tbuckley/cabot-search huggingface dataset:
Implications of postoperative complications on survival after cytoreductive surgery and HIPEC: A multi-institutional analysis of the United States HIPEC Collaborative.
Authors: Adriana C. Gamboa, Rachel M. Lee, Michael K. Turgeon, Ahmed Ahmed, Travis Edward Grotz, Keith F. Fournier, Sean Patrick Dineen, Jula Veerapong, Callisia Clarke, Harveshp Mogal, Sameer H. Patel, Laura A. Lambert, Daniel Erik Abbott, Mustafa Raoof, Fabian McCartney Johnston, Jordan Cloyd, Shishir K. Maithel, Charles A. Staley
Journal: Journal of Clinical Oncology (2020)

40 Background: Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. Methods: US HIPEC Collaborative (2000-17) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. Analysis was stratified by non-invasive appendiceal neoplasm vs invasive appendiceal/colorectal adenocarcinoma. POCs were grouped into infectious, cardiopulmonary, thromboembolic and intestinal dysmotility. Primary outcomes were 3-yr overall survival (OS) and recurrence-free survival (RFS). Results: Of 1304 pts, median age was 55 yrs, 41% were male (n = 537), 33% had non-invasive appendiceal (n = 426) and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the non-invasive appendiceal cohort, POCs were identified in 55% (n = 233) and OS and RFS did not differ between patients who experienced a complication and those who did not (OS 94 vs 94% p = 0.26; RFS 68 vs 60% p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased OS (59 vs 74% p &lt; 0.001) and RFS (32 vs 42% p &lt; 0.001). Infectious POCs were most common (35%; n = 196). On MV analysis accounting for gender, PCI and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared to no complication (HR 2.08 95%CI 1.48-2.93 p &lt; 0.01) or other types of complications (HR 1.7 95%CI 1.28-2.25 p &lt; 0.01). This association persisted for infectious POCs and reduced RFS (HR 1.61 95%CI 1.23-2.10 p &lt; 0.01). Conclusions: Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease like non-invasive appendiceal neoplasm. Of all complication types, infectious complications are the main driver for this association. The exact mechanism is not known, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious POCs.
Conversion surgery for advancedgastric cancer with peritoneal metastasis.
Authors: Masaki Nakamura, Mikihito Nakamori, Toshiyasu Ojima, Masahiro Katsuda, Keiji Hayata, Junya Kitadani, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2020)

450 Background: Patients with peritoneal metastasis have significantly poor prognosis. We have performed pretherapeutic staging laparoscopy (SL) to diagnose peritoneal metastasis for patients with large type 3, type 4 or serosa-invasive gastric cancer. When peritoneal metastasis disappears by chemotherapy for patients with positive peritoneal cytology (CY1) or peritoneal dissemination (P1), we perform the conversion surgery (CS). Methods: We retrospectively analyzed clinical outcomes of 134 patients with advanced gastric cancer who underwent SL between 2005 from 2016. We examined safety and usefulness of CS for patients with CY1 or P1. Results: CY0P0, CY1P0 and P1 were found in 67, 28 and 39 patients, respectively. The median survival time (MST) of patients with CY0P0, CY1P0 and P1 were 39, 21 and 11 months (CY0P0 vs CY1P0; p = 0.029, CY0P0 vs P1; p&lt;0.001, CY1P0 vs P1; p&lt;0.001). In patients with CY1P0, 20 of 26 patients who received chemotherapy underwent the second look SL, and 14 patients (54%) underwent CS (R0) as peritoneal cytology turned negative. These regimens of chemotherapy were S-1/CDDP (n = 9), Docetaxel/CDDP/S-1 (n = 2), SOX (n = 2) and S-1/Docetaxel (n = 1) and the median number of treatment courses was5courses. The MSTs of patients with or without CS were 40 months and 11 months (p&lt;0.001). Then, there was no difference in overall survival between patients with CS and patients with CY0P0 at the first SL (p = 0.866). All patients with P1received chemotherapy, and 11 of these patients underwent the second look SL. As peritoneal metastasis of 7 patients (18%) disappeared by chemotherapy, they underwent CS (R0). The MSTs of patients with or without CS were 31 months and 9 months (p = 0.026). Regarding complications after CS, surgical-site infection and interstitial pneumonia each occurred in one patient (grade II), and intestinal obstruction (grade IIIa) occurred in one patient. There was no mortality. Conclusions: This study suggests that CS is probably safe and may contribute to improve the survival rate of patients with peritoneal metastasis. Moreover, we developed the NSOX regimen, comprised of a combination nab-paclitaxel, S-1 and oxaliplatin, and have performed a phase I/II trial using the NSOX regimen (UMIN000030909).
Sixty seconds on . . . white bread
Authors: Jacqui Wise
Journal: BMJ (2020)

