tbuckley/cabot-search huggingface dataset:
Secondary Use of COVID-19 Symptom Incidence Among Hospital Employees as an Example of Syndromic Surveillance of Hospital Admissions Within 7 Days
Authors: Steven Horng, Ashley O’Donoghue, Tenzin Dechen, Matthew Rabesa, Ayad Shammout, Lawrence Markson, Venkat Jegadeesan, Manu Tandon, Jennifer P. Stevens
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Alternative methods for hospital occupancy forecasting, essential information in hospital crisis planning, are necessary in a novel pandemic when traditional data sources such as disease testing are limited. <h3>Objective</h3> To determine whether mandatory daily employee symptom attestation data can be used as syndromic surveillance to estimate COVID-19 hospitalizations in the communities where employees live. <h3>Design, Setting, and Participants</h3> This cohort study was conducted from April 2, 2020, to November 4, 2020, at a large academic hospital network of 10 hospitals accounting for a total of 2384 beds and 136 000 discharges in New England. The participants included 6841 employees who worked on-site at hospital 1 and lived in the 10 hospitals' service areas. <h3>Exposure</h3> Daily employee self-reported symptoms were collected using an automated text messaging system from a single hospital. <h3>Main Outcomes and Measures</h3> Mean absolute error (MAE) and weighted mean absolute percentage error (MAPE) of 7-day forecasts of daily COVID-19 hospital census at each hospital. <h3>Results</h3> Among 6841 employees living within the 10 hospitals' service areas, 5120 (74.8%) were female individuals and 3884 (56.8%) were White individuals; the mean (SD) age was 40.8 (13.6) years, and the mean (SD) time of service was 8.8 (10.4) years. The study model had a MAE of 6.9 patients with COVID-19 and a weighted MAPE of 1.5% for hospitalizations for the entire hospital network. The individual hospitals had an MAE that ranged from 0.9 to 4.5 patients (weighted MAPE ranged from 2.1% to 16.1%). For context, the mean network all-cause occupancy was 1286 during this period, so an error of 6.9 is only 0.5% of the network mean occupancy. Operationally, this level of error was negligible to the incident command center. At hospital 1, a doubling of the number of employees reporting symptoms (which corresponded to 4 additional employees reporting symptoms at the mean for hospital 1) was associated with a 5% increase in COVID-19 hospitalizations at hospital 1 in 7 days (regression coefficient, 0.05; 95% CI, 0.02-0.07;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This cohort study found that a real-time employee health attestation tool used at a single hospital could be used to estimate subsequent hospitalizations in 7 days at hospitals throughout a larger hospital network in New England.
Diabetes following acute pancreatitis
Authors: Phil A Hart, David Bradley, Darwin L Conwell, Kathleen Dungan, Somashekar G Krishna, Kathleen Wyne, Melena D Bellin, Dhiraj Yadav, Dana K Andersen, Jose Serrano, Georgios I Papachristou
Journal: The Lancet. Gastroenterology & hepatology (2021)
G2M checkpoint signaling among six-cell proliferation-related pathway as a biomarker for prediction and prognosis in pancreatic cancer.
Authors: Masanori Oshi, Lan Le, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe
Journal: Journal of Clinical Oncology (2021)

e16264 Background: Given the poor survival and severe side effects of treatments for pancreatic cancer, prognostic and predictive biomarkers to guide management are in urgent need. We hypothesized that the cell proliferation-related pathway is associated with drug response and survival in pancreatic cancer. Methods: Six hallmark cell proliferation-related gene sets (G2M checkpoint, E2F targets, MYC targets V1 and V2, mitotic spindle, p53 pathway) defined by MSigDB in gene set variant analysis (GSVA) was evaluated in 3 independent cohorts, TCGA-PDAC ( n = 176), GSE57495 ( n = 63), and GSE62452 ( n = 69). Results: Although G2M and E2F correlated strongly with each other (Spearman’s r = 0.976), Mitotic and p53 pathway scores correlated highly with the other cell function gene sets. All pathways were significantly associated with high expression of MKI67 and with proliferation score (all p &gt; 0.001), but none with pathologically complete resection (R0). Mitotic spindle pathway alone associated with high cytolytic activity ( p = 0.020). All pathways were significantly associated with high expression of KRAS and TP53 genes and with high rate of KRAS gene alteration except for MYC v1. G2M, E2F, and p53 pathways were significantly associated with high rate of TP53 gene alteration ( p = 0.026, 0.011, and 0.07, respectively). Interestingly, different pathway correlated with AUC of different agents, such as gemcitabine (mitotic: r=0.706 [ p = 0.01]), paclitaxel (MYC v2: r = -0.636 [ p &lt; 0.05]), apatinib (mitotic: r = -0.556 [ p = 0.03]), palbociclib (E2F: r =0.675 [ p &lt; 0.01]), and sorafenib (G2M: r = -0.593 [ p = 0.03]), for pancreatic cancer. Among all six pathways, only G2M was significantly associated with worse patient survival consistently in all 3 cohorts. Conclusions: Each proliferation-related pathway was predictive of the unique agent, and the G2M score predicts survival of pancreatic cancer.
Assessment of National Comprehensive Cancer Network (NCCN) guideline adherence for lung cancer in a community teaching hospital during COVID-19 pandemic.
Authors: Mahati Paravathaneni, Vihitha Thota, Bohdan Baralo, Sana Mulla, Eugene Jinkyu Choi, Rajesh Thirumaran
Journal: Journal of Clinical Oncology (2021)

