tbuckley/cabot-search huggingface dataset:
Mounting Clarity on Enteral Feeding in Critically Ill Patients
Authors: Katelin M. Morrissette, Renee D. Stapleton
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

conceivable that the same result could be more easily obtained by conventional dialysis, where the dialysate solutions are engineered to target a given strong ion difference.Either way, the manipulation of strong ion difference to achieve specific therapeutic effects is slowly gaining traction, and similar approaches have recently been shown to enhance respiratory support (15,16).Whatever the future holds for these therapies, it behooves us to start teaching the physicochemical approach to our medical students and junior colleagues sooner rather than later.
Immunotherapy of lymphomas
Authors: Stephen M. Ansell, Yi Lin
Journal: Journal of Clinical Investigation (2020)

Lymphoid malignancies typically promote an infiltrate of immune cells at sites involved by the disease. While some of the immune cells present in lymphoma have effector function, the immune system is unable to eradicate the malignant clone. Therapies that optimize immune function therefore have the potential to improve the outcome of lymphoma patients. In this Review, we discuss immunologic approaches that directly target the malignant cell as well as approaches to optimize both the innate and adaptive immune response to the tumor. While many of these therapies have shown single-agent activity, the future will clearly require thoughtful combinations of these approaches.
Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model
Authors: Nilay S. Sethi, Osamu Kikuchi, Gina N. Duronio, Matthew D. Stachler, James M. McFarland, Ruben Ferrer-Luna, Yanxi Zhang, Chunyang Bao, Roderick Bronson, Deepa Patil, Francisco Sanchez-Vega, Jie-Bin Liu, Ewa Sicinska, Jean-Bernard Lazaro, Keith L. Ligon, Rameen Beroukhim, Adam J. Bass
Journal: Nature Genetics (2020)
厳格なカロリーコントロール研究(TICACOS):重症患者における栄養補給の前向きランダム化対照パイロット研究
Authors: Singer Pierre, Anbar Ronit, Cohen Jonathan, Shapiro Haim, Shalita-Chesner Michal, Lev Shaul, Grozovski Elad, Theilla Miryam, Frishman Sigal, Madar Zecharia
Journal: Intensive Care Medicine (2011)
Australian Government releases face masks to protect against coronavirus
Authors: Tony Kirby
Journal: The Lancet Respiratory Medicine (2020)

The Australian Federal Government has released 500 000 protective masks to general practitioners (GPs) and other health workers across the country to protect them from infection by the novel coronavirus (2019-nCoV) following an appeal by the Royal Australian College of GPs (RACGP). The college president, Dr Harry Nespolon, made the appeal because of the shortage of protective masks available to health-care workers due to the recent bushfire crisis engulfing the country.
Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility
Authors: Mihnea Paul Dragomir, Scott Kopetz, Jaffer A Ajani, George Adrian Calin
Journal: Gut (2020)

One of the most unexpected discoveries in molecular oncology, in the last decades, was the identification of a new layer of protein coding gene regulation by transcripts that do not codify for proteins, the non-coding RNAs. These represent a heterogeneous category of transcripts that interact with many types of genetic elements, including regulatory DNAs, coding and other non-coding transcripts and directly to proteins. The final outcome, in the malignant context, is the regulation of any of the cancer hallmarks. Non-coding RNAs represent the most abundant type of hormones that contribute significantly to cell-to cell communication, revealing a complex interplay between tumour cells, tumour microenvironment cells and immune cells. Consequently, profiling their abundance in bodily fluids became a mainstream of biomarker identification. Therapeutic targeting of non-coding RNAs represents a new option for clinicians that is currently under development. This review will present the biology and translational value of three of the most studied categories on non-coding RNAs, the microRNAs, the long non-coding RNAs and the circular RNAs. We will also focus on some aspirational concepts that can help in the development of clinical applications related to non-coding RNAs, including using pyknons to discover new non-coding RNAs, targeting human-specific transcripts which are expressed specifically in the tumour cell and using non-coding RNAs to increase the efficiency of immunotherapy.
Genetic variants in immunogenic cell death (ICD) relating genes to predict outcome in metastatic colorectal cancer (mCRC): Data from FIRE-3, TRIBE and MAVERICC trials.
Authors: Hiroyuki Arai, Yi Xiao, Fotios Loupakis, Sebastian Stintzing, Jingyuan Wang, Francesca Battaglin, Shivani Soni, Wu Zhang, Christoph Mancao, Bodour Salhia, Shannon M Mumenthaler, Daniel J Weisenberger, Gangning Liang, Chiara Cremolini, Volker Heinemann, Alfredo Falcone, Joshua Millstein, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2020)

