Hepatitis B virus e antigen induces atypical metabolism and differentially regulates programmed cell deaths of macrophages.

Macrophages can undergo M1-like proinflammatory polarization with low oxidative phosphorylation (OXPHOS) and high glycolytic activities or M2-like anti-inflammatory polarization with the opposite metabolic activities. Here we show that M1-like macrophages induced by hepatitis B virus (HBV) display high OXPHOS and low glycolytic activities. This atypical metabolism induced by HBV attenuates the antiviral response of M1-like macrophages and is mediated by HBV e antigen (HBeAg), which induces death receptor 5 (DR5) via toll-like receptor 4 (TLR4) to induce death-associated protein 3 (DAP3). DAP3 then induces the expression of mitochondrial genes to promote OXPHOS. HBeAg also enhances the expression of glutaminases and increases the level of glutamate, which is converted to α-ketoglutarate, an important metabolic intermediate of the tricarboxylic acid cycle, to promote OXPHOS. The induction of DR5 by HBeAg leads to apoptosis of M1-like and M2-like macrophages, although HBeAg also induces pyroptosis of the former. These findings reveal novel activities of HBeAg, which can reprogram mitochondrial metabolism and trigger different programmed cell death responses of macrophages depending on their phenotypes to promote HBV persistence.

A Framework for Quality Control in Quantitative Proteomics.

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow, from planning to analysis. We share vignettes applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at the protein and peptide levels allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis (Skyline), longitudinal QC metrics (AutoQC), and server-based data deposition (PanoramaWeb). We propose that this integrated approach to QC is a useful starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible. Data are available on Panorama Public and ProteomeXchange under the identifier PXD051318.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Association of High BMI With Morbidity and Mortality in Common Emergency General Surgery Procedures.

INTRODUCTION: Emergency general surgery (EGS) patients are at increased risk for postoperative morbidity and mortality. Obesity is a risk factor for poor outcomes in this population. Our study aimed to explore the association of body mass index (BMI) with postoperative outcomes in patients requiring common EGS procedures. METHODS: A retrospective review of the 2018-2020 National Surgical Quality Improvement Program database identified patients undergoing four common EGS procedures: large bowel resection, small bowel resection, cholecystectomy, and appendectomy. Patients were classified by BMI: normal weight (18.5-24.9 kg/m2), obesity classes I (30-34.9 kg/m2), II (35-39.9 kg/m2), III (40-49.9 kg/m2), and IV (≥50 kg/m2). Main outcomes of interest were major adverse event (MAE) and mortality. RESULTS: From 2018 to 2020, a total of 82,540 patients underwent one of four common EGS procedures. On unadjusted analysis, obesity class IV had higher mortality rates compared to classes I-III (6.2% vs 3.1%, P < 0.001). Patients in obesity classes I-III had lower odds of MAE and death relative to those of normal weight. Compared to other patients with obesity, those in obesity class IV were at increased risk of MAE (odds ratio 1.27; 95% confidence interval 1.13-1.44) and death (odds ratio 1.69; 95% confidence interval 1.34-2.13). CONCLUSIONS: Patients with varying degrees of obesity have different risk profiles following common EGS procedures. While patients in lower obesity classes had reduced odds of adverse outcomes, those with BMI ≥50 kg/m2 were particularly at greater risk for postoperative morbidity and mortality. This vulnerable population warrants further investigation and increased vigilance to ensure high-quality care.

Inertial Sensor Gait Analysis of Trendelenburg Gait in Patients Who Have Hip Osteoarthritis.

