Probable antibody-mediated rejection in kidney transplantation is a rare and challenging phenotype to define: Findings from a single-center study.

The Banff 2022 consensus introduced probable antibody-mediated rejection (AMR), characterized by mild AMR histologic features and human leukocyte antigen (HLA) donor-specific antibody (DSA) positivity. In a single-center observational cohort study of 1891 kidney transplant recipients transplanted between 2004 and 2021, 566 kidney biopsies were performed in 178 individual HLA-DSA-positive transplants. Evaluated at time of the first HLA-DSA-positive biopsy of each transplant (N = 178), 84 of the 178 (47.2%) of first biopsies were scored as no AMR, 22 of the 178 (12.4%) as probable AMR, and 72 of the 178 (40.4%) as AMR. The majority (77.3%) of probable AMR cases were first diagnosed in indication biopsies. Probable AMR was associated with lower estimated glomerular filtration rate (mL/min/1.73m2) than no AMR (20.2 [8.3-32.3] vs 40.1 [25.4-53.3]; P = .001). The one-year risk of (repeat) AMR was similar for probable AMR and AMR (subdistribution hazard ratio (sHR), 0.99; 0.42-2.31; P = .97) and higher than after no AMR (sHR, 3.05; 1.07-8.73; P = .04). Probable AMR had a higher five-year risk of transplant glomerulopathy vs no AMR (sHR, 4.29; 0.92-19.98; P = 06), similar to AMR (sHR, 1.74; 0.43-7.04; P = .44). No significant differences in five-year risk of graft failure emerged between probable AMR and AMR (sHR, 1.14; 0.36-3.58; P = .82) or no AMR (sHR, 2.46; 0.78-7.74; P = .12). Probable AMR is a rare phenotype, however, sharing significant similarities with AMR in this single-center study. Future studies are needed to validate reproducible diagnostic criteria and associated clinical outcomes to allow for defining best management of this potentially relevant phenotype.

Documentation and classification of hospital pharmacist interventions: A scoping review.

The practice of documenting pharmacist interventions (PIs) has been endorsed by many hospital pharmacists' societies and organizations worldwide. Current systems for recording PIs have been developed to generate data on better patient and healthcare outcomes, but harmonization and transferability are apparently minimal. The present work aims to provide a descriptive and comprehensive overview of the currently utilized PI documentation and classification tools contributing to increased evidence systematization. A systematic literature search was conducted in PubMed, Scopus, Web of Science and the Cumulative Index to Nursing and Allied Health Literature. Studies from 2008, after the release of the Basel Statements, were included if interventions were made by hospital or clinical pharmacists in a global hospital setting. Publications quality assessment was accomplished using the Mixed Methods Appraisal Tool. A total of 26 studies were included. Three studies did not refer to the documentation/classification method, 10 used an in-house developed documentation/classification method, seven used externally developed documentation/classification tools and six described method validation or translation. Evidence confirmed that most documentation/classification systems are designed in-house, but external development and validation of PI systems to be used in hospital practice is gradually increasing. Reports on validated PI documentation/classification tools that are being used in hospital clinical practice are limited, including in countries with advanced hospital pharmacy practice. Needs and gaps in practice were identified. Further research should be conducted to understand why using validated documentation/classification methods is not a disseminated practice, knowing patients' and organizational advantages.

The clinical utility and relevance in clinical practice of DSM-5 specifiers for major depressive disorder: A Delphi expert consensus study.

Major depressive disorder (MDD) is a heterogeneous syndrome, associated with different levels of severity and impairment on the personal functioning for each patient. Classification systems in psychiatry, including ICD-11 and DSM-5, are used by clinicians in order to simplify the complexity of clinical manifestations. In particular, the DSM-5 introduced specifiers, subtypes, severity ratings, and cross-cutting symptom assessments allowing clinicians to better describe the specific clinical features of each patient. However, the use of DSM-5 specifiers for major depressive disorder in ordinary clinical practice is quite heterogeneous. The present study, using a Delphi method, aims to evaluate the consensus of a representative group of expert psychiatrists on a series of statements regarding the clinical utility and relevance of DSM-5 specifiers for major depressive disorder in ordinary clinical practice. Experts reached an almost perfect agreement on statements related to the use and clinical utility of DSM-5 specifiers in ordinary clinical practice. In particular, a complete consensus was found regarding the clinical utility for ordinary clinical practice of using DSM-5 specifiers. The use of specifiers is considered a first step toward a "dimensional" approach to the diagnosis of mental disorders.