187 Background: ICD is an immune response against dead-cell antigens from cancer cells treated with cytotoxic and/or targeted therapies. Oxaliplatin (OHP) and cetuximab (Cet) are distinct drugs to elicit ICD, while most other anticancer agents kill cancer cells in a nonimmunogenic manner. We hypothesized that genetic variants in ICD-related genes could predictive efficacy of OHP and/or Cet in mCRC. Methods: We analyzed data of mCRC patients enrolled in three 1st-line randomized trials [FIRE-3: FOLFIRI+Cet vs FOLFIRI+bevacizumab (Bev), TRIBE: FOLFOXIRI+Bev vs FOLFIRI+Bev and MAVERICC: FOLFOX+Bev vs FOLFIRI+Bev]. Genomic DNA from blood samples was genotyped through the OncoArray, a custom array manufactured by Illumina. Candidate 14 SNPs in five ICD-related genes ( CALR, HMGB1, ANXA1, LRP1 and P2RX7) were tested for association with progression-free survival (PFS) and overall survival (OS), using Cox proportional hazards model. We tested treatment-by-SNP interactions in the following cohorts: combined TRIBE and MAVERICC (OHP-containing treatment vs non-OHP-containing treatment), and FIRE-3 (FOLFIRI+Cet vs FOLFIRI+Bev). An interaction p-value (i p) &lt; 0.05 was considered significant. Results: Totally, 890 patients’ SNPs were available (FIRE-3: n = 236, TRIBE: n = 324, and MAVERICC: n = 330). In the combined TRIBE and MAVERICC cohorts [the reference of hazard ratio (HR) is non-OHP-containing treatment], a significant interaction was observed in ANXA1 rs1050305 (A/A: HR 0.96, Any G: HR 2.62, i p &lt; 0.01), LRP1 rs1466535 (G/G: HR 1.39, Any A: HR 0.91, i p = 0.02), P2RX7 rs2230911 (C/C: HR 0.98, Any G: HR 1.76, i p = 0.03) and P2RX7 rs208294 (C/C: HR 1.82, Any T: HR 0.93, i p &lt; 0.01) on OS. For PFS, that was observed in CALR rs110222 (G/G: HR 1.30, Any A: HR 0.87, i p = 0.02), HMGB1 rs1045411 (C/C: HR 0.85, Any T: HR 1.30, i p = 0.04) and HMGB1 rs1360485 (T/T: HR 0.81, Any C: HR 1.40, i p &lt; 0.01). However, in the FIRE-3 cohort, no significant interactions were observed in any SNPs. Conclusions: Our results showed for the first time that SNPs in ICD-related genes may predict efficacy of OHP-containing treatment in mCRC. But the predictive values for Cet efficacy was not evident.
Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status.
Authors: Luke R.G. Pike, Trevor J. Royce, Amandeep R. Mahal, Daniel W. Kim, William L. Hwang, Brandon A. Mahal, Nina N. Sanford
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background  Socioeconomic factors affecting outcomes of HPV-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized.  Methods  A custom SEER database identified adult patients with primary nonmetastatic SCCHN and known HPV status diagnosed in 2013 through 2014. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (aORs) and 95% confidence intervals reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals for cancer-specific mortality (CSM), including a disease subsite * HPV status * race interaction term.  Results  A total of 4,735 patients with nonmetastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with an oropharyngeal primary, male sex, and higher education, and negatively associated with uninsured status, single marital status, and nonwhite race (P≤.01 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (aHR, 0.55; 95% CI, 0.34-0.88; P=.01) and uninsured status was associated with higher CSM (aHR, 3.12; 95% CI, 1.19-8.13; P=.02). These associations were not observed in HPV-negative or nonoropharynx SCCHN. Accordingly, there was a statistically significant disease subsite * HPV status * race interaction (Pinteraction  Conclusions  Nonwhite race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, whereas no such associations were observed in HPV-negative or nonoropharyngeal SCCHN. These results suggest that despite having clinically favorable disease, nonwhite patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.
Precision medicine in colorectal cancer: Gaps in patients’ literacy of biomarkers and genetic testing.
Authors: Ronit Yarden, Tamara Springer
Journal: Journal of Clinical Oncology (2020)