BACKGROUND: Gait abnormalities such as Trendelenburg gait (TG) in patients who have hip osteoarthritis (OA) have traditionally been evaluated using clinicians' visual assessment. Recent advances in portable inertial gait sensors offer more sensitive, quantitative methods for gait assessment in clinical settings. This study sought to compare sensor-derived metrics in a cohort of hip OA patients when stratified by clinical TG severity. METHODS: There were 42 patients who had hip OA and were grouped by TG severity (mild, moderate, and severe) through visual assessment by a single arthroplasty surgeon who had > 30 years of experience. After informed consent, wireless inertial sensors placed at the midpoint of the intercristal line collected gait parameters including pelvic shift, support time, toe-off symmetry, impact, and cadence. Clinical data on hip strength, range of motion, and Kellgren-Lawrence grade were collected. RESULTS: Worsening TG severity had a higher mean Kellgren-Lawrence grade (2.5 versus 3.2 versus 3.4; P = .014) and reduced passive hip abduction (P = .004). Severe TG group demonstrated predominantly contralateral pelvic shift (n = 9 of 10, 90.0%), while ipsilateral shift was more frequently detected in moderate (n = 10 of 18, 55.6%) and mild groups (n = 9 of 14, 64.3%; P = .021). Contralateral single support time bias was greatest in severe TG (35.7% versus 50.0 versus 90.0%; P = .027). Asymmetric toe-off, impact, and support times were observed in all groups. CONCLUSIONS: Traditional understanding of TG is that truncal shift occurs to the ipsilateral side. Using sensor-based measurements, the present study demonstrates a shift of the weight-bearing axis toward the contralateral side with increasing TG severity, which has not been previously described. Inertial sensors are feasible, quantitative gait measuring tools, and may reveal subtle patterns not readily discernible by traditional methods.

Does Femoral Stem Design Influence Periprosthetic Fracture Incidence and Morphology in Total Hip Arthroplasty?

BACKGROUND: As the incidence of total hip arthroplasty (THA) increases, the number of periprosthetic femur fractures (PFF) will also rise. The surgical approach and stem design have been shown to influence the rate of PFF. This study evaluated PFF in cementless THA done through the posterior approach and described how stem design influences intraoperative and early postoperative fracture incidence and morphology. METHODS: A retrospective review of 3,183 primary THAs for osteoarthritis from 2013 to 2021 was performed. Demographics, comorbidities, femoral stem designs, intraoperative and early postoperative PFFs (< 90 days), and aseptic femoral revisions were recorded. Stems were classified as single-wedge taper (Type 1), double-wedge taper (Type 2), or ream and broach (Type 3). There were 1,192 Type 1, 240 Type 2, and 1,726 Type 3 femoral stems. The PFF and aseptic femoral revisions were compared with univariable and multivariable analyses. Cox regression and Kaplan-Meier analyses evaluated survival to femoral revision. RESULTS: In this population, 25 patients (0.8%) had an intraoperative or early postoperative PFF. Patients who had PFFs were older (68 versus 63; P = 0.03) and more likely to be women (76 versus 24%; P = 0.02). Type 2 stems had a significantly higher incidence of all-cause PFFs when compared to Type 1 (3.6 versus 0.7%; P < 0.01) and Type 3 (3.6 versus 0.4%; P < 0.01) stems. Type 2 stems also had a higher incidence of Vancouver B2 PFFs when compared to Type 3 stems (0.8 versus 0.05%; P = 0.04). Stem design was not associated with PFF or all-cause femoral revision. There were no differences in survival to femoral revision. CONCLUSION: Double-wedge taper stems may be associated with increased intraoperative and early postoperative PFFs, including those requiring femoral stem revision. However, there was no statistically significant difference in late PFF, aseptic loosening, or femoral revision.

Unsuspected Positive Intraoperative Cultures in Aseptic Revision Knee Arthroplasty: Prevalence, Management, and Infection-Free Survivorship.

