tbuckley/cabot-search huggingface dataset:
TCT-129 Efficacy of Urinary Liver-type Fatty Acid-binding Protein Level for Patients with Acute Kidney Injury Following Coronary Angiography in Acute Coronary Syndrome
Authors: Keisuke Kojima, None Tadateru Takayama, Nobuhiro Murata, Naotaka Akutsu, Mitsumasa Sudo, Daisuke Kitano, Daisuke Fukamachi, Takafumi Hiro, Atsushi Hirayama, Yasuo Okumura
Journal: Journal of the American College of Cardiology (2018)
Validation of neoadjuvant rectal cancer (NAR) score as a surrogate endpoint for overall survival in real-life practice settings.
Authors: Y. Nancy You, Thomas J. George, Yi-Ju Chiang, Cathy Eng, Prajnan Das, George J. Chang, A. Dasari, Amanda Cuddy, Yun Yang, Greg Yothers
Journal: Journal of Clinical Oncology (2018)

3517 Validation Of Neoadjuvant Rectal Cancer (NAR) Score As A Surrogate Endpoint For Overall Survival In Real-life Practice Settings Background: Response to neoadjuvant therapy(NT) for rectal cancer(RC) correlates with long-term outcome. Pathologic complete response(pCR) has been used as an early endpoint in RC clinical trials, but is limited by its binary nature. NAR, a composite score available after resection, is a novel short-term surrogate endpoint. The association between overall survival(OS) and NAR has not been validated in clinical practice outside of clinical trials. Methods: The National Cancer Database (2004-2013) was queried for patients with non-metastatic RC and known staging and survival data (N = 47,833). Those who underwent neoadjuvant chemoradiation (45-54 Gy) and proctectomy formed the study cohort (N = 19,831). NAR was defined as [5 ypN - 3 (cT - ypT) + 12]2/9.61. Patients were categorized by ypCR, pathologic stage, and NAR score (Table). OS was calculated by the Kaplan-Meier method and compared using log-rank tests. Results: Clinical stage was II (N = 9929, 50.0%) or III (N = 9932, 50.0%). After NT, 2490 patients (12.6%) achieved pCR (ypT0N0); another 5727 (28.9%) were downstaged (ypT1-2N0). The median NAR was 15.0 (Interquartile range: 8.4-26.6). After 4.2 years of follow-up, OS correlated with pCR, pathologic stage, and NAR categories (Table). Conclusions: Similar to data from clinical trials, NAR demonstrated predictive validity for OS in real-life practice. Nearly half of the RC patients nationwide had high NAR, and quartiling NAR offered best stratification of OS, highlighting the advantage of NAR as a versatile continuous measure of NT response. Category No. of patients (%) 5-year OS p-value Complete pathologic response (pCR) < 0.001 Yes 2490 (12.6) 88.9 No 17341 (87.4) 75.2 Pathologic stage < 0.001 ypT0N0 2490 (12.6) 88.9 ypT1-2N0 5727 (28.9) 86.4 ypT3,4 or N+ 11614 (58.5) 69.8 NAR risk (as defined from NSABP R04) < 0.001 Low ( < 8) 3629 (18.3) 88.0 Intermediate (8-16) 9793 (49.4) 81.0 High ( > 16) 6409 (32.3) 64.6 NAR quartiles < 0.001 1st ( < = 8.4) 3629 (25.0) 88.0 2nd (8.5-15.0) 9793 (25.0) 81.0 3rd (15.1-26.6) 1431 (25.0) 75.2 4th ( > 26.6) 1978 (25.0) 61.7
Romiplostim Treatment of Chemotherapy-Induced Thrombocytopenia
Authors: Gerald A. Soff, Yimei Miao, Gemma Bendheim, Jeanette Batista, Jodi V. Mones, Rekha Parameswaran, Cy R. Wilkins, Sean M. Devlin, Ghassan K. Abou-Alfa, Andrea Cercek, Nancy E. Kemeny, Debra M. Sarasohn, Simon Mantha
Journal: Journal of Clinical Oncology (2019)

Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment.We conducted a phase II randomized trial of romiplostim versus untreated observation in patients with solid tumors with CIT. Before enrollment, patients had platelets less than 100,000/μL for at least 4 weeks, despite delay or dose reduction of chemotherapy. Patients received weekly titrated romiplostim with a target platelet count of 100,000/μL or more, or were monitored with usual care. The primary end point was correction of platelet count within 3 weeks. Twenty-three patients were treated in a randomization phase, and an additional 37 patients were treated in a single-arm, romiplostim phase. Resumption of chemotherapy without recurrent CIT was a secondary end point.The mean platelet count at enrollment was 62,000/μL. In the randomization phase, 14 of 15 romiplostim-treated patients (93%) experienced correction of their platelet count within 3 weeks, compared with one of eight control patients (12.5%; P < .001). Including all romiplostim-treated patients (N = 52), the mean platelet count at 2 weeks of treatment was 141,000/μL. The mean platelet count in the eight observation patients at 3 weeks was 57,000/μL. Forty-four patients who achieved platelet correction with romiplostim resumed chemotherapy with weekly romiplostim. Only three patients (6.8%) experienced recurrent reduction or delay of chemotherapy because of isolated CIT.This prospective trial evaluated treatment of CIT with romiplostim. Romiplostim is effective in correcting CIT, and maintenance allows for resumption of chemotherapy without recurrence of CIT in most patients.
Pathologic response to neoadjuvant therapy with nab-paclitaxel plus carboplatin followed by anthracycline regimen in triple-negative breast cancer.
Authors: Juan David Cardenas, Elia Martinez, Blanca Lourdes Trujillo Alba, Carmen Esteban Esteban, Ana Rosa Rubio Salvador, Ana Dominguez Barahona, Cristina Romero, Raquel Sanchez-Simon, Maria Garcia Avila, Jose Ignacio Chacon
Journal: Journal of Clinical Oncology (2018)

e12660 Background: Triple-negative breast cancer (TNBC) is a poor prognosis subtype of breast cancer. We are lacking of definitive effective combinations in TNBC. So, it is warranted to explore new combinations. Neo-adjuvant setting is one of the most effective scenarios to explore a treatment efficacy. We aimed to evaluate efficacy of Nab-paclitaxel plus Carboplatin followed by anthracycline regimen by pathologic complete response (pCR) in women with TNBC. Secondary endpoints were toxicity profile and breast conserving surgery. Methods: Women with stage II or III disease were included. Hormone receptors and HER2 negativity was confirmed by immunohistochemistry and/or FISH. Patients received Nab-paclitaxel 125 mg/m2 plus Carboplatin AUC2 on days 1, 8 every 21 for four cycles followed by Epirubicin 90 mg/m2 and Cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles and subsequent surgery. We obtained informed consent from all patients. Magnetic Resonance was done in all cases at diagnosis and before surgery. Results: Twenty patients with clinical stage II (55%) or III (45%) TNBC were treated between Jan 2015 and Feb 2018. The median age of the patients was 55 years (35-77 years). Eighteen patients (90%) received 12 cycles of treatment and 2 (10%) ten and eleven cycles respectively; in all cases followed by surgery with or without radiotherapy. The rate of pCR was 60% (12/20) in breast and axilla. Conservative surgery was performed in 60% of patients (12/20). The 3/4 grade toxicities were leucopenia 10% (2), neutropenia 30% (6), febrile neutropenia 10% (2), allergy 5% (1), peripheral neurotoxicity 5% (1). Four of six neutropenia were during the anthracycline regimen. After a median follow-up of 15.7 months (5.0–36.9) 90% (18/20) of patients are alive without disease, two patients (10%) had early local relapse and distant relapse respectively and are deceased. Conclusions: Nab-paclitaxel plus carboplatin followed by anthracycline regimen combination as neoadjuvant treatment in TNBC achieved an encouraging rate of pCR, allowing conservative surgery in over 2/3 of patients. Toxicities were not severe in most patients and hematologic toxicity was manageable with G-CSF.
Abstract 19613: Role on Late Gadolinium Enhancement in Non Ischemic Cardiomyopathy - A Meta Analysis
Authors: Arun Kannan, Kalyan Prudhvi, Gajapathiraju Chamarthi, Gurusaravanan Kutti-Sridharan, Rajesh Janardhanan
Journal: Circulation (2016)