55 Background: Colorectal cancer (CRC) is the second leading cause of cancer death in the united states. Despite some advances, mortality is high and the 5-year overall survival from metastatic disease (mCRC) is only 14%. CRC is a heterogeneous disease with multiple subtypes defined by location, microsatellite integrity, specific genetic alterations and potentially age. The identification of specific driving mutation/s led to the development of targeted therapies. Patients are eligible for these treatments based on their personalized tumor biomarker profile. ASCO guidelines recommend that all patients with mCRC are tested for KRAS mutations. This mutation is present in ~40% of CRC patients, and serves as a biomarker for lack of response to EGFR therapy. Similarly, high microsatellite instability (MSI-H) suggests an inferior response to commonly used chemotherapy and favorable response to immunotherapy. Methods: We conducted an online survey to assess patients, survivors and caregivers’ knowledge and understanding of biomarker testing. Results: Among the 210 participants in this cross-sectional study, 81% of participants reported ‘no familiarity’ with the term biomarkers at the time of diagnosis, while 73% reported awareness at the time of the survey. Yet, when presented with specific biomarkers, majority of participants were not familiar with any of those biomarkers. Of the 103 stage IV respondents, only 14% were familiar with the four common CRC biomarkers, and only 1 in 4 reported their tumor was tested prior to treatment initiation. Nearly half of the respondents cited their physician and medical team as the main source of biomarker information (46%) while the other half reported their medical team never informed them of biomarkers. Overall, 50% of participants indicated that advocacy groups, medical websites, and various online resources were their main sources of biomarker information. Disparities of biomarker awareness were noted based on gender, age, and area of residency. Conclusions: Taken together, patients do not fully comprehend the meaning and implications of biomarker testing. Medical teams should make a greater effort to inform their patients early on in their treatment.
Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy
Authors: Mary Safy-Khan, Johannes W G Jacobs, Maria J H de Hair, Paco M J Welsing, Michael D Edwardes, Xavier M Teitsma, Yves Luder, Jenny Devenport, Jacob M van Laar, Attila Pethoe-Schramm, Johannes W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2020)

In rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.To determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.Data of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.No statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.No effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.
Effects of duration of initial treatment on postoperative complications in pancreatic cancer.
Authors: Naoya Takeda, Suguru Yamada, Hideki Takami, Fuminori Sonohara, Masamichi Hayashi, Isaku Yoshioka, Kazuto Shibuya, Koshi Matsui, Katsuhisa Hirano, Toru Watanabe, Yuuko Tohmatsu, Nana Kimura, Shozo Hojo, Shigeaki Sawada, Tomoyuki Okumura, Takuya Nagata, Yasuhiro Kodera, Tsutomu Fujii
Journal: Journal of Clinical Oncology (2020)