Activity, triage levels and impact of the pandemic on hospital emergency departments: A multicentre cross-sectional study.

AIM: Describe the activity of hospital emergency departments (EDs) and the sociodemographic profile of patients in the eight public hospitals in Spain, according to the different triage levels, and to analyse the impact of the SARS-CoV-2 pandemic on patient flow. DESIGN: An observational, descriptive, cross-sectional and retrospective study was carried out. METHODS: Three high-tech public hospitals and five low-tech hospitals consecutively included 2,332,654 adult patients seen in hospital EDs from January 2018 to December 2021. Hospitals belonging to the Catalan Institute of Health. The main variable was triage level, classified according to a standard for the Spanish structured triage system known as Sistema Español de Triaje. For each of the five triage levels, a negative binomial regression model adjusted for year and hospital was performed. The analysis was performed with the R 4.2.2 software. RESULTS: The mean age was 55.4 years. 51.4% were women. The distribution of patients according to the five triage levels was: level 1, 0.41% (n = 9565); level 2, 6.10% (n = 142,187); level 3, 40.2% (n = 938,203); level 4, 42.6% (n = 994,281); level 5, 10.6% (n = 248,418). The sociodemographic profile was similar in terms of gender and age: as the level of severity decreased, the number of women, mostly young, increased. In the period 2020-2021, the emergency rate increased for levels 1, 2 and 3, but levels 4 and 5 remained stable. CONCLUSION: More than half of the patients attended in high-technology hospital EDs were of low severity. The profile of these patients was that of a young, middle-aged population, mostly female. The SARS-CoV2 pandemic did not change this pattern, but an increase in the level of severity was observed. IMPACT: What problem did the study address? There is overcrowding in hospital EDs. What were the main findings? This study found that more than half of the patients attended in high-technology hospital EDs in Spain have low or very low levels of severity. Young, middle-aged women were more likely to visit EDs with low levels of severity. The SARS-CoV2 pandemic did not change this pattern, but an increase in severity was observed. Where and on whom will the research have an impact? The research will have an impact on the functioning of hospital EDs and their staff. PATIENT OR PUBLIC CONTRIBUTION: Not applicable.

The ballistic articular structure injury classification (BASIC) system: clarifying ballistic articular injuries.

PURPOSE: This study aims to (1) devise a classification system to categorize and manage ballistic fractures of the knee, hip, and shoulder; (2) assess the reliability of this classification compared to current classification schemas; and (3) determine the association of this classification with surgical management. METHODS: We performed a retrospective review of a prospectively collected trauma database at an urban level 1 trauma centre. The study included 147 patients with 169 articular fractures caused by ballistic trauma to the knee, hip, and shoulder. Injuries were selected based on radiographic criteria from plain radiographs and CT scans. The AO/OTA classification system's reliability was compared to that of the novel ballistic articular injury classification system (BASIC), developed using a nominal group approach. The BASIC system's ability to guide surgical decision-making, aiming to achieve stable fixation and minimize post-traumatic arthritis, was also evaluated. RESULTS: The BASIC system was created after analysing 73 knee, 62 hip, and 34 shoulder fractures. CT scans were used in 88% of cases, with 44% of patients receiving surgery. The BASIC classification comprises five subgroups, with a plus sign indicating the need for soft tissue intervention. Interrater reliability showed fair agreement for AO/OTA (k = 0.373) and moderate agreement for BASIC (k = 0.444). The BASIC system correlated strongly with surgical decisions, with an 83% concurrence in treatment choices based on chart reviews. CONCLUSIONS: Conventional classification systems provide limited guidance for ballistic articular injuries. The BASIC system offers a pragmatic and reproducible alternative, with potential to inform treatment decisions for knee, hip, and shoulder ballistic injuries. Further research is needed to validate this system and its correlation with patient outcomes. LEVEL OF EVIDENCE: Level III, Diagnostic Study.