BACKGROUND: The purpose of this study was to evaluate the management and outcomes of aseptic revision total knee arthroplasty (arTKA) with unsuspected positive cultures (UPCs) compared to those with sterile cultures. METHODS: The institutional database at a single tertiary center was retrospectively reviewed for arTKA from January 2013 to October 2023. Patients who met Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) based on available preoperative infectious workup, received antibiotic spacers, or did not have at least 1 year of follow-up were excluded. Patients were stratified based on intraoperative cultures into 4 cohorts: sterile cultures, 1 UPC, ≥ 2 UPCs with different organisms, and ≥ 2 UPCs with the same organism. Univariable analyses were used to compare these groups. Kaplan-Meier survivorship analysis assessed infection-free survival at 5 years, and Cox proportional hazards regressions were used to evaluate factors that influence infection-free survival. A total of 691 arTKAs at a mean follow-up of 4.2 years were included in the study. Of these, 49 (7.1%) had 1 UPC with a new organism, 10 (1.4%) had ≥2 UPCs of the same organism, and 2 (0.2%) had ≥2 UPCs with different organisms. RESULTS: Postoperative antibiotics were prescribed to 114 (16.5%) patients-13 (26.5%) with 1 UPC, 6 (60.0%) with ≥2 UPCs of the same organism, and 0 (0.0%) of patients who had ≥2 UPCs of different organisms. There were no differences in infection-free survival at 5 years between patients who had sterile cultures and 1 UPC (96 versus 89%; P = .39) nor between sterile cultures and ≥2 UPCs of different organisms (96 versus 100%; P < .72). However, patients who had ≥2 UPCs of the same organism had significantly worse infection-free survival at 5 years compared to patients who had sterile cultures (58 versus 96%; P < .001). Cox proportional hazards regression suggested that when adjusting for covariates, an American Society of Anesthesiologists classification of ≥3 (hazard ratio [HR] = 3.1; P = .007), ≥2 UPCs of the same organism (HR = 11.0; P < .001), 1 UPC (HR = 4.2; P = .018), and arTKA with hinge constructs (HR = 4.1; P = .008) were associated with increased risk of rerevision for PJI. CONCLUSIONS: Patients who had 1 UPC or ≥2 UPCs with different organisms had similar infection-free survival at 5 years as patients who had sterile cultures. However, patients who had ≥2 UPCs of the same organism had significantly worse infection-free survival at 5 years. Overall, 1 UPC or ≥2 UPCs of the same organism at the time of arTKA may suggest the patient is at higher risk of rerevision for PJI. More studies are needed to determine what interventions can be implemented to mitigate this risk.

Are Asian Americans BIPOC (Black, Indigenous, and People of Color)? Internalization of the model minority stereotype and COVID-19 racial bias on interracial solidarity toward Black Americans.

OBJECTIVES: Collective minoritized identities such as Black, Indigenous, and People of Color (BIPOC) may promote cross-racial solidarity. However, Asian Americans occupy a racially triangulated position as the "buffer minority" stereotyped as both the model minority and perpetual foreigner, complicating their inclusion in the BIPOC identity. The present study examined how the model minority and perpetual foreigner stereotypes relate to Asian Americans' perceived belongingness and identification with the BIPOC identity and, in turn, their interracial solidarity toward Black Americans. METHOD: A path analysis was conducted using cross-sectional data from a sample of 312 Asian Americans (Mage = 41.19, 69.87% college graduates, 46.79% foreign-born) to examine direct and indirect effects on Black community activism orientation (BCAO), with internalized model minority stereotype (MMS) and experiences of COVID-19 racial bias (CVRB) as exogenous predictors and perceived BIPOC inclusion and BIPOC self-identification as mediators. RESULTS: The BIPOC variables demonstrated a direct and positive association with BCAO. Furthermore, internalized MMS negatively related to BCAO through the sum effect of decreased perceived BIPOC inclusion and BIPOC self-identification, while experiences of CVRB positively related to BCAO through the sum effect of increased perceived BIPOC inclusion and BIPOC self-identification. CONCLUSIONS: Asian Americans' perceived BIPOC inclusion and BIPOC self-identification are shaped by their racially triangulated position, characterized by both the inhibiting effect of internalized MMS and the promoting effect of experiences of CVRB. This heightened or diminished BIPOC self-concept subsequently influenced their willingness to engage in interracial solidarity for Black Americans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Evaluating the Performance of the Astral Mass Analyzer for Quantitative Proteomics Using Data-Independent Acquisition.

We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data-independent acquisition, the Thermo Scientific Orbitrap Astral mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific Orbitrap mass spectrometers, which have long been the gold standard for high-resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high-quality quantitative measurements across a wide dynamic range. We also use a newly developed extracellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5000 plasma proteins in a 60 min gradient with the Orbitrap Astral mass spectrometer.

Dynamic Data-Independent Acquisition Mass Spectrometry with Real-Time Retrospective Alignment.