Well, it may be about to get healthier after scientists discovered how to double the fibre content of white flour. Researchers from the University of Bristol, Rothamsted Research Institute in Hertfordshire, and the John Innes Centre in Norwich genetically screened 150 different wheat varieties from around the world. Not a small task as the wheat genome is much bigger than the human genome—with around 150 000 genes compared with about 25 000 …
Abstract 9248: The Impact of Heart Failure Progression on Post-Left Ventricular Assist Device Survival: An Analysis of the INTERMACS Registry
Authors: Sanjay Maniar, David Naftel, Susan Myers, Veli K Topkara, Eric Novak, Gregory Ewald, James K Kirklin, Douglas L Mann
Journal: Circulation (2012)

Background: Proper timing of implantation of continuous flow left ventricular assist devices (CF-LVAD) is an important management decision in patients with advancing heart failure (HF). Previous risk models derived from earlier generation rotary pump devices may not be applicable with CF-VADs. The purpose of this study was to develop a clinically applicable statistical model for predicting 1-year outcomes among patients with progressive HF receiving a CF-LVAD. Methods: We analyzed data from all adult primary CF-LVAD (with or without RVAD) patients from June 2006 to December 2010 entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database with 12 months of follow-up (n=2810). Variables entered into the statistical model included patient demographics, pre-implant laboratory data and clinical condition, device strategy, and INTERMACS level (1-7). Parametric proportional hazard analysis was used to identify risk factors for death. Results: The significant (p &lt; 0.05) components of the INTERMACS CF-VAD model are illustrated in the Table. As shown, BIVAD support, INTERMACS levels 1 and 2, and prior CABG imparted the highest risk of dying at 1 year. This model also revealed several modifiable risk factors, including BMI, nutritional status, renal and hepatic function, that predicted mortality after CF-VAD implantation. For example, the model predicts that a 10% worsening of renal and hepatic functions in a 45 year old bridge to transplant (BTT) candidate carries ~ 10.9% (13.8% to 15.3%) increased risk of dying at 1 year. Conclusion: This risk model allows clinicians to weigh the “cost of waiting” to implant CF-LVADs in patients with advancing HF, and provides a simple method for determining the 1-year mortality in patients with advanced HF receiving a CF-LVAD.
On the cause and consequences of IgE to galactose-α-1,3-galactose: A report from the National Institute of Allergy and Infectious Diseases Workshop on Understanding IgE-Mediated Mammalian Meat Allergy
Authors: Thomas A.E. Platts-Mills, Scott P. Commins, Tilo Biedermann, Marianne van Hage, Michael Levin, Lisa A. Beck, Maria Diuk-Wasser, Uta Jappe, Danijela Apostolovic, Michael Minnicozzi, Marshall Plaut, Jeffrey M. Wilson
Journal: Journal of Allergy and Clinical Immunology (2020)
Comparison of immune-related gene expression between primary and metastatic site in advanced gastric cancer patients with peritoneal dissemination.
Authors: Naoki Takahashi, Yutaka Matano, Akihiko Tsujibata, Kozue Murayama, Shoichi Miyazawa, TOMOHIRO MATSUSHIMA, Satoshi Shimizu, Yosuke Kumekawa, Takako Yoshii, Masako Asayama, Hiroki Hara
Journal: Journal of Clinical Oncology (2020)