Background: Patients with non-ischemic cardiomyopathy (NICM) have high mortality due to sudden cardiac deaths from hemodynamically significant ventricular arrhythmias (VA). This is due to the presence of myocardial fibrosis and/or scarring. Late gadolinium enhancement (LGE) has been shown to predict the presence of myocardial fibrosis. We performed a meta-analysis to evaluate the role of LGE in patients with NICM. Methods: A systematic literature search was performed in PubMed and EMBASE database for clinical trials evaluating LGE in NICM. All cause mortality, cardiac mortality and major arrhythmic events (defined as VA and sudden cardiac deaths from VA) outcomes were evaluated. We conducted meta-analysis assuming random effects by using RevMan (Version 5.3.5 Copenhagen, Denmark). Results were calculated with 95% CI and was considered statistically significant if 2[[Unsupported Character - Codename ­]]sided alpha error was <.05. Results: A total of 23 studies (n=5,282) were included in the meta-analys...
Letter by Tong et al Regarding Article, “Efficacy and Safety of the Use of Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Concomitant Aspirin Therapy: A Meta-Analysis of Randomized Trials”
Authors: Suiyang Tong, Liangliang Zhang, Jacob Joseph
Journal: Circulation (2018)
Health-related quality of life in patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation: Results from the ALCYONE trial.
Authors: Katharine Gries, John Fastenau, Ying Chen, Jianping Wang, Kai Fai Ho, Susan Wroblewski, Maria-Victoria Mateos, Jesus San-Miguel, Michele Cavo, Ming Qi
Journal: Journal of Clinical Oncology (2018)

8042 Background: ALCYONE, an ongoing multicenter, open-label, Phase 3 trial of subjects with newly diagnosed multiple myeloma not eligible for high-dose chemotherapy with stem cell transplantation due to coexisting conditions or age ≥ 65 years, demonstrated significant progression-free survival (PFS) with daratumumab, bortezomib, melphalan, and prednisone (D-VMP) treatment compared with VMP alone. Measuring patient-reported outcomes (PROs) alongside disease progression provides the patient perspective on quality of survival and the value of health-related quality of life (HRQoL) for treatment decisions. Methods: The European Organization for Research and Treatment of Cancer Questionnaire (EORTC QLQ-C30) and EuroQol Questionnaire (EQ-5D-5L) visual analog scale (VAS) were completed using an electronic device (ePRO) at baseline and every 3 months during treatment; interim results presented for first 12 months. Key secondary endpoints included EORTC QLQ-C30 Global Health Status (GHS) and VAS scores. Treatment differences were assessed using repeated measures, mixed-effects model. Percent subjects achieving meaningful improvement based on established clinically important differences was summarized. Results: Study population included D-VMP (n = 350) and VMP (n = 356) subjects. Compliance rates > 90% at baseline and > 70% through month 12. Significantly better HRQoL in the D-VMP arm was observed at month 3 for GHS (p = 0.026) [Table]. Meaningful improvement in GHS was reported in 59.7% of D-VMP subjects compared to 52.0% VMP subjects (OR: 1.37; 95% CI: 1.02, 1.85). Similar HRQoL improvements were observed with the VAS. Conclusions: Patients experienced meaningful improvement in HRQoL over the course of therapy with more achieving meaningful change when treated with D-VMP. Improvements in HRQoL were consistent with the clinical benefit showing superior PFS of D-VMP over VMP alone. Clinical trial information: NCT02195479.GHS Change from baseline. D-VMP VMP n LS Means (95% CI) n LS Means (95% CI) Month 3 261 7.6 (5.3, 9.8) 244 4.1 (1.8, 6.5) Month 6 233 8.7 (6.4, 11.1) 212 8.9 (6.5, 11.4) Month 9 226 10.7 (8.3, 13.1) 189 10.4 (7.8, 13) Month 12 220 11.5 (9.1, 13.9) 179 10.5 (7.9, 13.2)
A phase I, first-in-human study of MGD006/S80880 (CD123 x CD3 DART) in AML/MDS.
Authors: Norbert Vey, Jan Kenneth Davidson-Moncada, Geoffrey L. Uy, David Rizzieri, Hanna Jean Khoury, Matthew Charles Foster, John E. Godwin, Max S. Topp, Giovanni Martinelli, Fabio Ciceri, Matteo Giovanni Carrabba, Gerwin A Huls, Antje Wegener, Kathy C. Tran, Michele Shannon, Jichao Sun, Jon M. Wigginton, John F. DiPersio
Journal: Journal of Clinical Oncology (2017)

