Strategies aimed at preventing long-term opioid use in trauma and orthopaedic surgery: a scoping review.

BACKGROUND: Long-term opioid use, which may have significant individual and societal impacts, has been documented in up to 20% of patients after trauma or orthopaedic surgery. The objectives of this scoping review were to systematically map the research on strategies aiming to prevent chronic opioid use in these populations and to identify knowledge gaps in this area. METHODS: This scoping review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. We searched seven databases and websites of relevant organizations. Selected studies and guidelines were published between January 2008 and September 2021. Preventive strategies were categorized as: system-based, pharmacological, educational, multimodal, and others. We summarized findings using measures of central tendency and frequency along with p-values. We also reported the level of evidence and the strength of recommendations presented in clinical guidelines. RESULTS: A total of 391 studies met the inclusion criteria after initial screening from which 66 studies and 20 guidelines were selected. Studies mainly focused on orthopaedic surgery (62,1%), trauma (30.3%) and spine surgery (7.6%). Among system-based strategies, hospital-based individualized opioid tapering protocols, and regulation initiatives limiting the prescription of opioids were associated with statistically significant decreases in morphine equivalent doses (MEDs) at 1 to 3 months following trauma and orthopaedic surgery. Among pharmacological strategies, only the use of non-steroidal anti-inflammatory drugs and beta blockers led to a significant reduction in MEDs up to 12 months after orthopaedic surgery. Most studies on educational strategies, multimodal strategies and psychological strategies were associated with significant reductions in MEDs beyond 1 month. The majority of recommendations from clinical practice guidelines were of low level of evidence. CONCLUSIONS: This scoping review advances knowledge on existing strategies to prevent long-term opioid use in trauma and orthopaedic surgery patients. We observed that system-based, educational, multimodal and psychological strategies are the most promising. Future research should focus on determining which strategies should be implemented particularly in trauma patients at high risk for long-term use, testing those that can promote a judicious prescription of opioids while preventing an illicit use, and evaluating their effects on relevant patient-reported and social outcomes.

Nanopore sequencing of clonal IGH rearrangements in cell-free DNA as a biomarker for acute lymphoblastic leukemia.

Background: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, and patients with relapsed ALL have a poor prognosis. Detection of ALL blasts remaining at the end of treatment, or minimal residual disease (MRD), and spread of ALL into the central nervous system (CNS) have prognostic importance in ALL. Current methods to detect MRD and CNS disease in ALL rely on the presence of ALL blasts in patient samples. Cell-free DNA, or small fragments of DNA released by cancer cells into patient biofluids, has emerged as a robust and sensitive biomarker to assess cancer burden, although cfDNA analysis has not previously been applied to ALL. Methods: We present a simple and rapid workflow based on NanoporeMinION sequencing of PCR amplified B cell-specific rearrangement of the (IGH) locus in cfDNA from B-ALL patient samples. A cohort of 5 pediatric B-ALL patient samples was chosen for the study based on the MRD and CNS disease status. Results: Quantitation of IGH-variable sequences in cfDNA allowed us to detect clonal heterogeneity and track the response of individual B-ALL clones throughout treatment. cfDNA was detected in patient biofluids with clinical diagnoses of MRD and CNS disease, and leukemic clones could be detected even when diagnostic cell-count thresholds for MRD were not met. These data suggest that cfDNA assays may be useful in detecting the presence of ALL in the patient, even when blasts are not physically present in the biofluid sample. Conclusions: The Nanopore IGH detection workflow to monitor cell-free DNA is a simple, rapid, and inexpensive assay that may ultimately serve as a valuable complement to traditional clinical diagnostic approaches for ALL.

Case Report: Syndrome of Remitting Seronegative Symmetrical Synovitis with Pitting Edema-A Rare but Treatable Condition in Palliative Medicine.

The syndrome of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare diagnosis that is often missed due to lack of both definitive diagnostic criteria and awareness of the disease. This case report describes a patient with chronic lymphocytic leukemia whose diagnosis of RS3PE was possibly delayed due to concomitant treatment-related arthralgias. The pathophysiology, presentation, and treatment of RS3PE are discussed. Greater awareness of malignancy-related RS3PE is crucial from a palliative care perspective as typical opioid pain management will prove ineffective and delay appropriate treatment.

Biological Investigations of Ru(II) Complexes With Diverse ß-diketone Ligands.

