tbuckley/cabot-search huggingface dataset:
Abstract 17437: Do Patients With Uncomplicated Non-ST Segment Acute Coronary Syndromes Require Admission to Critical Care Units?
Authors: Sean van Diepen, Meng Lin, Jeffrey A Bakal, Finlay A McAlister, Padma Kaul, Jason N Katz, Chritopher B Fordynce, Danielle A Southern, Michelle M Graham, Stephen B Wilton, L K Newby, Christopher B Granger, Justin A Ezekowitz
Journal: Circulation (2015)

Background: Clinical practice guidelines recommend admitting patients with stable non-ST segment elevation acute coronary syndrome (NSTE ACS) to telemetry units, yet up to two thirds of patients are admitted to critical care units (CCU). The outcomes of patients with stable NSTE ACS initially admitted to a CCU versus a cardiology ward with telemetry have not yet been described. Methods: We used a population-based dataset of 7,869 patients hospitalized with NSTE ACS admitted to hospitals in Alberta, Canada between April 1, 2007 and Mar 31, 2013 and excluded patients (n=589) who received CCU procedures or therapies on the day of admission. We compared outcomes among patients initially admitted to a CCU (n=5141) with those admitted to cardiology telemetry wards (n=2728). Results: Patients admitted to cardiology telemetry wards were older (median 69 vs 65 years, p&lt;0.001), and more likely to be female (37.2% vs 32.1%, p&lt;0.001) and have a history of prior myocardial infarction (14.3% vs 11.5%, p&lt;0.001). Patients admitted directly to cardiology telemetry wards had similar hospital stays (6.2 vs 5.7 days, p=0.29), fewer cardiac procedures (39.1% vs 45.8%, p&lt;0.001) and higher mean Charleston scores (1.3 vs 1.0, p&lt;0.001) compared with patients initially admitted to CCUs. There were no differences in the frequency of cardiac arrest (0.7% vs 0.9%, p=0.51), in-hospital mortality (1.3% vs 1.2%, adjusted odds ratio (aOR) 1.57; 95% CI, 0.98 to 2.52), 30-day all-cause mortality (1.6% vs 1.5%, aOR 1.50; 95% CI 0.82 to 2.75), or 30-day all-cause post-discharge readmission (10.6% vs 10.8%, aOR 1.07; 95% CI 0.90 to 1.28) between cardiology telemetry ward and CCU patients. Results were similar across low, intermediate, and high risk NSTE ACS Charleston subgroups and in patients with non-ST segment myocardial infarction or unstable angina. Conclusions: No differences in clinically important outcomes were observed between patients with NSTE ACS initially admitted to wards or CCUs. These findings suggest that stable NSTE ACS can be managed appropriately in telemetry wards and present an opportunity to reduce hospital costs and critical care capacity strain.
Outcome of Patients with Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Beyond First Complete Remission (CR1)
Authors: Georg Evers, Dietrich W. Beelen, Jan Braess, Cristina Sauerland, Hans-Jochem Kolb, Albrecht Reichle, Ernst Holler, Rainer Schwerdtfeger, Renate Arnold, Christoph Scheid, Utz Krug, Carsten Müller-Tidow, Christoph Schliemann, Jan-Henrik Mikesch, Georg Lenz, Bernhard J. Wörmann, Wolfgang Hiddemann, Wolfgang E. Berdel, Matthias Stelljes
Journal: Blood (2018)
Interobserver variation in predicting fracture risk in patients with long bone metastatic lesions.