TPS7070 Background: MGD006/S80880 is a novel CD123 x CD3 DART molecule designed to target CD123-positive cells for recognition and elimination by CD3-expressing T lymphocytes as effector cells. CD123, the alpha chain of the interleukin 3 receptor (IL-3Ra) is known to be highly expressed in &gt; 90% of AML patients and at least 50% of MDS patients. Based on these observations, targeting CD123 could be a promising strategy in the preferential ablation of AML and MDS cells. Methods: MGD006 is currently being evaluated in a Phase 1 dose-escalation and cohort expansion study in relapsed/refractory (R/R) AML or intermediate-2/high risk MDS. The objectives of the study are to determine the MTDS and safety profile, and describe the pharmacokinetics and preliminary activity of MGD006. Patients are dosed in 28-day cycles. All patients start with a lead-in continuous IV infusion of 30ng/kg/day for 3 days followed by 100ng/kg/day for 4 days. Subsequent weeks (2-4) are dosed in two different schedules. One arm receives MGD006 for 4 days on/3 days off and the second arm receives MGD006 for 7 days continuously at the maximal dose assigned to each cohort (up to 1000ng/kg/day). Beginning with the second cycle, all patients are administered MGD006 for 4 days on/3 days off at the maximal dose/cohort. Patients can continue on treatment until 2 cycles (8 weeks) after the attainment of a CR, maximum of 12 cycles of MGD006, DLT or treatment failure. Once the MTDS is identified, two cohorts of 24 patients each, one in AML and one in MDS, will be enrolled. Response is assessed by IWG or IPSS criteria for AML and MDS, respectively. Signs and symptoms of cytokine release syndrome (CRS), a common AE, are graded according to Lee criteria. The study continues to enroll patients with open sites in the US, France, Germany, Italy, and The Netherlands. ClinicalTrials.gov #NCT02152956. EudraCT #2015-003813-11.
David Oliver: Government’s approach to alcohol harm is incoherent
Authors: David Oliver
Journal: BMJ (2018)

For a decade or more we’ve been hearing big government rhetoric on prevention of ill health, promotion of wellbeing, and “parity of esteem” for mental health. Speaking at last week’s NHS Expo Conference, Public Health England’s chief executive, Duncan Selbie, said that NHS England’s 2014 Five Year Forward View had “told a fantastic story,” yet its ambitions for prevention hadn’t been implemented.12 With the upcoming 10 year plan,3 things had to change, he said.

In public health, prevention and treatment of alcohol misuse and its effects illustrate a huge mismatch between platitudes and practice.

The 2012 Health and Social Care Act shifted public health funding and provision to local authorities, ostensibly because local government has influence over wider societal determinants of health, such as education, housing, leisure, transport, and social care.4 But local government budgets have been cut hard ever since, with public health hit hard.56 In 2012-13 the ringfence on council budgets for drug and …
Dual time PET-CT for mediastinal nodal staging in patients diagnosed with non-small cell lung cancer in an area with high prevalence of infectious granulomatous disease (LACOG-0114).
Authors: Bruno Hochhegger, Maria Teresa Ruiz Tsukazan, Vanessa Rezende Bortolotto, Arthur Vieira, Carlos Cezar Fritscher, Mara Lise Zanini, Eduardo Herz Berdichevski, Eduardo Vilas, Vinicius Duval da Silva, José Antônio Lopes de Figueiredo Pinto, Leandro Genehr Fritscher, Louise Hartmann, Marcos Alba, Airton Schneider, Marcio Debiasi, Facundo Zaffaroni, Jeovany Martínez-Mesa, Carlos H. Barrios, Gustavo Werutsky
Journal: Journal of Clinical Oncology (2017)

e20083 Background: The role of dual-time-point PET/CT acquisition for mediastinal node staging in non-small cell lung cancer (NSCLC) is still controversial. Interpretation of PET/CT results is challenging in areas with high prevalence of infectious granulomatous diseases, whereas the use of dual-time PET/CT could reduce the false-positive results. This study aims to evaluate the performance of dual-time PET-CT for mediastinal node staging in patients with NSCLC in an area with high prevalence of infectious granulomatous diseases (i.e. 99 cases of tuberculosis per 100.000 habitants). Methods: Patients diagnosed with clinical stages I-III NSCLC performed dual-time-point PET/CT (images acquired in hour 1 and 2) followed by mediastinal lymph node biopsy. Different cut-offs for SUV were evaluated to test accuracy in each time-point. Results: One hundred patients were enrolled, of which 85 had mediastinal node biopsy after PET-CT. Median age was 65 years (range 47-80), 49 (58%) were male, 80 (94%) were current or former smokers, and 1 (1.2%) had history of tuberculosis. Dual-time-point acquisition results were similar to those in single-time-point (Table 1). The highest sensitivity (87%) and NPV (90%) was achieved when a cut-off SUV &gt; 0 was used. Conclusions: Dual-time point PET/CT did not improve accuracy of PET/CT-based LN staging in NSCLC in an area with high prevalence of infectious granulomatous diseases. [Table: see text]
Neutropenia related hospitalization risk in lung cancer patients with chemotherapy.
Authors: Qinli Ma, Abiy Agiro, Anupama Kurup Acheson, Sze-Jung Wu, Debra A. Patt, John Barron, Alan Rosenberg, Richard L. Schilsky, Gary H. Lyman
Journal: Journal of Clinical Oncology (2017)