The ß-diketone scaffold is a commonly used synthetic intermediate, and is a functional group found in natural products such as curcuminoids. This core structure can also act as a chelating ligand for a variety of metals. In order to assess the potential of this scaffold for medicinal inorganic chemistry, seven different κ2-O,O'-chelating ligands were used to construct Ru(II) complexes with polypyridyl co-ligands, and their biological activity was evaluated. The complexes demonstrated promising structure-dependent cytotoxicity. Three complexes maintained high activity in a tumor spheroid model, and all complexes demonstrated low in vivo toxicity in a zebrafish model. From this series, the best compound exhibited a ~ 30-fold window between cytotoxicity in a 3-D tumor spheroid model and potential in vivo toxicity. These results suggest that κ2-O,O'-ligands can be incorporated into Ru(II)-polypyridyl complexes to create favorable candidates for future drug development.

Avobenzone incorporation in a diverse range of Ru(II) scaffolds produces potent potential antineoplastic agents.

Four structurally distinct classes of polypyridyl ruthenium complexes containing avobenzone exhibited low micromolar and submicromolar potencies in cancer cells, and were up to 273-fold more active than the parent ligand. Visible light irradiation enhanced the cytotoxicity of some complexes, making them promising candidates for combined chemo-photodynamic therapy.

Drug Screening of Primary Patient Derived Tumor Xenografts in Zebrafish.

Patient derived xenograft models are critical in defining how different cancers respond to drug treatment in an in vivo system. Mouse models are the standard in the field, but zebrafish have emerged as an alternative model with several advantages, including the ability for high-throughput and low-cost drug screening. Zebrafish also allow for in vivo drug screening with large replicate numbers that were previously only obtainable with in vitro systems. The ability to rapidly perform large scale drug screens may open up the possibility for personalized medicine with rapid translation of results back to clinic. Zebrafish xenograft models could also be used to rapidly screen for actionable mutations based on tumor response to targeted therapies or to identify new anti-cancer compounds from large libraries. The current major limitation in the field has been quantifying and automating the process so that drug screens can be done on a larger scale and be less labor-intensive. We have developed a workflow for xenografting primary patient samples into zebrafish larvae and performing large scale drug screens using a fluorescence microscope equipped imaging unit and automated sampler unit. This method allows for standardization and quantification of engrafted tumor area and response to drug treatment across large numbers of zebrafish larvae. Overall, this method is advantageous over traditional cell culture drug screening as it allows for growth of tumor cells in an in vivo environment throughout drug treatment, and is more practical and cost-effective than mice for large scale in vivo drug screens.

Baseline diet modifies the effects of dietary change.

The Dietary Approaches to Stop Hypertension (DASH) eating pattern has been shown to reduce blood pressure (BP) in previous clinical trials. In the PREMIER study, an established behavioural intervention, with or without DASH, promoted greater weight loss than an advice-only control group, but effects of the DASH intervention on BP were weaker. In these analyses, PREMIER data were used to evaluate whether change in dairy product or fruit and vegetable (FV) intake during the first six intervention months impacted changes in weight and/or BP. Study participants were classified as having low or high intakes of dairy products (<1·5 v. ≥1·5 servings/d) and FV (<5 v. ≥5 servings/d) at baseline and 6 months. For dairy products, in particular, participants with higher baseline intakes tended to decrease their intakes during the intervention. In these analyses, subjects consuming <1·5 dairy servings/d at baseline whose intake increased during the intervention lost more weight than those whose intake decreased or remained low throughout (10·6 v. 7·0 pounds (4·8 v. 3·2 kg) lost, respectively, P = 0·002). The same was true for FV intake (11·0 v. 5·9 pounds (5·0 v. 2·7 kg) lost, P < 0·001). We also found synergistic effects of dairy products and FV on weight loss and BP reduction. Specifically, subjects who increased their intakes of dairy products and also consumed ≥5 servings of FV/d lost more weight and had greater reductions in BP than other groups; in addition, higher FV intakes had the greatest benefit to BP among those consuming more dairy products. These results provide evidence that the DASH pattern was most beneficial to individuals whose baseline diet was less consistent with DASH.

A qualitative study of e-cigarette emergence and the potential for renormalisation of smoking in UK youth.