Data-independent acquisition (DIA) mass spectrometry has grown in popularity in recent years, because of the reproducibility and quantitative rigor of a systematic tandem mass spectrometry (MS/MS) sampling method. However, traditional DIA methods may spend valuable instrument time acquiring MS/MS spectra with no usable information in them, affecting sensitivity and quantitative performance. We developed a DIA strategy that dynamically adjusts the MS/MS windows during the chromatographic separation. The method focuses MS/MS acquisition on the most relevant mass range at each point in time─increasing the quantitative sensitivity by increasing the time spent on each DIA window. We demonstrate an improved lower limit of quantification, on average, without sacrificing the number of peptides detected.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

Iron-Catalyzed Oxidative α-Amination of Ketones with Primary and Secondary Sulfonamides.

We report the iron-catalyzed α-amination of ketones with sulfonamides. Using an oxidative coupling approach, ketones can be directly coupled with free sulfonamides, without the need for prefunctionalization of either substrate. Primary and secondary sulfonamides are both competent coupling partners, with yields from 55% to 88% for deoxybenzoin-derived substrates.

Downregulation of miRNA-26 in chronic periodontitis interferes with innate immune responses and cell migration by targeting phospholipase C beta 1.

AIM: To evaluate the potential role of miR-26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization. MATERIALS AND METHODS: Expression of miR-26a-5p and miR-26b-5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non-surgical (scaling and root planing) therapy by RT-qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation. Cytokine expression was assessed in miR-26a-5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans or Pg lipopolysaccharide (LPS). Wound closure assays were performed in cells transfected with miR-26a-5p, while the impact on cytoskeletal organization was assessed by F-actin staining. RESULTS: miR-26a-5p and miR-26b-5p were downregulated in diseased gingiva and restored 4-6 weeks post-therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase C beta 1 as a bona fide novel target exhibiting antagonistic expression pattern in disease and post-therapy cohorts. miR-26a-5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement. CONCLUSIONS: Downregulated miR-26a-5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defence and wound healing.

Navigating puberty, identity, and race among transnationally, transracially adopted Korean American adolescents.

This exploratory study examined the relation between pubertal timing and dimensions of ethnic-racial identity among adopted Korean Americans raised transracially in White families. The study also examined whether internalized racism moderated the association between pubertal timing and ethnic-racial identity. Adopted Korean American adolescents (N = 202; 108 females; ages 13-19 years) completed measures of pubertal development, ethnic-racial identity, and internalized racism in 2007. There was no significant main effect of pubertal timing for either male or female adolescents. Internalized racism moderated the relation between pubertal timing and ethnic-racial identity clarity (B = -.16, p = .015) among male adolescents. Specifically, earlier pubertal timing was significantly associated with lower ethnic-racial identity clarity for male adolescents with higher levels of internalized racism.

Body Mass Index and American Society of Anesthesiologists Score Predict Perioperative Delays in Different Phases for Total Hip Arthroplasty.

Perioperative efficiency has become increasingly important with cost constraints and expanding indications for total hip arthroplasty (THA). We chose to analyze body mass index (BMI) and American Society of Anesthesiologists (ASA) score, in predicting perioperative efficiency. We retrospectively reviewed the institutional database for primary THAs from July 2015 to January 2018. Patient demographics and perioperative times lines were collected. A multivariable model was utilized to evaluate BMI (< 30, ≥ 30) and ASA (< 3, ≥ 3) for all outcomes. A total of 2,934 patients were included with mean age 62.0 (12.2) years, and 1,599 (54.5%) were female. A BMI ≥ 30 was associated with prolonged operative time (p < 0.001) while an ASA ≥ 3 was predictive of post-anesthesia care unit time (p < 0.001), physical therapy hours (p < 0.001), and length of stay (p < 0.001). Both BMI (p = 0.004) and ASA (p < 0.001) were associated with skilled nursing/rehabilitation dispositions. While BMI predicts prolonged operative time, ASA predicts perioperative delays for anesthesia, nursing, and physical therapy. (Journal of Surgical Orthopaedic Advances 32(3):169-172, 2023).

Putting Humpty Dumpty Back Together Again: What Does Protein Quantification Mean in Bottom-Up Proteomics?

Bottom-up proteomics provides peptide measurements and has been invaluable for moving proteomics into large-scale analyses. Commonly, a single quantitative value is reported for each protein-coding gene by aggregating peptide quantities into protein groups following protein inference or parsimony. However, given the complexity of both RNA splicing and post-translational protein modification, it is overly simplistic to assume that all peptides that map to a singular protein-coding gene will demonstrate the same quantitative response. By assuming that all peptides from a protein-coding sequence are representative of the same protein, we may miss the discovery of important biological differences. To capture the contributions of existing proteoforms, we need to reconsider the practice of aggregating protein values to a single quantity per protein-coding gene.

