bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel
Authors: Faramand Rawan , Jain Michael , Staedtke Verena , Kotani Hiroshi , Bai Renyuan , Reid Kayla , Lee Sae Bom , Spitler Kristen , Wang Xuefeng , Cao Biwei , Pinilla Javier , Lazaryan Aleksander , Khimani Farhad , Shah Bijal , Chavez Julio C. , Nishihori Taiga , Mishra Asmita , Mullinax John , Gonzalez Ricardo , Hussaini Mohammad , Dam Marian , Brandjes Brigett D. , Bachmeier Christina A. , Anasetti Claudio , Locke Frederick L. , Davila Marco L. 
Published: July 2020

AbstractPurpose:One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).Experimental Design:Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.Results:We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.Conclusions:These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
Antiproliferative Effects of Monoclonal Antibodies against (Pro)Renin Receptor in Pancreatic Ductal Adenocarcinoma
Authors: Rahman Asadur , Matsuyama Makoto , Ebihara Akio , Shibayama Yuki , Hasan Arif Ul , Nakagami Hironori , Suzuki Fumiaki , Sun Jiao , Kobayashi Tomoe , Hayashi Hiroki , Nakano Daisuke , Kobara Hideki , Masaki Tsutomu , Nishiyama Akira 
Published: July 2020

Abstract
We previously reported that silencing of the PRR gene, which encodes the (pro)renin receptor [(P)RR], significantly reduced Wnt/β-catenin–dependent development of pancreatic ductal adenocarcinoma (PDAC). Here, we examined the effects of a panel of blocking mAbs directed against the (P)RR extracellular domain on proliferation of the human PDAC cell lines PK-1 and PANC-1 in vitro and in vivo. We observed that four rat anti-(P)RR mAbs induced accumulation of cells in the G0–G1-phase of the cell cycle and significantly reduced proliferation in vitro concomitant with an attenuation of Wnt/β-catenin signaling. Systemic administration of the anti-(P)RR mAbs to nude mice bearing subcutaneous PK-1 xenografts significantly decreased tumor expression of active β-catenin and the proliferation marker Ki-67, and reduced tumor growth. In contrast, treatment with the handle region peptide of (pro)renin did not inhibit tumor growth in vitro or in vivo, indicating that the effects of the anti-(P)RR mAbs were independent of the renin–angiotensin system. These data indicate that mAbs against human (P)RR can suppress PDAC cell proliferation by hindering activation of the Wnt/β-catenin signaling pathway. Thus, mAb-mediated (P)RR blockade could be an attractive therapeutic strategy for PDAC.
ARX788, a Site-specific Anti-HER2 Antibody–Drug Conjugate, Demonstrates Potent and Selective Activity in HER2-low and T-DM1–resistant Breast and Gastric Cancers
Authors: Skidmore Lillian , Sakamuri Sukumar , Knudsen Nick A. , Hewet Amha Gebre , Milutinovic Snezana , Barkho Wisam , Biroc Sandra Lyn , Kirtley Jessica , Marsden Robin , Storey Kristine , Lopez Ianina , Yu Wayne , Fang Shiao-Yan , Yao Sulan , Gu Yi , Tian Feng 
Published: July 2020