Long-Term outcomes in adult patients with congenital heart disease considered for transplantation: A single center study.

BACKGROUND: Adult congenital heart disease (ACHD) patients pose unique challenges in identifying the time for transplantation and factors influencing outcomes. OBJECTIVE: To identify hemodynamic, functional, and laboratory parameters that correlate with 1- and 10-year outcomes in ACHD patients considered for transplantation. METHODS: A retrospective chart review of long-term outcomes in adult patients with congenital heart disease (CHD) evaluated for heart or heart + additional organ transplant between 2004 and 2014 at our center was performed. A machine learning decision tree model was used to evaluate multiple clinical parameters correlating with 1- and 10-year survival. RESULTS: We identified 58 patients meeting criteria. D-transposition of the great arteries (D-TGA) with atrial switch operation (20.7%), tetralogy of Fallot/pulmonary atresia (15.5%), and tricuspid atresia (13.8%) were the most common diagnosis for transplant. Single ventricle patients were most likely to be listed for transplantation (39.8% of evaluated patients). Among a comprehensive list of clinical factors, invasive hemodynamic parameters (pulmonary capillary wedge pressure (PCWP), systemic vascular pressure (SVP), and end diastolic pressures (EDP) most correlated with 1- and 10-year outcomes. Transplanted patients with SVP < 14 and non- transplanted patients with PCWP < 15 had 100% survival 1-year post-transplantation. CONCLUSION: For the first time, our study identifies that hemodynamic parameters most strongly correlate with 1- and 10-year outcomes in ACHD patients considered for transplantation, using a data-driven machine learning model.

Validation of the Thumbs food classification system as a tool to accurately identify the healthiness of foods.

The Thumbs food classification system was developed to assist remote Australian communities to identify food healthiness. This study aimed to assess: (1) the Thumbs system's alignment to two other food classification systems, the Health Star Rating (HSR) and the Northern Territory School Canteens Guidelines (NTSCG); (2) its accuracy in classifying 'unhealthy' (contributing to discretionary energy and added sugars) and 'healthy' products against HSR and NTSCG; (3) areas for optimisation. Food and beverage products sold between 05/2018 and 05/2019 in fifty-one remote stores were classified in each system. System alignment was assessed by cross-tabulating percentages of products, discretionary energy and added sugars sold assigned to the same healthiness levels across the systems. The system/s capturing the highest percentage of discretionary energy and added sugars sold in 'unhealthy' products and the lowest levels in 'healthy' products were considered the best performing. Cohen's κ was used to assess agreement between the Thumbs system and the NTSCG for classifying products as healthy. The Thumbs system classified product healthiness in line with the HSR and NTSCG, with Cohen's κ showing moderate agreement between the Thumbs system and the NTSCG (κ = 0·60). The Thumbs system captured the most discretionary energy sold (92·2 %) and added sugar sold (90·6 %) in unhealthy products and the least discretionary energy sold (0 %) in healthy products. Modifications to optimise the Thumbs system include aligning several food categories to the NTSCG criteria and addressing core/discretionary classification discrepancies of fruit juice/drinks. The Thumbs system offers a classification algorithm that could strengthen the HSR system.

State Categories, Bureaucracies of Displacement, and Possibilities from the Margins.

In this presidential address, I argue for the importance of state-created categories and classification systems that determine eligibility for tangible and intangible resources. Through classification systems based on rules and regulations that reflect powerful interests and ideologies, bureaucracies maintain entrenched inequality systems that include, exclude, and neglect. I propose adopting a critical perspective when using formalized categories in our work, which would acknowledge the constructed nature of those categories, their naturalization through everyday practices, and their misalignments with lived experiences. This lens can reveal the systemic structures that engender both enduring patterns of inequality and state classification systems, and reframe questions about the people the state sorts into the categories we use. I end with a brief discussion of the benefits that can accrue from expanding our theoretical repertoires by including knowledge produced in the Global South.

