Association of HLA mismatch and MTOR inhibitor regimens with malignancy and mortality after kidney transplantation

BackgroundThe association of mammalian target of rapamycin inhibitors (MTORI) with malignancies and mortality in kidney transplant recipients (KTR) with different degrees of human leukocyte antigen mismatch (HLA-mm) at transplant has not been previously studied.MethodsOur observational cohort study included 166, 256 adult KTRs in 2000–2018. Immunosuppression in the first post-transplant year were MTORIs in 13,056 (7.85%) and non-MTORIs in 153,200 (92.15%). We used Cox multivariable regression models to determine the cause-specific hazard ratio (HRcs) of non-melanoma skin cancer (NMSC),solid organ malignancies (SOM)] and all-cause death (death_ac); and the HR of the composite outcomes of NMSC or death_ac and SOM or death_ac associated with MTORI versus non-MTORI regimens in the overall study sample and the 0, 1–3, and 4–6 HLA-A, B and DR mm subgroups.ResultsNMSC risk was lower with MTORI than non-MTORI in all HLA-mm subgroups [(0 mm, HRcs = 0.67; 95% CI = 0.46–0.97, 1–3 mm, HRcs = 0.73; 95% CI = 0.61–0.87, 4–6 mm, HRcs = 0.69; 95% CI = 0.62–0.76)]. SOM risks were similar between regimens in the 0 HLA mm subgroup (HRcs = 1.10 (95% CI = 0.78–1.57) and lower with MTORI than non-MTORI in the 1–3, and 4–6 HLA-mm subgroups, [(HR = 0.84; (95% CI = 0.71–0.99), and (HR = 0.86; 95% CI = 0.78–0.94); respectively]. Risks of death_ac and composite outcomes (NMSC or death_ac and SOM or death_ac) were higher with MTORI than non-MTORI in almost all HLA-mm subgroups.ConclusionMTORIs are associated with protection from NMSC and SOM in almost all HLA-mm subgroups ca; however, their association with increased all-cause mortality in adult kidney transplant recipients needs further investigation.     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

The Association of Race/Ethnicity and Total Knee Arthroplasty Outcomes in a Universally Insured Population

BackgroundPrior studies have documented racial/ethnic disparities in the United States for total knee arthroplasty (TKA) outcomes. One factor cited as a potential mediator is unequal access to care. We sought to assess whether racial/ethnic disparities persist in a universally insured TKA population.MethodsA US integrated health system’s total joint replacement registry was used to identify elective primary TKA (2000-2016). Racial/ethnic differences in revision and 90-day postoperative events (readmission, emergency department [ED] visit, infection, venous thromboembolism, and mortality) were analyzed using Cox proportional hazard and logistic regression with adjustment for confounders.ResultsOf 129,402 TKA, 68.8% were white, 16.2% were Hispanic, 8.4% were black, and 6.6% were Asian. Compared to white patients, Hispanic patients had lower risks of septic revision (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.57-0.83) and infection (odds ratio [OR] = 0.42, 95% CI = 0.30-0.59), but a higher likelihood of ED visit (OR = 1.28, 95% CI = 1.22-1.34). Black patients had higher risks of aseptic revision (HR = 1.61, 95% CI = 1.42-1.83), readmission (OR = 1.13, 95% CI = 1.02-1.24), and ED visit (OR = 1.31, 95% CI = 1.23-1.39). Asian patients had lower risks of aseptic revision (HR = 0.67, 95% CI = 0.54-0.83), septic revision (HR = 0.78, 95% CI = 0.60-0.99), readmission (OR = 0.89, 95% CI = 0.79-1.00), and venous thromboembolism (OR = 0.59, 95% CI = 0.45-0.78).ConclusionWe observed differences in TKA outcome, even within a universally insured population. While lower risks in some outcomes were observed for Asian and Hispanic patients, the higher risks of aseptic revision and readmission for black patients and ED visit for black and Hispanic patients warrant further research to determine reasons for these findings to mitigate disparities.Level of EvidenceLevel III.     

