance and AMF association was quantified for each genotype to allow assessment of the phenotypic and genotypic relationships between traits. RESULTS: A "phosphate scavenging" root phenotype where individuals exhibit a high proportion of surface lateral roots was associated with a reduction in root system size across genotypes. A genetic correlation between "root system size" traits was observed with a network of pleiotropic QTL found to represent five "root system size" traits. By contrast, average root diameter and the distribution of roots appeared to be under two discrete methods of genetic control. A total of 18 QTL were associated with plant traits, 4 of which were associated with solidity that explained 46% of the observed variation. Investigations into the relationship between AMF association and root architecture found that a higher root density was associated with greater AMF colonisation across genotypes. However, no phenotypic correlation or genotypic association was found between low phosphate tolerance and the propensity for AMF association, nor root architectural traits when plants are grown under optimal nutrient conditions. CONCLUSIONS: Understanding the genetic relationships underpinning phosphate capture can inform the breeding of strawberry varieties with better nutrient use efficiency. Solid root systems were associated with greater AMF colonisation. However, low P-tolerance was not phenotypically or genotypically associated with root architecture traits in strawberry plants. Furthermore, a trade-off was observed between root system size and root architecture type, highlighting the energetic costs associated with a "phosphate scavenging" root architecture.

Oxidative Phosphorylation Dysfunction Modifies the Cell Secretome.

Mitochondrial oxidative phosphorylation disorders are extremely heterogeneous conditions. Their clinical and genetic variability makes the identification of reliable and specific biomarkers very challenging. Until now, only a few studies have focused on the effect of a defective oxidative phosphorylation functioning on the cell's secretome, although it could be a promising approach for the identification and pre-selection of potential circulating biomarkers for mitochondrial diseases. Here, we review the insights obtained from secretome studies with regard to oxidative phosphorylation dysfunction, and the biomarkers that appear, so far, to be promising to identify mitochondrial diseases. We propose two new biomarkers to be taken into account in future diagnostic trials.

[Descriptive analysis of medication errors notified by Primary Health Care: Learning from errors]. / Análisis descriptivo de los errores de medicación notificados en atención primaria: aprendiendo de nuestros errores.

INTRODUCTION AND OBJECTIVES: Aim of this study is to determine the setting, causes, and the harm of medication errors (ME) which are notified by Primary Health Care. MATERIAL AND METHODS: Setting: Primary Care Regional Health Service of Madrid. 2016. DESIGN: Descriptive and cross-sectional study. PARTICIPANTS: All ME (1,839) which were notified by Primary Care Centres by notification system of safety incidents between January 1st 2016 and November 17th 2016. MAIN MEASUREMENTS: Setting, real harm, potential harm, and cause of error. These items were classified by one researcher. Concordance was checked with another researcher. RESULTS: Just under half (47%) (95% CI: 44.8%-49.3%) of ME occurred in Primary Care Centre, 26.5% (95% CI: 24.5%-28.6%) of ME were patient medication errors, and 27.5% (95% CI: 24.1%-30.8%) of ME were potential severe harm errors. Prescribing errors were the cause of most ME in Primary Care Centre [27.4% (95% CI: 24.4%-30.4%)]. Communication between patients and doctors were the cause of most patient medication errors [66% (95% CI: 61.8%-70.2%)]. Patient mistakes and forgetfulness were also causes of patient medication errors. CONCLUSIONS: Half of all mediation errors hppened at Primary Care Center while one quarter of them were patient medication errors. One quarter of all ME were potential severe harm errors. The main causes were prescribing errors, failure of communication between patients and doctors, and patient mistakes and forgetfulness. Prescribing aid systems, communication improvements and patients aids should be implemented.

Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.

AIM: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations. METHOD: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts. RESULTS: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Brain magnetic resonance showed symmetric and bilateral cytotoxic lesions in the putamen and proliferation of the lenticular-striate arteries, latter spreading to the caudate and progressing to cavitation and volume loss. We identified a frameshift novel change (c.554_558delTTCTT; p.Tyr187AsnfsTer65) and a pathogenic missense change (c.371T>C; p.Ile124Thr) in the NDUFAF6 gene, which segregated with an autosomal recessive inheritance within the family. Patient mutations were associated with the absence of the NDUFAF6 protein and reduced activity and assembly of mature complex I in fibroblasts. By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6. A literature review of 14 NDUFAF6 patients showed a consistent phenotype of an early childhood insidious onset neurological regression with prominent dystonia associated with basal ganglia degeneration and long survival. INTERPRETATION: NDUFAF6-related Leigh syndrome is a relevant cause of childhood onset dystonia and isolated bilateral striatal necrosis. By genetic complementation, we could demonstrate the pathogenicity of novel genetic variants in NDUFAF6.

