tbuckley/cabot-search huggingface dataset:
Chronic obstructive pulmonary disease: diagnosis and management: summary of updated NICE guidance
Authors: Nicholas S Hopkinson, Andrew Molyneux, Joshua Pink, Marie C Harrisingh
Journal: BMJ (2019)

### What you need to know

There are 1.3 million people in the UK with a diagnosis of chronic obstructive pulmonary disease (COPD) and the condition is responsible for considerable morbidity and mortality.1 COPD is also a common cause of hospital admission. NHS England has now recognised respiratory disease as a priority area in the Long Term Plan,2 but Royal College of Physicians COPD Audits3 identify substantial deficiencies across the healthcare system, including marked under-provision of pulmonary rehabilitation, flu vaccination, and smoking cessation treatment.

This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE).10 The updated areas are mainly concerned with the management of stable COPD and include self management and education, assessment for lung volume reduction procedures, and home oxygen use. This article focuses on the newly updated sections, with reference to older recommendations where they are particularly important or needed for context.

Effective COPD management pathways require an integrated approach across primary and secondary care and involve a multidisciplinary team of health professionals. The guidance focuses on the need to ensure that good quality care is delivered wherever patients are seen. Specialist care, whether delivered in a hospital or community setting, may be indicated for people …
Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B Cell Malignancies: Results from a Phase I Dose Escalation Study
Authors: Gregory P. Coffey, Jiajia Feng, Andreas Betz, Anjali Pandey, Matt Birrell, Janet M. Leeds, Kenneth Der, Sabah Kadri, Pin Lu, Jeremy Segal, Lynn Wang, Glenn Michelson, John T Curnutte, Pamela B. Conley
Journal: Blood (2017)
Treatment and outcome of patients with brain metastases from non-small cell lung cancer (NSCLC)
Authors: A. Ali, J. R. Goffin, A. Arnold, P. M. Ellis
Journal: Journal of Clinical Oncology (2009)

e19058 Background: The prognosis of patients with brain metastases from NSCLC is generally poor. However, some reports suggest that the outlook of patients with brain metastases at the time of diagnosis may be similar to that of patients with advanced NSCLC without brain metastases. We undertook a retrospective review of NSCLC patients with brain metastases to examine the outcomes of care for patients with brain metastases from NSCLC. Methods: All new lung cancer patients seen in our institution between July 2005 and June 2007 were assessed for the development of brain metastases. Baseline characteristics, treatment and outcome data were extracted from the chart. The primary outcome of interest was a comparison of survival of patients with brain metastases at diagnosis compared with patients who developed brain metastases later. Results: 91 of 878 (10.4%) new patients seen over the 2 years developed brain metastases. There were 43 men and 48 women. The median age was 64 yrs (sd 10.6yrs). 45 patients had brain metastases at presentation while 46 developed brain metastases later. 34 (37%) had a solitary brain metastasis. 18 (20%) underwent surgical resection. The median overall survival for all patients was 7.8m. Patients with brain metastases at diagnosis had a significantly shorter overall survival than patients who developed brain metastases later (9.8m v 4.3m, p=0.001). Survival following diagnosis of brain metastases was similar for both groups (3.7m v 4.8m, p=0.53). Patients presenting with brain metastases were less likely to be referred to a medical oncologist (51% v 74%, p=0.02) and less likely to receive chemotherapy (18% v 41%, p=0.01). Conclusions: These data suggest that NSCLC patients with brain metastases at diagnosis have a significantly worse outcome than patients who develop brain metastases at a subsequent time point in their illness. Few patients received systemic therapy following diagnosis of brain metastases and further research is needed to determine the utility of chemotherapy in this patient group. No significant financial relationships to disclose.
How Would You Manage This Patient With Nonalcoholic Fatty Liver Disease?
Authors: Howard Libman, Z. Gordon Jiang, Elliot B. Tapper, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2019)