e20589 Background: Coronavirus disease 2019 (COVID-19) evolved into a worldwide pandemic leading to devastating complications. In healthcare, significant changes were made to reallocate resources to cater to an increasing number of hospital admissions and prevent infection spread. Reallocation of the health care staff led to the scarcity of care in outpatient facilities, including infusion centers, until the widespread adoption of Telehealth. Treating lung cancer patients with immunochemotherapy and radiotherapy has been incredibly challenging due to the pandemic, especially in regard to balancing malignancy treatment with limiting exposure of vulnerable patients to acute life-threatening infection. In addition, being unable to provide appropriate treatment to cancer patients can result in decreased functional capacity, loss of treatment window, and increased mortality. A multidisciplinary approach can prevent these outcomes by anticipating challenges early and streamlining resources appropriately to provide better patient care. In this study, we aimed to assess the adherence of NCCN guidelines for lung cancer at a community hospital in Philadelphia during the pandemic. Methods: A retrospective chart review was performed of patients diagnosed and receiving active treatment for primary lung cancer between March 1, 2020, and December 31, 2020, at Mercy Catholic Medical Center. Fifty cases of primary lung cancer undergoing active treatment were identified. Type and staging of lung cancer, NCCN guidelines’ adherence, COVID-19 exposure, and missed treatments were reviewed and analyzed. Results: Of the 50 cases reviewed, 92% had non-small cell lung cancer (NSCLC), and 8% had small cell lung cancer (SCLC). Among NSCLC, 72% had adenocarcinoma, 12% had squamous cell carcinoma, and 8% had large cell carcinoma. Stage IV lung cancer consisted of 46%, followed by 34% of stage I, 14% of stage III, and 6% of stage II. NCCN guideline-directed treatment was initiated in 88% (44/50) of the total patients, with the remaining 12% of the patients either refusing treatment (8%) or were lost to follow-up (4%). COVID-19 infection was diagnosed in 35% of the patients, of which 60% missed less than two chemotherapy sessions and 40% of COVID-19 positive patients who required hospitalization missed more than two cycles. 28% of patients missed treatment sessions due to other factors. This resulted in 61% (27/44) of patients having a disruption in NCCN guideline-directed treatment at some point during the pandemic. Conclusions: Our study results reflect upon the need for developing effective strategies in managing cancer patients. When possible, switching to oral regimens, redefining regimen administration intervals, postponing invasive investigations for asymptomatic patients, and utilizing telemedicine as appropriate should be considered.
Clinical rebirth of flavopiridol in chronic lymphocytic leukemia (CLL): Utilizing in vitro and in vivo pharmacodynamic measurements to improve efficacy and interrogate relevant mechanism(s) of action
Authors: Amy J. Johnson, David M. Lucas, Lisa L. Smith, Jamie M. S. Allison, Thomas S. Lin, Michael R. Grever, John C. Byrd
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1672 

