tbuckley/cabot-search huggingface dataset:
Derivation and Validation of a Risk Assessment Model for Immunomodulatory Drug–Associated Thrombosis Among Patients With Multiple Myeloma
Authors: Ang Li, Qian Wu, Suhong Luo, Greg S. Warnick, Neil A. Zakai, Edward N. Libby, Brian F. Gage, David A. Garcia, Gary H. Lyman, Kristen M. Sanfilippo
Journal: Journal of the National Comprehensive Cancer Network (2019)

Abstract Background: Although venous thromboembolism (VTE) is a significant complication for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), no validated clinical model predicts VTE in this population. This study aimed to derive and validate a new risk assessment model (RAM) for IMiD-associated VTE. Methods: Patients with newly diagnosed MM receiving IMiDs were selected from the SEER-Medicare database (n=2,397) to derive a RAM and then data from the Veterans Health Administration database (n=1,251) were used to externally validate the model. A multivariable cause-specific Cox regression model was used for model development. Results: The final RAM, named the “SAVED” score, included 5 clinical variables: prior surgery, Asian race, VTE history, age ≥80 years, and dexamethasone dose. The model stratified approximately 30% of patients in both the derivation and the validation cohorts as high-risk. Hazard ratios (HRs) were 1.85 ( P &lt;.01) and 1.98 ( P &lt;.01) for high- versus low-risk groups in the derivation and validation cohorts, respectively. In contrast, the method of stratification recommended in the current NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease had HRs of 1.21 ( P =.17) and 1.41 ( P =.07) for the corresponding risk groups in the 2 datasets. Conclusions: The SAVED score outperformed the current NCCN Guidelines in risk-stratification of patients with MM receiving IMiD therapy. This clinical model can help inform providers and patients of VTE risk before IMiD initiation and provides a simplified clinical backbone for further prognostic biomarker development in this population.
Race-based mortality as determined by intrinsic breast tumor subtype and p53 status.
Authors: Keith A. Dookeran, Firas M Dabbous, Benjamin J Booth
Journal: Journal of Clinical Oncology (2013)

e12519 Background: Race-based mortality differences have been reported for intrinsic breast tumor subtypes. p53 status has recently emerged as a marker of worse prognosis among African-American (AA) women with breast cancer; however, the impact of p53 status on mortality by specific subtype is not clear. Methods: Multivariable (age, stage and race adjusted) stratified (subtype and p53) analyses with proportional hazards regression models [hazard ratios (HR), 95% confidence intervals (CIs)] for all-cause mortality, in a cohort of 331 AA and 203 non-AA women (115 Hispanic, 88 non-Hispanic white) of lower socioeconomic status, consecutively treated for breast cancer at an urban hospital, with 60.4 months median follow-up, and known intrinsic subtype and p53 immunohistochemical status. Results: The Table shows the effect of p53 status and demonstrates increased mortality hazards across all subtype strata for AA women compared to non-AA. The largest change in hazards was observed for luminal A and HER2 subtype tumors with higher stage, but this pattern was also evident for lower stage tumors. Hazards of death were least increased across basal type tumors. Conclusions: Across each level of subtype, p53+ status increased the hazards of death in AA women with breast cancer. However, mortality hazards appeared most increased in women with luminal A and HER2 type tumors. [Table: see text]
Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL
Authors: Constantine S. Tam, Judith Trotman, Stephen Opat, Jan A. Burger, Gavin Cull, David Gottlieb, Rosemary Harrup, Patrick B. Johnston, Paula Marlton, Javier Munoz, John F. Seymour, David Simpson, Alessandra Tedeschi, Rebecca Elstrom, Yiling Yu, Zhiyu Tang, Lynn Han, Jane Huang, William Novotny, Lai Wang, Andrew W. Roberts
Journal: Blood (2019)
Staging <sup>18</sup>FDG-PET in newly diagnosed small cell lung cancer (SCLC): 15-year institutional experience
Authors: A. Azad, F. Chionh, A. Scott, S. White, P. L. Mitchell
Journal: Journal of Clinical Oncology (2009)

