tbuckley/cabot-search huggingface dataset:
Therapy preference scale: A novel questionnaire to understand patients’ preferences of cancer treatment.
Authors: Vijaya Raj Bhatt, Prajwal Dhakal, Christopher S Wichman, Bunny J Pozehl
Journal: Journal of Clinical Oncology (2019)

e23179 Background: Engaging patients in shared decision-making can help select an appropriate treatment for an individual and enhance patients’ experience and satisfaction with their care. This requires an in-depth understanding of patients’ values and preferences of various aspects of cancer treatment. A questionnaire to assess patient preferences is currently lacking. The purpose of our study was to develop a questionnaire that would fill this gap. Methods: We reviewed published literature to develop a theoretical framework to explain how cancer patients chose a specific therapy for themselves, and to identify key aspects of treatment that determine patients’ decisions about treatment. Three key domains (efficacy, safety and other characteristics of treatment such as need for hospital stay) were identified (Bhatt VR, J Geriatr Oncol. 2018 Nov 27 [Epub ahead of print]) and a mutli-dimensional self-report questionnaire with 49 items was developed. Each item was rated for relevance by 10 experts (oncologists, oncology nurses, advanced practice providers, social workers and pharmacists) to assess content validity (Lawshe formula) (Meas Eval Couns Dev, 47: 79–86). Ratings of ‘very relevant’ or ‘relevant’ were used to identify an essential question. Experts also suggested refinement of items. Three community members and 9 patients evaluated the instrument for face validity. Results: A content validity index for the questionnaire was 0.82. Face validity was confirmed. Based on input from the various stakeholders, the number of items, content, and format of the questionnaire was revised. The revised questionnaire includes a total of 36 items under four sections: safety (14 items), efficacy (4 items), treatment characteristics (8 items) and global items (10 items). Conclusions: We have developed a novel tool and established content and face validity. This self-report questionnaire can be used to understand patients’ preferences of cancer treatment. Further psychometric studies are planned to evaluate reliability and validity. Our ultimate goal is to use this tool to enhance communication between physicians and patients and facilitate shared decision-making.
Linked seasonal outbreaks of Salmonella Typhimurium among passerine birds, domestic cats and humans, Sweden, 2009 to 2016
Authors: Robert Söderlund, Cecilia Jernberg, Linda Trönnberg, Anna Pääjärvi, Erik Ågren, Elina Lahti
Journal: Eurosurveillance (2019)

In 2016, an outbreak of Salmonella Typhimurium (STm) with multilocus variable-number tandem repeat analysis (MLVA) profiles historically associated with passerine birds (2-[11-15]-[3-4]-NA-212) occurred among passerines, cats and humans in Sweden. Our retrospective observational study investigated the outbreak and revisited historical data from 2009–16 to identify seasonality, phylogeography and other characteristics of this STm variant. Outbreak isolates were analysed by whole-genome single nucleotide polymorphism (SNP) typing. The number of notified cases of passerine-associated STm among passerines, cats and humans per month and county, and their MLVA profiles, were compared to birdwatchers’ counts of passerines. Seasonal trend decomposition and correlation analysis was performed. Outbreak isolates did not cluster by host on SNP level. Passerine-associated STm was seasonal for birds, cats and humans, with a peak in March. Cases and counts of passerines at bird feeders varied between years. The incidence of passerine-associated STm infections in humans was higher in the boreal north compared with the southern and capital regions, consistent with passerine population densities. Seasonal mass migration of passerines appears to cause STm outbreaks among cats certain years in Sweden, most likely via predation on weakened birds. Outbreaks among humans can follow, presumably caused by contact with cats or environmental contamination.
Clinical Outcomes After Intensifying Antihypertensive Medication Regimens Among Older Adults at Hospital Discharge
Authors: Timothy S. Anderson, Bocheng Jing, Andrew Auerbach, Charlie M. Wray, Sei Lee, W. John Boscardin, Kathy Fung, Sarah Ngo, Molly Silvestrini, Michael A. Steinman
Journal: JAMA Internal Medicine (2019)