Abstract
First-generation antibody–drug conjugates (ADC) are heterogeneous mixtures that have shown clinical benefit, but generally exhibited safety issues and a narrow therapeutic window due, in part, to off-target toxicity caused by ADC instability. ARX788 is a next-generation, site-specific anti-HER2 ADC that utilizes a unique nonnatural amino acid–enabled conjugation technology and a noncleavable Amberstatin (AS269) drug-linker to generate a homogeneous ADC with a drug-to-antibody ratio of 1.9. ARX788 exhibits high serum stability in mice and a relatively long ADC half-life of 12.5 days. When compared in vitro against T-DM1 across a panel of cancer cell lines, ARX788 showed superior activity in the lower HER2-expressing cell lines and no activity in normal cardiomyocyte cells. Similarly, ARX788 significantly inhibited tumor growth, and generally outperformed T-DM1 in HER2-high and HER2-low expression xenograft models. Breast and gastric cancer patient-derived xenograft studies confirmed strong antitumor activity of ARX788 in HER2-positive and HER2-low expression tumors, as well as in a T-DM1-resistant model. The encouraging preclinical data support the further development of ARX788 for treatment of patients with HER2-positive breast and gastric cancer, including those who have developed T-DM1 resistance, and patients with HER2-low expression tumors who are currently ineligible to receive HER2-targeted therapy.
Primary Care Provider Beliefs and Recommendations About Colorectal Cancer Screening in Four Healthcare Systems
Authors: Ghai Nirupa R. , Jensen Christopher D. , Merchant Sophie A. , Schottinger Joanne E. , Lee Jeffrey K. , Chubak Jessica , Kamineni Aruna , Halm Ethan A. , Skinner Celette Sugg , Haas Jennifer S. , Green Beverly B. , Cannizzaro Nancy T. , Schneider Jennifer L. , Corley Douglas A. 
Published: July 2020

Abstract
Primary care provider's (PCP) perceptions of colorectal cancer screening test effectiveness and their recommendations for testing intervals influence patient screening uptake. Few large studies have examined providers’ perceptions and recommendations, including their alignment with evidence suggesting comparable test effectiveness and guideline recommendations for screening frequency. Providers (n = 1,281) within four healthcare systems completed a survey in 2017–2018 regarding their perceptions of test effectiveness and recommended intervals for colonoscopy and fecal immunochemical testing (FIT) for patients ages 40–49, 50–74, and ≥75 years. For patients 50–74 (screening eligible), 82.9% of providers rated colonoscopy as very effective versus 59.6% for FIT, and 26.3% rated colonoscopy as more effective than FIT. Also, for this age group, 77.9% recommended colonoscopy every 10 years and 92.4% recommended FIT annually. For patients ages 40–49 and ≥75, more than one-third of providers believed the tests were somewhat or very effective, although &gt;80% did not routinely recommend screening by either test for these age groups. Provider screening test interval recommendations generally aligned with colorectal cancer guidelines; however, 25% of providers believed colonoscopy was more effective than FIT for mortality reduction, which differs from some modeling studies that suggest comparable effectiveness. The latter finding may have implications for health systems where FIT is the dominant screening strategy. Only one-third of providers reported believing these screening tests were effective in younger and older patients (i.e., &lt;50 and ≥75 years). Evidence addressing these beliefs may be relevant if cancer screening recommendations are modified to include older and/or younger patients.
Cancer Research: The Lessons to Learn from COVID-19
Authors: Bailey Chris , Black James R.M. , Swanton Charles 
Published: July 2020

Abstract

Summary:
The COVID-19 pandemic has caused widespread disruption of cancer clinical trials due to the restrictions on nonessential services and the reallocation of resources, and at the same time the urgent global effort toward discovering therapies that treat or prevent COVID-19 infection has led to shortening of traditional regulatory timelines. This experience should stimulate similar urgency in the way future cancer research is conducted.
Combined Influences on North American Winter Air Temperature Variability from North Pacific Blocking and the North Atlantic Oscillation: Subseasonal and Interannual Time Scales
Authors: Luo Binhe , Luo Dehai , Dai Aiguo , Simmonds I. , Wu Lixin 
Published: July 2020