e19044 Background: 18 FDG-PET is not routinely used in the initial staging of SCLC despite evidence that it alters stage classification and management. Furthermore, the association between stage classification by PET and prognosis of newly diagnosed SCLC has not previously been directly assessed. We aimed to evaluate whether PET altered stage classification, management and prognosis when used to stage newly diagnosed SCLC. Methods: We retrospectively reviewed the medical records of 46 consecutive patients undergoing PET during initial staging for SCLC at Austin Health from 1993 to 2008 inclusive. Data collected included patient demographics, stage classification before and after PET, treatment history and date of death. Statistical analysis included estimation of overall survival (OS) by the Kaplan-Meier method using the log-rank test. Results: PET altered stage classification in 12 of 46 (26%) of patients. Stage alteration led to a change in treatment modality in 9 of these 12 patients. In addition, PET altered the target radiation field in another three patients. Therefore, PET had a significant impact on management in 12 of 46 (26%) of patients. Patients with limited disease (LD) on both conventional imaging and PET had significantly longer OS than patients with LD on conventional imaging that was upstaged to extensive disease (ED) on PET (median 557 days versus 172 days; log-rank p&lt;0.0001). Patients with ED on conventional imaging that was downstaged to LD on PET had significantly longer OS than patients with ED on both conventional imaging and PET (median 328 days versus 177 days; log-rank p=0.037). Conclusions: The use of 18 FDG-PET during staging for SCLC had a major impact on stage classification, management and prognostic stratification. The use of staging PET should be considered in patients with newly diagnosed SCLC. No significant financial relationships to disclose.
Technology could provide safety net for scan and x ray results lost in the system
Authors: Adrian O’Dowd
Journal: BMJ (2019)

Results from patient scans and x rays are sometimes lost and not acted on, with serious consequences, a report by the body that carries out independent investigations of patient safety concerns in NHS care in England has concluded.

To tackle this problem, the report by the Healthcare Safety Investigation Branch has recommended that patients be sent texts or emails suggesting they contact their GP if tests show abnormal results, as a safety net for results that go missing between different parts of the NHS.1

The agency carried out an England-wide investigation following the case of a 76 year old woman who had a chest x ray after a suspected heart …
STRASS (EORTC 62092): A phase III randomized study of preoperative radiotherapy plus surgery versus surgery alone for patients with retroperitoneal sarcoma.
Authors: Sylvie Bonvalot, Alessandro Gronchi, Cecile Le Pechoux, Carol Jane Swallow, Dirk C. Strauss, Pierre Meeus, Frits van Coevorden, Stephan Stoldt, Eberhard Stoeckle, Piotr Rutkowski, Claudia Sangalli, Charles Honoré, Marco Rastrelli, Chandrajit Raut, Peter Chung, Marco Fiore, Saskia Litiere, Sandrine Marreaud, Hans Gelderblom, Rick L.M. Haas
Journal: Journal of Clinical Oncology (2019)