423 Background: Immune checkpoints inhibitor (ICI) is effective and approved in some solid tumors including advanced gastric cancer (GC). Peritoneal dissemination is known as a poor prognostic factor and was reported to be associated with the resistance to ICI according to the previous reports. The aim of our study is to compare the immune-related gene expression between primary site and peritoneal lesion in advanced GC patients. Methods: Among advanced GC patients, we selected those who underwent surgical resection for both primary and peritoneal lesions simultaneously. Formalin-fixed paraffin-embedded (FFPE) tumor tissues of primary and peritoneal lesions were prepared and RNA was extracted by Maxwell RSC RNA FFPE kit (Promega). Immune-related gene expression was evaluated by using nCounter Max Analysis System (NanoString). We used nCounter PanCancer Immune Profiling Panel Kit which includes 770 immune-related genes. Results: Immune-related gene expression was evaluated by using twenty-four FFPE tumor tissues in twelve GC patients. Scatter plot and hierarchical clustering analyses showed that the pattern of immune-related gene expression was not much different between primary and peritoneal lesions beyond the individual differences. Regarding the T cell function, high expression of Immune-related genes was widely detected in patients with EB virus-positive (n = 2) and HER2-positive (n = 1). Gene expressions such as CD70, FAS, MAF and IL-3 were higher in peritoneal lesion compared with primary lesion (p &lt; 0.05). Whereas, expressions of F2RL1 and IL-11 were lower in peritoneal lesion compared with primary lesion (p &lt; 0.05). Conclusions: Our study indicated that there was not much difference of Immune-related gene expression between primary and peritoneal lesion in advanced GC patients. Positive status of EB virus and HER2 may be associated with high expression of immune-related genes. Further analysis to evaluate immune-related gene expression between primary and metastatic site may contribute the further understanding of cancer immunity in advanced GC.
People with non‐blanchable erythema are at higher risk of pressure ulcers
Authors: C. Shi, L.J. Bonnett, J.C. Dumville, N. Cullum
Journal: British Journal of Dermatology (2020)

Pressure ulcers, also known as bed sores, are injury to the skin mainly caused by prolonged pressure, for example in someone who is bedridden. Pressure ulcers occur in 470 to 3,210 per 10,000 patients in hospitals in the U.K., U.S.A., and Canada. Their severity is graded from stage 1 (the least severe) to stage 4 (the most severe). For patients and carers, it is important to know what normal skin is and to regularly check skin changes over the common places where pressure ulcers may appear (e.g. the bottom, heels, and lower back). Non‐blanching erythema – skin redness that does not turn white when pressed – is an important skin change. This study, undertaken by researchers from the University of Manchester and University of Liverpool, U.K., aimed to find out whether people with non‐blanching erythema are more likely to develop pressure ulcers in future than those without non‐blanching erythema. The authors used systematic review and individual‐level data analysis methods to summarise evidence from thirteen studies (with 68,077 people), and to analyse individual‐level data of 3,223 patients. Their analysis showed that people with non‐blanchable erythema had 2.72 times the odds of developing a new pressure ulcer of Stage 2 or above within 28 days, compared with those without non‐blanchable erythema. This means that if 73 people per 1,000 without non‐blanchable erythema develop new pressure ulcers of Stage 2+ within 28 days, 176 people per 1,000 with non‐blanchable erythema will probably develop new ulcers. The authors conclude that people with non‐blanching erythema are more likely to develop new pressure ulcers of Stage 2 or above within 28 days, than people without non‐blanching erythema. It is important for medical staff to identify non‐blanchable erythema and to intervene appropriately to prevent pressure ulcers. This summary relates to the study: Nonblanchable erythema for predicting pressure ulcer development: a systematic review with an individual participant data meta‐analysis
A new vision for WHO's European Region: united action for better health
Authors: Hans Kluge
Journal: The Lancet Public Health (2020)

In the past two decades the way we live our lives has changed almost beyond recognition. Digitisation, globalisation, migration, and urbanisation, climate change, and resource scarcity have resulted in a more complex, multipolar world. In the health sector, the increasing needs of our citizens, driven by demographic change and rising expectations, rising costs of providing health care, an ever-growing number of innovative medicines, and shortages of health-care workers are challenges facing all European countries today.
Immunotherapy in metastatic melanoma: A sociodemographic analysis of the National Cancer Database.
Authors: Amie Patel, Justin Moyers, Gayathri Nagaraj
Journal: Journal of Clinical Oncology (2020)