AbstractWinter surface air temperature (SAT) over North America exhibits pronounced variability on subseasonal, interannual, decadal, and interdecadal time scales. Here, reanalysis data from 1950–2017 are analyzed to investigate the atmospheric and surface ocean conditions associated with its subseasonal to interannual variability. Detrended daily SAT data reveal a known warm west/cold east (WWCE) dipole over midlatitude North America and a cold north/warm south (CNWS) dipole over eastern North America. It is found that while the North Pacific blocking (PB) is important for the WWCE and CNWS dipoles, they also depend on the phase of the North Atlantic Oscillation (NAO). When a negative-phase NAO (NAO−) coincides with PB, the WWCE dipole is enhanced (compared with the PB alone case) and it also leads to a warm north/cold south dipole anomaly in eastern North America; but when PB occurs with a positive-phase NAO (NAO+), the WWCE dipole weakens and the CNWS dipole is enhanced. The PB events concurrent with the NAO− (NAO+) and SAT WWCE (CNWS) dipole are favored by the Pacific El Niño–like (La Niña–like) sea surface temperature mode and the positive (negative) North Pacific mode. The PB-NAO+ has a larger component projecting onto the SAT WWCE dipole during the La Niña winter than during the El Niño winter because a more zonal wave train is formed. Strong North American SAT WWCE dipoles and enhanced projections of PB-NAO+ events onto the SAT WWCE dipole component are also readily seen for the positive North Pacific mode. The North Pacific mode seems to play a bigger role in the North American SAT variability than ENSO.
Placement of Surgical Feeding Tubes Among Patients With Severe Traumatic Brain Injury Requiring Exploratory Abdominal Surgery
Authors: Cha Peter I. , Jou Ronald M. , Spain David A. , Forrester Joseph D. 
Published: July 2020

Objectives The purpose of this study was to identify trauma patients who would benefit from surgical placement of an enteral feeding tube during their index abdominal trauma operation. Methods We performed a retrospective analysis of all patients admitted to 2 level I trauma centers between January 2013 and February 2018 requiring urgent exploratory abdominal surgery. Results Six-hundred and one patients required exploratory abdominal surgery within 24 hours of admission after trauma activation. Nineteen (3% of total) patients underwent placement of a feeding tube after their initial exploratory surgery. On multivariate analysis, an intracranial Abbreviated Injury Scale ≥4 (odds ratio [OR] = 9.24, 95% CI 1.09-78.26, P = .04) and a Glasgow Coma Scale ≤8 (OR = 4.39, 95% CI 1.38-13.95, P = .01) were associated with increased odds of requiring a feeding tube. All patients who required a feeding tube had an Injury Severity Score ≥15. While not statistically significant, patients with an open surgical feeding tube compared with interventional radiology/percutaneous endoscopic gastrostomy placement had lower median intensive care unit length of stay, fewer ventilator days, and shorter median total hospital length of stay. Conclusions Trauma patients with severe intracranial injury already requiring urgent exploratory abdominal surgery may benefit from early, concomitant placement of a feeding tube during the index abdominal operation, or at fascial closure.
Outcomes With Age Combinations in Living Donor Kidney Transplantation
Authors: Aslam Sadaf , Buggs Jacentha , Wasserman Jacob , Chaves Kendall , Rogers Ebonie , Kumar Ambuj , Huang James 
Published: July 2020

Introduction Reevaluation of donor criteria, including age, is needed to combat organ shortages, lengthy wait times, and anticipated recipient mortality rates. The purpose of this study was to evaluate donor and recipient (D/R) age combinations and patient and graft survival outcomes. Methods Single-organ, living donor kidney transplantations (LDKTs) from 2012 to 2018 were retrospectively reviewed. Donors and recipients were placed into “older” and “younger” age categories of 50 years and above or below age 50, then analyzed with SPSS version 25. Results We performed 347 LDKTs. Younger-to-older pairings had significantly higher rates of smoking in recipient (53.6%) and hepatitis C (5.5%), but shorter hospital stays (5.3 days). Older-to-younger pairings had the longest hospital stays (7.4 days) but the shortest cold ischemic time (2.3 hours). Notably, there was no significant variance in delayed graft function (first-week dialysis) between groups. Regarding complication rates, only bleeding within 30 days, highest in older-to-older pairings (7.7%), and renal complications, highest in older-to-younger pairings, significantly varied between groups. Interestingly, though younger-to-older cases had the longest mean graft survival time, older kidneys lasted 537 days longer in older recipients than in younger recipients. Discussion These results indicate there is not a one-size-fits-all approach when considering outcomes of donor/recipient age-pairings in LDKT, as significant correlations did not consistently favor one age-pairing over others. Regardless of age-pairing, LDKT provides gold standard treatment and expands the availability of organs. Future research into the impact of age-pairing on specific variables, national or multicenter studies, and protocol development for evaluating donor/recipient age-pairings is needed.
Predicting Delayed Complications After Esophagectomy in the Current Era of Early Discharge and Enhanced Recovery
Authors: Barrie J. , Cockbain A. , Tsachiridi M. , Surendrakumar V. , Maxwell M. , Tamhankar A. P. 
Published: July 2020