Flavopiridol is a broad cyclin dependent kinase (CDK) inhibitor that exhibited promising pre-clinical activity in CLL and other cancers. In vitro , flavopiridol has been noted to promote a rapid decrease in Mcl-1 and XIAP expression in CLL cells. This was presumed to be secondary to inhibition of CDK9 and CDK7 and subsequent global transcription inhibition by preventing RNA Polymerase II (RPII) phosphorylation. Despite potent pre-clinical activity of flavopiridol, previous clinical trials in CLL and other diseases using a one-, 24-, and 72-hour schedule of administration demonstrated either marginal or no activity. Significant plasma protein binding of flavopiridol in human serum relative to fetal bovine serum prompted our group to perform pharmacokinetic modeling, which suggested an optimal dosing schedule of 30-minute IV bolus followed by four-hour continuous infusion. A mature phase I dose escalation study of single agent flavopiridol, utilizing this schedule included 23 relapsed and refractory, genetically high risk CLL patients, demonstrated a 43% response rate and a dose limiting toxicity of acute tumor lysis syndrome. In conjunction with this study, we sought to explore the in vitro modulation of select flavopiridol targets in human serum and the relevance of these to in vivo observations. In vitro, we demonstrated that Mcl-1 protein level dramatically decreased after four hours, while XIAP, Bcl-2, and Bax levels did not change. Diminishment of Mcl-1 mRNA was noted as early as 30 minutes post-treatment with flavopiridol. Of interest, no change in RPII phosphorylation was detected at concentrations where Mcl-1 protein and mRNA were decreased. We next sought to determine if similar modulation of Mcl-1 occurred in vivo following treatment. In two of three responding patients, significant diminishment of Mcl-1 protein, but not XIAP, Bcl-2, Bax, RPII, or RPII phosphorylation, was noted. In five non-responding patients, there was either no change or an increase in Mcl-1 protein. Our preliminary in vitro and in vivo data suggest that flavopiridol is influencing an alternative transcription factor responsible for Mcl-1 expression in CLL, and not global transcription via inhibition of RPII. Additionally, we demonstrate the value of translational in vitro and in vivo studies in CLL for both interrogating the mechanism of action of new therapeutic agents and optimizing the schedule of administration in human phase I studies.
Frequency, characteristics, and subsequent treatment (Tx) of real-world patients (pts) who discontinue hedgehog inhibitors (HHIs) as first-line (1L) systemic Tx for advanced basal cell carcinoma (aBCC).
Authors: Charles Lance Cowey, Chieh-I Chen, Kathleen M. Aguilar, Kalatu Davies, Patrick R. LaFontaine, Matthew G. Fury, Timothy Geoffrey Bowler, Asieh Golozar, Jessica J. Jalbert
Journal: Journal of Clinical Oncology (2021)

e18740 Background: HHIs are the only approved 1L systemic Tx for aBCC and Tx options following HHI Tx failure are limited. The objective of this study was to assess frequency, characteristics, and subsequent Tx patterns of pts with aBCC discontinuing 1L HHIs due to toxicity or disease progression. Methods: We conducted a retrospective cohort study using electronic health records of pts treated in The US Oncology Network (Network), a community-based network of &gt; 450 oncology clinics. We identified adults (18+ years) with aBCC, not treated for another primary malignancy in the past 3 years, with ≥2 Network visits who discontinued 1L HHI monotherapy between January 2012 and November 2019 due to documented toxicity or progression without evidence of complete response (CR) who subsequently initiated second-line (2L) systemic Tx (2L initiators) or not (2L non-initiators). To exclude pts potentially using neoadjuvant HHIs, we required 2L non-initiators to be followed for ≥90 days after HHI discontinuation and excluded pts who underwent surgery or radiation during this period. Index date was Tx initiation for 2L initiators and 90 days after HHI discontinuation for 2L non-initiators. We describe cohort attrition and characteristics of 2L initiators and 2L non-initiators as well as Txs initiated among 2L initiators. Results: We identified 138 aBCC pts treated with HHIs regardless of line of therapy with fully accessible charts: 115/138 (83.3%) received HHIs as 1L systemic therapy for aBCC; 73/115 (63.5%) discontinued 1L HHIs; 37/73 (50.7%) discontinued due to documented toxicity or progression without evidence of CR. 4/37 pts (10.8%) initiated 2L systemic Tx (1 carboplatin &amp; paclitaxel; 1 cemiplimab; 1 nivolumab; 1 pembrolizumab) within a median of 75 days (range: 2‒130) from HHI discontinuation. 2L initiators were 68.7 years of median age (range: 48.4‒71.1); 100% female; 75% White; 75% immunocompetent; 100% treated with 1L vismodegib for a median of 8.6 months (range: 6.8‒42.2); 100% discontinued 1L HHIs due to documented disease progression. We identified 15 2L non-initiators; median age 80.2 years (range: 49.6‒90+); 20% female; 100% White; 86.7% immunocompetent; 100% treated with 1L vismodegib for a median of 6.8 months (range: 1.9‒20.6); 93.3% discontinued 1L HHIs due to documented toxicity and 6.7% due to progression. Conclusions: In this small cohort of aBCC pts discontinuing 1L HHIs, ̃50% discontinued due to toxicity or disease progression. There was no clear standard of care among pts who experienced HHI Tx failure, with only a minority initiating subsequent 2L Tx. Effective Tx strategies for pts who do not respond to or cannot tolerate HHIs are needed.
Camrelizumab combined with albumin paclitaxel and cisplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Huilai Lv, Yang Tian, Chao Huang, Zhenhua Li, Ziqiang Tian
Journal: Journal of Clinical Oncology (2021)