87 Background: Metastatic melanoma carries poor prognosis and traditional chemotherapy has limited efficacy, but immune checkpoint inhibitors (ICIs) have drastically improved disease outcomes since first approved in 2011. Access to these costly agents in the real-world setting can be challenging. We aimed to assess the demographic and socioeconomic factors associated with receipt of immunotherapy in Stage IV melanoma using National Cancer Database (NCDB). Methods: NCDB first classified ICIs as immunotherapy agents in 2013, hence we queried the database to identify patients with Stage IV melanoma from 2013 to 2016. Patients were divided into receipt of immunotherapy or no receipt of immunotherapy; those without documentation of either were excluded. Factors compared between the two groups included age, sex, diagnosis year, Charlson-Deyo score, insurance and state Medicaid expansion status, income, treatment region, and facility type. Survival analyses were performed by Kaplan-Meier method. Logistic Regression was used to examine factors associated with immunotherapy receipt. Results: 9512 Stage IV melanoma patients had documented immunotherapy status during 2013 to 2016. 36.0% of patients received immunotherapy. Median overall survival (mOS) for all-comers was 10.1 months with improved survival for those who received immunotherapy compared to those who did not (mOS 18.4 v 7.4 months; p&lt;0.01). Regression analysis revealed increased receipt of immunotherapy was associated with diagnosis in states with Medicaid expansion (OR: 1.16, 95% CI:1.002-0.1.340) compared to non-expansion; west north central (OR:1.433; 95%CI:1.139-1.804) and mountain (OR:1.433; 95%CI:1.132-1.813) regions when compared to pacific; academic/research program (OR:1.923; 95%CI:1.592-2.323) and integrated cancer programs (OR:1.362; 95%CI:1.094-1.695) compared to community program. Charlson-Deyo Scores of 1-3, lower Income, increased age, and less high school graduation were associated with decreased immunotherapy receipt. Conclusions: Improved survival is realized in those who receive immunotherapy for stage IV melanoma. Socio-demographic factors show discrepant receipt of immunotherapy.
Exploring the genomic landscape of hepatobiliary cancers to establish a novel molecular subtype classification.
Authors: Anthony Joseph Scholer, Mary Garland-Kledzik, Debopyria Ghosh, Juan Santamaria-Barria, Adam Khader, Javier Orozco, Melanie Goldfarb, Diego M. Marzese
Journal: Journal of Clinical Oncology (2020)

562 Background: The current understanding of the genomic landscape of hepatobiliary cancer (HBC) is limited. Recent genomic and epigenomic studies have demonstrated that various cancers of different tissue origins can have similar molecular phenotypes. Therefore, the aim of this study is to evaluate the genomic alterations of HBCs as a first step towards creating a novel molecular subtype classification. Methods: A multidimensional analysis of next-generation sequencing for the genomic landscape of HBCs was conducted using mutational data from the AACR-Genomics Evidence Neoplasia Information Exchange database (v. 5.0). From 61 gene mutation platforms, we found 42 genes common to all HBC cases. Associations between histomolecular characteristics of HBCs (hepatocellular (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC)) with gene mutations (classified by COSMIC CENSUS) were analyzed using Pearson’s χ2 test. Results: A total of 1,017 alterations were identified in 61 genes (516 missense variant, 157 gene amplifications, 101 inactivating mutations, 106 truncating mutations, 84 upstream gene variants, 37 gene homozygous deletions, 16 gene rearrangements) in 329 patients: 115 (35%) CCA, 87 (26.4%) GBC, and 127 (38.6%) HCC. The majority 77.8% (256) of tumors harbored at least two mutations and 38.9% (128) had at least one alteration, with GBC having a higher average number of alterations (3.28) than HCC (3.23) and CCA (2.49) However, HCCs had the higher maximum number of alterations compared to CCA and GBC (p &lt; 0.05). The ten genes most frequently altered across all the HBCs were TP53, TERT, CTNNB1, KRAS, ARID1A, CDKN2A, IDH1, PIK3CA, MYC, and SMAD4 with disparities in the distribution of genes altered repeatedly observed (p &lt; 0.001). IDH1 mutations were associated with CCA, CTNNB1 and TERT mutations with HCC, and TP53 mutations with both HCC and GBC. Conclusions: HBC subtypes appear to have unique mutational landscapes, but also significant overlap of genetic signatures. Therefore, further exploratory genetic and epigenomic research is needed to develop a histomolecular classification algorithm that can be used for prognostic and therapeutic stratification of these cancers.
Whole genome and transcriptome analysis and the link between insulin receptor aberration and diabetes in PDAC.
Authors: Michael Lee, James T. Topham, Steve Kalloger, Shehara Ramyalini Mendis, Erica S. Tsang, Joanna Karasinska, Jonathan M. Loree, David F. Schaeffer, Daniel John Renouf
Journal: Journal of Clinical Oncology (2020)