Authors: Benjamin Deheshi, Antonella Racano, Osama Alshaya, Nathan Evaniew, Dyda Dao, Forough Farrokhyar, Michelle Ghert
Journal: Journal of Clinical Oncology (2014)

e20524 Background: Metastatic bone disease (MBD) is the most common malignant process affecting the long bones, with pathologic fractures carrying a large burden for patients. In 1989, Mirels proposed a scoring system to predict fracture risk in patients with MBD. Subsequent studies have shown low specificity of Mirels’ criteria with potential for unnecessary surgery and morbidity. The objective of this study was to determine the inter-observer reliability of Mirels’ criteria, subjective fracture risk prediction and first-line treatment. Methods: We surveyed 15 orthopaedic surgeons, 11 orthopaedic oncology surgeons, 3 radiologists and 5 radiation oncologists. Participants were asked to review 7 clinical cases and assess Mirels’ criteria, risk of pathologic fracture, and make treatment recommendations. They were blinded to treatment and outcomes. To assess inter-rater reliability, Krippendorrf's alpha (Kα) values were calculated. Kα values of >0.667 indicates sufficient level reliability while Kα values over >0.800 indicates good reliability. Results: With respect to lesion site, overall inter-rater reliability was sufficient at 0.75 (95% CI: 0.67-0.83), but low for the other 3 Mirels’ criteria: lesion appearance (0.45, 95% CI: 0.32-0.58), axial diameter (0.47, 95% CI: 0.36-0.58) and pain (0.18, 95% CI: -0.01-0.36). When asked to predict pathologic fracture risk, overall reliability was sufficient at 0.68 (95% CI: 0.62-0.75); highest among radiologists (0.89, 95% CI: 0.81-0.96) and lowest among orthopaedic oncology surgeons (0.60, 95% CI: 0.52-0.67). Conversely, overall reliability regarding first-line treatment was considerably lower at 0.16 (95% CI: 0.09-0.22); highest among radiation oncologists (0.42, 95% CI: 0.16-0.64). Surgery and radiation were the most frequent first-line treatment options. Conclusions: The results of this survey show that the reliability of Mirels’ criteria, “expert” opinion on fracture risk, and subsequent treatment for patients with MBD is less than ideal. These results highlight a need for future tools to accurately identify reliable clinical and radiographic variables that are most predictive of fracture risk and guide appropriate treatment.
Differences in clinical characteristics and overall survival in never-smokers with lung squamous cell carcinoma.
Authors: Wanling Zeng, Wan-Teck Lim, Eng-Huat Tan, Chee-Keong Toh, Daniel Shao-Weng Tan
Journal: Journal of Clinical Oncology (2014)

e12527 Background: Lung cancer is the leading cause of cancer mortality globally. Although smoking has been established as a major risk factor, there is a growing interest in never smokers who developed lung cancers. Never smokers with squamous cell carcinoma (SCC) of the lung is uncommon. We sought to investigate the clinical characteristics and overall survival between never smokers and smokers diagnosed with lung SCC. Methods: We analyzed 399 patients from a retrospective database of patients who were diagnosed with lung SCC in National Cancer Centre Singapore (NCCS) from May 1998 to March 2013. Case records were reviewed to confirm clincopathological characteristics and overall survival. Comparisons of clinical data between the never smokers and smokers were performed using chi square test for nominal variables and Mann Whitney U test for ordinal and continuous variables. Overall survival was evaluated by Kaplan Meier method and multivariate Cox proportional hazards model. Results: In total, 380 patients were included in the study and 19 patients were excluded due to missing clinical data and survival status. All had histologically confirmed squamous cell carcinoma. No patients had a 2nd primary cancer in the female cervix or head and neck region. There were 47 (12.4%) never smokers and 333 (87.6%) smokers. A significantly higher proportion of never smokers was female (63.8% vs 9.3%, p<0.001). Never smokers were diagnosed at an earlier age (57.2 vs 67.3, p<0.001), were diagnosed at a more advanced stage (59.6% vs 27.0%, p<0.001) and had fewer co-morbidities (31.9% vs 49.5%, p=0.023) compared to smokers. However, there was no statistical significant in overall survival between never smokers and smokers after adjusting for confounding variables (HR= 0.828, p=0.326). The age at diagnosis, staging, ECOG performance status and treatment were independent prognostic factors for overall survival. Conclusions: Differences in clinical characteristics between the never smokers and smokers with lung SCC were observed although there was no difference in overall survival. As such, larger studies may be warranted to further characterize lung SCC in never smokers.
