Multi‐center kidney paired donation (KPD) is an exciting new transplant option that has not yet approached its full potential. One barrier to progress is accurate virtual crossmatching for KPD ...waitlists with many highly sensitized patients. Virtual crossmatch results from a large multi‐center consortium, the National Kidney Registry (NKR), were analyzed to determine the effectiveness of flexible center‐specific criteria for virtual crossmatching. Approximately two‐thirds of the patients on the NKR waitlist are highly sensitized (>80% CPRA). These patients have antibodies against HLA‐A (63%), HLA‐B (66%), HLA‐C (41%), HLA‐DRB1 (60%), HLA‐DRB3/4/5 (18–22%), HLA‐DQB1 (54%) and HLA‐DPB1 (26%). With donors typed for these loci before activation, 91% of virtual crossmatches accurately predicted an acceptable cell‐based donor crossmatch. Failed virtual crossmatches were attributed to equivocal virtual crossmatches (46%), changes in HLA antibodies (21%), antibodies against HLA‐DQA (6%), transcription errors (6%), suspected non‐HLA antibodies (5%), allele‐specific antibodies (1%) and unknown causes (15%). Some failed crossmatches could be prevented by modifiable factors such as more frequent assessment of HLA antibodies, DQA1 typing of donors and auditing data entry. Importantly, when transplant centers have flexibility to define crossmatch criteria, it is currently feasible to use virtual crossmatching for highly sensitized patients to reliably predict acceptable cell‐based crossmatches.
When centers have flexibility to define unacceptable antigens, virtual crossmatching can be used to reliably predict acceptable cell‐based crossmatches for highly sensitized patients.
Mechanical thrombectomy is beneficial for patients with acute ischemic stroke and a proximal anterior occlusion, but it is unclear if these results can be extrapolated to patients with an M2 ...occlusion. The purpose of this study was to examine the technical aspects, safety, and outcomes of mechanical thrombectomy with a stent retriever in patients with an isolated M2 occlusion who were included in 3 large multicenter prospective studies.
We included patients from the Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), Solitaire With the Intention For Thrombectomy (SWIFT), and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) studies, 3 large multicenter prospective studies on thrombectomy for ischemic stroke. We compared outcomes and technical details of patients with an M2 with those with an M1 occlusion. All patients were treated with a stent retriever. Imaging data and outcomes were scored by an independent core laboratory. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b/3.
We included 50 patients with an M2 and 249 patients with an M1 occlusion. Patients with an M2 occlusion were older (mean age, 71 versus 67 years; P = .04) and had a lower NIHSS score (median, 13 versus 17; P < .001) compared with those with an M1 occlusion. Procedural time was nonsignificantly shorter in patients with an M2 occlusion (median, 29 versus 35 minutes; P = .41). The average number of passes with a stent retriever was also nonsignificantly lower in patients with an M2 occlusion (mean, 1.4 versus 1.7; P = .07). There were no significant differences in successful reperfusion (85% versus 82%, P = .82), symptomatic intracerebral hemorrhages (2% versus 2%, P = 1.0), device-related serious adverse events (6% versus 4%, P = .46), or modified Rankin Scale score 0-2 at follow-up (60% versus 56%, P = .64).
Endovascular reperfusion therapy appears to be feasible in selected patients with ischemic stroke and an M2 occlusion.
We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time ...projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03) ton yr exposure used for this search, the intrinsic ^{85}Kr and ^{222}Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3) events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10^{-47} cm^{2} for a WIMP mass of 28 GeV/c^{2} at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure.
We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target ...reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.
While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges ...that have limited its adoption in United States and Canada. A consensus conference was convened March 29–30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.
The authors present a report from a consensus conference that aimed to identify and address the full spectrum of theoretical and practical obstacles that have hindered the optimal implementation of kidney paired donation in the United States.
We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the ...DAMIC detector at SNOLAB of 2–6×10−22 A cm−2. We evaluate the charge distribution of pixels that collect <10e− for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c−2. We also present new constraints on hidden-photon dark matter with masses in the range 1.2–30 eV c−2.