Rethinking the advantage of zero‐HLA mismatches in unrelated living donor kidney transplantation: implications on kidney paired donation

The OPTN/UNOS Kidney Paired Donation (KPD) Pilot Program allocates priority to zero‐HLA mismatches. However, in unrelated living donor kidney transplants (LDKT)—the same donor source in KPD—no study has shown whether zero‐HLA mismatches provide any advantage over >0 HLA mismatches. We hypothesize that zero‐HLA mismatches among unrelated LDKT do not benefit graft survival. This retrospective SRTR database study analyzed LDKT recipients from 1987 to 2012. Among unrelated LDKT, subjects with zero‐HLA mismatches were compared to a 1:1–5 matched (by donor age ±1 year and year of transplantation) control cohort with >0 HLA mismatches. The primary endpoint was death‐censored graft survival. Among 32,654 unrelated LDKT recipients, 83 had zero‐HLA mismatches and were matched to 407 controls with >0 HLA mismatches. Kaplan–Meier analyses for death‐censored graft and patient survival showed no difference between study and control cohorts. In multivariate marginal Cox models, zero‐HLA mismatches saw no benefit with death‐censored graft survival (HR = 1.46, 95% CI 0.78–2.73) or patient survival (HR = 1.43, 95% CI 0.68–3.01). Our data suggest that in unrelated LDKT, zero‐HLA mismatches may not offer any survival advantage. Therefore, particular study of zero‐HLA mismatching is needed to validate its place in the OPTN/UNOS KPD Pilot Program allocation algorithm.     

Risk factors associated with Hepatitis E virus infection in kidney transplant recipients in a single tertiary Center in the United States

BackgroundHepatitis E virus (HEV), the causative agent of hepatitis E, is a common but self-limiting disease. However, in immunosuppressed kidney transplant 47 recipients (KTRs), HEV infection can become chronic. We investigated risk factors associated with HEV infection among 271 KTRs at the Johns Hopkins Hospital transplanted between 1988 and 2012.MethodsHEV infection was defined as having positive anti-HEV IgM, anti-HEV IgG, or HEV RNA. The risk factors included: age at transplant, sex, hemodialysis/peritoneal dialysis, plasmapheresis, transfusions, community urbanization, and other socioeconomic factors. Logistic regression was used to determine independent risk factors associated with HEV infection.ResultsOut of 271 KTRs, 43 (16%) had HEV infection though not active disease. HEV infection in KTRs was associated with older age (≥45 years; OR = 4.04; 95% CI = 1.81–57 10.03; p = 0.001) and living in communities with low proportions of minorities (OR = 0.22; 95% 58 CI = 0.04–0.90; p = 0.046).ConclusionKTRs who had HEV infection may be at an increased risk of developing chronic HEV.     

Dickkopf-1 Expression as a Marker for Predicting Clinical Outcome in Esophageal Squamous Cell Carcinoma

Background and Objectives  Dickkopf-1 (DKK1) is the inhibitor of the canonical Wnt signaling pathway, however it is highly transactivated in various cancers, suggesting the presence of unknown mechanism. Its implication in human esophageal squamous cell carcinoma (ESCC) has not been sufficiently investigated. Patients and Methods  We evaluated DKK1 protein expression in resected specimens from 170 patients with ESCC by immunohistochemistry. Tumors were categorized as positive or negative for DKK1. The relationships between DKK1 expression in ESCC and various clinicopathological parameters and prognosis (disease-free survival; DFS) were analyzed separately. Results  Immunohistochemically, 72 (42.4%) tumors were DKK1 positive while no significant staining was observed in the normal squamous epithelium except for few basal cells. There was no significant relationship between DKK1 expression in ESCC and any of the clinicopathological parameters tested in this study. Patients with DKK1-positive tumors had poorer DFS than those with negative ESCC (5-year DFS; 31.5% versus 53.6%, P = 0.0062). Univariate analysis showed a significant relationship between pT [hazard ratio (HR) = 2.944, 95% confidence interval (CI) = 1.713–5.059, P < 0.0001], number of pN (HR = 2.836, 95% CI = 1.866–4.309, P < 0.0001), lymphatic invasion (HR = 2.892, 95% CI = 1.336–6.262, P = 0.0070), and DKK1 expression (HR = 1.763, 95% CI = 1.167–2.663, P = 0.0071) and DFS. Multivariate analysis including the above four parameters identified pT (HR = 2.053, 95% CI = 1.157–3.645, P = 0.0140), pN number (HR = 2.107, 95% CI = 1.362–3.260, P = 0.0008), and DKK1 expression (HR = 1.813, 95% CI = 1.195–2.751, P = 0.0052) as independent and significant prognostic factors for DFS. Conclusion  Our data suggest the usefulness of DKK1 as a novel predictor of poor prognosis of patients with ESCC after curative resection and also as a therapeutic target for future tailored therapies against ESCC.     