Clazakizumab for desensitization in highly sensitized patients awaiting transplantation.

Alloantibodies are a significant barrier to successful transplantation. While desensitization has emerged, efficacy is limited. Interleukin-6 (IL-6) is an important mediator of inflammation and immune cell activation. Persistent IL-6 production increases the risk for alloantibody production. Here we report our experience with clazakizumab (anti-IL-6) for desensitization of highly HLA-sensitized patients (HS). From March 2018 to September 2020, 20 HS patients were enrolled in an open label pilot study to assess safety and limited efficacy of clazakizumab desensitization. Patients received PLEX, IVIg, and clazakizumab 25 mg monthly X6. If transplanted, graft function, pathology, HLA antibodies and regulatory immune cells were monitored. Transplanted patients received standard immunosuppression and clazakizumab 25 mg monthly posttransplant. Clazakizumab was well tolerated and associated with significant reductions in class I and class II antibodies allowing 18 of 20 patients to receive transplants with no DSA rebound in most. Significant increases in Treg and Breg cells were seen posttransplant. Antibody-mediated rejection occurred in three patients. The mean estimated glomerular filtration rate at 12 months was 58 ± 29 ml/min/1.73 m2 . Clazakizumab was generally safe and associated with significant reductions in HLA alloantibodies and high transplant rates for highly-sensitized patients. However, confirmation of efficacy for desensitization requires assessment in randomized controlled trials.

Machine learning-supported interpretation of kidney graft elementary lesions in combination with clinical data.

Interpretation of kidney graft biopsies using the Banff classification is still heterogeneous. In this study, extreme gradient boosting classifiers learned from two large training datasets (n = 631 and 304 cases) where the "reference diagnoses" were not strictly defined following the Banff rules but from central reading by expert pathologists and further interpreted consensually by experienced transplant nephrologists, in light of the clinical context. In three external validation datasets (n = 3744, 589, and 360), the classifiers yielded a mean ROC curve AUC (95%CI) of: 0.97 (0.92-1.00), 0.97 (0.96-0.97), and 0.95 (0.93-0.97) for antibody-mediated rejection (ABMR); 0.94 (0.91-0.96), 0.94 (0.92-0.95), and 0.91 (0.88-0.95) for T cell-mediated rejection; >0.96 (0.90-1.00) with all three for interstitial fibrosis-tubular atrophy. We also developed a classifier to discriminate active and chronic active ABMR with 95% accuracy. In conclusion, we built highly sensitive and specific artificial intelligence classifiers able to interpret kidney graft scoring together with a few clinical data and automatically diagnose rejection, with excellent concordance with the Banff rules and reference diagnoses made by a group of experts. Some discrepancies may point toward possible improvements that could be made to the Banff classification.

Long-term outcomes of resection versus transplantation for neuroendocrine liver metastases meeting the Milan criteria.

Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from consecutive patients undergoing either curative resection or transplantation for liver-only NELM meeting Milan criteria at a single center between 1984 and 2019. Patients who fit Milan criteria were 48 in the transplantation group and 56 in the resection group. After a median follow-up of 158 months for the transplantation group and 126 for the resection group, the 10-year survival rate was 93% for transplantation and 75% for resection (p = .007). The 10-year disease-free survival rate was 52% for transplantation and 18% for resection (p < .001). Transplantation was associated with improved survival at univariate analysis. The median disease-free interval between surgery and recurrence was 78 months for transplantation vs. 24 months for resection (p < .001). The transplantation group had more multisite recurrences (12/25, 48% vs. 5/42, 12% in the resection group, p = .001), while most recurrences in the resection group were intra-hepatic (37/42, 88%, versus 2/25, 8% in the transplantation group). In conclusion, LT was associated with improved survival outcomes in NELM meeting the Milan criteria compared with LR.

Awarding additional MELD points to the shortest waitlist candidates improves sex disparity in access to liver transplant in the United States.