Low-Dose Interleukin-2 Therapy Enhances Cytotoxicity of CD56bright NK Cells in Patients with Chronic Gvhd
Authors: Tomohiro Kubo, Rizwan Romee, John Koreth, Roger Belizaire, Yusuke Kamihara, Hongye Liu, Takeru Asano, Jennifer Whangbo, Masahiro Hirakawa, Sarah Nikiforow, Mahasweta Gooptu, Vincent T. Ho, Corey S. Cutler, Edwin P. Alyea, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz
Journal: Blood (2018)
Next Generation Sequencing-Based Mutational Profile of Therapy-Related AML and De Novo AML: Results from a Single Pediatric Institution in Argentina
Authors: Patricia Laura Rubio, Maria Sara Felice, Matias Juanes, Gabriel Veneruzzo, Francisco Martin Garcia, Jorge Alberto Digiorge, Maria Eugenia Ducatelli, Adriana Medina, Matias Pujana, Myriam Ruth Guitter, Jorge Gabriel Rossi, Cristina Noemi Alonso
Journal: Blood (2018)
Ibrutinib Therapy in Patients with Waldenstrom Macroglobulinemia: Outcomes Outside of Clinical Trial Setting
Authors: Jithma Prasad Abeykoon, Saurabh Zanwar, Sikander Ailawadhi, Jeremy Larsen, Morie A. Gertz, Wilson I Gonsalves, Francis K. Buadi, Shaji K. Kumar, S. Vincent Rajkumar, Rebecca L King, David J Inwards, Martha Q. Lacy, Thomas M. Habermann, Angela Dispenzieri, Thomas E. Witzig, Nelson Leung, Miriam Hobbs, David Dingli, Robert A. Kyle, Stephen M. Ansell, Prashant Kapoor
Journal: Blood (2018)
Letter by Moris et al Regarding Article, “Cardioprotective Role of Myeloid-Derived Suppressor Cells in Heart Failure”
Authors: Dimitrios Moris, Georgia-Sofia Karachaliou, Georgios Karaolanis
Journal: Circulation (2019)

al 1 highlighting the role of myeloid-derived suppressor cells (MDSCs) in an animal model of heart failure (HF).The striking finding of the study was the cardioprotective role of MDSCs in HF via antihypertrophic effects on cardiomyocytes and anti-inflammatory effects through interleukin-10 and nitric oxide.Furthermore, MDSCs derived from patients with HF also inhibited T-cell proliferation and interferongamma (IFN-γ). 1 Data reported from animal studies on the field of transplant immunology demonstrated that IFN-γ signaling controls many downstream effector molecules such as CD-40, CD-86, and programmed death-ligand 1 (PD-L1). 2 PD-L1 expressed on mesenchymal cells plays a critical role in immune tolerance via ligation to its receptor, PD-1, which is highly expressed on activated T cells, resulting in their apoptosis.The latter was a recent and novel observation by Morita et al, 3 who noted that IFN-γ originating from the alloreactive T-effector cells stimulates mesenchymal cells, resulting in upregulated PD-L1 expression which, in turn, facilitates the death of T-effector cells.Also, studies on myocardial inflammation showed that the PD-1/ PD-L1 pathway works together with other control mechanisms to keep the heart safe from T cells. 4Taking this knowledge into account, it is important for authors to provide data regarding PD-1/PD-L1 pathway expression in their experiment and the potential role of this pathway in myocardial hypertrophy.With the availability of these data, a better understanding of the PD-1/PD-L1 pathway as a therapeutic target in HF could be achieved.Circulating cytokines, such as interleukin-1b, interleukin-6, tumor necrosis factor-α, and IFN-γ, have been shown to induce inducible nitric oxide synthase expression, leading to nitrogen-reactive species generation, mediating the depressant effects of cytokines in the heart. 5Recent studies have demonstrated that the number of CD11b + CD11c -cells were followed by those of CD4 + forkhead box P3 (Foxp3 + ; T regulatory) Treg cells, suggesting a close relationship of the 2 cell populations in the setting of transplant tolerance. 2Inducible nitric oxide synthase activity seems to play a crucial role in the ability of MDSCs to inhibit T-cell proliferation, mainly by attenuating the production of IFN-γ and tumor necrosis factor-α and promoting the expansion of Tregs and expression of PD-L1. 2,3We were wondering whether the authors had available data on the role of Tregs and its contribution to the antihypertrophic effect of MDSCs in the HF setting.All in all, we congratulate the authors for elucidating the role of MDSCs in the development and regression of HF.We hope that they will find our queries of interest for further experimental research on the field.
Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial
Authors: Anne-Sophie Wedell-Neergaard, Louise Lang Lehrskov, Regitse Højgaard Christensen, Grit Elster Legaard, Emma Dorph, Monica Korsager Larsen, Natja Launbo, Sabrina Ravn Fagerlind, Sidsel Kofoed Seide, Stine Nymand, Maria Ball, Nicole Vinum, Camilla Noerfelt Dahl, Marie Henneberg, Mathias Ried-Larsen, Janus Damm Nybing, Robin Christensen, Jaya Birgitte Rosenmeier, Kristian Karstoft, Bente Klarlund Pedersen, Helga Ellingsgaard, Rikke Krogh-Madsen
Journal: Cell Metabolism (2018)
Phase II trial of sunitinib in patients with thymic epithelial tumors (TET).