Risk factors for renal allograft survival with China novel donation category: Donation after brain death followed by cardiac arrest

IntroductionTo meet the need for transplantable organs, a new donation program was initiated by the Chinese government. This novel policy created three categories for deceased organ donations: donation after circulatory death cardiac death (DCD), donation after brain death (DBD), and donation after brain death followed by circulatory death (DBCD) meaning complete cardiac arrest. In fact, the DBCD method is a combination of both DBD and DCD methods. A DBCD donor meets the criteria of for brain death, but the organ procurement begins after the withdrawal of life support and the subsequent cardiac arrest death. The purpose of this study was to evaluate the long-term outcomes of kidney transplantation in our center with the DBCD policy. Potential risk factors for affecting the renal allograft survival were also analyzed based on our data.MethodA retrospective study, involving 421 kidney transplants derived from 214 donors, was conducted between December 2011 and October 2019. In particular, 373 (88.6%) transplanted organs met the criteria for DBCD, and 48 (11.4%) for DCD. The log-rank test was used to compare the difference in survival. The Cox regression analysis was used for risk factor screening.ResultAnalysis showed that the DBCD group was better than the DCD group in terms of overall (p = 0.031) as well as death-censored (p = 0.026) allograft survival using the log-rank test. A Cox regression analysis revealed that increasing donor age (p = 0.002, HR = 1.820/10 years incremental older), increasing recipient age (p = 0.028, HR = 1.521/10 years increment older), prolonged dialysis duration (p = 0.007, HR = 1.018), occurrence episodes of acute rejection (p = 0.016, HR = 2.697), delayed graft function (p = 0.012, HR = 2.962), mismatch ≥4 HLA loci (p = 0.038, HR = 3.606), and warm ischemia time > 15 min (p = 0.022, HR = 2.915), were all independent risk factors affecting the graft survival.ConclusionThe new DBCD policy of donation produced acceptable results similar or even better than the DCD practice. Based on our analysis, the graft survival of DBCD transplants may be better than DCD transplants. The main risk factors for allograft loss included an increasing donor age, recipient age, warm ischemia time > 15 min, prolonged dialysis duration, acute rejection, delayed graft function, and HLA mismatch ≥4 HLA loci.     

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study

PurposeIn the MONALEESA-3 Phase III trial of patients with hormone receptor–positive human epidermal growth factor receptor–negative advanced breast cancer, ribociclib plus fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS). Here, we present patient-reported outcomes from the trial, including health-related quality of life (HRQOL).MethodsPatients were randomized (2:1) to receive ribociclib plus fulvestrant or placebo plus fulvestrant. Time to definitive 10% deterioration (TTD) from baseline in HRQOL (global health status [GHS] from the EORTC QLQ-C30 questionnaire) and pain (BPI-SF questionnaire) were assessed using Kaplan-Meier estimates; a stratified Cox regression model was used to estimate the hazard ratio (HR) and 95% CIs.ResultsDeterioration ≥10% in the EORTC-QLQ-C30 GHS was observed in 33% of patients in the ribociclib group vs 34% of patients in the placebo (reference) group (HR for TTD ≥ 10% = 0.81 [95% CI, 0.62–1.1]). Similar findings were noted for TTD ≥5% (HR = 0.79 [95% CI, 0.61–1.0]) and TTD ≥15% (HR = 0.81 [95% CI, 0.60–1.08]). TTD ≥10% in emotional functioning (HR = 0.76 [95% CI, 0.57–1.01]) trended in favor of the ribociclib group, whereas results for fatigue and pain were similar between arms. TTD ≥10% in BPI-SF pain severity index score (HR = 0.77 [95% CI, 0.57–1.05]) and worst pain item score (HR = 0.81 [95% CI, 0.58–1.12]) trended in favor of ribociclib vs placebo.ConclusionsIn addition to significantly prolonging PFS and OS compared with placebo plus fulvestrant, adding ribociclib to fulvestrant maintains HRQOL.     