Since the introduction of the MELD-based allocation system, women are now 30% less likely than men to undergo liver transplant (LT) and have 20% higher waitlist mortality. These disparities are in large part due to height differences in men and women though no national policies have been implemented to reduce sex disparities. Patients were identified using the Scientific Registry of Transplant Recipients (SRTR) from 2014 to 2019. Patients were categorized into five groups by first dividing into thirds by height then dividing the shortest third into three groups to capture more granular differences in the most disadvantaged patients (<166 cm). We then used LSAM to model waitlist outcomes in five versions of awarding additional MELD points to shorter candidates compared to current policy. We identified two proposed policy changes LSAM scenarios that resulted in improvement in LT and death percentage for the shortest candidates with the least negative impact on taller candidates. In conclusion, awarding an additional 1-2 MELD points to the shortest 8% of LT candidates would improve waitlist outcomes for women. This strategy should be considered in national policy allocation to address sex-based disparities in LT.

Role of time from transplantation to biopsy in histologic ABMR: A single center report.

BACKGROUND: Allograft biopsies with lesions of Antibody-Mediated Rejection (ABMR) with Microvascular Inflammation (MVI) have shown heterogeneous etiologies and outcomes. METHODS: To examine factors associated with outcomes in biopsies that meet histologic ABMR criteria, we retrospectively evaluated for-cause biopsies at our center between 2011 and 2017. We included biopsies that met the diagnosis of ABMR by histology, along with simultaneous evaluation for anti-Human Leukocyte Antigen (HLA) donor-specific antibodies (DSA). We evaluated death-censored graft loss (DCGL) and used a principal component analysis (PCA) approach to identify key predictors of outcomes. RESULTS: Out of the histologic ABMR cohort (n = 118), 70 were DSA-positive ABMR, while 48 had no DSA. DSA(+)ABMR were younger and more often female recipients. DSA(+)ABMR occurred significantly later post-transplant than DSA(-)ABMR suggesting time-dependence. DSA(+)ABMR had higher inflammatory scores (i,t), chronicity scores (ci, ct) and tended to have higher MVI scores. Immunodominance of DQ-DSA in DSA(+)ABMR was associated with higher i+t scores. Clinical/histologic factors significantly associated with DCGL after biopsy were inputted into the PCA. Principal component-1 (PC-1), which contributed 34.8% of the variance, significantly correlated with time from transplantation to biopsy, ci/ct scores and DCGL. In the PCA analyses, i, t scores, DQ-DSA, and creatinine at biopsy retained significant correlations with GL-associated PCs. CONCLUSIONS: Time from transplantation to biopsy plays a major role in the prognosis of biopsies with histologic ABMR and MVI, likely due to ongoing chronic allograft injury over time.

Decreased frequency of transplantation and lower post-transplant survival free of re-transplantation in LVAD patients with the new heart transplant allocation system.

PURPOSE: To evaluate the effect of the new heart transplant (HT) allocation system in left ventricular assist device (LVAD) supported patients listed as bridge to transplantation (BTT). METHODS: Adult patients who were listed for HT between October 18, 2016 and October 17, 2019, and were supported with an LVAD, enrolled in the UNOS database were included in this study. Patients were classified in the old or new system if they were listed or transplanted before or after October 18, 2018, respectively. RESULTS: A total of 3261 LVAD patients were listed for transplant. Of these, 2257 were classified in the old and 1004 in the new system. The cumulative incidence of death or removal from the transplant list due to worsening clinical status at 360-days after listing was lower in the new system (4% vs. 7%, P = .011). LVAD Patients listed in the new system had a lower frequency of transplantation within 360-days of listing (52% vs. 61%, P < .001). A total of 1843 LVAD patients were transplanted, 1004 patients in the old system and 839 patients in the new system. The post-transplant survival at 360 days was similar between old and new systems (92.3% vs. 90%, P = .08). However, LVAD patients transplanted in the new system had lower frequency of the combined endpoint, freedom of death or re-transplantation at 360 days (92.2% vs. 89.6%, P = .046). CONCLUSION: The new HT allocation system has affected the LVAD-BTT population significantly. On the waitlist, LVAD patients have a decreased cumulative frequency of transplantation and a concomitant decrease in death or delisting due to worsening status. In the new system, LVAD patients have a decreased survival free of re-transplantation at 360 days post-transplant.