11001 Background: The predominant pattern of failure of retroperitoneal sarcoma (RPS), frequently associated with subsequent death, is locoregional recurrence. Unlike in limbs, the efficacy of radiotherapy (RT) combined with surgery is not established. Methods: STRASS is a randomized, multicentre, international trial. Eligible patients had histologically-proven localized primary RPS, operable and suitable for radiotherapy. Patients were randomized 1:1 to preoperative RT (3D-CRT or IMRT) 50.4 Gy followed by surgery (RT/S group) or surgery alone (S group), stratified by hospital and performance status (0-1 vs 2). Primary endpoint is abdominal recurrence-free survival (ARFS; local relapse after complete resection, peritoneal sarcomatosis, R2 surgery, progressive disease during RT or unresectable disease). IDMC recommended a sensitivity analysis in which local progression on RT is not regarded as an event for patients who subsequently achieve complete surgical resection. Secondary endpoints were recurrence-free survival, overall survival, acute toxicity profile of RT, perioperative and late complications, and QoL. The study was designed to provide 90% power to show an increase of 20% in the 5-year ARFS rate, from 50% to 70% (corresponding to a HR of 0.52) at 2-sided 5% significance level. Results: 266 patients from Europe, USA and Canada were randomized between January 2012 and April 2017; 198 patients (74.5 %) had liposarcoma (LPS). Eighteen patients were designated ineligible. Overall rate of re-operation for any complication was 10.1%: 13 (10.9%) and 12 (9.4%) patients in RT/S versus S groups. 19 pts (14%) progressed during RT, 4 of whom did not undergo surgery. 3-year ARFS was 60.4% (95% Confidence interval (CI) 51.4-68.2%) and 58.7% (49.5- 66.7%) (HR = 1.01, 95%CI 0.71-1.44, p=0.954) in RT/S versus S groups. In the sensitivity analysis, 3-year ARFS was 66.0% (57.1-73.5%) and 58.7% (49.5-66.7%) in RT/S versus S groups (HR = 0.84, 95% CI 0.58-1.21, p=0.340). In the LPS subgroup, 3-year ARFS (sensitivity analysis) was 71.6% (61.3-79.6%) and 60.4% (49.8-69.5%) in RT/S versus S groups (HR = 0.64, 95%CI 0.40-1.01, p =0.049). Conclusion: STRASS failed to demonstrate a benefit of pre-operative RT for RPS. In the exploratory analysis, preoperative RT may benefit the LPS subgroup. Funding Source: EORTC and EUROSARC FP7 278472. Clinical trial information: EORTC 62092.
Mapping exclusive breastfeeding in Africa between 2000 and 2017
Authors: Natalia V. Bhattacharjee, Lauren E. Schaeffer, Laurie B. Marczak, Jennifer M. Ross, Scott J. Swartz, James Albright, William M. Gardner, Chloe Shields, Amber Sligar, Megan F. Schipp, Brandon V. Pickering, Nathaniel J. Henry, Kimberly B. Johnson, Celia Louie, Michael A. Cork, Krista M. Steuben, Alice Lazzar-Atwood, Dan Lu, Damaris K. Kinyoki, Aaron Osgood-Zimmerman, Lucas Earl, Jonathan F. Mosser, Aniruddha Deshpande, Roy Burstein, Lauren P. Woyczynski, Katherine F. Wilson, John D. VanderHeide, Kirsten E. Wiens, Robert C. Reiner, Ellen G. Piwoz, Rahul Rawat, Benn Sartorius, Nicole Davis Weaver, Molly R. Nixon, David L. Smith, Nicholas J. Kassebaum, Emmanuela Gakidou, Stephen S. Lim, Ali H. Mokdad, Christopher J. L. Murray, Laura Dwyer-Lindgren, Simon I. Hay
Journal: Nature Medicine (2019)

Exclusive breastfeeding (EBF)—giving infants only breast-milk (and medications, oral rehydration salts and vitamins as needed) with no additional food or drink for their first six months of life—is one of the most effective strategies for preventing child mortality1–4. Despite these advantages, only 37% of infants under 6 months of age in Africa were exclusively breastfed in 20175, and the practice of EBF varies by population. Here, we present a fine-scale geospatial analysis of EBF prevalence and trends in 49 African countries from 2000–2017, providing policy-relevant administrative- and national-level estimates. Previous national-level analyses found that most countries will not meet the World Health Organization’s Global Nutrition Target of 50% EBF prevalence by 20256. Our analyses show that even fewer will achieve this ambition in all subnational areas. Our estimates provide the ability to visualize subnational EBF variability and identify populations in need of additional breastfeeding support. Exclusive breastfeeding in Africa is highly varied within and between countries, with many countries unlikely to reach World Health Organization 2025 targets without urgent action.
Provider mix and costs associated with treatment of patients with bone metastases secondary to prostate cancer.
Authors: Kenneth M. Shermock, Sean D Sullivan, Scott David Ramsey, Brian S. Seal
Journal: Journal of Clinical Oncology (2012)