Predicting the survival benefit of local surgery in patients aged 70 years or older with stage IV breast cancer: A population-based analysis

PurposeThe aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery.MethodsA total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed.ResultsPatients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627–0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568–0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509–0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709–1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713–1.275], P = 0.737).ConclusionOlder female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.     

Tamoxifen related side effects and their impact on breast cancer incidence: A retrospective analysis of the randomised IBIS-I trial

BackgroundStudies in the adjuvant setting have shown that endocrine therapy related side effects predict breast cancer recurrence risk. Here, we assess the relationship between early reported side effects and incidence of breast cancer in women randomised to tamoxifen for cancer prevention in the International Breast Intervention Study (IBIS)–I trial.MethodsWomen randomised to tamoxifen in the IBIS-I trial and for whom side effect status was known at the 6-month follow-up visit were included in this analysis. Side effects included in this analysis were hot flushes, vaginal discharge, and vaginal dryness. The primary endpoint was all breast cancer and secondary endpoint was oestrogen receptor (ER) positive breast cancer. Cox proportional hazard models were used to investigate breast cancer incidence in the tamoxifen group with and without side effects reported within 6 months of randomisation.ResultsWomen randomised to tamoxifen and reporting hot flushes at the 6-month follow-up visit had a non-statistically significant increase in breast cancer compared to those without hot flushes (HR = 1.26 (0.98–1.62), P = 0.08). A significant higher breast cancer risk was observed for postmenopausal women who reported hot flushes at the 6-month follow-up visit compared to those without hot flushes (HR = 1.59 (1.12–2.26), P = 0.01). A higher risk was observed for ER-positive breast cancer in postmenopausal women (HR = 1.81 (1.19–2.74), P = 0.01). No significant associations between gynaecological side effects and breast cancer occurrence was observed.ConclusionsOverall, no association between side effects reported at 6 months and subsequent breast cancer occurrence was observed. Some side effects might be useful markers for breast cancer occurrence in postmenopausal women.     

No Difference in the Rate of Periprosthetic Joint Infection in Patients Undergoing the Posterolateral Compared to the Direct Anterior Approach

BackgroundThere remains inconsistent data about the association of surgical approach and periprosthetic joint infection (PJI). We sought to evaluate the risk of reoperation for superficial infection and PJI after primary total hip arthroplasty (THA) in a multivariate model.MethodsWe reviewed 16,500 primary THAs, collecting data on surgical approach and all reoperations within 1 year for superficial infection (n = 36) or PJI (n = 70). Considering superficial infection and PJI separately, we used Kaplan–Meier survivorship to assess survival free from reoperation and a Cox Proportional Hazards multivariate models to assess risk factors for reoperation.ResultsBetween direct anterior approach (DAA) (N = 3,351) and PLA (N = 13,149) cohorts, rates of superficial infection (0.4 versus 0.2%) and PJI (0.3 versus 0.5%) were low and survivorship free from reoperation for superficial infection (99.6 versus 99.8%) and PJI (99.4 versus 99.7%) were excellent at both 1 and 2 years. The risk of developing superficial infection increased with high body mass index (BMI) (hazard ratio [HR] = 1.1 per unit increase, P = .003), DAA (HR = 2.7, P = .01), and smoking status (HR = 2.9, P = .03). The risk of developing PJI increased with the high BMI (HR = 1.04, P = .03), but not surgical approach (HR = 0.68, P = .3).ConclusionIn this study of 16,500 primary THAs, DAA was independently associated with an elevated risk of superficial infection reoperation compared to the PLA, but there was no association between surgical approach and PJI. An elevated patient BMI was the strongest risk factor for superficial infection and PJI in our cohort.Level of EvidenceIII, retrospective cohort study.     

The efficacy of neutralizing monoclonal antibodies in transplant recipients with mild-to-moderate COVID-19

IntroductionTransplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs.MethodsForty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O₂) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab.ResultsCasirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O₂ ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763–0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878–0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511–0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205–0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3–5 days after hospitalization than in those without, at 7–9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL).ConclusionCasirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression.     