BACKGROUND: Growth of e-cigarette use among smokers has raised concerns over uptake by non-smokers, particularly young people. Legislative changes aimed in part at reducing youth exposure to e-cigarettes include the EU Tobacco Products Directive (TPD). A core justification for such measures is the belief that e-cigarettes can lead to tobacco smoking through mechanisms of renormalisation including: mimicking and normalizing the act of smoking; increasing product acceptability via marketing; nicotine exposure. These mechanisms are here explored in relation to findings from qualitative research. METHODS: This paper reports results from twenty-one group interviews with 14-15 year olds in Wales, England and Scotland, conducted as part of an ongoing evaluation of the impact of the TPD on youth smoking and e-cigarette use. Interviews were conducted around the end of the transitional period for TPD implementation, and explored perceptions of e-cigarettes and tobacco, as well as similarities and differences between them. RESULTS: Young people differentiated between tobacco and e-cigarettes, rejecting the term e-cigarette in favour of alternatives such as 'vapes'. Experimental or occasional use was common and generally approved of where occurring within social activity with peers. However, regular use outside of this context was widely disapproved of, unless for the purpose of stopping smoking. Increased prevalence of e-cigarettes did not challenge strongly negative views of smoking or reduce perceived harms caused by it, with disapproval of smoking remaining high. Nicotine use was variable, with flavour a stronger driver for choice of e-liquid, and interest more generally. CONCLUSION: The extent to which participants differentiated between vaping and smoking, including styles and reasons for use in adults and young people; absence of marketing awareness; and continued strong disapproval of smoking provides limited support for some of the potential mechanisms through which e-cigarettes may renormalise smoking. However caution over nicotine exposure is still necessary.

Correction: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

This article was originally published under a CC BY NC SA License, but has now been made available under a CC BY 4.0 License.

'Why us?' Causal attributions of childhood cancer survivors, survivors' parents and community comparisons - a mixed methods analysis.

INTRODUCTION: Understanding the cause of their cancer is important for many cancer patients. Childhood cancer survivors'/survivors' parents' beliefs about cancer etiology are understudied. We aimed to assess survivors'/parents' beliefs about what causes childhood cancer, compared with beliefs in the community. We also investigated the influence of clinical and socio-demographic characteristics on the participants' beliefs about cancer etiology. METHODS: This two-stage study investigated the participants' beliefs, by using questionnaires assessing causal attributions related to childhood cancer (stage 1) and then undertaking telephone interviews (stage 2; survivors/survivors' parents only) to get an in-depth understanding of survivors'/survivors' parents beliefs. We computed multivariable regressions to identify factors associated with the most commonly endorsed attributions: bad luck/chance, environmental factors and genetics. We analyzed interviews using thematic analysis. RESULTS: Six hundred one individuals (64.6% survivors and 35.4% survivors' parents) and 510 community comparisons (53.1% community adults, 46.9% community parents) completed the question on causal attributions. We conducted 87 in-depth interviews. Survivors/survivors' parents (73.9%) were more likely to believe that chance/bad luck caused childhood cancer than community participants (42.4%). Community participants more frequently endorsed that genetics (75.3%) and environmental factors (65.3%) played a major role in childhood cancer etiology (versus survivors' and survivors' parents: genetics 20.6%, environmental factors: 19.3%). Community participants, participants with a first language other than English, and reporting a lower quality of life were less likely to attribute bad luck as a cause of childhood cancer. Community participants, all participants with a higher income and higher education were more likely to attribute childhood cancer etiology to environmental factors. CONCLUSION: Causal attributions differed between survivors/survivors' parents and community participants. Most of the parents and survivors seem to understand that there is nothing they have done to cause the cancer. Understanding survivors' and survivors' parents' causal attributions may be crucial to address misconceptions, offer access to services and to adapt current and future health behaviors.

Validation of the What Matters Index: A brief, patient-reported index that guides care for chronic conditions and can substitute for computer-generated risk models.