Transient elevations of blood pressure (BP) are common in hospitalized older adults and frequently lead practitioners to prescribe more intensive antihypertensive regimens at hospital discharge than the patients were using before hospitalization.To investigate the association between intensification of antihypertensive regimens at hospital discharge and clinical outcomes after discharge.In this retrospective cohort study, patients 65 years and older with hypertension who were hospitalized in Veterans Health Administration national health system facilities from January 1, 2011, to December 31, 2013, for common noncardiac conditions were studied. Data analysis was performed from October 1, 2018, to March 10, 2019.Discharge with antihypertensive intensification, defined as receiving a prescription at hospital discharge for a new or higher-dose antihypertensive than was being used before hospitalization. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not receive antihypertensive intensifications at hospital discharge.The primary outcomes of hospital readmission, serious adverse events, and cardiovascular events were assessed by competing risk analysis. The secondary outcome was the change in systolic BP within 1 year of hospital discharge.The propensity-matched cohort included 4056 hospitalized older adults with hypertension (mean [SD] age, 77 [8] years; 3961 men [97.7%]), equally split between those who did vs did not receive antihypertensive intensifications at hospital discharge. Groups were well matched on all baseline covariates (all standardized mean differences <0.1). Within 30 days, patients receiving intensifications had a higher risk of readmission (hazard ratio [HR], 1.23; 95% CI, 1.07-1.42; number needed to harm [NNH], 27; 95% CI, 16-76) and serious adverse events (HR, 1.41; 95% CI, 1.06-1.88; NNH, 63; 95% CI, 34-370). At 1 year, no differences were found in cardiovascular events (HR, 1.18; 95% CI, 0.99-1.40) or change in systolic BP among those who did vs did not receive intensifications (mean BP, 134.7 vs 134.4; difference-in-differences estimate, 0.6 mm Hg; 95% CI, -2.4 to 3.7 mm Hg).Among older adults hospitalized for noncardiac conditions, prescription of intensified antihypertensives at discharge was not associated with reduced cardiac events or improved BP control within 1 year but was associated with an increased risk of readmission and serious adverse events within 30 days.
A single institution retrospective analysis of basosquamous carcinoma of the head and neck
Authors: P. Clement, J. Verheezen, S. Nuyts, V. Vanderpoorten, R. Sciot
Journal: Journal of Clinical Oncology (2006)

15530 Background: Basosquamous Cell Carcinoma (BSCC) of the larynx, hypopharynx and base of tongue represents 1% of all head and neck tumours. It is considered a more aggressive disease than squamous cell carcinoma, based on higher incidence of advanced stage disease (60% lymph node-involvement and 40% metastases at diagnosis). Therefore, a treatment regimen including chemotherapy is often recommended in addition to surgery and/or radiotherapy in the literature. Methods: We retrospectively analyzed the data of all patients diagnosed with BSCC of the head and neck at the University Hospital of Leuven between 1993 and 2003, and report here the stage at diagnosis, treatment modality, disease evolution, progression free and overall survival. Results: Seven patients where diagnosed with BSCC in the head and neck region. Six patients were male. Three of the tumours were localised in the larynx, two at the base of tongue, and two in the oral cavity. The AJCC stages of disease ranged from I to IVa. Three patients had lymph node involvement at diagnosis. Six patients were treated with surgery in combination with radiotherapy. One patient was treated with cryotherapy before brachytherapy was applied. Five patients have no evidence of disease with a follow up of 4, 5, 6, 10 and 11 years, respectively. One patient died of an unknown cause 18 months after treatment. Only one of the seven patients, developed metastases during follow up. This patient had BSCC of the base of tongue, and was diagnosed with lungmetastases 16 months after surgery and radiotherapy. He was treated with the combination of Doxorubicine, Cisplatin and Fluorouracil. A partial response was confirmed after six cycles. Eight months after the last treatment cycle, there is still no evidence of disease progression. Conclusions: BSCC is a rare tumour of the head and neck. Seven patients were treated at the University hospital of Leuven in the period between 1993 and 2003 with a median progression free and overall survival of more than 5 years. Only one patient developed metastases, and was consequently treated with chemotherapy, inducing a continuing partial remission 8 months after treatment. In contrast to what is reported in the literature we do not confirm a high incidence of metastases at diagnosis nor a high mortality rate. No significant financial relationships to disclose.
Increased Survival by Pulmonary Treatment of Established Lung Metastases with Dual STAT3/CXCR4 Inhibition by siRNA Nanoemulsions
Authors: Zhaoting Li, Gang Chen, Ling Ding, Yixin Wang, Chenfei Zhu, Kaikai Wang, Jing Li, Minjie Sun, David Oupicky
Journal: Molecular Therapy (2019)
Identification of Children With High-Intensity Neurological Impairment
Authors: Joanna E. Thomson, James A. Feinstein, Matt Hall, James C. Gay, Breann Butts, Jay G. Berry
Journal: JAMA Pediatrics (2019)