658 Background: Early studies raised concerns over whether preoperative treatment led to postoperative complications or even death. In contrast, recent studies have reported that initial treatment (IT) prior to resection of pancreatic ductal adenocarcinoma (PDAC) is safe, with no significant increase in overall morbidity or mortality, despite evidence for more advanced disease. In this study, we analyzed the clinical impact of chemotherapy or chemoradiotherapy as IT, focusing on treatment duration, on morbidity and mortality in patients with resected PDAC. Methods: We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for &lt; 8 months and 20 treated ≥8 months. We compared rates of postoperative Clavien–Dindo grade ≥III complications between the groups. Multivariate logistic regression analysis was used to find independent predictors of complications. Results: The upfront surgery and IT groups did not significantly differ in overall postsurgical complications. The rate of postoperative pancreatic fistula was significantly less in the IT group. Rates of other complications did not significantly differ, except for severe infection and delayed gastric emptying. Initiation of adjuvant chemotherapy was later in the IT group than in the upfront surgery group (43.2 vs 57.8 days, P &lt; 0.001). In contrast, rates of overall complications significantly differed between the &lt; 8 months and ≥8 months IT groups, although their background clinical factors did not differ. In multivariate analysis, operative procedure (distal pancreatectomy and distal pancreatectomy with celiac axis resection) (odds ratio [OR] 6.950, P = 0.0416) and IT ≥8 months (OR: 4.508, 95%, P = 0.0156) were independent predictive factors for postoperative complications. Conclusions: The incidence of postoperative complication was similar between the upfront surgery group and the IT group, however, it was significantly higher in the ≥8 months IT group in patients who underwent PDAC resection.
Addressing the physician-scientist pipeline: strategies to integrate research into clinical training programs
Authors: Sallie R. Permar, Rebecca A. Ward, Katherine J. Barrett, Stephanie A. Freel, Rasheed A. Gbadegesin, Christopher D. Kontos, Patrick J. Hu, Katherine E. Hartmann, Christopher S. Williams, Jatin M. Vyas
Journal: Journal of Clinical Investigation (2020)
Oncology precision medicine for hepatobiliary and pancreatic cancer: Insights and updates upon an institutional review.
Authors: Geoffrey Bellini, Nicholas Sich, Jennifer Jo Godden, James L. Weese, Wesley Allan Papenfuss, Aaron Chevinsky, Antony Ruggeri, Michael A. Thompson
Journal: Journal of Clinical Oncology (2020)

570 Background: Hepatobiliary cancers - hepatocellular carcinoma (HCC), intra or extrahepatic cholangiocarcinoma (I/EC), and gallbladder carcinoma (GB) - and pancreatic adenocarcinoma (PC) do have actionable alterations (AA). The importance of testing early in a patient’s (pts) course to identify oncology precision medicine (OPM) options could be paramount for progression free survival (PFS). Methods: We identified pts with HCC, IC, EC, GB or PC in our OPM database since the centralization of our system. Pts who underwent molecular panel testing had AA’s identified and stratified by cancer type. Treatment course was analyzed using swimmers plots. Results: 456pts were diagnosed with HCC, IC, EC, GB or PC. 104/456pts (23%) were ordered for molecular testing and 88/456pts (19.3%) completed testing: 18/88pts (20.4%) I/EC, 2/88pts (2.3%) HCC, 5/88pts (5.7%) GB, and 63/88pts (71.6%) PC. Of the PC pts, 3/63 (4.8%) had a BRCA mutation. These pts did not receive targeted therapy. Overall, 5/88pts (5.7%) had a BRAF mutation (2 PC, 2 I/EC, 1GB). Thus, 8/88 (9.1%) of tested pts became eligible for some form of targeted therapy over their treatment course. Of those with a BRAF mutation, only 2/5 pts had OPM testing sent with initial diagnostic workup, and 2/5 eventually began targeted therapy. One had a progression free survival (PFS) of 2.5months while the other discontinued secondary to toxicity. Conclusions: Our data showed that we are testing a minority of pts with pancreas and hepatobiliary cancers. Of those tested, it may have occurred too late in the course of illness to improve outcomes. Given the potential utility of uncovering potential germline alterations like BRCA1/2 as well as pragmatic AAs including somatic BRCA and BRAF, we are moving to a more systematic evaluation of pts to capture and respond to these issues. [Table: see text]
Optimal identification of human conventional and nonconventional (CRTH2–IL7Rα–) ILC2s using additional surface markers
Authors: Sucai Liu, Kapil Sirohi, Mukesh Verma, Jerome McKay, Lidia Michalec, Anand Sripada, Tomas Danhorn, Donald Rollins, James Good, Magdalena M. Gorska, Richard J. Martin, Rafeul Alam
Journal: Journal of Allergy and Clinical Immunology (2020)
Diastolic Heart Failure in Patients With the Fontan Circulation
Authors: Werner Budts, William J. Ravekes, David A. Danford, Shelby Kutty
Journal: JAMA Cardiology (2020)