Background Enhanced recovery protocols after esophagectomy aim to discharge patients by day 7. A small risk of delayed complications exists. We aimed to assess whether C-reactive protein (CRP) levels on day 7 could help predict delayed complications and assist safe discharge. Methods All consecutive esophagectomies over 3 years were retrospectively reviewed. Patients were categorized on day 7 into (1) those clinically unsafe for discharge; (2) those clinically safe for discharge; and (3) those considered safe for discharge but develop a delayed complication. CRP level on day 7 and the trend in CRP levels between days 3 and 7 were compared. Results A total of 140 patients underwent esophagectomy, of which 64 patients (46%) had at least one complication. On day 7, 62 (44%) patients were considered clinically unsafe for discharge; 74 (53%) were considered safe for discharge; and 4 (3%) were safe but developed a delayed complication. No patient with delayed complication had a day 7 CRP level < 84 mg/L. CRP trend did not help predict delayed complications. Conclusions The actual CRP level on day 7 after esophagectomy, rather than the trend, can predict delayed complications. Early discharge after esophagectomy should be desisted if the clinical picture is better than the actual blood results.
Cost-Effective Approach to the Laparoscopic Appendectomy
Authors: DeMare Alexander M. , Luehmann Natalie C. , Kawak Samer , Abbott Emily E. , Long Jordan , Akay Begum , Brahmamdam Pavan , Iacco Anthony A. , Novotny Nathan M. 
Published: July 2020

Background Surgeons can help reduce health care spending by selecting affordable and efficient instruments. The laparoscopic appendectomy (LA) is commonly performed and can serve as a model for improving health care cost. Methods We retrospectively reviewed all adult patients who underwent LA for non-perforated appendicitis from March 2015 to November 2017. Our objective was to determine which combination of disposable instruments afforded the lowest total operative cost without compromising postoperative outcomes. Results In total, 1857 consecutive patients were reviewed from 2 hospitals. After determining the 8 most commonly utilized combinations of disposable instruments, 846 patients were ultimately analyzed. The combination of a LigaSure, Endoloop, and an EndoBag (LEB) had the shortest median operative time (25 minutes, P < .001) and lowest median total operative cost ($1893, P < .001). Conclusions The LEB instrument combination rendered the shortest operative time, lowest total operative cost, and can be used to maximize surgical value during LA.
Comparison of CHA2DS2-VASc and C2HEST scores for predicting the incidence of atrial fibrillation among patients with end-stage renal disease
Authors: Hu Wei-Syun , Lin Cheng-Li 
Published: July 2020

Purpose: The authors have studied assessment of CHA2DS2-VASc score versus C2HEST score in atrial fibrillation risk prediction in end-stage renal disease patients. Methods: The authors conducted this study by Longitudinal Health Insurance Database 2000. The authors totally enrolled 4,601 end-stage renal disease patients. The predictive capability of atrial fibrillation by using CHA2DS2-VASc and C2HEST score was estimated by area under the receiver operating characteristic curve (AUROC). Results: The AUROC for CHA2DS2-VASc score in predicting atrial fibrillation events was 0.5786, and AUROC for C2HEST score for atrial fibrillation prediction was 0.5983. Conclusion: Both scores yield almost identical AUROC values implying no difference in predictive power. Further work is warranted to verify the prognostic value of the current scores.
Investigation of chronic venous insufficiency in patients with sleep disorders due to restless legs syndrome
Authors: Yolgösteren Atıf , Leba Leyla Köse , Demir Aylin Bican 
Published: July 2020