Placental Heterogeneity in Stillbirth and Its Relations to Maternal Exogenous Characteristics.

INTRODUCTION: Heterogeneous patterns of placental lesions in stillbirth signal important variations in placental histopathology that may be diagnostic in stillbirth. We explore placental heterogeneity and its associations with maternal characteristics (including HIV) using latent class analysis. METHODS: Placental and maternal data and slides were assessed retrospectively for 122 confirmed stillbirths (gestational age ≥ 28 weeks) delivered at a major South African academic hospital between January 2016-July 2018. The slides were reviewed by 2 pathologists and classified using the Amsterdam Consensus Classification System. Latent class analyses were conducted on raw data. RESULTS: We identify 5 latent placental classes in stillbirth based on similarity in patterns of observed diagnostic criteria and their associations with maternal characteristics. Three classes bear similarity to generalized patterns of placental injury identified previously. Our study shows that intrauterine infection was the commonest histopathological condition associated with stillbirth in our setting. Novel findings include 2 classes, distinguished by high placental RPH and maternal HIV, respectively, and the non-emergence of a class distinguished by VUE. CONCLUSION: The size and content of the latent classes and their similarity/dissimilarity to the more generalized patterns identified previously suggest potential new avenues for investigation and theory development concerning the role of the placenta in stillbirth and the impact of HIV.

Revisiting the changes in the Banff classification for antibody-mediated rejection after kidney transplantation.

The Banff classification for antibody-mediated rejection (ABMR) has undergone important changes, mainly by inclusion of C4d-negative ABMR in Banff'13 and elimination of suspicious ABMR (sABMR) with the use of C4d as surrogate for HLA-DSA in Banff'17. We aimed to evaluate the numerical and prognostic repercussions of these changes in a single-center cohort study of 949 single kidney transplantations, comprising 3662 biopsies that were classified according to the different versions of the Banff classification. Overall, the number of ABMR and sABMR cases increased from Banff'01 to Banff'13. In Banff'17, 248 of 292 sABMR biopsies were reclassified to No ABMR, and 44 of 292 to ABMR. However, reclassified sABMR biopsies had worse and better outcome than No ABMR and ABMR, which was mainly driven by the presence of microvascular inflammation and absence of HLA-DSA, respectively. Consequently, the discriminative performance for allograft failure was lowest in Banff'17, and highest in Banff'13. Our data suggest that the clinical and histological heterogeneity of ABMR is inadequately represented in a binary classification system. This study provides a framework to evaluate the updates of the Banff classification and assess the impact of proposed changes on the number of cases and risk stratification. Two alternative classifications introducing an intermediate category are explored.

i-IFTA and chronic active T cell-mediated rejection: A tale of 2 (DeKAF) cohorts.

Inflammation in areas of fibrosis (i-IFTA) in posttransplant biopsies is part of the diagnostic criteria for chronic active TCMR (CA TCMR -- i-IFTA ≥ 2, ti ≥ 2, t ≥ 2). We evaluated i-IFTA and CA TCMR in the DeKAF indication biopsy cohorts: prospective (n = 585, mean time to biopsy = 1.7 years); cross-sectional (n = 458, mean time to biopsy = 7.8 years). Grouped by i-IFTA scores, the 3-year postbiopsy DC-GS is similar across cohorts. Although a previous acute rejection episode (AR) was more common in those with i-IFTA on biopsy, the majority of those with i-IFTA had not had previous AR. There was no association between type of previous AR (AMR, TCMR) and presence of i-IFTA. In both cohorts, i-IFTA was associated with markers of both cellular (increased Banff i, t, ti) and humoral (increased g, ptc, C4d, DSA) activity. Biopsies with i-IFTA = 1 and i-IFTA ≥ 2 with concurrent t ≥ 2 and ti ≥ 2 had similar DC-GS. These results suggest that (a) i-IFTA≥1 should be considered a threshold for diagnoses incorporating i-IFTA, ti, and t; (b) given that i-IFTA ≥ 2,t ≥ 2, ti ≥ 2 can occur in the absence of preceding TCMR and that the component histologic scores (i-IFTA,t,ti) each indicate an acute change (albeit i-IFTA on the nonspecific background of IFTA), the diagnostic category "CA TCMR" should be reconsidered.