The Fontan circulation, accomplished by direct surgical connection of the vena cavae to the pulmonary arteries, can be an effective palliation for patients with a single ventricle. However, failure of the Fontan circulation can result from mechanical obstruction, cardiac arrhythmias, increasing pulmonary vascular resistance, or deteriorating ventricular performance. Although systolic ventricular failure can usually be identified by a combination of clinical signs, symptoms, and imaging findings, diastolic ventricular dysfunction is likely an underrecognized cause of Fontan failure. Methods for detection of impaired diastolic function in a single ventricle are evolving, and established techniques appropriate in the biventricular heart lack validation in single ventricle. Association of biomarkers, cardiac magnetic resonance, and echocardiographic findings with invasively acquired pressure-volume loop data in humans may offer a way forward to accurate, noninvasive diagnosis. Today, therapy for severe diastolic ventricular dysfunction in the Fontan circulation is often disappointing and may require consideration of a ventricular assist device or even cardiac transplant. Progress toward improved outcomes of the Fontan palliation likely depends on successful innovation in primary prevention strategies and the development of more effective pharmacotherapy.
Travel distance and time to adjuvant chemotherapy in veterans with colorectal cancer.
Authors: Richard Lewis Martin, Gretchen C. Edwards, Lauren R. Samuels, Christianne L. Roumie
Journal: Journal of Clinical Oncology (2020)

84 Background: Patients from rural areas have well described disparities in quality cancer care. We hypothesized that longer travel distance is associated with less chemotherapy acceptance and less timely treatment. Methods: We reviewed 705 electronic medical records of patients with colorectal surgeries from January 1, 2000 to December 31, 2015 at the Veterans Health Administration Tennessee Valley Healthcare System. Two trained abstractors reviewed standard elements (k = 0.79 – 0.92). The study sample included patients with pathological stage high risk II or III CRC and excluded those with metastatic disease or documented National Comprehensive Cancer Network (NCCN) defined medical exclusions from chemotherapy. Primary exposure was distance to care calculated from central zip code of residence to Nashville infusion center. Primary outcomes were receipt of any chemotherapy, and days from surgery to first treatment (truncated at 120 days). We analyzed 2 populations; chemotherapy received and a second sensitivity population who were eligible for, but did not receive, chemotherapy (no documentation of NCCN ineligibility or declined). Results: Of 705 colorectal resections, we excluded 262 for non-cancer, 220 for stage I or low risk stage II, and 46 for NCCN exclusion criteria, yielding 177 cases: 120 colon and 57 rectal. Most patients were male (98%) and white (85%); median age was 64 [Interquartile Range 60, 70]. Distribution by travel distance was 60/177 [33.9%] &lt; 50 miles, 61/177 [34.5%] 50-99 miles, and 56/177 [31.6%] &gt; 100 miles. Of all eligible patients, 123/177 [69.5%] patients received chemotherapy and 54/177 [30.5%] did not receive chemotherapy. Among receivers, median times to treatment were 52 days [40, 61] &lt; 50 miles; 48.5 [40,61] 50-99 miles; and 54 [43,77] &gt; 100 miles, p = 0.3. Patients not receiving chemotherapy varied by distance: 15/60 (25%) &lt; 50 miles; 18/61 (30%) 50-99 miles; 21/56 (38%) &gt; 100 miles, p = 0.3. Including non-receivers, median times to treatment were 58 days [43, 120] &lt; 50 miles; 58.5 [46.5, 120] 50-99 miles; and 80 [48.5, 120] &gt; 100 miles, p = 0.1. Conclusions: Distance to care may influence acceptability of chemotherapy. Understanding patient/provider reasons for omission merits exploration.