tbuckley/cabot-search huggingface dataset:
Circulating miR-203 secreted from metastatic tissues could exacerbate myopenia in colorectal cancer patients.
Authors: Yoshinaga Okugawa, Yuji Toiyama, Keun Hur, Shozo Ide, Tadanobu Shimura, Hiroyuki Fujikawa, Hiromi Yasuda, Takeshi Yokoe, Junichiro Hiro, Masaki Ohi, Masato Kusunoki
Journal: Journal of Clinical Oncology (2020)

181 Background: Sarcopenia is commonly observed in advanced cancer patients with distant metastases. In addition, biological functions of microRNAs (miRNAs) in cell-to-cell communication by incorporating into neighboring or distal cells has been gradually elucidated in various diseases, including sarcopenia, have been established. Methods: First, we quantified miR-203 expression, a key miRNA involved in cell-to-cell communication, by qRT-PCR and in situ hybridization in 58 pairs of primary CRC (pCRC) and corresponding matched liver metastasis (LM) tissues. We further evaluated miR-203 levels using pCRC tissues and matched preoperative serum to clarify its clinical significance in independent 183 CRC patients. Second, we assessed psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using preoperative computed tomography imaging to clarify its clinical burden and correlations with miR-203 levels in CRC patients. Functional analysis of miR-203 overexpression was investigated in human skeletal muscle cells (SkMC), and cells were analyzed for proliferation and apoptosis. Expression of several, putative, miR-203-target genes was also validated in SkMC cells. Results: MiR-203 expression was significantly upregulated in LM compared with matched pCRC tissues. Serum miR-203 levels were significantly upregulated in a stage-dependent manner, and high miR-203 expression was associated with poor survival in patients with CRC in both patient cohorts. In contrast to IMAC, decreased PMI significantly correlated with well-established disease development factors, and decreased PMI was an independent prognostic factor for both overall survival, and disease-free survival in CRC patients. Although tissue miR-203 expression did not significantly correlate with the body composition status, serum miR-203 expression negatively correlated with preoperative PMI level. Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via downregulation of BIRC5 (Survivin) expression in SkMC cell. Conclusions: Assessment of serum miR-203 could be used for risk assessment of metastasis-related myopenia in CRC.
Prognostic Awareness in Adult Oncology and Palliative Care
Authors: Phyllis N. Butow, Josephine M. Clayton, Ronald M. Epstein
Journal: Journal of Clinical Oncology (2020)

Communicating prognosis clearly and empathically can foster accurate prognostic awareness in patients with advanced cancer and their family members. Whereas patients and doctors desire clear prognostic communication, it presents many challenges in oncologic and palliative care settings. Patients with advanced cancer often have poor prognostic awareness as a result of deficiencies in doctor communication and understandable-and potentially adaptive-attempts by patients and families to reduce the threat of death and maintain hope. Interventions to promote prognostic discussion have largely succeeded in increasing the frequency, but not necessarily the quality, of such discussions, yet have failed to improve prognostic awareness. Because clear communication of prognosis is an ethical mandate, more research is needed to provide an evidence base for teaching and practice in this area.
Traction-assisted colorectal endoscopic submucosal dissection using an endoloop for large semipedunculated lesions
Authors: Maiko Takita, Eiji Sakai, Takashi Muramoto, Ken Ohata
Journal: Endoscopy (2020)