Nonalcoholic fatty liver disease (NAFLD), a common diagnosis in the United States and other developed countries, has been increasing in prevalence. The American Association for the Study of Liver Diseases recently published updated practice guidelines for diagnosing and managing NAFLD, including the following recommendations: Routine screening for NAFLD in high-risk groups is not advised because of uncertainties surrounding test and treatment options, along with a lack of knowledge about cost-effectiveness and long-term benefits. Noninvasive studies, including biomarkers from laboratory tests and liver stiffness measured through elastography, are clinically useful tools for identifying advanced fibrosis in patients with NAFLD. Liver biopsy should be considered in patients with NAFLD who are at increased risk for nonalcoholic steatohepatitis (NASH) or advanced fibrosis. Weight loss of at least 3% to 5% generally reduces NASH, but greater weight loss (7% to 10%) is needed to improve most histopathologic features, including fibrosis. Pharmacologic therapies (such as pioglitazone and vitamin E) should be considered only in patients with biopsy-proven NASH. Patients with NAFLD should not consume heavy amounts of alcohol, although insufficient data exist to provide advice about other levels of alcohol use. Here, 2 clinicians with expertise in this area debate whether to screen for NAFLD in primary care, how to monitor patients with NAFLD, and what interventions should be used to manage this condition.
Risk factors leading to grading changes within 300 low-grade soft tissue sarcomas.
Authors: Tanja Koshrawipour, Ingo Stricker, Andrea Tannapfel, Lars Steinstraesser, Stefan Langer, Andrej Ring
Journal: Journal of Clinical Oncology (2012)

10059 Background: Soft tissue sarcomas (STS) are rare, mesenchymal derived tumors. Based on malignancy, three grades are distinguished with G1 equaling low grade, G2 intermediate grade and G3 high grade, respectively. Studies have shown that some G1 tumors which underwent complete surgical resection reoccurred as lesions with a grading shift from G1 to higher malignancy. This grading change is referred to as up grading. Patients with grading changes were thoroughly examined in our study. Our aim was to find possible risk factors for up gradings, such as age, localization of tumor and tumor type. Methods: This retrospective case control study evaluated 333 Patients, who, between 1996 to 2011 were treated for G1 STS at Bergmannsheil Bochum, university clinic. These patients received complete initial surgical resection. Among our 333 patients, 9.9% (n=33) developed up gradings of their STS. These were then reviewed more closely in the aim of finding possible risk factors. We did not exclude any patients from our data or deliberately pick any grading changers and regard our collective as randomly sampled. The processed data includes age, gender, tumor type, tumor localization, occurrence of recidive and grading change. Results: Patients with up gradings were found to have a higher mean age of 4, 5 years than reference collective. The tumor type has a strong, statistically significant effect on grading change as patients with fibrosarcomas have a threefold risk of developing up gradings when compared to patients with other G1 STS. Conclusions: Our results indicate that age and tumor type play the key role in the development of up gradings in low malignant STS .Patients aged 60 and above diagnosed with fibrosarcomas are at a 3 times higher risk of developing a grading change as opposed to patients younger than 60 with other low grade STS than fibrosarcoma. We discussed the significance of these risk factors and argued whether, in addition to wide tumor resection, a short term postoperative radiotherapy should be applied for these patients to improve therapeutical outcome.
Baseline predictors of survival in metastatic colorectal cancer.
Authors: Anni Ravnsbæk Jensen, Camilla J S Kronborg
Journal: Journal of Clinical Oncology (2012)

e14105 Background: Patients with non-resectable metastatic colorectal cancer can survive several years with palliative chemotherapy and newer biological agents. However, survival varies greatly within this group. The aim of the present study was to identify baseline predictors of overall mortality in an unselected cohort of patients with metastatic colorectal cancer. Methods: Clinical information was collected from patient files in consecutive patients treated with palliative chemotherapy from August 2007 until June 2011. The primary outcome was overall survival. Cox regression analysis was used to examine the effect of predictive variables on time to outcome. The variables analysed were: Gender, age, performance status, primary tumor site (colon or rectum), status of primary tumor (resected or un-resected), metachronous metastases, more than two metastatic sites, liver-only metastases, and low albumin. Results: We included 314 patients (Median age 64.5 IQ (57-70) years, 194 (61.8%) male). Median follow-up for survival was 471 days IQ (257-708). One-year survival was 79%, CI (74-84%). Median overall survival was 676 days, CI (577-750). Following baseline variables were independent predictors of all-cause mortality: Primary tumor site colon HR: 1.49, CI (1.03-2.16), p=0.036, un-resected primary tumor HR 2.92, CI (1.85-4.62), p&lt;0.001, metachronous metastases HR 1.72, CI (1.06-2.79), p=0.027 and more than two metastatic sites HR 3.46, CI (1.71-6.99), p=0.001. Both Performance status and low albumin were statistically significant in the univariate analysis, but not in the multivariate analysis. Conclusions: In daily clinical practice, baseline predictors of mortality in metastatic colorectal cancer were colon as the primary tumor site, un-resected primary tumor, metachronous metastases, and more than two metastatic sites.
Heat-shock (H-S) and trabectedin efficacy in human soft-tissue sarcoma (STS) cells in vitro.
Authors: Eric Kampmann, Dominique Harnicek, Ana Sofia Cardoso Martins, Berina Eppink, Eike Gallmeier, Lars Lindner, Roland Kanaar, Rolf D. Issels
Journal: Journal of Clinical Oncology (2013)