Accreditation of endocrine surgery units.

BACKGROUND/PURPOSE: A key measure to maintain and improve the quality of healthcare is the formal accreditation of provider units. The European Society of Endocrine Surgeons (ESES) therefore proposes a system of accreditation for endocrine surgical centers in Europe to supplement existing measures that promote high standards in the practice in endocrine surgery. METHODS: A working group analyzed the current healthcare situation in the field of endocrine surgery in Europe. Two surveys were distributed to ESES members to acquire information about the structure, staffing, caseload, specifications, and technology available to endocrine surgery units. Further data were sought on tracer diagnoses for quality standards, training provision, and research activity. Existing accreditation models related to endocrine surgery were included in the analysis. RESULTS: The analysis of existing accreditation models, available evidence, and survey results suggests that a majority of ESES members aspire to a two-level model (termed competence and reference centers), sub-divided into those providing neck endocrine surgery and those providing endocrine surgery. Criteria for minimum caseload, number and certification of staff, unit structure, on-site collaborating disciplines, research activities, and training capacity for competence center accreditation are proposed. Lastly, quality indicators for distinct tracer diagnoses are defined. CONCLUSIONS: Differing healthcare structures, existing accreditation models, training models, and varied case volumes across Europe are barriers to the conception and implementation of a pan-European accreditation model. However, there is consensus on accepted standards required for accrediting an ESES competence center. These will serve as a basis for first-stage accreditation of endocrine surgery units.

Development of a novel physico-chemically and microbiologically stable oral solution of flecainide for pediatrics.

There is as yet no commercialized preparation for oral administration of flecainide acetate (FA) to children. In such cases, manipulation of commercial tablets is the usual practice in pharmacy services of hospitals and compounding pharmacies, to provide a suitable dosage form for this vulnerable pediatric population group. In this study, we have formulated FA as an oral solution, as an alternative to the suspension elaborated from commercial tablets. Due to this sensitivity of young patients, we have used the pure active pharmaceutical ingredient (API) and the lowest permitted levels of pediatric excipients. Despite being a highly soluble API, only one of the formulations appears as a transparent solution due to complete FA solubilization. The proposed formulation is physico-chemically and microbiologically stable and the mass and dose uniformity is appropriate for 30 days' storage at 25 °C.

De- and recellularization of the pig uterus: a bioengineering pilot study.

Absolute uterine factor infertility, or the absence of a functional uterus, has a prevalence of 3%-5% in the general population. Despite the great strides being made in reproductive medicine, patients diagnosed with absolute uterine factor infertility remain untreatable. The only available solution has been gestational surrogacy, but recently the Brannström group presented a viable alternative by reporting the first successful live birth after uterus transplantation. Similar to other transplantations, this approach has inherent limitations such as the paucity of donor organs and the need for long-term immunosuppression. Whole organ de- and recellularization, a novel tissue engineering approach within the field of regenerative medicine, could eventually provide another solution. Several groups have described animal models in which they have performed decellularization of whole uteri, while maintaining the extracellular matrix to enable recellularization attempts. Our work offers a new perspective; in decellularizing the porcine uterus, this constitutes the first pilot study using large whole reproductive organs. We demonstrated the preservation of a reusable/functional extracellular matrix while maintaining its vascular network. Furthermore, we report the first use of human side population stem cells in the successful recellularization of small acellular disk scaffolds procured from the decellularized organs. To conclude, this research opens new avenues in whole uterus bioengineering, opening the way towards the transplantation of functional bioengineered uteri into humans.

Safety of Adrenaline Use in Anaphylaxis: A Multicentre Register.