Endoscopic submucosal dissection (ESD) for large semipedunculated lesions remains a challenging technique [1]. These lesions often have severe fibrosis or display muscle retracting sign during ESD. Despite the recent advantages of traction-assisted colorectal ESD [2] [3], the efficacy of this technique is rarely investigated for such lesions. Here we describe a case of traction-assisted ESD using an endoloop (MAJ-254; Olympus, Tokyo, Japan) for the treatment of a large semipedunculated lesion in the right colon ([Video 1]).
RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness
Authors: Tanya Novak, Mark W. Hall, Douglas R. McDonald, Margaret M. Newhams, Anushay J. Mistry, Angela Panoskaltsis-Mortari, Peter M. Mourani, Laura L. Loftis, Scott L. Weiss, Keiko M. Tarquinio, Barry Markovitz, Mary E. Hartman, Adam Schwarz, Wolfgang G. Junger, Adrienne G. Randolph, Ronald C. Sanders, Olivia K. Irby, Glenda Hefley, David Tellez, Katri Typpo, Barry Markovitz, Heidi Flori, Natalie Cvijanovich, Nick Anas, Adam Schwarz, Ofelia Vargas-Shiraishi, Anil Sapru, Patrick McQuillen, Angela Czaja, Peter Mourani, Matthew Paden, Keiko Tarquinio, Cheryl L. Stone, Juliane Bubeck Wardenburg, Neethi Pinto, Vicki Montgomery, Janice E. Sullivan, Adrienne G. Randolph, Anna A. Agan, Stephanie Ash, Anushay Mistry, Margaret Newhams, Stephen C. Kurachek, Allan Doctor, Mary Hartman, Edward Truemper, Sidharth Mahapatra, Machelle Dawson, Kate Ackerman, L. Eugene Daugherty, Ryan Nofziger, Steve Shein, Mark W. Hall, Lisa Steele, Lisa Hanson-Huber, Neal J. Thomas, Debra Spear, Julie Fitzgerald, Scott Weiss, Jenny L. Bush, Kathryn Graham, Renee Higgerson, LeeAnn Christie, Laura L. Loftis, Nancy Jaimon, Rainer Gedeit, Kathy Murkowski
Journal: Journal of Allergy and Clinical Immunology (2020)
Gene expression profiling of unresectable pancreatic cancer patients treated with gemcitabine, nab-paclitaxel, metformin, and dietary supplements (DS).
Authors: Vincent Chung, Paul Henry Frankel, Stephen Shibata, Isa Mambetsariev, Holly Yin, Tamara Mirzapoiazova, Bolot Mambetsariev, Prakash Kulkarni, Dean Lim, Daneng Li, Joseph Chao, Marwan Fakih, Andrea Bild, Raju K. Pillai, Orn Adalsteinsson, Steven Hirsh, Ravi Salgia
Journal: Journal of Clinical Oncology (2020)

736 Background: Pancreatic cancer commonly causes weight loss and many patients take supplements to improve nutrition but also for any potential anticancer properties. We conducted a pilot trial evaluating a standardized combination of dietary supplements, metformin and gemcitabine plus nab-paclitaxel chemotherapy. Methods: The supplements were custom designed by a nutritionally trained oncologist. 17 supplements were given as 12 pills and 2 smoothie packets divided twice per day. Patients began metformin on day (D)-6 to evaluate GI tolerance before starting the DS on D-3. On D1, gemcitabine and nab-paclitaxel chemotherapy was administered at standard doses. Serum samples were collected D-6, C1D1, C3D1 and at the end of treatment. RNA was extracted from PBMC samples and a total of 48 samples were analyzed from 19 patients. NanoString Human Immune Profiling and PanCancer Pathways were performed to evaluate changes in gene expression with treatment. Results: The differential expression of genes was small with dietary supplements alone and in combination with chemotherapy. After 2 months of treatment, 17 genes were upregulated while 4 genes were down regulated. At the time of tumor resistance, 33 genes were upregulated while 17 genes were downregulated. We observed downregulation of tumor suppressor gene expression with upregulation in growth factor pathways. Interestingly, SPRY2 mRNA expression was also up regulated which functions as a negative feedback regulator of multiple receptor tyrosine kinases. Conclusions: Increasing number of genes were upregulated with continued treatment. The most common pathway affected was cell cycle and apoptosis. During the initial supplement run-in period from D-6 to C1D1, IL-8 mRNA expression was upregulated the most. IL-8 is a neutrophil chemotactic factor secreted by cells involved in the innate immune response as well as pancreatic cancer cells associated with a pro-inflammatory state. Treatment with gemcitabine and nab-paclitaxel decreased the IL-8 mRNA expression. Additional studies with longer course treatment with supplements alone would be required to explore its impact on differential gene expression.
Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors
Authors: Enli Liu, David Marin, Pinaki Banerjee, Homer A. Macapinlac, Philip Thompson, Rafet Basar, Lucila Nassif Kerbauy, Bethany Overman, Peter Thall, Mecit Kaplan, Vandana Nandivada, Indresh Kaur, Ana Nunez Cortes, Kai Cao, May Daher, Chitra Hosing, Evan N. Cohen, Partow Kebriaei, Rohtesh Mehta, Sattva Neelapu, Yago Nieto, Michael Wang, William Wierda, Michael Keating, Richard Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: New England Journal of Medicine (2020)