INTRODUCTION: Current health care delivery relies on complex, computer-generated risk models constructed from insurance claims and medical record data. However, these models produce inaccurate predictions of risk levels for individual patients, do not explicitly guide care, and undermine health management investments in many patients at lesser risk. Therefore, this study prospectively validates a concise patient-reported risk assessment that addresses these inadequacies of computer-generated risk models. METHODS: Five measures with well-documented impacts on the use of health services are summed to create a "What Matters Index." These measures are: 1) insufficient confidence to self-manage health problems, 2) pain, 3) bothersome emotions, 4) polypharmacy, and 5) adverse medication effects. We compare the sensitivity and predictive values of this index with two representative risk models in a population of 8619 Medicaid recipients. RESULTS: The patient-reported "What Matters Index" and the conventional risk models are found to exhibit similar sensitivities and predictive values for subsequent hospital or emergency room use. The "What Matters Index" is also reliable: akin to its performance during development, for patients with index scores of 1, 2, and ≥3, the odds ratios (with 95% confidence intervals) for subsequent hospitalization within 1 year, relative to patients with a score of 0, are 1.3 (1.1-1.6), 2.0 (1.6-2.4), and 3.4 (2.9-4.0), respectively; for emergency room use, the corresponding odds ratios are 1.3 (1.1-1.4), 1.9 (1.6-2.1), and 2.9 (2.6-3.3). Similar findings were replicated among smaller populations of 1061 mostly older patients from nine private practices and 4428 Medicaid patients without chronic conditions. SUMMARY: In contrast to complex computer-generated risk models, the brief patient-reported "What Matters Index" immediately and unambiguously identifies fundamental, remediable needs for each patient and more sensibly directs the delivery of services to patient categories based on their risk for subsequent costly care.

Development of a care guidance index based on what matters to patients.

INTRODUCTION: Targeting resources for a designated higher-risk subgroup is a strategy for chronic care management. However, risk-designation has several limitations: it is inaccurate, seldom helpful for care guidance, and potentially misallocates care away from many patients. METHODS: To address limitations of risk designation, we tested a "what matters index" (WMI) in 19,593 adult patients with chronic conditions. The WMI contains five binary measures: insufficient confidence to manage health problems, level of pain, emotional problems, polypharmacy, and adverse medication effects. We examined its sum for association with patient-reported quality of life and prior emergency or hospital use. We compared its accuracy to a prototypic risk-designation model. RESULTS: The WMI was a good indicator for quality of life and in three diverse test populations it was strongly associated with the use of hospital and emergency services. For example, a sum of WMI ≥2 was associated with twice as many average uses as none; for ≥3, uses were three times higher. However, since relatively few patients use costly care, both the WMI and a prototypic risk-designation model had comparably low-positive predictive values. The WMI uses the patient voice to identify needs strongly associated with quality of life. Akin to risk designation models, the WMI can be used to place patients into groups associated with levels of costly services, but neither is likely to forecast costly service use for individuals. However, unlike risk-designation models, the WMI is based on measures that will immediately guide care for every patient.

Effect of adding a mobile health intervention to a multimodal antimicrobial stewardship programme across three teaching hospitals: an interrupted time series study.

Objectives: To evaluate the impact of adding a mobile health (mHealth) decision support system for antibiotic prescribing to an established antimicrobial stewardship programme (ASP). Methods: In August 2011, the antimicrobial prescribing policy was converted into a mobile application (app). A segmented regression analysis of interrupted time series was used to assess the impact of the app on prescribing indicators, using data (2008-14) from a biannual point prevalence survey of medical and surgical wards. There were six data points pre-implementation and six data points post-implementation. Results: There was an increase in compliance with policy (e.g. compliance with empirical therapy or expert advice) in the two specialties of medicine (6.48%, 95% CI = -1.25 to 14.20) and surgery (6.63%, 95% CI = 0.15-13.10) in the implementation period, with a significant sudden change in level in surgery ( P < 0.05). There was an increase, though not significant, in medicine (15.20%, 95% CI = -17.81 to 48.22) and surgery (35.97%, 95% CI = -3.72 to 75.66) in the percentage of prescriptions that had a stop/review date documented. The documentation of indication decreased in both medicine (-16.25%, 95% CI = -42.52 to 10.01) and surgery (-14.62%, 95% CI = -42.88 to 13.63). Conclusions: Introducing the app into an existing ASP had a significant impact on the compliance with policy in surgery, and a positive, but not significant, effect on documentation of stop/review date in both specialties. The negative effect on the third indicator may reflect a high level of compliance pre-intervention, due to existing ASP efforts. The broader value of providing an antimicrobial policy on a digital platform, e.g. the reach and access to the policy, should be measured using indicators more sensitive to mHealth interventions.

Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 µg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.

