Analysis of the Effects of Day-Time vs. Night-Time Surgery on Renal Transplant Patient Outcomes

Sleep deprivation and disruption of the circadian rhythms could impair individual surgical performance and decision making. For this purpose, this study identified potential confounding factors on surgical renal transplant patient outcomes during day and night. Our retrospective cohort study of 215 adult renal cadaver transplant recipients, of which 132 recipients were allocated in the "day-time" group and 83 recipients in the "night-time" group, primarily stratified the patients into two cohorts, depending on the start time. Within a 24 h operational system, "day-time" was considered as being from 8 a.m. to 8 p.m. and "night-time" from 8 p.m. to 8 a.m.. Primary outcomes examined patient and graft survival after three months and one year. Secondary outcomes included the presence of acute rejection (AR) and delayed graft function (DGF), as well as the rate of postoperative complications. In log-rank testing, "day-time" surgery was associated with a significantly higher risk of patient death (p = 0.003), whereas long-term graft survival was unaffected by the operative time of day. The mean cold ischemia time (CIT), which was 12.4 ± 5.3 h in the "night-time" group, was significantly longer compared to 10.7 ± 3.6 for those during the day (p = 0.01). We observed that "night-time" kidney recipients experienced more wound complications. From our single-centre data, we conclude that night-time kidney transplantation does not increase the risk of adverse events or predispose the patient to a worse outcome. Nevertheless, further research is required to explore the effect of fatigue on nocturnal surgical performance

Videotaping of surgical procedures and outcomes following extraperitoneal laparoscopic radical prostatectomy for clinically localised prostate cancer

Background: Video-recording of emerging minimally invasive surgical procedures is likely to become an integral component of patient record-keeping in the future for prostate cancer treatment. No prior work has shown the impact of videotaping of laparoscopic prostatectomy on patient outcomes. Our aim was to determine correlation between independent peer review of videotaping quality scores of extraperitoneal laparoscopic prostatectomy (ELRP) with complications, re-admissions, functional and early oncological outcomes.Study design, setting, and participants: We conducted a single-institution prospective cohort study comparing videotaping quality scores with the outcomes of ELRP in men with localised prostate cancer. Videotaping of surgical procedures were scored by two experienced laparoscopic surgeons using a validated scoring method. Validated record-linkage methodology and self-reported questionnaires were used to assess surgical complications, re-admissions, functional and oncological outcomes based on a common identifier called as community health index (CHI) number. Pearson correlation coefficients were calculated between the different covariates with statistical significance considered at p&lt;0.05. Multivariate analyses assessed oncological outcomes (positive surgical margins/biochemical recurrence), post-operative complications and re-admission into hospital following initial hospital discharge with quality of surgical procedure.Results: 200 men were recruited into the study. 51 (25.5%) participants had post-operative complications. Record-linkage methodology identified 18 (9%) participants had re-admissions within 90 days of the procedure. 13 (6.5%) of these men required percutaneous drainage with hospital stay following re-admissions ranged between 3-12 days. 10 (5.0%) participants had intra/perioperative complications. 23 (11.5%) men reported to primary care physicians for various indications. Higher quality surgical technique videotaped scores (assessed by independent peer review) had a significant correlation with early continence recovery at 3 months post procedure, (p=0.013), but lost statistical significance with overall continence at 1 year. No statistical correlation was observed between videotaped scores and oncological outcomes (positive surgical margins/biochemical recurrence), post-operative complications and readmission into hospital.   Conclusions: Quality of surgical procedure assessed by independent third party videotaping score predicted early resumption of continence following extraperitoenal laparoscopic radical prostatectomy, however it did not predict complications, oncological or functional outcome as assessed using patient reported outcomes at 12 months.<br/

Vortex pinning by natural defects in thin films of YBa2Cu3O7−δ

Although vortex pinning in laser-ablated YBa2Cu3O7−δ films on (100) SrTiO3 is dominated by threading dislocations, many other natural pinning sites are present. To identify the contribution from twin planes, surface corrugations and point defects, we manipulate the relative densities of all defects by post-annealing films with various as-grown dislocation densities, ndisl. While a universal magnetic field B dependence of the transport current density js(B, T) is observed (independently of ndisl, temperature T and the annealing treatment), the defect structure changes considerably. Correlating the microstructure to js(B, T), it becomes clear that surface roughness, twins and point defects are not important at low magnetic fields compared to linear defect pinning. Transmission electron microscopy indicates that threading dislocations are not part of grain boundaries nor are they related to the twin domain structure. We conclude that js(B, T) is essentially determined by pinning along threading dislocations, naturally induced during the growth process. Even in high magnetic fields, where the vortex density outnumbers ndisl, it appears that linear defects stabilize the vortex lattice by means of the vortex–vortex interaction.

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Inside and out: the activities of senescence in cancer.

The core aspect of the senescent phenotype is a stable state of cell cycle arrest. However, this is a disguise that conceals a highly active metabolic cell state with diverse functionality. Both the cell-autonomous and the non-cell-autonomous activities of senescent cells create spatiotemporally dynamic and context-dependent tissue reactions. For example, the senescence-associated secretory phenotype (SASP) provokes not only tumour-suppressive but also tumour-promoting responses. Senescence is now increasingly considered to be an integrated and widespread component that is potentially important for tumour development, tumour suppression and the response to therapy.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nrc377