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations.
Phase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + PEGPH20 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC).
Authors: Andrew H. Ko, Jeeyun Lee, MARIA ALSINA, Jaffer A. Ajani, Yung-Jue Bang, Hyun Cheol Chung, Jill Lacy, Charles D. Lopez, Do-Youn Oh, Eileen Mary O'Reilly, Jens T Siveke, Simon Allen, Nedal Jaffer Abdulla Al-Sakaff, Hila Barak, Janet Lau, Shi Li, Anne-Cecile Retiere, Colby Shemesh, Xiaosong Zhang, Kyu-Pyo Kim
Journal: Journal of Clinical Oncology (2020)

4540 Background: The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to identify early efficacy signals and safety of treatment (tx) combinations across cancers. Within MORPHEUS, atezo (anti–PD-L1) was tested with PEGylated recombinant human hyaluronidase (PEGPH20), an anti–stromal and extracellular matrix modulator, in patients (pts) with metastatic (m) PDAC or advanced/mGC. Methods: In 2 separate randomized trials, eligible pts with 2L mPDAC or mGC received atezo (1200 mg IV q3w) + PEGPH20 (3 µg/kg IV on D1, 8, 15). Control tx for M-PDAC (NCT03193190) was mFOLFOX6 or gemcitabine + nab-paclitaxel. In M-GC (NCT03281369), control tx was ramucirumab + paclitaxel. Primary endpoints were ORR (investigator-assessed RECIST 1.1) and safety. Results: Pts were followed up for ≥ 18 wk in M-PDAC (data cutoff: Aug 5, 2019) and ≥ 24 wk in M-GC (data cutoff, Jul 11, 2019). In M-PDAC, 66 pts received atezo + PEGPH20 and 42 received control in both preliminary and expansion phases. Confirmed ORRs were 6.1% (95% CI: 1.7, 14.8) and 2.4% (95% CI: 0.06, 12.6), respectively. Duration of response ranged from 5.3 to 11.3 mo in tx arm and was 3.9 mo in control. Median PFS was 1.5 mo (95% CI: 1.4, 2.6) and 2.3 mo (95% CI: 1.6, 4.0), respectively. Median OS was 7.1 mo (95% CI: 4.6, 9.5) and 6.8 mo (95% CI: 5.6, 8.3). Updated survival data will be presented. Respectively, 62.2% and 59.5% of pts had Gr 3-4 AEs; Gr 5 AEs were seen in 4.5% and 2.4% of pts; serious AEs (SAEs) occurred in 45.5% and 45.2% of pts; 16.7% and 4.8% of pts had tx-related AEs leading to tx withdrawal. The most common tx-related AEs were myalgia (65.2%) and peripheral edema (28.8%) in the combination arm. In M-GC, 13 pts received atezo + PEGPH20 and 12 received control. Confirmed ORRs were 0% (95% CI: 0, 24.7) and 16.7% (95% CI: 2.1, 48.4), respectively. Gr 3-4 AEs were seen in 30.8% and 75.0% of pts, respectively. No Gr 5 AEs occurred in either arm. SAEs occurred in 7.7% and 50.0% of pts, respectively. Only 1 pt in the control arm had a tx-related AE leading to tx withdrawal. While tumor hyaluronan (HA) appears to be associated with poor prognosis in the M-PDAC control, there was no clear association between HA levels and response to atezo + PEGPH20. PK data will also be presented. Conclusions: Limited efficacy was seen with the chemotherapy-free combination of atezo + PEGPH20 in PDAC. No efficacy was seen in GC. The safety of atezo + PEGPH20 was consistent with each agent’s known safety profile; no new safety signals were identified. Clinical trial information: NCT03193190 .
An overview of clinical decision support systems: benefits, risks, and strategies for success
Authors: Reed T. Sutton, David Pincock, Daniel C. Baumgart, Daniel C. Sadowski, Richard N. Fedorak, Karen I. Kroeker
Journal: npj Digital Medicine (2020)