This cross-sectional study describes and evaluates the effectiveness of a refined coding system for distinguishing children with high-intensity neurological impairment from those with lower-intensity neurological conditions.
New anti-IL-7Rα monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models
Authors: Julie A. Hixon, Caroline Andrews, Lila Kashi, Casey L. Kohnhorst, Emilee Senkevitch, Kelli Czarra, Joao T. Barata, Wenqing Li, Joel P. Schneider, Scott T. R. Walsh, Scott K. Durum
Journal: Leukemia (2019)
MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1
Authors: Huai-Chia Chuang, Chih-Chi Chang, Chiao-Fang Teng, Chia-Hsin Hsueh, Li-Li Chiu, Pu-Ming Hsu, Ming-Ching Lee, Chung-Ping Hsu, Yi-Rong Chen, Yi-Chung Liu, Ping-Chiang Lyu, Tse-Hua Tan
Journal: Cancer Research (2019)

Overexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif-containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1. SIGNIFICANCE: These findings show the critical role of the GLK-IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.
Airway epithelium–shifted mast cell infiltration regulates asthmatic inflammation via IL-33 signaling
Authors: Matthew C. Altman, Ying Lai, James D. Nolin, Sydney Long, Chien-Chang Chen, Adrian M. Piliponsky, William A. Altemeier, Megan Larmore, Charles W. Frevert, Michael S. Mulligan, Steven F. Ziegler, Jason S. Debley, Michael C. Peters, Teal S. Hallstrand
Journal: Journal of Clinical Investigation (2019)

Asthma is a heterogeneous syndrome that has been subdivided into physiologic phenotypes and molecular endotypes. The most specific phenotypic manifestation of asthma is indirect airway hyperresponsiveness (AHR), and a prominent molecular endotype is the presence of type 2 inflammation. The underlying basis for type 2 inflammation and its relationship to AHR are incompletely understood. We assessed the expression of type 2 cytokines in the airways of subjects with and without asthma who were extensively characterized for AHR. Using quantitative morphometry of the airway wall, we identified a shift in mast cells from the submucosa to the airway epithelium specifically associated with both type 2 inflammation and indirect AHR. Using ex vivo modeling of primary airway epithelial cells in organotypic coculture with mast cells, we show that epithelial-derived IL-33 uniquely induced type 2 cytokines in mast cells, which regulated the expression of epithelial IL33 in a feed-forward loop. This feed-forward loop was accentuated in epithelial cells derived from subjects with asthma. These results demonstrate that type 2 inflammation and indirect AHR in asthma are related to a shift in mast cell infiltration to the airway epithelium, and that mast cells cooperate with epithelial cells through IL-33 signaling to regulate type 2 inflammation.
Abstract 16199: From Door to Balloon to Door to Unload: Shifting the Paradigm of Cardioprotective Therapy for Ischemia Reperfusion Injury in Acute Myocardial Infarction
Authors: Navin K Kapur, Vikram Paruchuri, Emily E Mackey, Gerard H Daly, Xiaoying Qiao, Jose A Urbano-Moral, Prerna Nepali, George Perides, Richard H Karas
Journal: Circulation (2012)