Solid organ transplant recipients (SOTRs) are at increased risk of developing and dying from cancer. However, controversies exist around cancer screening in this population owing to reduced life ...expectancy and competing causes of death. This systematic review assesses the availability, quality and consistency of cancer screening recommendations in clinical practice guidelines (CPGs). We systematically searched bibliographic databases and gray literature to identify CPGs and assessed their quality using AGREE II. Recommendations were extracted along with their supporting evidence. Thirteen guidelines were included in the review. CPGs for kidney recipients were the most frequent source of screening recommendations, and recommendations for skin cancer screening were most frequently presented. Some screening recommendations differed from those for the general population, based on literature demonstrating higher cancer incidence among SOTRs versus direct evidence of screening effectiveness. Relevant stakeholders such as oncology specialists, primary care providers and public health experts were not involved in the formulation of the screening recommendations. In conclusion, although several guidelines make recommendations for cancer screening in SOTRs, the availability of cancer screening recommendations varied considerably by transplanted organ. More studies are required to inform cancer screening recommendations in SOTRs, and guideline development should involve transplant patients, oncologists and cancer screening specialists.
This systematic review assesses cancer screening recommendations in posttransplant care clinical practice guidelines and finds that although 13 guidelines make recommendations for cancer screening in transplant recipients, the availability of recommendations varies considerably by transplanted organ and that relevant stakeholders were not involved in the formulation of screening recommendations. See Blosser's editorial on page 9.
Myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of ...patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment.
We sequenced coding exons from 69 myeloid cancer genes in patients with myeloproliferative neoplasms, comprehensively annotating driver mutations and copy-number changes. We developed a genomic classification for myeloproliferative neoplasms and multistage prognostic models for predicting outcomes in individual patients. Classification and prognostic models were validated in an external cohort.
A total of 2035 patients were included in the analysis. A total of 33 genes had driver mutations in at least 5 patients, with mutations in JAK2, CALR, or MPL being the sole abnormality in 45% of the patients. The numbers of driver mutations increased with age and advanced disease. Driver mutations, germline polymorphisms, and demographic variables independently predicted whether patients received a diagnosis of essential thrombocythemia as compared with polycythemia vera or a diagnosis of chronic-phase disease as compared with myelofibrosis. We defined eight genomic subgroups that showed distinct clinical phenotypes, including blood counts, risk of leukemic transformation, and event-free survival. Integrating 63 clinical and genomic variables, we created prognostic models capable of generating personally tailored predictions of clinical outcomes in patients with chronic-phase myeloproliferative neoplasms and myelofibrosis. The predicted and observed outcomes correlated well in internal cross-validation of a training cohort and in an independent external cohort. Even within individual categories of existing prognostic schemas, our models substantially improved predictive accuracy.
Comprehensive genomic characterization identified distinct genetic subgroups and provided a classification of myeloproliferative neoplasms on the basis of causal biologic mechanisms. Integration of genomic data with clinical variables enabled the personalized predictions of patients' outcomes and may support the treatment of patients with myeloproliferative neoplasms. (Funded by the Wellcome Trust and others.).
Clinical practice guidelines recommend a multidisciplinary approach to cancer care that brings together all relevant disciplines to discuss optimal disease management. However, the literature is ...characterized by heterogeneous definitions and few reviews about the processes and outcomes of multidisciplinary care. The objective of this scoping review was to identify and classify the definitions and characteristics of multidisciplinary care, as well as outcomes and interventions for patients with breast cancer.
A systematic search for quantitative and qualitative studies about multidisciplinary care for patients with breast cancer was conducted for January 2001 to December 2017 in the following electronic databases: medline, embase, PsycInfo, and cinahl. Two reviewers independently applied our eligibility criteria at level 1 (title/abstract) and level 2 (full-text) screening. Data were extracted and synthesized descriptively.
The search yielded 9537 unique results, of which 191 were included in the final analysis. Two main types of multidisciplinary care were identified: conferences and clinics. Most studies focused on outcomes of multidisciplinary care that could be variously grouped at the patient, provider, and system levels. Research into processes tended to focus on processes that facilitate implementation: team-working, meeting logistics, infrastructure, quality audit, and barriers and facilitators.
Approaches to multidisciplinary care using conferences and clinics are well described. However, studies vary by design, clinical context, patient population, and study outcome. The heterogeneity of the literature, including the patient populations studied, warrants further specification of multidisciplinary care practice and systematic reviews of the processes or contexts that make the implementation and operation of multidisciplinary care effective.
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