Computerized clinical decision support systems, or CDSS, represent a paradigm shift in healthcare today. CDSS are used to augment clinicians in their complex decision-making processes. Since their first use in the 1980s, CDSS have seen a rapid evolution. They are now commonly administered through electronic medical records and other computerized clinical workflows, which has been facilitated by increasing global adoption of electronic medical records with advanced capabilities. Despite these advances, there remain unknowns regarding the effect CDSS have on the providers who use them, patient outcomes, and costs. There have been numerous published examples in the past decade(s) of CDSS success stories, but notable setbacks have also shown us that CDSS are not without risks. In this paper, we provide a state-of-the-art overview on the use of clinical decision support systems in medicine, including the different types, current use cases with proven efficacy, common pitfalls, and potential harms. We conclude with evidence-based recommendations for minimizing risk in CDSS design, implementation, evaluation, and maintenance.
An intersectional investigation of race and sex on receipt of adjuvant chemotherapy in stage III colon cancer.
Authors: Amina Dhahri, Estrella M. Carballido, Seth Felder, Sean Patrick Dineen, Benjamin D Powers
Journal: Journal of Clinical Oncology (2020)

86 Background: Race and sex disparities exist for receipt of adjuvant chemotherapy (AC) for stage III colon cancer. However, most studies have not used an intersectional approach, which assesses the cumulative effects of different identities (e.g., Black women) instead of treating each as distinct, independent variables. Using this approach, we assessed the summative impact of these identities on receipt of AC for stage III colon cancer. Methods: The National Cancer Database was queried from 2004 to 2015 for patients who underwent surgery for stage III colon cancer and were healthy enough for AC. Receipt of AC was assessed chi-squared and multivariable logistic regression analyses. Results: 92,696 patients were identified. White patients had higher rates of care at community cancer centers. Black patients had higher rates of treatment at academic cancer programs (p &lt; 0.001). Overall 83.5% received AC. Black males and females had higher rates of AC (86.5% and 86.2%, respectively) compared to White males and females (85.3% and 80.5%), respectively (p &lt; 0.001). In adjusted analysis, Black males had the lowest odds of AC (OR 0.73), followed by Black females (OR 0.89) and White females (OR 0.91). When evaluated by age &lt; 65 years and adjusting for potential confounders, Black men remained the least likely group to receive AC (OR 0.70). Black females had similar odds of receipt of AC (OR 0.99) and White females had increased odds (OR 1.22) relative to White males. Conclusions: Despite higher rates of treatment at academic centers, Black males and females had lower odds of receipt of AC after adjusting for confounders. Younger Black males persisted with the lowest odds of AC, although younger Black females had odds similar to younger White males. Additional research is necessary to identify drivers of these disparities and interventions to ameliorate them. [Table: see text]
Quattro-II study: A multicenter randomized phase II study comparing capoxiri plus bevacizumab with FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer as the first-line treatment.
Authors: Akihito Tsuji, Takayuki Yoshino, Takeharu Yamanaka, Hideaki Bando, Hironaga Satake, Kentaro Yamazaki, Hiroya Taniguchi, Eiji Oki, Masahito Kotaka, Koji Oba, Yoshinori Miyata, Kei Muro, Yoshito Komatsu, Hideo Baba, Takeshi Kato
Journal: Journal of Clinical Oncology (2020)