Background We aimed to investigate of chronic venous insufficiency on patients with sleep disorder due to restless legs syndrome. Method Five hundred forty-one cases on whom polysomnography was performed due to sleep disorder were evaluated retrospectively. Forty patients with restless legs syndrome were determined. They were examined by history, physical examination, and duplex ultrasonography in terms of chronic venous insufficiency. The sleep stage rates of both groups were compared (that the rate of total sleep time in polysomnography to sleep stages is expressed as minute and percentage has been defined as sleep stage rate). Result Chronic venous insufficiency was identified in 20 out of 40 patients (group 1; female, 90%). In group 2, there were patients with only restless legs syndrome but with no chronic venous insufficiency (female, 80%). The mean ages of both groups were 56.4 ± 11.8 and 54.3 ± 14.7 years. Stage 1 sleep rate in group 1 was 5% ± 2.7 and in group 2 was 8% ± 3.8 (p = 0.006). Periodic limb movement index (polysomnography finding evaluating involuntary leg movements during sleep) was 11.4 ± 17.5 in group 1, and it was 29.4 ± 37.9 in group 2 (p = 0.006). Conclusion We recommend that chronic venous insufficiency should be investigated in patients with primary restless legs syndrome diagnosis.
Type of anti-thrombotic therapy for venous stenting in patients with non-thrombotic iliac vein lesions does not influence the development of in-stent restenosis
Authors: Tran Maxwell A , Lakhanpal Priya , Lakhanpal Sanjiv , Satwah Vinay K , Lakhanpal Gaurav , Pappas Peter J 
Published: July 2020

Background In patients receiving stents for symptomatic non-thrombotic iliac vein lesions, many clinicians prescribe anti-thrombotic medications. Whether or not anti-coagulation post-venous stenting improves stent patency is unknown. The aim of this investigation is to determine whether prophylactic post-operative anti-thrombotic therapy improves stent patency and/or prevents in-stent restenosis. Methods The medical records and venous ultrasounds for 389 patients stented for non-thrombotic iliac vein lesions were retrospectively reviewed. Patients were categorized into three anti-thrombotic regimens: Clopidogrel, Aspirin and Clopidogrel, and Apixaban or Rivaroxaban. Patients were routinely assessed for restenosis and stent patency at 6, 26, and 52 weeks and treated with anti-thrombotics for 90 days. Results Freedom from in-stent restenosis at 6, 26, and 52 weeks were Clopidogrel (91.50, 82.91, 80.95%), Aspirin and Clopidogrel (88.68, 80.03, 80.03%), and Apixaban or Rivaroxaban (91.03, 85.11, 83.18%). Primary patencies were Clopidogrel (98.77, 98.77, 98.10%), Aspirin and Clopidogrel (100, 95.74, 95.74%), and Apixaban or Rivaroxaban (98.70, 98.70, 96.71%). There were no statistically significant differences. Conclusions The type of post-operative anti-thrombotic therapy for non-thrombotic iliac vein lesions does not appear to improve stent patency or prevent the development of in-stent restenosis.
Palliative care in the emergency department: A survey assessment of patient and provider perspectives
Authors: Woods Emily J , Ginsburg Alexander D , Bellolio Fernanda , Walker Laura E 
Published: July 2020

Background: Palliative care has been identified as an area of low outpatient referral from our emergency department, yet palliative care has been shown to improve the quality of patient’s lives. Aim: This study investigates both provider and patient perspectives on palliative care for the purpose of identifying barriers to increased palliative care utilization within our healthcare system. Design: Two surveys were developed, one for patients/caregivers and one for healthcare providers. Setting/participants: This was a single-center study completed at a quaternary academic emergency department. A survey was sent to emergency medicine providers with 47% response rate. Research staff approached Emergency Department patients who had been identified to be high risk to fill out paper surveys with 76% response rate. Results: Only 28% of patients had already undergone palliative care, with an additional 25% interested in palliative care. Nearly half of the patients felt that they needed more resources to prevent hospital visits. Patients identified low understanding of palliative care and difficulty accessing appointments as barriers to consultation. Among providers, 98% indicated that they had patients who would benefit from palliative care. A majority of providers highlighted patient understanding of palliative care and access to appointments as barriers to palliative care. Notably, 52% of providers reported that emergency medicine provider knowledge was a barrier to palliative care consultation. Conclusions: Despite emergency department patients’ self-identified need for resources and emergency medicine providers’ recognition of patients who would benefit from palliative care, few patients receive palliative care consultation.