e13540 Background: Regional hyperthermia improves response and survival when combined with chemotherapy in patients with high-risk STSs (Issels, R.D. Lancet Oncol 2010). Trabectedin is the first marine-derived antineoplastic drug approved in Europe for the treatment of advanced STS after failure of anthracyclines and ifosfamide, or for patients who are unsuited to receive these drugs. Trabectedin’s cytotoxicity is associated with the induction of lethal DNA double-strand breaks (DSB). The rationale to combine trabectedin with H-S is that heat-exposure sensitizes tumor cells by inhibiting the repair of induced DSBs (Krawczyk, P.M. PNAS 2011). Methods: Combinations of trabectedin and H-S at clinically relevant temperatures were examined in 3 different human cell lines: Osteosarcoma (U2Os), liposarcoma (SW872) and synovial sarcoma (SW982). Cells were treated with trabectedin at the dose of 500-4000 pM for 3 hours. H-S was applied in an incubator at 41.8°C and 43°C for 90 or 150 min before, during or after trabectedin incubation. Cytotoxicity was assessed measuring clonogenic survival of cells. Expression of BRCA2, which recruits homologous recombination repair recombinase Rad 51 to DSBs, was measured by Western Blot (WB). Recruitment of Rad 51 and the amount of gH2AX positive DSB-repair-foci were analysed by immunocytochemistry (ICC). Results: All cell lines showed reduced viability after increasing doses of trabectedin at 37°C. Combined treatment with trabectedin and H-S additionally enhanced cytotoxicity of trabectedin with strongest effects observed after simultaneous administration of both. WB-analysis showed strong heat-dependent reduction of BRCA2 expression. ICC revealed that recruitment of Rad 51 to DSBs was reduced after heat exposure at 41.8°C and abolished after exposure at 43°C. Accordingly, combined treatment significantly increased the amount of cells with severe DNA damage (&gt;50 DSBs). Conclusions: Combined treatment with trabectedin and H-S in vitro resulted in significantly enhanced cytotoxicity that was accompanied by elevated DNA-damage in term of DSB-accumulation. The mechanisms of interaction between trabectedin and H-S concerning DNA repair are under investigation.
Functionally Competent DNA Damage-Free Induced Pluripotent Stem Cell–Derived Cardiomyocytes for Myocardial Repair
Authors: Ramaswamy Kannappan, James F. Turner, Jessica M. Miller, Chengming Fan, Amanda G. Rushdi, Namakkal Soorappan Rajasekaran, Jianyi Zhang
Journal: Circulation (2019)
Effect of exogenous triiodothyronine [T3] on free thyroxine depletion and tumor response: A compassionate care study.
Authors: Aleck Hercbergs
Journal: Journal of Clinical Oncology (2013)