TPS267 Background: The first-line FOLFOXIRI with Bevacizumab (BEV) is highly effective and regarded as one of standard-of-care treatments in patients (pts) with metastatic colorectal cancer (mCRC) despite a high incidence of adverse events (AEs) such as neutropenia and diarrhea. The AXEPT, Asian Phase III study showed CAPIRI+BEV [Capecitabine (CAP: 1600 mg/m 2 ), Irinotecan (IRI: 200 mg/m 2 ) and BEV (7.5 mg/m 2 )] q3wk was non-inferior to FOLFIRI+BEV in pts with the second-line mCRC, with a lower incidence hematologic toxicity favoring CAPIRI+BEV over FOLFIRI+BEV. Based on these, a reduced dose of CAP and IRI regimen in combination with Oxaliplatin (OX) and BEV, CAPOXIRI+BEV may be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: QUATTRO-II is an open-label, multicenter, randomized phase II study. Key eligibility criteria are as follows; age ≥20 years, ECOG performance status (PS) 0-1 (≥71 years age: PS 0), adequate organ function, and UGT1A1 single-heterozygous (UGT1A1*1/*6 or *1/*28) or wild-type (*1/*1) genotype. Pts are randomized to either the recommended dose of CAPOXIRI+BEV or FOLFOXIRI+BEV (OX: 85 mg/m 2 , IRI: 165 mg/m 2 , l-leucovorin: 200 mg/m 2 , 5-FU: 3200 mg/m 2 ), with the strata of RAS/ BRAF status, previous adjuvant OX, tumor sidedness, and UGT1A1 status. Induction triplet chemotherapy plus BEV treatments are administered for up to 4 months followed by fluoropyrimidine plus BEV maintenance. The recommended dose of CAPOXIRI+BEV will be determined as a safety-lead-in before moving forward to the phase II main part. The primary endpoint is progression-free survival (PFS). The similarity of PFS between the two arms is evaluated by observing whether the point estimate of hazard ratio (HR) for PFS falls in between 0.80 and 1.25. Ensuring 70% probability that the observed HR will be “0.8&lt;HR&lt;1.25” under the assumption of the true HR of 1.0, a total of 100 patients will be needed with 3-year study period. Secondary endpoints included overall survival, overall response rate, safety, and patient-reported outcome (FACT/GOG-Ntx4). The enrollment started in October 2019. Clinical trial information: NCT04097444.
Relationship between perioperative change of total psoas muscle area and cancer prognosis in esophageal carcinoma.
Authors: Kazuaki Matsui, Hirofumi Kawakubo, Satoru Matsuda, Shuhei Mayanagi, Tomoyuki Irino, Rieko Nakamura, Kazumasa Fukuda, Norihito Wada, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2020)