Fluorescence Imaging for Cancer Screening and Surveillance.

The advent of fluorescence imaging (FI) for cancer cell detection in the field of oncology is promising for both cancer screening and surgical resection. Particularly, FI in cancer screening and surveillance is actively being evaluated in many new clinical trials with over 30 listed on Clinical Trials.gov . While surgical resection forms the foundation of many oncologic treatments, early detection is the cornerstone for improving outcomes and reducing cancer-related morbidity and mortality. The applications of FI are twofold as it can be applied to high-risk patients in addition to those undergoing active surveillance. This technology has the promise of highlighting lesions not readily detected by conventional imaging or physical examination, allowing disease detection at an earlier stage of development. Additionally, there is a persistent need for innovative, cost-effective imaging modalities to ameliorate healthcare disparities and the global burden of cancer worldwide. In this review, we outline the current utility of FI for screening and detection in a range of cancer types.

Femtogram Resolution of Iron Content on a Per Cell Basis: Ex Vivo Storage of Human Red Blood Cells Leads to Loss of Hemoglobin.

The magnetic characteristics of hemoglobin (Hb) changes with the binding of dioxygen (O2) to the heme prosthetic groups of the globin chains: from paramagnetic ferrous Hb to diamagnetic ferrous oxyhemoglobin (oxyHb) with reversibly bound O2, or paramagnetic ferric methemoglobin (metHb). When multiplied over the number of Hb molecules in a red blood cell (RBC), the effect is detectable through motion analysis of RBCs in a high magnetic field and gradient. This motion is referred to as magnetophoretic mobility, which can be conveniently expressed as a fraction of the cell sedimentation velocity. In this Article, using a previously developed and reported instrument, cell tracking velocimetry (CTV), we are able to detect difference in Hb concentration in two RBC populations to a resolution of 1 × 107 Hb molecules per cell (4 × 107 atoms of Fe per cell or 4-5 femtograms of Fe). Similar resolution achieved with inductively coupled plasma-mass spectrometry requires on the order of 105-106 cells and provides an average, whereas CTV provides a measurement for each cell. CTV analysis revealed that RBCs lose, on average, 17% of their Hb after 42 days of storage, the maximum FDA-approved length of time for the cold storage of RBCs in additive solution. This difference in Hb concentration was the result of routine RBC storage; clinical implications are discussed.

TET2 binds the androgen receptor and loss is associated with prostate cancer.

Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine proximal to KLK3. A gene co-expression network identified using TCGA prostate tumour RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signalling. Decreased TET2 mRNA expression in TCGA PCa tumours is strongly associated with reduced patient survival, indicating reduced expression in tumours may be an informative biomarker of disease progression and perhaps metastatic disease.

Isolation demand from carbapenemase-producing Enterobacteriaceae screening strategies based on a West London hospital network.

OBJECTIVE: To estimate the isolation demands arising from high-risk specialty-based screening for carbapenemase-producing Enterobacteriaceae (CPE), and the potential fraction of CPE burden detected. METHODS: Clinical specialty groups from three London hospitals were ranked by incidence of carbapenem resistance among Escherichia coli and Klebsiella spp. Contact precaution bed-days were estimated for three screening strategies: Strategy 1, 'circulation science and renal medicine'; Strategy 2, Strategy 1 plus 'specialist services'; and Strategy 3, Strategy 2 plus 'private patients'. Isolation bed occupancy rates and potential CPE detection rates were estimated. RESULTS: Of 99,105 admissions to the three hospitals in Financial Year 2014/15, Strategies 1, 2 and 3 would have screened 4371 (4.4%), 7482 (7.6%), and 13,542 (13.7%) patients, respectively. The specialties' isolation bed occupancy rates varied between 3% and 696% depending on strategy, number of consecutive tests, and whether or not pre-emptive isolation had been applied. Expected detection rates of the potential CPE burden in the hospital network would have varied between 17.1% and 47.5%. CONCLUSIONS: High-risk specialty-based screening has the potential to detect nearly half of the potential CPE burden, and would be more pragmatic than patient-level risk-factor-based screening. Pre-emptive isolation increases isolation requirements substantially. CPE screening strategies need to balance risk and resources.

Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States.

Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987-2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116 208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95% confidence interval 5.27-6.13), especially for papillary RCC (SIR 13.3 versus 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p-trend < 0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.