The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T ...cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials.
The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.
The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity ...than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results.
With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report.
A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results.
A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.
Diffraction Assisted Image Correlation (DAIC) measures three-dimensional (3D) full-field deformations using a single camera. This is accomplished by placing transmission diffraction gratings between ...the specimen and camera to produce multiple views of the specimen at different angles. The angle at which the image appears depends on the wavelength of light used for illumination, the pitch of the gratings being used, and the diffraction order of the image. In this work, DAIC is modified for use at a higher range of temperatures by using ultraviolet (UV) light for illumination and filtering out the visible spectrum light emitted by high temperature samples. These images were then used for 3D displacement and strain measurements using stereo digital image correlation (3D-DIC). This method was first tested at room temperature by comparing results to known deformation applied as rigid body motion. It was then demonstrated to be effective in making displacement and strain measurements up to a temperature of 900 °C.
Staphylococcus aureus bacteraemia (SAB) is a common, serious infection that is associated with high rates of morbidity and mortality. Evidence suggests that infectious disease consultation (IDC) ...improves clinical management in patients with SAB. We examined whether the introduction of a routine bedside IDC service for adults with SAB improved clinical management and outcomes compared to telephone consultation. We conducted an observational cohort study of 571 adults with SAB at a teaching hospital in the United Kingdom between July 2006 and December 2012. A telephone consultation was provided on the day of positive blood culture in all cases, but an additional bedside IDC was provided after November 2009 (routine IDC group). Compared to patients in the pre-IDC group, those in the routine IDC group were more likely to have a removable focus of infection identified, echocardiography performed and follow-up blood cultures performed. They also received longer courses of antimicrobial therapy, were more likely to receive combination antimicrobial therapy and were more likely to have SAB recorded in the hospital discharge summary. There was a trend towards lower mortality at 30 days in the routine IDC group compared to the pre-IDC group (12% vs. 22%, p 0.07). Our findings suggest that routine bedside IDC should become the standard of care for adults with SAB.
Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to ...evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy.
Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined.
Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P =.005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age </= 3 months at diagnosis was significant for EFS (P =. 043), it was less significant for survival (P =.077). The only other significant factor predictive for improved survival was favorable Shimada histopathologic classification. Sites of metastatic involvement (liver, skin, or bone marrow) and surgical resection of the primary tumor were not significant for survival.
This study confirms the favorable biologic features and excellent survival of infants with stage IV-S neuroblastoma with minimal therapy. Infants younger than 2 months old at diagnosis with rapidly progressive abdominal disease may benefit from earlier and more intensive treatment.
Body mass index (BMI)–based body fat equations from Womersley (BMIWOMERSLEY), Jackson (BMIJACKSON), Deurenberg (BMIDEURENBERG), and Gallagher (BMIGALLAGHER) are practical in clinical and field ...settings. However, research has shown these prediction equations produce large error, which may be due to the inability of BMI to account for differences in fat mass and fat-free mass. Thus, accounting for variations in muscular strength via relative handgrip (RHG) strength could help enhance the accuracy of a BMI-based body fat equation.
PURPOSEThe purpose of the current study was twofold1) to develop a new BMI-based body fat equation that includes the measurement of RHG (BMINICKERSON) and 2) to cross-validate BMINICKERSON, BMIWOMERSLEY, BMIJACKSON, BMIDEURENBERG, and BMIGALLAGHER against a four-compartment criterion.
METHODSThe development and cross-validation samples consisted of 230 and 110 participants, respectively. Criterion body fat percent was determined with a four-compartment model. RHG was calculated by summing the max of each handgrip strength measurement and dividing by body mass. BMI (kg·m), RHG (kg·kg), age (yr), ethnicity (Hispanic or non-Hispanic White), and sex (male or female) were entered into a stepwise regression to calculate BMINICKERSON.
RESULTSBMINICKERSON was calculated as followsbody fat percent = 21.504 – (12.484 × RHG) – (7.998 × sex) + (0.722 × BMI). In the cross-validation sample, BMINICKERSON produced lower constant error (CE) and total error (TE) values (CE = –0.11%, TE = 4.28%) than all other BMI-based body fat equations (CE = 0.89%–1.90%, TE = 5.71%–6.87%). Furthermore, the 95% limits of agreement were lower for BMINICKERSON ± 8.47% than previous BMI-based body fat equations (95% limits of agreement = ±11.14% to 13.33%).