314 Background: As surgery for esophageal carcinoma in the elderly people has been increasing, sarcopenia is a severe problem not only in complications, but also in long-term prognosis. However, the relationship between perioperative skeletal muscle loss especially in the early postoperative period and long-term prognosis has not been clarified. Methods: This study retrospectively analyzed 152 patients with thoracic esophageal carcinoma who had underwent radical esophagectomy in our institution from April 2008 to March 2015 (Patients with postoperative hospital stay longer than 6 weeks were excluded). As an index of perioperative sarcopenia, total psoas muscle area (TPA) was measured before surgery (as baseline), at postoperative day (POD) 7 and postoperative month (POM) 6 from CT images. We investigated the correlation between the change of TPA and the postoperative survival. Results: Of 152 patients, 52 (34.2%) showed a TPA decrease from baseline to POD 7, and 98 (64.5%) showed a TPA decrease from baseline to POM 6. At the time of POD 7, overall survival (OS) decreased significantly in a TPA decrease group (P = 0.008, 5-year survival rate: non-decrease group 82.3% / decrease group 56.8%). Recurrence free survival (RFS) was also significantly decreased in a TPA decrease group (P &lt; 0.001, 5-year recurrence free survival rate: non-decrease group 73.7% / decrease group 44.9%). On the other hand, at the time of POM 6, OS and also RFS had no significant difference between decrease and non-decrease groups. In univariate analysis for OS, pStage ≥3 and TPA decrease at POD 7 had poor prognosis. In multivariate analysis for OS, pStage ≥3 (HR:5.516, P &lt; 0.001, 95%CI:2.634-11.551) and TPA decrease at POD 7 (HR:2.036, P = 0.047, 95%CI:1.010-4.103) were also independent poor prognostic factors. In the univariate analysis for RFS, pStage ≥3, TPA decrease at POD 7 and age ≥60 years had poor prognosis. In multivariate analysis, pStaeg ≥3 (HR:3.831, P &lt; 0.001, 95%CI:2.182-6.728) and TPA decrease at POD 7 (HR:1.942, P = 0.021, 95%CI:1.104-3.416) were independent poor prognostic factors. Conclusions: Our findings suggest that the TPA decrease early in a postoperative period has poor prognosis on OS and also RFS.
Association Between Hospital Volume, Processes of Care, and Outcomes in Patients Admitted With Heart Failure
Authors: Dharam J. Kumbhani, Gregg C. Fonarow, Paul A. Heidenreich, Phillip J. Schulte, Di Lu, Adrian Hernandez, Clyde Yancy, Deepak L. Bhatt
Journal: Circulation (2018)

Background: Hospital volume is frequently used as a structural metric for assessing quality of care, but its utility in patients admitted with acute heart failure (HF) is not well characterized. Accordingly, we sought to determine the relationship between admission volume, process-of-care metrics, and short- and long-term outcomes in patients admitted with acute HF. Methods: Patients enrolled in the Get With The Guidelines-HF registry with linked Medicare inpatient data at 342 hospitals were assessed. Volume was assessed both as a continuous variable, and quartiles based on the admitting hospital annual HF case volume, as well: 5 to 38 (quartile 1), 39 to 77 (quartile 2), 78 to 122 (quartile 3), 123 to 457 (quartile 4). The main outcome measures were (1) process measures at discharge (achievement of HF achievement, quality, reporting, and composite metrics); (2) 30-day mortality and hospital readmission; and (3) 6-month mortality and hospital readmission. Adjusted logistic and Cox proportional hazards models were used to study these associations with hospital volume. Results: A total of 125 595 patients with HF were included. Patients admitted to high-volume hospitals had a higher burden of comorbidities. On multivariable modeling, lower-volume hospitals were significantly less likely to be adherent to HF process measures than higher-volume hospitals. Higher hospital volume was not associated with a difference in in-hospital (odds ratio, 0.99; 95% confidence interval [CI], 0.94–1.05; P =0.78) or 30-day mortality (hazard ratio, 0.99; 95% CI, 0.97–1.01; P =0.26), or 30-day readmissions (hazard ratio, 0.99; 95% CI, 0.97–1.00; P =0.10). There was a weak association of higher volumes with lower 6-month mortality (hazard ratio, 0.98; 95% CI, 0.97–0.99; P =0.001) and lower 6-month all-cause readmissions (hazard ratio, 0.98; 95%, CI 0.97–1.00; P =0.025). Conclusions: Our analysis of a large contemporary prospective national quality improvement registry of older patients with HF indicates that hospital volume as a structural metric correlates with process measures, but not with 30-day outcomes, and only marginally with outcomes up to 6 months of follow-up. Hospital profiling should focus on participation in systems of care, adherence to process metrics, and risk-standardized outcomes rather than on hospital volume itself.