Authors: Anish Thomas, Arun Rajan, Arlene W Berman, Christina E. Brzezniak, Aaron John Spittler, Corey Allan Carter, Udayan Guha, Yisong Wang, Eva Szabo, Patrick J. Loehrer, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2014)

7525 Background: There are no standard treatments for patients with advanced TETs after failure of platinum-based chemotherapy. In thymic carcinoma, KIT over-expression and mutations are found in about 80% and 8% cases respectively. Expression of angiogenic markers correlates with invasiveness of TETs. This non-randomized, phase II trial evaluated the efficacy of sunitinib, whose targets include KIT and vascular endothelial growth factors (VEGFR), in TETs. Methods: Patients with TET who had progressive disease following at least one platinum-based chemotherapy were enrolled. Sunitinib was administered orally at 50 mg once daily in 6 week cycles for 4 weeks followed by 2 weeks off until disease progression. Tumor response was assessed by CT scans every 6 weeks. Correlative studies included exome sequencing of 197 cancer related genes and peripheral blood T cell subset analyses. Primary end point was objective response rate in 2 parallel cohorts [thymoma (T) and thymic carcinoma (TC)]. Results: Between May 2012 and October 2013, 24 patients with TC [median age 58 (41-81); males 63%] and 16 with T [median age 54 (31-74); males 44%] enrolled. Median of 4 (range, 1-11) and 5 (range, 1-12) cycles were administered in patients with TC and T respectively. Among 23 evaluable patients with TC, there were 6 (26%) partial responses, 15 (65%) stable disease [including 9 (39%) minor responses: 10-29% reduction] and 2 (9%) progressive disease. After median follow up of 13.9 months, the median progression-free survival (mPFS) for TC was 6.7 months and median overall survival (mOS) 16.3 months. In contrast, only 1 of 16 (6%) patients with T had a partial response, 12 (75%) stable disease [including 3 (19%) minor responses] and 3 (19%) progressive disease. After median follow-up of 12.7 months, the mPFS was 8.5 months for T and mOS not reached. Most common grade 3 or 4 sunitinib-related adverse events were lymphopenia, fatigue, oral pain and thrombocytopenia. KIT mutations were absent in 20 tumors assessed, which included 11 TC and 4 partial responders. Conclusions: Sunitinib demonstrated anti-tumor activity unprecedented for a targeted agent in previously treated patients with TC. Activity was modest in T. Tumor sequencing and T cell subset analyses will be presented. Clinical trial information: NCT01621568.
Pulmonary venoplasty in lung cancer surgery: A report of nine cases.
Authors: Jiandong Mei, Lunxu Liu
Journal: Journal of Clinical Oncology (2014)

e18526 Background: Pulmonary resection combined with venoplasty is rarely performed with the aim of preserving more pulmonary function for selected patients. The objective of this study is to determine the feasibility and long term results of pulmonary venoplasty in surgical treatment of non-small cell lung cancer (NSCLC). Methods: Between 2006 and 2012, nine patients with proven NSCLC underwent anatomic pulmonary resection combined with venoplasty. The indications of vascular plasty included six cases of tumor in the middle lobar orifice involving the superior pulmonary vein, one case of metastatic lymph node involving the superior pulmonary vein, one case of venous injury due to dense adhesion and one case of injury due to venous anatomic variation. The operations were carried out with venous partial resection in four patients and sleeve resection in five patients. The vessel was reconstructed with continuous suture using 5-0 Prolene stitches. Results: The operations were finished within 110 to 410 min (median, 270 min). Blood loss ranged from 200 to 600 ml (median, 290ml) and no blood transfusion was required. Three patients had stage IIIa-N1 NSCLC, two patients had stage IIIa-N2 disease, and the other four patients were staged as Ia, Ib, IIa and IV NSCLC, respectively. The patients recovered uneventfully and were discharged home in 5 to 10 days (median, 7 days) after surgery. Postoperative follow up varied from 7 to 83 months and ideal patency of the pulmonary vein was confirmed in all patients. One patient was lost to follow up. Two patients died of metastasis 7 and 8 months after surgery respectively. Three patients had metastatic diseases at 14, 32 and 35 months after surgery, and they are still alive during 56-, 50- and 48-month follow-up. The other three patients have no signs of recurrence or metastasis during 16-, 39- and 83-month follow-up, respectively. Conclusions: Pulmonary resection combined with venoplasty is mainly performed in cases of middle lobar tumor involving the superior pulmonary vein. The operation is safe and feasible.It may be beneficial to some patients in preserving more pulmonary parenchyma and long term survival may be achieved in selected patients.