e22077 Background: A thyroid hormone receptor on plasma membrane integrin av β3 initiates the actions of the hormone thyroxine [T4] on cancer cell proliferation and angiogenesis, initiated nongenomically, independently of the classical thyroid nuclear receptor. In studies of recurrent glioma, induced hypothyroidism significantly prolonged survival but associated fatigue has restricted acceptance of this approach. Triiodothyronine[T3] is the metabolically dominant hormone but in physiological extracellular concentrations is 10-100 fold less mitogenic than T4 in solid tumor models (R Meng et al., PLoS 2011; 6[11]:e27547). Exogenous T3 also maintains eumetabolism but inhibits TSH release to induce free T4 depletion [FT4D] defined as[&lt; 0.93 ng/dL.] Maximal therapeutic free T4 depletion [FT4D] by T3 may therefore be feasible if combined with methimasole[MET]. Aims of study: Retrospective analysis of 1.) exogenous T4 withdrawal and 2.) daily exogenous T3 [ET3] and MET on tumor response and survival Methods: 21 Patients at geographically dispersed sites with recurrent or stage IV solid tumors: GBM 8 patients, brain stem glioma 1, pancreas 1, salivary gland 2, Lacrimal duct 1, breast 1, mesothelioma 1, ovarian 4, lung 2. 1.) In 7 patients exogenous T4 was terminated and replaced by exogenous T3 [ET3] 15 to 30μg daily in three divided doses. 2.) 15 euthyroid patients received 15-30μg ET3 and 20-40 mg. methimasole [MET] daily to induce [FT4D] usually obtained within 6-10 weeks. Results: There was no treatment related toxicity. 3/7 patients had PR to withdrawal of T4 only. 20/21 patients experienced PR[16] or CR[4]. to concurrent or sequential chemo,hormonal or radiation therapy for an overall response rate of 90% CHT elicited repeated responses in some patients. The 6 month PFS for the GBM cohort [n=8] was 70%. Two survived 36 and 53 months. For other solid tumor types survival was above /in the 90th percentile of reported survival studies. Conclusions: A high response rate was observed in advanced compassionate care cancer patients undergoing exogenous T3 modulated FTD. Tumor response to exogenous T4 withdrawal is a novel observation with potentially important therapeutic implications.
Retrospective analysis of 132 patients with stage I seminoma: Observation versus adjuvant radiation or chemotherapy in a single institution.
Authors: Estela Vega, Almudena Cascales, Guillermo De Velasco, Maria Angeles Cabeza Rodriguez, Lucia Parrilla, Maria Colmenero, Ray Manneh, Rafael D'Ambrosi, Tomas Pascual, Sofia Rodriguez Garcia, Natalia Valdiviezo, Silvia Gomez Ordonez, Miriam Dorta, Sandra Guardado, Adela Bartolome, Carmen Lechuga, Jose Fermin Perez Regadera, Eduardo Lanzos Gonzalez, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2012)

e15033 Background: Classically, radiotherapy (RT) has been the standard adjuvant treatment for stage I seminoma patients. Improvements in early relapse diagnosis have led high cure rates. Two cycles of adjuvant carboplatin present similar efficacy to radiotherapy with less toxicity have led to re-examination of the standard treatment approach. Methods: Retrospective study of 132 patients diagnosed with stage I seminoma from 1980-2010 who received whether treatment with RT, chemotherapy (Cht) or active surveillance (AS) after orchiectomy at one Universitary Hospital. The objective was to determine the relapse-free survival (RFS), overall survival (OS), and disease -specific survival (DSS). Results: Of the 132 patients, 68 were treated with prophylactic irradiation (paraaortic ± pelvic nodes, the median total dose radiation 26 Gy at 2 Gy per fraction), 33 with adjuvant chemotherapy (31 had carboplatin x 2, 2 had BEP x 2), and 31 underwent surveillance. Among the RT patients (median follow-up 121months), mean age was 40 years (range: 20-70) with mean tumor size of 5.5 cm (range: 1-14). 6% of them had rete testis involvement and 15% vascular invasion. There was 1 relapse with a median disease-free survival (DFS) of 103 months and no deaths from seminoma. RFS was 98% at 10 years. OS and DSS were 100% at 10years. Among the chemotherapy patients mean age was 30 years (range: 18-66) with mean tumor size of 6,18cm (range: 1,5-10). 9% of them had rete testis involvement and 60 % vascular invasion. With a median follow-up of 66 months, there was 1 relapse. Five-year RFS was 97%, OS and DSS were 100%. Among the observation patients (median follow-up 148 months), mean age was 35 years (range: 20-78) with mean tumor size of 3,7cm (range: 1,3-7). 6% of them had rete testis involvement and 6 % vascular invasion. There were 6 relapses with no deaths from seminoma. RFS was 80%, specific OS and DSS was 100% at 10 years. Of the patients who relapsed, all were rendered disease-free with chemotherapy; with non evidence disease at last follow-up. Conclusions: Consistent with published trials both radiotherapy, chemotherapy or active surveillance are safe and effective treatments with similar oncologic results.
Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Awais Malik, Ravi Masson, Steven Singh, Wen-Chih Wu, Milton Packer, Bertram Pitt, Finn Waagstein, Charity J. Morgan, Richard M. Allman, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2019)
Correlation of minimal residual disease negativity (MRD-) with prognosis in high-risk myeloma (HRM).
Authors: Chutima Kunacheewa, Krina K. Patel, Hans Chulhee Lee, Sheeba K. Thomas, Behrang Amini, Samer Srour, Qaiser Bashir, Muzaffar H. Qazilbash, Donna M. Weber, Sattva Swarup Neelapu, Robert Z. Orlowski, Lei Feng, Pei Lin, Elisabet Esteve Manasanch
Journal: Journal of Clinical Oncology (2019)