e15175 Background: Treatment of patients with bone metastases secondary to prostate cancer can involve several provider types and combinations of chemotherapy, surgery, radiation, and pharmaceutical treatment. This study evaluated the combinations of provider types and associated treatment patterns for a cohort of patients with bone metastases secondary to prostate cancer. Methods: Continuously enrolled patients older than 20 years of age in the MarketScan database between January 2004 and December 2010 with evidence of bone metastases (ICD9 code 198.5 or treatment with zolderonic acid, pamidronate, or demosumab) were included. Inpatient and outpatient medical claims data were used to define provider combinations. Treatment patterns were determined from prescription fill/refill claims and procedure codes from inpatient and outpatient medical claims. Results: A total of 4,493 patients had evidence of bone metastases. A radiologist was involved in care for a vast majority (n=4,054, 90%). Less than half of the population, (n=1,751, 39%) had an oncologist actively involved in care. Most patients (n=2633, 59%) had both an urologist and a radiologist involved in their care. The most common combinations of providers were urologist and radiologist (n=998, 22%); urologist, radiologist, and surgeon (n=951, 21%), and urologist, radiologist, and oncologist (n=781, 17%). About 15% (n=684) of patients had a surgeon, urologist, oncologist, and radiologist involved in their care. Only approximately half (n=2,274, 51%) of the population had evidence of receiving radiation therapy, suggesting that the radiologist plays a diagnostic role for many patients. A vast majority of patient were prescribed hormone therapy (89%) and 76% were prescribed steroid agents (mostly glucocorticoids). Less than half of the population (n=1,838, 41%) received surgery related to their prostate cancer. Conclusions: There is significant variation in combinations of provider types and associated treatment patterns for patients who have bone metastases secondary to prostate cancer. Follow-up studies should examine optimal conditions for different provider mixes and treatment patterns.
Avoiding a Tyranny of the Majority: Public Deliberation as Citizen Science, Sensitive Issues, and Vulnerable Populations
Authors: Mary A. Ott, Amelia S. Knopf
Journal: The American Journal of Bioethics (2019)

Citizen science is touted as a means of making science more inclusive and democratic. However, when citizens are drawn from societies with significant socioeconomic and racial disparities, citizen ...
Have we outgrown the reduced social motivation theory of autism?
Authors: Kristen Gillespie-Lynch
Journal: Behavioral and Brain Sciences (2019)

Abstract Although refreshing, Jaswal &amp; Akhtar's critique of the reduced social motivation theory omits reference to Asperger's work and to changes in the diagnostic criteria over time. I situate the theory in the historical contexts that shaped – and eventually contradicted – it to highlight its dehumanizing aspects while emphasizing that critiques should be rooted in recognition of the diversity of the spectrum.
Letter to the editor: Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections
Authors: Shelly Bolotin, Natasha S Crowcroft, Stephanie L Hughes, Gaston De Serres
Journal: Eurosurveillance (2019)

Preview this article: Letter to the editor: Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/30/eurosurv-24-30-5-1.gif
Abstract 5880: Localization of the Binding Site for Fibrin-Derived Peptide P3 in the αIIb β-Propeller of Integrin αIIbβ3
Authors: Nataly P Podolnikova, Tatiana P Ugarova
Journal: Circulation (2009)

The currently available anti-thrombotic agents target the interaction of platelet integrin αIIbβ3 (GPIIbIIIa) with fibrinogen during platelet aggregation, an initial step of thrombus formation. How...
Factors associated with an increased risk of recurrence in women with ovarian granulosa cell tumors.
Authors: Anuj Suri, Neil S. Horowitz, Ebony B. Carter, Sheri Denslow, Paola A. Gehrig
Journal: Journal of Clinical Oncology (2012)