Long-term immunological outcomes of early subclinical inflammation on surveillance kidney allograft biopsies.

The long-term impact of early subclinical inflammation (SCI) through surveillance biopsy has not been well studied. To do this, we recruited a prospective observational cohort that included 1000 sequential patients who received a kidney transplant from 2013-2017 at our center. A total of 586 patients who underwent a surveillance biopsy in their first year post-transplant were included after excluding those with clinical rejections, and those who were unable to undergo a surveillance biopsy. Patients were classified based on their biopsy findings: 282 with NSI (No Significant Inflammation) and 304 with SCI-T (SCI and Tubulitis) which was further subdivided into 182 with SC-BLR (Subclinical Borderline Changes) and 122 with SC-TCMR (Subclinical T Cell Mediated Rejection, Banff 2019 classification of 1A or more). We followed the clinical and immunological events including Clinical Biopsy Proven Acute Rejection [C-BPAR], long-term kidney function and death-censored graft loss over a median follow-up of five years. Episodes of C-BPAR were noted at a median of two years post-transplant. Adjusted odds of having a subsequent C-BPAR was significantly higher in the SCI-T group [SC-BLR and SC-TCMR] compared to NSI 3.8 (2.1-7.5). The adjusted hazard for death-censored graft loss was significantly higher with SCI-T compared to NSI [1.99 (1.04-3.84)]. Overall, SCI detected through surveillance biopsy within the first year post-transplant is a harbinger for subsequent immunological events and is associated with a significantly greater hazard for subsequent C-BPAR and death-censored graft loss. Thus, our study highlights the need for identifying patients with SCI through surveillance biopsy and develop strategies to prevent further alloimmune injuries.

Gender and Racial/Ethnic Disparities in Operative Volumes of Graduating General Surgery Residents.

INTRODUCTION: Gender disparities in resident operative experience have been described; however, their etiology is poorly understood, and racial/ethnic disparities have not been explored. This study investigated the relationship between gender, race/ethnicity, and surgery resident case volumes. MATERIALS AND METHODS: A retrospective analysis of graduating general surgery resident case logs (2010-2020) at an academic medical center was performed. Self-reported gender and race/ethnicity data were collected from program records. Residents were categorized as underrepresented in medicine (URM) (Black, Hispanic, Native American) or non-URM (White, Asian). Associations between gender and URM status and major, chief, and teaching assistant (TA) mean case volumes were analyzed using t-tests. RESULTS: The cohort included 80 residents: 39 female (48.8%) and 17 URM (21.3%). Compared to male residents, female residents performed fewer TA cases (33 versus 47, P < 0.001). Compared to non-URM residents, URM residents graduated with fewer major (948 versus 1043, P = 0.008) and TA cases (32 versus 42, P = 0.038). Male URM residents performed fewer TA cases than male non-URM residents (32 versus 50, P = 0.031). Subanalysis stratified by graduation year demonstrated that from 2010 to 2015, female residents performed fewer chief (218 versus 248, P = 0.039) and TA cases (29 versus 50, P = 0.001) than male residents. However, from 2016 to 2020, when gender parity was achieved, no significant associations were observed between gender and case volumes. CONCLUSIONS: Female and URM residents perform fewer TA and major cases than male non-URM residents, which may contribute to reduced operative autonomy, confidence, and entrustment. Prioritizing gender and URM parity may help decrease case volume gaps among underrepresented residents.

Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation.

Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5-6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R-) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group (n = 56) received <5 mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG (P < .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12-3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.

Function and longevity of renal grafts from high-KDPI donors.

BACKGROUND: High kidney-donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. METHODS: We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I-KDPI ≤ 25% (n = 151), Group II-KDPI 26-50% (n = 182), Group III-KDPI 51-75% (n = 176), and Group IV-KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5-years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group. FINDINGS: High-KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups (P = .06). Although patient survival was signigicantly lower for recipients of high-KDPI grafts, death-censored graft survival was similar among the four KDPI groups (P = .33). CONCLUSIONS: The shorter functional survival of high-KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.