Effect of recipient gender and donor‐specific antibodies on antibody‐mediated rejection after heart transplantation

Gender‐difference regarding antibody‐mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor‐specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single‐institution 6‐year cohort (2010‐2015), time to AMR was assessed, comparing men with women by survival analysis with a 1‐year death‐censored follow‐up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA‐, size‐ and sex‐mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1 year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard‐ratio [adj. HR] = 1.78 [1.06‐2.99]), P = .03) and the presence of pfDSA (adj. HR = 3.20 [1.80‐5.70], P < .001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR = 2.2 (P = .026) and MFI of pfDSA (per 1 MFI‐increase) adj. HR = 1.0002 (P < .0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender‐related difference in the severity of pfDSA.     

Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study

PurposeTo identify prognostic factors of invasive–disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice.MethodsWe performed a retrospective study using data from the Côte d’Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS.ResultsA total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65–5.32], p < 0.0001). Receiving aromatase inhibitors (AI) was associated with a lower risk of recurrence (HR = 0.70, 95%CI [0.54–0.90], p = 0.055) compared to tamoxifen. Compared to women with no comorbidities, women with 1 or 2 comorbidities were more likely to receive AI (OR = 1.63, 95%CI [1.22–2.17], p = 0.0009).ConclusionsComorbidities, age at diagnosis and previous treatment were associated with iDFS in non-metastatic HR + BC patients. This study also showed that women who received tamoxifen for their cancer experienced worse iDFS compared to women treated with AI.     

Impact of psychiatric comorbidities on outcomes related to thyroid and parathyroid operations

BackgroundWe examined the effect of psychiatric comorbidities on perioperative surgical outcomes and the leading causes of readmissions in patients who underwent thyroid and parathyroid operations.MethodPatient information was retrieved from the Nationwide Readmission Database (2010–2017). Multivariate analysis was used to identify predictors for hospital readmissions.ResultsA total of 181,007 and 53,808 patients underwent thyroid and parathyroid operations, respectively. Of those, 8,468 (4.7%) and 6,112 (11.4%) patients were readmitted within 30 days. Psychiatric comorbidities were more frequent in readmitted cohorts after thyroidectomies (14.9% vs 10.4%; P < .001) and parathyroidectomies (16.8% vs 11.5%; P < .001), with anxiety being the most frequent cause (thyroid: 7.87%, parathyroid: 6.8%). Psychiatric comorbidities were associated with greater risk of in-hospital mortality (thyroid: odds ratio = 2.07, 95% confidence interval = 1.13–3.53; P = .015 and parathyroid: odds ratio = 1.67, 95% confidence interval = 1.04–2.70; P = .005), postoperative complications (thyroid: odds ratio = 1.528, 95% confidence interval = 1.473–1.585; P < .001 and parathyroid: odds ratio = 3.26, 95% confidence interval = 2.84–3.73; P < .001), prolonged duration of stay (thyroid: beta coefficient = 1.142, 95% confidence interval = 1.076–1.207; P < .001 and parathyroid: beta coefficient = 2.15, 95% confidence interval = 1.976–2.32; P < .001), and 30-day readmissions (thyroid: hazard ratio = 1.18, 95% confidence interval = 1.03–1.18; P = .047 and parathyroid: hazard ratio = 1.23, 95% confidence interval = 1.11–1.36; P < .001). Psychosis had the greatest risk of readmission (thyroid: hazard ratio = 1.51 and parathyroid: hazard ratio = 1.42), and dementia (odds ratio = 2.58) had the greatest risk of postoperative complications.ConclusionConcomitant psychiatric conditions after thyroid and parathyroid operations were associated with increased risk of postoperative complications, prolonged hospital stays, and greater rates of readmissions.     

Molecular-level HLA mismatch is associated with rejection and worsened graft survival in heart transplant recipients – a retrospective study

The aim was to evaluate the association of molecular-level human leukocyte antigen (HLA) mismatching with post-transplant graft survival, rejection, and cardiac allograft vasculopathy (CAV). We retrospectively analyzed all primary cardiac transplant recipients between 01/1984-06/2016. 1167 patients fulfilled inclusion criteria and had HLA typing information available. In 312 donor-recipient pairs, typing at serological split antigen level was available. We used the Epitope MisMatch Algorithm to calculate the number of amino acid differences in antibody-verified HLA eplets (amino acid mismatch load (AAMM)) between donor and recipient. Patients with a higher HLA-DR AAMM load had inferior 1-year graft survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01–1.28). The HLA-AB AAMM load showed no impact on graft survival. In the subgroup with available split-level information, we observed an inferior graft survival for a higher HLA-DR AAMM load 3 months after transplantation (HR, 1.22; 95% CI, 1.04–1.44) and a higher risk for rejection for an increasing HLA-AB (HR, 1.70; 95% CI, 1.29–2.24) and HLA-DR (HR, 1.32; 95% CI, 1.09–1.61) AAMM load. No impact on the development of CAV was found. Molecular-level HLA mismatch analysis could serve as a tool for risk stratification after heart transplantation and might take us one step further into precision medicine.     