5063 Background: There is emerging data in different malignancies, including gynecologic cancers, demonstrating factors independent of a patient’s tumor characteristics, which are associated with an increased risk of cancer recurrence. The goal of this study is to determine demographic and prognostic factors affecting recurrence of disease (RD) in women with ovarian granulosa cell tumors (GCT). Methods: A dual-institution retrospective analysis of patients diagnosed with GCT between 1995 and 2010. Demographics including age, race, BMI, stage, diabetes (DM), adjuvant treatment, and progression free survival (PFS) were extracted. Hazard ratios for recurrence were estimated by univariate and multivariate Cox regression models Results: One hundred nine women identified with a median age of 50 (range 12-87). Fifty-six (57.1%) were Caucasian, 32 (32.7%) African American, and 10 (10.2%) were other. Median BMI was 29 (range 12-57). Twenty-one patients had DM. The majority of women had stage I disease (89.0%), 7 (6.4%) had stage II/III disease, and 5 were unstaged. In univariate analysis, DM showed the strongest association with recurrence (HR 3.56, 95% CI: 1.57-8.11). Non-white race was also associated with higher risk of RD, though the association was not statistically significant (HR 1.74, 95% CI: 0.78-3.87). The association between DM and RD was also found in multivariate analysis controlling for all factors including non-white race and BMI (HR 2.99, 95% CI: 1.11-8.08). Only 19 (17%) patients received adjuvant chemotherapy consisting of one of two different adjuvant chemotherapy regimens bleomycin, etoposide, and cisplatin or paclitaxel and carboplatin, however there was no difference in outcome based on chemotherapy regimen (p=0.24). Conclusions: This is the largest study analyzing factors associated with risk of recurrence in women with ovarian GCT. Studies have demonstrated higher morbidity among diabetic patients with breast and colon cancer and this may be modifiable with metformin. Our results emphasize that diabetes is one of the strongest predictors of recurrent disease in patients with ovarian GCT. Further studies are necessary to evaluate the effect of other factors such as adjuvant chemotherapy.
Mobility assessment using wearable technology in patients with late-onset Pompe disease
Authors: Alaa Hamed, Christopher Curran, Chad Gwaltney, Pronabesh DasMahapatra
Journal: npj Digital Medicine (2019)

Late-onset Pompe disease (LOPD) is a rare genetic disorder due to the absence or deficiency of acid alpha-glucosidase enzyme resulting in slowly progressing reduction of muscle strength, causing difficulties with mobility and respiration. Wearable technologies offer novel options to evaluate mobility in a real-world setting. LOPD patients self-reporting LOPD, ≥18 years, US residents, walking (with or without aid), and not on invasive ventilation were recruited for a 6- to 8-week wearable study via patient organizations. Eligible patients were shipped a wearable tracker (Fitbit One™) and completed self-assessment questionnaires. Mobility outcome measures were median step count and peak 1-min activity. In the analyses cohort (N = 29), engagement in data sharing was high (94% of patients uploaded data for more than half the study days). Mean age was 43 years, 90% were females, and 93% were diagnosed in adulthood. Mean delay in diagnosis was 10 years; most had disease onset for ≥10 years (55%); some required walking aid (17%) and breathing assistance (38%). Mean step count differed by age (20-39 years: 4071 vs. 40-69 years: 2394, p < 0.01), diagnostic delay (<10 years: 3584 vs. ≥10 years: 2232, p < 0.05), disease duration (<10 years: 4219 vs. ≥10 years: 2462, p < 0.05), and ambulatory status (aided: 1883 vs. unaided: 3408, p < 0.05). Patient-reported "fatigue and pain" score was inversely correlated with step count (Pearson's r = -0.42, p < 0.05) and peak 1-min activity (Pearson's r = -0.49, p < 0.01). This study illustrates a new approach to measure mobility in LOPD patients and establishes a framework for future outcomes data collection.
KLF4 in Macrophages Attenuates TNFα-Mediated Kidney Injury and Fibrosis
Authors: Yi Wen, Xiaohan Lu, Jiafa Ren, Jamie R. Privratsky, Bo Yang, Nathan P. Rudemiller, Jiandong Zhang, Robert Griffiths, Mukesh K. Jain, Sergei A. Nedospasov, Bi Cheng Liu, Steven D. Crowley
Journal: Journal of the American Society of Nephrology (2019)

Polarized macrophage populations can orchestrate both inflammation of the kidney and tissue repair during CKD. Proinflammatory M1 macrophages initiate kidney injury, but mechanisms through which persistent M1-dependent kidney damage culminates in fibrosis require elucidation. Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor that suppresses inflammatory signals, is an essential regulator of macrophage polarization in adipose tissues, but the effect of myeloid KLF4 on CKD progression is unknown.