e16021 Background: The pathologic complete response (pCR) rate is improved by neoadjuvant therapy in locally advanced ESCC, but occurs less than 10% of patients(pts) with neoadjuvant chemotherapy agents. Immunotherapy has become a new promising treatment. Camrelizumab (anti-PD-1) is standard of care as second-line therapy for advanced ESCC in China. Therefore, we intended to evaluate the efficacy and safety of Camrelizumab combined with albumin paclitaxel and cisplatin as neoadjuvant therapy for pts with locally advanced ESCC. Methods: We retrospectively analysed locally advanced ESCC pts with clinical stage Ⅱ-ⅣA. Eligible pts were aged 18–75 years with no prior any therapy. Pts received 2-4 cycles neoadjuvant therapy which including Camrelizumab (200mg IV q3w), albumin paclitaxel (260 mg/m 2 IV q3w) and cisplatin (75 mg/m 2 IV q3w). Surgery was performed 4-6 weeks after neoadjuvant therapy. The primary endpoint was pCR, the secondary endpoints were major pathologic response (MPR), R0 resection rate, objective response rate (ORR), disease-free survival (DFS) and safety. Results: From Jul 27 2019 to Sep 26 2020,16 pts were enrolled and available evaluated. 8 pts (50%) had clinical complete response (cCR), and the ORR was 87.5% (14/16). All pts underwent surgery and surgical treatment was not delayed. The pCR was 43.8% (7/16), MPR was 75% (12/16). Notably, R0 resection rate was 100% (16/16). None of 16 pts progressed, the DFS was not yet achieved. The average intraoperative blood loss was 131ml (100-200ml) and the average hospitalization time after operation was 14 days (11-21 days). No patient developed anastomotic leak and other surgical treatment-related toxicity. The grade 1-2 treatment-related AEs were reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 3,18.8%), weakness (n = 2, 12.5%), Myelosuppression (n = 1, 6.2%) and hypothyroidism (n = 1, 6.2%). No serious AEs resulted in termination of treatment, and treatment-related death was not observed. Conclusions: The addition of camrelizumab to albumin paclitaxel and carboplatin was demonstrated encouraging clinical efficacy and acceptable safety as neoadjuvant therapy, and might be a favorable option for pts with locally advanced ESCC. Further registered clinical trials are expected.
Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease
Authors: Zhihan Wang, Kai Guo, Pan Gao, Qinqin Pu, Ping Lin, Shugang Qin, Na Xie, Junguk Hur, Changlong Li, Canhua Huang, Min Wu
Journal: Theranostics (2021)

With increasing incidence and prevalence of inflammatory bowel disease (IBD), it has become one of the major public health threats, and there is an urgent need to develop new therapeutic agents. Although the pathogenesis of IBD is still unclear, previous research has provided evidence for complex interplays between genetic, immune, microbial, and environmental factors. Here, we constructed a gene-microbiota interaction-based framework to discover IBD biomarkers and therapeutics.
Abstract 13409: Glycine Levels are Associated With Improvements in Submaximal Blood Pressure Response After Endurance Exercise Training
Authors: Jeremy M Robbins, Bennet Peterson, Jordan Morningstar, Tuomo Rankinen, Mark A Sarzynski, Claude Bouchard, Robert E Gerszten
Journal: Circulation (2019)

Background: Glycine is a non-essential amino acid that has been inversely associated to coronary heart disease (CHD), with recent data suggesting that this relationship may be mediated by lower blo...
The use of quasi-experimental design methods to evaluate and improve the impact of acute care centers on oncologic emergencies.
Authors: John W. Sweetenham, Basit Iqbal Chaudhry, Benjamin Teng, Andrew Yue, Nora Connor
Journal: Journal of Clinical Oncology (2021)