8024 Background: MRD is a standard measurement for response assessment in MM. Despite new treatments, HRM patients continue to have poor prognosis. We evaluated the impact of MRD- in high vs standard (SRM) risk patients. Methods: We retrospectively evaluated all consecutive MM/plasma cell leukemia patients who had routine MRD testing by 1-tube 8-color advanced flow cytometry with 2,000,000 events and sensitivity level 10 -5 at our center from 2015-2018 after initial therapy. Kaplan-Meier and log-rank test were used to assess survival estimates and differences between study groups. Results: 136 patients with MRD testing after initial therapy/autologous transplant (ASCT) were identified. Patient and disease characteristics are included in Table. At a median follow-up of 14 months (1-36), PFS and OS were significantly worse in HRM vs SRM. During the study period, 50% of HRM had progressed (relapse and/or death) vs 20% in SRM (p=0.0006). No patients with SRM died, but 4 (14%) in the HRM group did (p=0.0007). Regardless of MRD status, HRM patients had statistically significant worse PFS than SRM; at median f/u 10% SRM MRD-; 20% SRM MRD+; 40%HRM MRD-; 45% HRM MRD+ had either relapsed or died (p=0.0041). MRD status did not impact OS in either group (p=0.0914), however longer follow up is needed to assess survival. Conclusions: Genetic abnormalities (FISH/GEP) remain a powerful prognostic indicator for myeloma regardless of MRD status. For newly diagnosed myeloma patients treated with novel triple initial therapy and frontline ASCT, achieving MRD negative status didn’t mitigate the poor prognosis outcomes of HRM. [Table: see text]
Blood mRNA signature to predict survival in patients with metastatic melanoma treated with tremelimumab.
Authors: Yvonne M. Saenger, Jay Magidson, Bobby Chi-Hung Liaw, Karl Wassmann, William Barker, Sara Harcharik, David Fisher, William K. Oh, Philip Friedlander
Journal: Journal of Clinical Oncology (2013)

9080 Background: Tremelimumab (Ticilimumumab, Pfizer), a monoclonal antibody targeting CTLA-4, a T cell inhibitory molecule, has shown activity in metastatic melanoma. Ipilimumab (Yervoy, BMS), another antibody targettingCTLA-4, improves survival relative to a peptide vaccine and is now FDA approved. A minority of patients will achieve durable tumor control with CTLA-4 blockade and biomarkers are urgently needed to identify those patients. Methods: 170 inflammatory, melanoma-specific and CTLA4-pathway related mRNA transcripts were measured using RT-PCR in pre-treatment peripheral blood samples from 218 patients with refractory melanoma receiving tremelimumab in a multi-center phase II study. A 2-class latent model yielded a risk score based on 4-genes that was highly predictive of survival (p&lt;0.001), and was used to categorize patients into low, medium and high-risk groups. An independent cohort of 260 treatment naïve melanoma patients receiving tremelimumab as part of a multi-center phase III study was then used to validate the risk score as well as the 3 risk groups defined using the pre-specified cut-points. Results: There was no significant difference between the two cohorts in terms of age, gender, stage of disease or ECOG status. Median time of follow up was 297 days for the training cohort and 386 days for the validation cohort. 67% of patients in the training cohort and 70% of patients in the validation died during time of follow-up. Collectively, the ability of the 170 genes to predict survival exhibited a high degree of consistency across the cohorts (p &lt; 0.001). A 4-gene model including cathepsin D (CTSD), Phopholipase A2 group VII (PLA2G7), Thioredoxin reductase 1 (TXNRD-1) and Interleukin 1 receptor associated kinase 3 (IRAK3) predicted survival in the validation cohort (p=0.001 by log rank test). Multivariable cox analysis showed that the 4-gene model added to the predictive value of clinical predictors (p&lt;0.0001). Conclusions: Expression levels of CTSD, PLA2G7, TXNRD1, and IRAK3 in peripheral blood are predictive of survival in melanoma patients treated with ticilimumab (αCTLA-4). Blood mRNA signatures should be further explored to define patient subsets likely to benefit from immunotherapy.
Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT
Authors: Maria H. Gilleece, Myriam Labopin, Bipin N. Savani, Ibrahim Yakoub-Agha, Gerard Socié, Tobias Gedde-Dahl, Didier Blaise, Jennifer L. Byrne, Charles Craddock, Jan J. Cornelissen, William Arcese, Edouard Forcade, Charles Crawley, Emmanuelle Polge, Mohamad Mohty, Arnon Nagler
Journal: Leukemia (2019)