e18290 Background: We sought to describe outcomes following granulocyte-colony stimulating factor (G-CSF) prophylaxis in patients with lung cancer receiving chemotherapy regimens with low to intermediate risk for inducing neutropenia related hospitalization. Methods: We identified 11,233 lung cancer (all histologies) patients ≥ 18 years from 14 commercial US health plans. All patients received first cycle chemotherapy during 2008–2013. 5,423 patients received one of the 3 regimens: carboplatin and paclitaxel, cisplatin and etoposide, carboplatin and etoposide. Primary prophylaxis (PP) was defined as G-CSF administration within 5 days of chemotherapy. Outcome was neutropenia, fever, or infection-related hospitalization within 21 days. Regression and number-needed-to-treat (NNT) analyses were used. Results: A total of 11,233 patients received any chemotherapy (21.2% PP), were older (median years 64 PP; 64 no PP) and had at least 1 non-cancer comorbidity (79.8% PP; 77.9% no PP). About 2,776 patients received Carbo/Paclitaxel (13.9% PP), 1,356 patients received Cisp/Etop (23% PP) and 1,291 patients received Carbo/Etop (45.8% PP) regimens. PP was associated with lower risk of neutropenia related hospitalization for any chemotherapy (4.7% PP; 7.5% no PP; odds ratio [OR] 0.61; 95% CI 0.49 – 0.74), for Cisp/Etop (5.1% PP; 8.8% no PP; OR 0.56; 95% CI 0.32 – 0.97) and Carbo/Etop (5.6% PP; 11% no PP; OR 0.48; 95% CI 0.31 – 0.73), but not Carbo/Paclitaxel (5.7% PP; 6.7% no PP; OR 0.84; 95% CI 0.53 – 1.32) regimens. Based on NNT, the total cost of PP for 36 patients with any chemotherapy regimen to avoid one hospitalization would be $128,952 (mean hospitalization cost = $11,900, Standard Deviation [SD] = $9,541). For 28 patients with Cisp/Etop, it would be $101,920 (mean hospitalization cost = $16,957, SD = $16,135). For 19 patients with Carbo/Etop, it would be $63,270 (mean hospitalization cost = $11,356, SD = $6,949). Conclusions: Primary G-CSF prophylaxis was associated with some benefit in lowering neutropenia-related hospitalization in patients with lung cancer receiving Cisp/Etop and Carbo/Etop regimens, although the cost to treat patients remains high. Future studies need to examine the value of continued G-CSF use in subsequent cycles.
Abstract 314: Sensory Innervation of the Papillary Muscle: A Neural Link Between Mitral Valve Prolapse and Malignant Ventricular Arrhythmias?
Authors: Krishan J Patel, Olujimi A Ajijola, Michael Fishbein, Kalyanam Shivkumar
Journal: Circulation Research (2016)

Background: Malignant mitral valve prolapse (MVP) identifies a subset of patients with MVP associated with ventricular arrhythmias (VAs), including sudden cardiac death (SCD). We hypothesized that papillary muscles, which see significant mechanical stress in MVP, are richly innervated with sensory nerves, which induce severe autonomic imbalance on the heart and may trigger malignant VAs. Methods and Results: Longitudinal sections of the anterior and posterior left ventricular papillary muscles, right ventricular outflow tract (RVOT), ventricular septum, and basolateral left ventricular wall (LV) of Yorkshire pigs (n=8) were excised, formalin-fixed, paraffin-embedded, and sectioned. Immuno-staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and calcitonin-gene related peptide (CGRP), a sensory afferent neuron marker, was performed. Areas of immunoreactivity (IR) for CGRP were verified by direct comparison to PGP9.5 IR. The density of CGRP was then compared across anatomical regions. The mean CGRP IR area was 1229.44 ± 116.65 μm 2 /nucleus in papillary muscles, while in the septum, basolateral LV, and RVOT, the CGRP stained areas were 699.36 ± 88.28 μm 2 /nucleus, 681.51 ± 81.90 μm 2 /nucleus, and 381.98 ± 31.14 μm 2 /nucleus, respectively (p&lt;0.001). There was no significant difference between CGRP IR area in the anterior papillary muscle (1091.36 ± 189.82 μm 2 /nucleus) and the posterior papillary muscle (1347.79 ± 140.50 μm 2 /nucleus) (p&gt;0.3). Conclusions: There is a significantly greater amount of afferent innervation in the papillary muscle compared to the septum, basolateral LV, and RVOT. This enrichment of afferent innervation warrants further study to understand how afferent neurotransmission during abnormal mitral valve function may impact ventricular electrophysiology.