e13515 Background: Reducing avoidable hospital and emergency department (ED) use are national priorities in cancer care. Acute care centers (ACCs) that expand access for patients with oncologic emergencies are increasingly implemented as alternatives to inpatient and ED care. The impact of these ACCs is uncertain. Additionally, how to rigorously evaluate these interventions and to iteratively improve their effectiveness remains unclear as infrastructure interventions such as ACCs are not amenable to experimental manipulation. Methods: We are developing a novel quasi-experimental framework for evaluating and improving the effectiveness of an ACC intervention at the Simmons Comprehensive Cancer Center (SCCC) of the University of Texas Southwestern. SCCC covers one of the largest geographic regions of any academic medical center in the country, creating challenges addressing access to care. Drawing on the Andersen model for healthcare utilization we hypothesize that ACC effectiveness is mediated through enabling factors, particularly distance. Our initial evaluation framework draws on an untreated control group design with multiple pretest and post-test samples. The control group is comprised of patients living in zip codes farther away from the ACC. Additional analytic work will assess the feasibility of adding a matching cohort group structure based on factors such as onset of illness and matching individual patient episodes based on risk adjustment parameters. If the ACC is later expanded to other sites, the design can be further developed by adding a switching replications methodology to augment the quasi-experiment. Data collection draws on claims data provided through SCCC’s participation in Medicare’s Oncology Care Model (OCM). Results: Over OCM’s initial four performance periods (each six months long), all-cause risk adjusted hospitalization rates for SCCC patients ranged from 25.2% to 27.2%. All-cause risk adjusted OCM ED use ranged from 28.1 to 29.9%. Seeking to improve performance for both, SCCC leadership initially implemented a temporary urgent care clinic in August 2018. This initial prototype clinic was formalized into an operational ACC in August 2020. Evaluation of the impact of this ACC intervention is ongoing. Conclusions: ACCs represent potentially important means to reduce avoidable hospital and ED use. However, complex infrastructure interventions are not amenable to experimental evaluations assessing their impact, and it remains difficult to gain insights into how to tailor services through these interventions to support patients with oncologic urgencies and emergencies. Quasi-experimental approaches when integrated alongside ACC interventions represent promising mechanisms of evaluation and continuous quality improvement.
Selpercatinib efficacy and safety in patients with <i>RET</i>-altered thyroid cancer: A clinical trial update.
Authors: Eric Jeffrey Sherman, Lori J. Wirth, Manisha H. Shah, Maria E. Cabanillas, Bruce Robinson, Janessa J. Laskin, Matthias Kroiss, Vivek Subbiah, Alexander E. Drilon, Jennifer Wright, Victoria Soldatenkova, Pearl Plernjit French, Antoine Italiano, Daniela Weiler
Journal: Journal of Clinical Oncology (2021)

6073 Background: Selpercatinib, is a first-in-class, highly selective, CNS active and potent RET inhibitor approved in multiple countries for treatment of RET-fusion positive lung or thyroid cancers. Reported is an update of efficacy and safety results in RET-altered thyroid cancer, with a longer follow up (30 Mar 2020 data cutoff vs 16 Dec 2019) and additional enrolment. Methods: Patients (pts) with RET-mutant medullary thyroid cancer (MTC) and RET-fusion positive thyroid cancer (TC) were enrolled in the global (16 countries, 89 sites) Phase 1/2 LIBRETTO-001 trial (NCT03157128). The primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), clinical benefit rate (CBR; CR+PR+SD ≥16 weeks), and safety. The integrated analysis set (IAS, n = 143) includes efficacy evaluable MTC pts previously treated with cabozantinib and/or vandetanib (cabo/vande). The primary analysis set (PAS), a subset of IAS, is the first 55 enrolled pts. Cabo/vande naïve MTC pts (N = 112) and TC pts with prior systemic treatment (N = 22) were also analyzed. Safety population includes all pts who received ≥1 dose of selpercatinib (MTC N = 315; TC N = 42) by data cutoff. Results: For MTC patients, the ORR for IAS was 69.2%, in the PAS it was 69.1%, and 71.4% for cabo/vande naïve MTC pts. The ORR for TC pts (n = 22) was 77.3% (see table). Most treatment-emergent adverse events (TEAEs) were low grade; the most common (≥25% of MTC and/or TC pts treated with selpercatinib) were dry mouth, diarrhea, hypertension, fatigue and constipation for both MTC and TC pts, increased ALT/AST, peripheral edema and headache in MTC pts and nausea in TC pts. 4.8% of MTC and TC pts discontinued selpercatinib due to TEAEs but only 1.9% with MTC and none with TC discontinued due to treatment-related adverse events. Conclusions: In this updated analysis, selpercatinib continued to show marked and durable antitumor activity in pts with RET-altered thyroid cancers. Selpercatinib was well tolerated and no new safety concerns were identified. A global, randomized, phase 3 trial (LIBRETTO-531) evaluating selpercatinib compared to cabo/vande in kinase inhibitor naïve MTC pts is ongoing. Clinical trial information: NCT03157128. [Table: see text]