Hepatitis E virus infection and rejection in kidney transplant recipients

BackgroundHepatitis E virus (HEV) infection has been associated with immune-mediated kidney diseases in developing countries. However, its relationship with kidney transplant outcomes has never been studied. We investigated the association between HEV infection and kidney graft rejection among kidney transplant recipients (KTRs).MethodsWe conducted a matched cohort and longitudinal study utilizing banked sera following kidney transplantation during 1988–2012. Studies with evidence of post-transplantation HEV infection were identified by positive ELISA tests (anti-HEV IgM or anti-HEV IgG seroconversion) or positive HEV PCR and matched to KTR controls with negative HEV ELISA and PCR tests in a 1:5 ratio by age, sex, crossmatch status, immunosuppression era, and time of HEV testing. Outcome data collected included time to first kidney graft rejection, transaminases, and glomerular filtration rates. Log-ranked test was used to analyze survival.ResultsOf 271 KTRs, 9 (3%) had evidence of post-transplantation HEV infection and were compared to 45 negative, matched controls. Median age at transplantation was 46 years. Kidney graft rejection was reported in 8 (89%) of cases and 21 (47%) of controls. Median time to first episode of kidney graft rejection was 17.4 months in cases and 30.8 months in controls (p = 0.029), with a higher hazard of developing kidney graft rejection in cases (HR = 3.23, 95% CI: 1.19–8.79). Lower mean glomerular filtration rates over time were observed in cases (35 mL/min/1.73m²) versus controls (42.4 mL/min/1.73m²) but did not reach significance (p = 0.24).ConclusionSubjects with evidence of post-transplantation HEV infection demonstrated earlier kidney graft rejection compared to controls.     

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

PurposeAmong metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy.MethodsThe ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified.ResultsOf the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively.ConclusionThe duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.     

A Comparison of Risk of Dislocation and Cause-Specific Revision Between Direct Anterior and Posterior Approach Following Elective Cementless Total Hip Arthroplasty

BackgroundUse of the direct anterior approach (DAA) for total hip arthroplasty (THA) has increased over the last decade. We sought to investigate whether (1) a difference exists in dislocation risk for DAA compared with posterior THA, (2) a difference exists in risk for specific revision reasons, and (3) the likelihood of adverse 90-day postoperative events differs.MethodsWe conducted a cohort study using data from Kaiser Permanente’s Total Joint Replacement Registry. Patients aged ≥18 years who underwent primary cementless THA for osteoarthritis with a highly cross-linked polyethylene liner were included (2009-2017). Multivariable Cox proportional hazards regression was used to evaluate dislocation and cause-specific revision risks, and multivariable logistic regression was used to evaluate 90-day emergency department visits, 90-day unplanned readmissions, and 90-day complications (including deep infection, deep vein thrombosis, and pulmonary embolism).ResultsOf 38,399 primary THA, 6428 (16.7%) were DAA. All-cause revision at 2-years follow-up was 1.78% (95% confidence interval [CI] = 1.46-2.17) for DAA and 2.28% (95% CI = 2.11-2.45) for posterior. After adjusting for covariates, DAA had a lower risk of dislocation (hazard ratio [HR] = 0.39, 95% CI = 0.29-0.53), revision for instability (HR = 0.33, 95% CI = 0.18-0.58), revision for periprosthetic fracture (HR = 0.57, 95% CI = 0.34-0.96), and readmission (odds ratio = 0.82, 95% CI = 0.67-0.99) compared with posterior approach but a higher risk of revision for aseptic loosening (HR = 2.26, 95% CI = 1.35-3.79).ConclusionWhile the DAA associated with lower risks of dislocation and revision for instability and periprosthetic fracture, it is associated with a higher revision risk for aseptic loosening. Surgeons should discuss these risks with their patients.