Life underneath the VCA umbrella: Perspectives from the US Uterus Transplant Consortium.

The parallel emergence of uterus transplantation (UTx) and other transplantation innovations including face and hand transplantation led to the categorization of the uterus as a vascular composite allograft (VCA). With >60 transplants and >20 births worldwide, UTx is transitioning rapidly from a research endeavor to an effective treatment option for women with uterine factor infertility. While it originally made sense to group the innovations under one umbrella, it is time to revisit the designation of UTx as a VCA. We describe how UTx needs unique policy, procedural codes, insurance contracts, and educational initiatives. We contend that separating UTx from VCAs may become necessary in the future to avoid hindering the growth and regulation of this field.

The 2018 Banff Working Group classification of definitive polyomavirus nephropathy: A multicenter validation study in the modern era.

Polyomavirus nephropathy (PVN) remained inadequately classified until 2018 when the Banff Working Group published a new 3-tier morphologic classification scheme derived from in-depth statistical analysis of a large multinational patient cohort. Here we report a multicenter "modern-era" validation study that included 99 patients with definitive PVN transplanted post January 1, 2009 and followed the original 2018 study design. Results validate the PVN classification, that is, the 3 PVN disease classes predicted clinical presentation, allograft function, and outcome independent of therapeutic intervention. PVN class 1 compared to classes 2 and 3 was diagnosed earlier (16.9 weeks posttransplant [median], P = .004), and showed significantly better function at 24 months postindex biopsy (serum creatinine 1.75 mg/dl, geometric mean, vs class 2: P = .037, vs class 3: P = .013). Class 1 presented during long-term follow-up with a low graft failure rate: 5% class 1, vs 30% class 2, vs 50% class 3 (P = .009). Persistent PVN was associated with an increased risk for graft failure (and functional decline in class 2 at 24 months postdiagnosis; serum creatinine with persistence: 2.48 mg/dL vs 1.65 with clearance, geometric means, P = .018). In conclusion, we validate the 2018 Banff Working Group PVN classification that provides significant clinical information and enhances comparative data analysis.

Correcting the sex disparity in MELD-Na.

MELD-Na appears to disadvantage women awaiting liver transplant by underestimating their mortality rate. Fixing this problem involves: (1) estimating the magnitude of this disadvantage separately for each MELD-Na, (2) designing a correction for each MELD-Na, and (3) evaluating corrections to MELD-Na using simulated allocation. Using Kaplan-Meier modeling, we calculated 90-day without-transplant survival for men and women, separately at each MELD-Na. For most scores between 15 and 35, without-transplant survival was higher for men by 0-5 percentage points. We tested two proposed corrections to MELD-Na (MELD-Na-MDRD and MELD-GRAIL-Na), and one correction we developed (MELD-Na-Shift) to target the differences we quantified in survival across the MELD-Na spectrum. In terms of without-transplant survival, MELD-Na-MDRD overcorrected sex differences while MELD-GRAIL-Na and MELD-Na-Shift eliminated them. Estimating the impact of implementing these corrections with the liver simulated allocation model, we found that MELD-Na-Shift alone eliminated sex disparity in transplant rates (p = 0.4044) and mortality rates (p = 0.7070); transplant rates and mortality rates were overcorrected by MELD-Na-MDRD (p = 0.0025, p = 0.0006) and MELD-GRAIL-Na (p = 0.0079, p = 0.0005). We designed a corrected MELD-Na that eliminates sex disparities in without-transplant survival, but allocation changes directing smaller livers to shorter candidates may also be needed to equalize women's access to liver transplant.