BACKGROUND: The use of intramuscular adrenaline to treat anaphylaxis is suboptimal, despite being the first-line treatment recommended by national and international anaphylaxis guidelines. Fear of potentially severe side effects may be one of the underlying factors. The aim of this study was to assess the incidence and severity of adverse side effects after the use of adrenaline in anaphylaxis, as well as potential risk factors. METHODS: Observational study based on a multicenter online registry of cases of adrenaline administration for suspected anaphylaxis. RESULTS: 277 registered valid cases were included: 138 (51.49%) female, median age 29 years (12-47), and 6 children under 2 years with a median age of 9 months (1-21). Side effects occurred in 58 cases (21.64%), with tremors, palpitations, and anxiety being the most frequent. There was a significant association of developing side effects with older age, higher dose of adrenaline, or use of the intravenous route. Potentially severe adverse effects (high blood pressure, chest discomfort, or ECG alterations) occurred only in 8 cases (2.99%); in these cases, no differences were found according to age or adrenaline dose, but again, intravenous administration was associated with more severe adverse events. CONCLUSION: This study shows that side effects affect less than 1 in 5 patients who receive adrenaline for an anaphylactic reaction, and are usually mild and transient. Therefore, in an emergency situation such as anaphylaxis, restricting adrenaline administration due to potential adverse effects would, in general, not be justified.

A new three-locus model for rootstock-induced dwarfing in apple revealed by genetic mapping of root bark percentage.

Rootstock-induced dwarfing of apple scions revolutionized global apple production during the twentieth century, leading to the development of modern intensive orchards. A high root bark percentage (the percentage of the whole root area constituted by root cortex) has previously been associated with rootstock-induced dwarfing in apple. In this study, the root bark percentage was measured in a full-sib family of ungrafted apple rootstocks and found to be under the control of three loci. Two quantitative trait loci (QTLs) for root bark percentage were found to co-localize to the same genomic regions on chromosome 5 and chromosome 11 previously identified as controlling dwarfing, Dw1 and Dw2, respectively. A third QTL was identified on chromosome 13 in a region that has not been previously associated with dwarfing. The development of closely linked sequence-tagged site markers improved the resolution of allelic classes, thereby allowing the detection of dominance and epistatic interactions between loci, with high root bark percentage only occurring in specific allelic combinations. In addition, we report a significant negative correlation between root bark percentage and stem diameter (an indicator of tree vigour), measured on a clonally propagated grafted subset of the mapping population. The demonstrated link between root bark percentage and rootstock-induced dwarfing of the scion leads us to propose a three-locus model that is able to explain levels of dwarfing from the dwarf 'M.27' to the semi-invigorating rootstock 'M.116'. Moreover, we suggest that the QTL on chromosome 13 (Rb3) might be analogous to a third dwarfing QTL, Dw3, which has not previously been identified.

DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.

BACKGROUND: DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer. METHODS: Baseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment. RESULTS: The DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type. CONCLUSIONS: These data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.

ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis.

BACKGROUND: The phenotype of renal involvement in anti-neutrophil cytoplasmic antibodies (ANCA) vasculitis has a major influence on survival, and histological subgrouping of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate this histological subgrouping and to investigate the additional value of ANCA serotype in the prediction of renal outcome. METHODS: Data were retrospectively collected from the time of diagnosis by systematic review of medical records from 136 patients with renal biopsies recruited to cohorts from the UK and Spain, over 15 years. The end point, renal survival, was the composite of end-stage renal disease (ESRD) or death from any cause. The occurrence of ESRD, Stage 4 Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease, was assessed separately, in order to establish a severity index risk of chronic kidney disease. RESULTS: Renal survival at 5 years was 96% in the focal, 86% in the crescentic, 81% in the mixed and 61% in the sclerotic subgroups (P = 0.03). Myeloperoxidase (MPO)-ANCA was associated with more severe disease when compared with PR3-ANCA, as demonstrated by a lower frequency of focal and higher frequency of sclerotic subgroups, by more advanced interstitial fibrotic change and by lower glomerular filtration rate at diagnosis and worse renal function at 1 and 2 years. CONCLUSIONS: We have confirmed the predictive value for renal survival of the ANCA vasculitis histology classification in a multi-centre study. We found a worse renal outcome in patients with tubulointerstitial fibrosis and atrophy. MPO-ANCA positive patients had a worse renal prognosis due to more severe glomerular injury. These results contribute to patient stratification in renal vasculitis for therapeutic, epidemiological and basic research.