Management of an acute myocardial infarction (AMI) focuses on rapid coronary reperfusion to limit myocardial injury, known as the Door to Balloon time. Despite timely coronary recanalization, myoca...
In type 2 diabetes, a primary care–led weight management program increased weight loss and diabetes remission at 2 years
Authors: Anupam Goel
Journal: Annals of Internal Medicine (2019)

Source Citation Lean ME, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019;7:344-55. 30852132
Similarities in Clinical and Psychosocial Characteristics of Functional Diarrhea and Irritable Bowel Syndrome With Diarrhea
Authors: Prashant Singh, Ha-Neul Lee, Vikram Rangan, Sarah Ballou, Joseph Lembo, Jesse Katon, Courtney McMahon, Daniel Friedlander, Johanna Iturrino, Judy Nee, Anthony Lembo
Journal: Clinical Gastroenterology and Hepatology (2019)
The spectrum of genomic alterations in young adult non-small cell lung cancer (NSCLC).
Authors: Geoffrey R. Oxnard, Jennifer C. Heng, Stacy L. Mach, Peter C. Lo, Mohit Butaney, David Michael Jackman, Pasi A. Janne
Journal: Journal of Clinical Oncology (2013)

8077 Background: Identification of targetable genomic alterations in patients (pts) with NSCLC can have a profound impact on treatment and clinical outcomes. Given the complexity and cost of comprehensive genomic testing, clinical characteristics enriching for targetable genomic alterations are of interest. We hypothesized that young adults with NSCLC would have a higher prevalence of targetable genomics alterations compared to the general NSCLC population. Methods: An institutional database of pts with NSCLC was reviewed in an IRB-approved fashion to identify subjects with age &lt; 40 at diagnosis. Clinical characteristics and risk factors were reviewed. Tumor genotyping for alterations in EGFR, KRAS, ALK, BRAF, HER2, and ROS1was pursued as part of an institution-wide genomics protocol. Targeted next-generation sequencing (NGS) of wild-type cases is underway. Results: From 2032 subjects with NSCLC, we identified 70 diagnosed at an age &lt; 40 (3.4%). Pt characteristics: median age 35 (range 20-39); 63% never-smokers, 33% with ≥10 pack-years; 74% adeno, 9% squam, 14% undifferentiated, 3% neuroendocrine; 19% had a family history of lung cancer; 61% stage IV at diagnosis. Median survival from date of advanced disease was 15.8 months. Genotyping was performed on 51 pts with adeno or undifferentiated histology: 14 with EGFR mutations (27%), 5 with KRAS mutations (10%), 8 with ALK rearrangements (16%), 0 with BRAF mutations, 1 with a HER2 insertion (2%), 1 with a ROS1 rearrangement (2%). Compared to a reference prevalence from the Lung Cancer Mutation Consortium (Kris et al, ASCO, 2011), KRAS mutations were less common (p=0.01) and ALK rearrangements were more common (p&lt;0.01). NGS of 2 cases to date has identified one pt with a novel 21 base-pair insertion mutation in FGFR2, not present in germline tissue. Conclusions: 47% (CI: 33%-60%) of pts diagnosed with NSCLC under age 40 harbor a targetable alteration in EGFR, ALK, HER2, or ROS1. These patients may be enriched for targetable genotypes and deserving of a unique treatment approach, and additionally represent an attractive population for genomic discovery.Supported in part by the Bonnie J. Addario Lung Cancer Foundation and the Conquer Cancer Foundation of ASCO.
CKD-732, a novel angiogenesis inhibitor: Evaluation of antitumor effect in vivo and preclinical studies in combination with oxaliplatin and capecitabine in colorectal cancer
Authors: Dal-Hyun Kim, Gyu Tae Park, Jae Hoon Choi, In Chang Hwang, Dong Wook Lee, Nam Song Choi, Sungsook Lee, Hong Woo Lee, Soon Kil Ahn, Chung Il Hong
Journal: Cancer Research (2008)