743 Background: Pancreatic ductal adenocarcinoma’s (PDAC) association with diabetes development remains poorly understood. The insulin receptor ( INSR) can divert insulin signaling from metabolic to oncogenic pathway activation through alternative splicing of INSR in several cancer types. Methods: 54 treatment naïve patients with metastatic PDAC underwent fresh tumour biopsy in the BC Cancer Personalized Oncogenomics (POG) and PanGen studies (NCT02155621, NCT02869802) for whole genome (WGA) and transcriptome analysis (RNASeq). Copy status and expression of INSR were correlated with T2DM status, Moffitt subtypes, and overall survival (OS). The findings were then correlated with 92 resected PDAC from the International Cancer Genome Consortium (ICGC). Results: 13/54 (24%) had confirmed T2DM at enrollment, and had poorer OS compared to non-diabetic PDAC patients, independent of Moffitt subtype, HR 3.2 (1.5-6.5), p =0.001. Diabetics were more likely to have hypertension (64 v 11%, p &lt;0.001), dyslipidemia (57 v 16%, p=0.013), and to be older (61.5 v 58 years, p=0.014) and smokers (71.4 v 21.6%, p=0.015). WGA revealed significant enrichment of heterozygous INSR copy loss in T2DM (69%) compared to all other patients (24%; p=0.03) and an enrichment of INSR copy loss for metastatic PDAC relative to resected PDAC in ICGC (35 v 18%, p=0.03). Heterozygous INSR copy loss (n = 17/54) was an independent predictor of worse OS (10.8 v 15.1 months, HR 2.29 (1.20-4.36), p=0.012), and it interacted with diabetes status (p=0.023). Moffitt basal (vs. classical) subtype (n = 17/54, of which 8/17 have INSR copy loss) was also an independent predictor of OS with HR 4.3 (2.1-8.7), p&lt;0.001. Whilst there was no interaction between INSR status and Moffitt subtype on OS (p=0.727), INSR expression is lower in basal subtype, p&lt;0.001. Conclusions: Presence of T2DM in our cohort is an independent predictor of worse OS, consistent with published literature. Alteration in the insulin signalling pathway with heterozygous copy loss of INSR was associated with poorer prognosis, diabetes development and overlapped with Moffitt basal subtype.
Network analysis to reveal BTK as a link between myeloid and T cells in TLR signaling in colorectal cancer.
Authors: Justin Hummel, Yuanyuan Shen, Iiulia Innokenteva, Christos Papageorgiou, Chi-Ren Shyu, Jonathan B. Mitchem
Journal: Journal of Clinical Oncology (2020)

30 Background: Colorectal cancer (CRC) is the second-leading cause of cancer mortality in the US today. Recent advances in immunotherapy have only been shown to benefit a limited subgroup of patients with CRC. In other malignancies, activation of Toll-like receptors (TLRs) has been shown to overcome resistance to immunotherapy, such as immune checkpoint inhibition (ICI). In this study, using publicly available data and informatics-based analysis, we identified BTK as a critical link between TLR signaling and T cells in the CRC tumor microenvironment. Methods: Using RNA-seq data from The Cancer Genome Atlas (TCGA) and the Microenvironment Cell Populations (MCP)-Counter, abundance scores were generated for the tumor microenvironment of each patient. A curated TLR gene panel was generated using Reactome and GO. Pearson analysis was used to evaluate each pairwise combination of genes and cell-types. Significance was determined by the correlation coefficient, r ≥ | 0.7 | with a p-value &lt; 0.05. Network analysis was performed using the Girvan–Newman algorithm to establish critical connections across these features. Results: After establishing a 453 gene TLR panel and creating MCP-Counter scores, correlation analysis demonstrated strong correlations between 54 different genes and 7 cell-types. As expected the most genes were associated with monocytic lineage cells' (30) and 'myeloid dendritic cells' (7). Only 5 genes were significantly associated with 'T cells'. Genes and cell-types that were highly correlated were then further analyzed for network association. From this analysis, BTK was identified as a critical edge acting as the primary link between ‘myeloid cells’ and ‘T cells’. Conclusions: Developing novel strategies for the treatment of CRC is critical and immunotherapy represents an area ripe for advancement. Informatics based analysis combined with publicly available data provides us with an opportunity to shape pre-clinical and translational studies. Using this approach, we have identified BTK as a critical link between myeloid cells and T cells in the tumor microenvironment in CRC. Further studies in our laboratory will focus confirming these findings for translation into patients.