The success of immunotherapy highlights a possible role for immunity in controlling cancer during remission for patients with cancer in the general population. A prior cancer diagnosis is common ...among solid organ transplant candidates, and immunosuppressive medications administered to transplant recipients may increase recurrence risk.
Using linked data from the United States solid organ transplant registry and 13 cancer registries, we compared overall and cancer-specific survival among patients with cancer who did versus did not receive subsequent transplantation. We used Cox regression in cohort and matched analyses, controlling for demographic factors, cancer stage, and time since cancer diagnosis.
The study included 10,524,326 patients with cancer, with 17 cancer types; 5,425 (0.05%) subsequently underwent solid organ transplantation. The median time from cancer diagnosis to transplantation was 5.7 years. Transplantation was associated with reduced overall survival for most cancers, especially cervical, testicular, and thyroid cancers adjusted hazard ratios (aHR) for overall mortality, 3.43-4.88. In contrast, transplantation was not associated with decreased cancer-specific survival for any cancer site, and we observed inverse associations for patients with breast cancer (aHRs for cancer-specific mortality, 0.65-0.67), non-Hodgkin lymphoma (0.50-0.51), and myeloma (0.39-0.42).
Among U.S. patients with cancer, subsequent organ transplantation was associated with reduced overall survival, likely due to end-stage organ disease and transplant-related complications. However, we did not observe adverse associations with cancer-specific survival, partly reflecting careful candidate selection.
These results do not demonstrate a detrimental effect of immunosuppression on cancer-specific survival and support current management strategies for transplant candidates with previous cancer diagnoses.
To develop a predictive model of oncologic outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection after neoadjuvant or induction chemotherapy use.
Early recurrence ...following surgical resection for PDAC is common. The use of neoadjuvant chemotherapy prior to resection may increase the likelihood of long-term systemic disease control. Accurately characterizing an individual's likely oncologic outcome in the perioperative setting remains challenging.
Data from patients with PDAC who received chemotherapy prior to pancreatectomy at a single high-volume institution between 2007 and 2018 were captured in a prospectively collected database. Core clinicopathologic data were reviewed for accuracy and survival data were abstracted from the electronic medical record and national databases. Cox-proportional regressions were used to model outcomes and develop an interactive prognostic tool for clinical decision-making.
A total of 581 patients were included with a median overall survival (OS) and recurrence-free survival (RFS) of 29.5 (26.5-32.5) and 16.6 (15.8-17.5) months, respectively. Multivariable analysis demonstrates OS and RFS were associated with type of chemotherapeutic used andthe number of chemotherapy cycles received preoperatively. Additional factors contributing to survival models included: tumor grade, histopathologic response to therapy, nodal status, and administration of adjuvant chemotherapy. The models were validated using an iterative bootstrap method and with randomized cohort splitting. The models were well calibrated with concordance indices of 0.68 and 0.65 for the final OS and RFS models, respectively.
We developed an intuitive and dynamic decision-making tool that can be useful in estimating OS, RFS, and location-specific disease recurrence rates. This prognostic tool may add value to patient care in discussing the benefits associated with surgical resection for PDAC.
We present a fabrication process for fully superconducting interconnects compatible with superconducting qubit technology. These interconnects allow for the three dimensional integration of quantum ...circuits without introducing lossy amorphous dielectrics. They are composed of indium bumps several microns tall separated from an aluminum base layer by titanium nitride which serves as a diffusion barrier. We measure the whole structure to be superconducting (transition temperature of 1.1 K), limited by the aluminum. These interconnects have an average critical current of 26.8 mA, and mechanical shear and thermal cycle testing indicate that these devices are mechanically robust. Our process provides a method that reliably yields superconducting interconnects suitable for use with superconducting qubits.
In systems biology, inference of functional associations among genes is compelling because the construction of functional association networks facilitates biomarker discovery. Specifically, such gene ...associations in human can help identify putative biomarkers that can be used as diagnostic tools in treating patients. Although biomedical literature is considered a valuable data source for this task, currently only a limited number of webservers are available for mining gene-gene associations from the vast amount of biomedical literature using text mining techniques. Moreover, these webservers often have limited coverage of biomedical literature and also lack efficient and user-friendly tools to interpret and visualize mined relationships among genes. To address these limitations, we developed GAIL (Gene-gene Association Inference based on biomedical Literature), an interactive webserver that infers human gene-gene associations from Gene Ontology (GO) guided biomedical literature mining and provides dynamic visualization of the resulting association networks and various gene set enrichment analysis tools. We evaluate the utility and performance of GAIL with applications to gene signatures associated with systemic lupus erythematosus and breast cancer. Results show that GAIL allows effective interrogation and visualization of gene-gene networks and their subnetworks, which facilitates biological understanding of gene-gene associations. GAIL is available at http://chunglab.io/GAIL/.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the ...availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.
Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance ...compared. We compared their diagnostic performance in an independent population.
We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm).
EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9;
= 1.33 × 10
) and specificity (98.1%; 95% CI, 97.3 to 98.8;
= 3.53 × 10
). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (
= .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively.
We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is ...typically diagnosed at advanced stages, in which disease-free survival is <50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.
We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N = 21) and age- and sex-matched controls (N = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.
EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.
EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.
Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations.
Incompatible living donor kidney transplant recipients (ILDKTr) require desensitization to facilitate transplantation, and this substantial upfront immunosuppression may result in serious ...complications, including cancer.
To characterize cancer risk in ILDKTr, we evaluated 858 ILDKTr and 12 239 compatible living donor kidney transplant recipients (CLDKTr) from a multicenter cohort with linkage to the US transplant registry and 33 cancer registries (1997-2016). Cancer incidence was compared using weighted Cox regression.
Among ILDKTr, the median follow-up time was 6.7 y (maximum 16.1 y) for invasive cancers (ascertained via cancer registry linkage) and 5.0 y (maximum 16.1 y) for basal and squamous cell carcinomas (ascertained via the transplant registry and censored for transplant center loss to follow-up). Invasive cancers occurred in 53 ILDKTr (6.2%) and 811 CLDKTr (6.6%; weighted hazard ratio wHR 1.01; 95% confidence interval CI, 0.76-1.35). Basal and squamous cell carcinomas occurred in 41 ILDKTr (4.8%) and 737 CLDKTr (6.0%) (wHR 0.99; 95% CI, 0.69-1.40). Cancer risk did not vary according to donor-specific antibody strength, and in an exploratory analysis, was similar between CLDKTr and ILDKTr for most cancer types and according to cancer stage, except ILDKTr had a suggestively increased risk of colorectal cancer (wHR 3.27; 95% CI, 1.23-8.71); however, this elevation was not significant after correction for multiple comparisons.
These findings indicate that the risk of cancer is not increased for ILDKTr compared with CLDKTr. The possible elevation in colorectal cancer risk is unexplained and might suggest a need for tailored screening or prevention.
Summary Background No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody ...targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy. Methods Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov , number NCT00965250. Findings 49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1–46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24·0 months (IQR 17·3–36·9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5–29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0–26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3–4 adverse events in both cohorts combined were hyperglycaemia (five 10%), lipase elevation (three 6%), and weight loss, tumour pain, and hyperuricaemia (two each 4%). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab. Interpretation Cixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation. Funding Division of Cancer Treatment and Diagnosis at the National Cancer Institute (National Institutes of Health), ImClone Systems.
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