LB-96  CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate], a novel fumagillin derivative, showed a comparable antiangiogenic effect to TNP-470 in vitro and in vivo. The antitumor and antimetastatic effects of CKD-732 (s.c.) were studied alone or in combination with cytotoxic agents-adriamycin (i.p.), cisplatin (i.p.) and 5-FU (i.p.), using rodent or human tumors. CKD-732 (180 mg/kg, q2d x 5) inhibited growth of PC-3, MDA-MB-231, CX-1, LX-1, SKOV-3, Hep3B and SNU-16 human tumors by 64, 70, 74, 69, 69, 65 and 68%, respectively, comparable to TNP-470 [Inhibition rate (IR), 63~75%], but the effect was stronger than fumagillin (IR, 44~48%) at the highest dose. CKD-732 (90 mg/kg, 2 times/week) prolonged the life of mice bearing PC-3 and A375-SM by 236.7 and 197.1%, respectively, whereas fumagillin, adriamycin and cisplatin increased the life span by less than 90% at the highest dose in both tumors. CKD-732 (150 mg/kg, q2d x 6) reduced the number of pulmonary metastatic foci of i.v. inoculated LLC and B16BL6 rodent tumor by 89.7% and 90.5%, respectively, comparable to TNP-470 (IR, 89.5% and 90.3%), but the effect was superior to fumagillin, adriamycin and cisplatin (IR,
Adjuvant chemotherapy in non-small cell lung cancer (NSCLC): Referral and utilization patterns
Authors: T. Al-Fayea, N. Saint-Jacques, K. Virik, W. Morzycki, T. Younis
Journal: Journal of Clinical Oncology (2007)

6590 Background: Adjuvant chemotherapy in Non Small Cell Lung Cancer (NSCLC) has become a new standard of care. However, referral and utilization patterns for adjuvant chemotherapy outside of clinical trials remain unknown. Methods: All patients with NSCLC who underwent curative-intent surgery in Nova Scotia, Canada, in year 2005 were identified. Data were abstracted from the provincial cancer registry, and the patients’ charts at the two provincial cancer centers. A retrospective exploratory analysis was conducted utilizing logistic regression models to determine the statistically significant variables associated with referral to medical oncology and/or utilization of adjuvant chemotherapy. Results: 108 patients who underwent curative-intent surgery (67% lobectomy, 15% pneumonectomy, and 19% wedge resection) for NSCLC (38% IA, 23% IB, 4% IIA, 21% IIB, 12% IIIA, and 2% IIIB) were identified. The median age was 66 years, and 56% were males. Common histologies included adenocarcinoma (43%), squamous cell carcinoma (32%), large cell carcinoma (7%), and broncheoalveolar carcinoma (7%). A referral to medical oncology for consideration of adjuvant chemotherapy was observed in 41% (44/108) of all patients including 62% (41/66) of those with stage &gt; IA. Lower referral rate was associated with older age, stage I, and wedge resection while higher referral rate was associated with younger age, more advanced stage, large cell carcinoma subtype, and pneumonectomy. Adjuvant chemotherapy was prescribed in 27% (29/108) of all patients, including 41% (27/66) of those with stage &gt; IA, and in 66% (29/44) of the patients referred to medical oncology. Of those referred to medical oncology, older patients and those who underwent wedge resection were less likely to receive chemotherapy. Of all patients, higher chemotherapy utilization was associated with younger age and more advanced stages. Conclusions: Adjuvant chemotherapy utilization in patients with resected NSCLC is low overall, especially among older patients and those with early-stage disease. However, a high proportion of the patients referred to medical oncology receive chemotherapy. Improved referral rates to medical oncology may increase the overall utilization rates of adjuvant chemotherapy in NSCLC. No significant financial relationships to disclose.