CONCLUSIONCurrent study results confirm that previous BMI-based body fat equations produce large error in Hispanics and non-Hispanic Whites but can be improved by accounting for RHG. Allied health professionals are encouraged to use BMINICKERSON in clinical and field settings for adiposity assessments.
ATLAS is the largest particle detector under construction at CERN Geneva. Frequency scanning interferometry (FSI), also known as absolute distance interferometry, will be used to monitor shape ...changes of the SCT (semiconductor tracker), a particle tracker in the inaccessible, high radiation environment at the centre of ATLAS. Geodetic grids with several hundred fibre-coupled interferometers (30 mm to 1.5 m long) will be measured simultaneously. These lengths will be measured by tuning two lasers and comparing the resulting phase shifts in grid line interferometers (GLIs) with phase shifts in a reference interferometer. The novel inexpensive GLI design uses diverging beams to reduce sensitivity to misalignment, albeit with weaker signals. One micrometre precision length measurements of grid lines will allow 10 m.m precision tracker shape corrections to be fed into ATLAS particle tracking analysis. The technique was demonstrated by measuring a 400 mm interferometer to better than 400 nm and a 1195 mm interferometer to better than 250 nm. Precise measurements were possible, even with poor quality signals, using numerical analysis of thousands of intensity samples. Errors due to drifts in interferometer length were substantially reduced using two lasers tuned in opposite directions and the precision was further improved by linking measurements made at widely separated laser frequencies.
The process of humoral rejection is multifaceted and has different manifestations in the various types of organ transplants. Because this process is emerging as a leading cause of graft loss, a ...conference was held in April 2003 to comprehensively address issues regarding humoral rejection.
Though humoral rejection may result from different factors, discussion focused on a paradigm caused by antibodies, typically against donor HLA antigens, leading to the term ‘antibody‐mediated rejection’ (AMR). Conference deliberations were separated into four workgroups: The Profiling Workgroup evaluated strengths and limitations of different methods for detecting HLA reactive antibody, and created risk assessment guidelines for AMR; The Diagnosis Workgroup reviewed clinical, pathologic, and serologic criteria for assessing AMR in renal, heart and lung transplant recipients; The Treatment Workgroup discussed advantages, limitations and possible mechanisms of action for desensitization protocols that may reverse AMR; and The Basic Science Workgroup presented animal and human immunologic models for humoral rejection and proposed potential targets for future intervention. This work represents a comprehensive review with contributions from experts in the fields of Transplantation Surgery, Medicine, Pathology, Histocompatibility, Immunology, and clinical trial design. Immunologic barriers once considered insurmountable are now consistently overcome to enable more patients to undergo organ transplantation.
Background
Increased acute postoperative pain intensity has been associated with the development of persistent postsurgical pain (PPP) in mechanistic and clinical investigations, but it remains ...unclear which aspects of acute pain explain this linkage.
Methods
We analysed clinical postoperative pain intensity assessments using symbolic aggregate approximations (SAX), a graphical way of representing changes between pain states from one patient evaluation to the next, to visualize and understand how pain intensity changes across sequential assessments are associated with the intensity of postoperative pain at 1 (M1) and 6 (M6) months after surgery. SAX‐based acute pain transition patterns were compared using cosine similarity, which indicates the degree to which patterns mirror each other.
Results
This single‐centre prospective cohort study included 364 subjects. Patterns of acute postoperative pain sequential transitions differed between the ‘None’ and ‘Severe’ outcomes at M1 (cosine similarity 0.44) and M6 (cosine similarity 0.49). Stratifications of M6 outcomes by preoperative pain intensity, sex, age group, surgery type and catastrophising showed significant heterogeneity of pain transition patterns within and across strata. Severe‐to‐severe acute pain transitions were common, but not exclusive, in patients with moderate or severe pain intensity at M6.
Conclusions
Clinically, these results suggest that individual pain‐state transitions, even within patient or procedural strata associated with PPP, may not alone offer good predictive information regarding PPP. Longitudinal observation in the immediate postoperative period and consideration of patient‐ and surgery‐specific factors may help indicate which patients are at increased risk of PPP.
Significance
Symbolic aggregate approximations of clinically obtained, acute postoperative pain intraday time series identify different motifs in patients suffering moderate to severe pain 6 months after surgery.
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