Phase I Study of Ixazomib in Addition to Chemotherapy for the Treatment of Acute Myeloid Leukemia in Older Adults
Authors: Philip C. Amrein, Eyal C. Attar, Traci M. Blonquist, Andrew M. Brunner, Gabriela S. Hobbs, Hanno Hock, Steven McAfee, Jenna A. Moran, Meghan Bergeron, Julia Foster, Christina Bertoli, Kristin McGregor, Molly Macrae, Meghan Burke, Tanya T. Behnan, Tina T. Som, Aura Y. Ramos, Megan K. Vartanian, Jennifer Lombardi Story, Donna S Neuberg, Amir T. Fathi
Journal: Blood (2018)
A randomized phase II, open-label study of sipuleucel-T with concurrent or sequential enzalutamide in metastatic castration-resistant prostate cancer (mCRPC).
Authors: David I. Quinn, Daniel Peter Petrylak, Christopher Michael Pieczonka, Andrew Sandler, Todd DeVries, Nadeem A. Sheikh, Charles G. Drake
Journal: Journal of Clinical Oncology (2014)

e16071^ Background: For patients with mCRPC, there are multiple agents available, particularly in the early setting. Sipuleucel-T, an autologous cellular immunotherapy, and enzalutamide, an androgen receptor inhibitor, are both approved in the US and EU for the treatment of certain patients with mCRPC. Given the lack of potential cross resistance and data suggesting that androgen ablation may potentiate the immunotherapeutic effects of vaccines, combining these agents may be a beneficial treatment approach for mCRPC. The randomized, open-label phase II STRIDE trial (P12-2) is underway to evaluate this combination. Methods: Patients with asymptomatic or minimally symptomatic mCRPC were randomized 1:1 to receive sipuleucel-T with enzalutamide (160 mg QD for 52 weeks) started 2 weeks prior to (concurrent arm [A]) or 10 weeks following (sequential arm [B]) sipuleucel-T initiation. The primary endpoint is the peripheral T cell immune response to the immunizing antigen, PA2024. An exploratory endpoint is time to prostate-specific antigen (PSA) recurrence. Results: As of January 14, 2013, 22 patients have been enrolled. A total of 6 patients have completed sipuleucel-T treatment (3 in arm A and 3 in arm B); all received 3 infusions. There were no significant differences in product potency between the arms; the median cumulative CD54 upregulation (a measure of antigen-presenting cell [APC] activation) was 35.3 vs 26.6 and CD54+ cell counts were 1.9 vs 1.8 x109 in arms A and B, respectively. In all patients, APC activation was greater at infusion 2 vs 1 indicating an immunologic prime boost. Pre- and post-culture cellular composition did not differ between the arms. Conclusions: Preliminary data from P12-2 suggest that sipuleucel-T can be manufactured during concurrent enzalutamide treatment with similar product potency as sipuleucel-T alone. Patients receiving sipuleucel-T with concurrent enzalutamide appear to achieve an immunologic prime boost, consistent with other studies of sipuleucel-T. Additional data, including sipuleucel-T-induced peripheral immune responses, from >20 patients will be presented at the meeting. Clinical trial information: NCT01981122.
Mapping the Evolution of T Cell Transcriptional States during DLI Response and Resistance Using Single-Cell Data
Authors: Pavan Bachireddy, Elham Azizi, Vinhkhang N Nguyen, Shuqiang Li, Donna S Neuberg, Robert J. Soiffer, Jerome Ritz, Edwin P. Alyea, Dana Pe'er, Catherine J. Wu
Journal: Blood (2018)
Association Between Antidepressant Drug Use and Hip Fracture in Older People Before and After Treatment Initiation
Authors: Jon Brännström, Hugo Lövheim, Yngve Gustafson, Peter Nordström
Journal: JAMA Psychiatry (2019)

Treatment with antidepressants has been associated with hip fracture. This association could restrict the treatment options, especially in older patients.To investigate the association between antidepressant drug treatment and hip fracture starting 1 year before the initiation of treatment.In this nationwide cohort study, 204 072 individuals in the Prescribed Drugs Register of Sweden's National Board of Health and Welfare aged 65 years or older who had a prescription of antidepressants filled between July 1, 2006, and December 31, 2011, were matched by birth year and sex to 1 control participant who was not prescribed antidepressants (for a total of 408 144 people in the register). Outcome data were collected from 1 year before to 1 year after the index date (date of prescription being filled). Data analysis was performed from July 1, 2005, to December 31, 2012.First filled prescription of an antidepressant drug.Incident hip fractures occurring in the year before and year after initiation of antidepressant therapy were registered. Associations were investigated using multivariable conditional logistic regression models and flexible parametric models.Of the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.The present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.