tbuckley/cabot-search huggingface dataset:
Abstract 21002: Comparison of Clinical Outcomes of Patients With Acute Heart Failure and Recovered Ejection Fraction versus Preserved or Reduced Ejection Fraction
Authors: Jae Yeong Cho, Kye Hun Kim, Sang Eun Lee, Hyun Jai Cho, Hae-Yeoung Lee, Jin-Oh Choi, Eun-Seok Jeon, Min-Seok Kim, Jae-Joong Kim, Kyung-Kuk Hwang, Shung Chull Chae, Sang Hong Baek, Seok-Min Kang, Dong-Ju Choi, Byung-Su Yoo, Youngkeun Ahn, Hyun-Young Park, Myeong-Chan Cho, Byung-Hee Oh
Journal: Circulation (2017)

Introduction: Recent studies showed that patients with chronic heart failure with recovered ejection fraction (HFrecEF) have better clinical outcomes than those with preserved ejection fraction (HFpEF). However, there is lack of data about HF prognosis according to EF change in acute heart failure (AHF). Therefore, the aim of this study was to investigate the prognosis of HFrecEF compared to HFpEF in patients with AHF. Methods: A total of 5,625 cohort patients with AHF enrolled in Korean AHF registry (KorAHF). Of them, 2,632 patients underwent follow-up echocardiography with measurement of EF. They were divided into three groups according to EF change: HF with reduced EF (HFrEF) (n=1,522, 68.6±14.5 years, 818 males), HFpEF (n=281, 72.6±13.5 years, 115 males), and HFrecEF (n=829, 67.6±14.2 years, 341 males). HFrEF was defined as AHF patients with EF &lt;50%, HFpEF as EF &gt;=50%, and HFrecEF as EF&gt;=50% with previous EF &lt;50%. Primary end-point was all-cause mortality at 1-year follow up. Results: Patients were older (72.6±13.5 vs. 67.6±14.2 vs. 68.6±14.5 years, p&lt;0.001) and more likely to be female (59.1% vs. 41.1% vs. 46.3%, p=0.058) in HFpEF group than in HFrecEF and HFrEF group. Systolic BP was lowest (136.7±31.1 vs. 128.6±29.9 vs. 131.9±29.7 mmHg, p&lt;0.001) in the HFrecEF group. In echocardiographic exam, EF was lowest in the HFrecEF group (60.0±6.4% vs. 30.4±10.1% vs. 37.8±15.8%, p&lt;0.001) and E/e’ was highest (18.7±10.9 vs. 22.0±12.0 vs. 21.2±11.3, p&lt;0.001). Ischemic etiology was less evident in the HFpEF group (22.1% vs. 40.0% vs. 39.0%, p&lt;0.001), but valvular (29.5%), hypertensive (6.8%), and tachycardic etiologies (12.8%) were more frequent in the HFpEF group. In clinical outcomes, 1-year death was highest in the HFrecEF group (13.9% vs. 18.3% vs. 16.6%, p=0.752) and rehospitalization rate was comparable between the groups (42.7% vs. 41.9% vs. 45.5%, 0.141). Kaplan-Meier survival analysis showed that 1-year mortality in the HFrecEF group was marginally higher than that in the HFpEF group (p=0.046 by log rank test). Conclusions: AHF patients in HFrecEF group had higher mortality than those in HFpEF group. Recovery from acute depressed LV function may not always warrant favorable clinical outcomes in long-term follow-up.
Patterns of VC Decline in Amyotrophic Lateral Sclerosis. A More Robust Prognostication?
Authors: Ahmet Baydur
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Amyotrophic lateral sclerosis (ALS) is a progressive disease of the upper and lower motor neurons that leads to skeletal (including respiratory) muscle weakness.The decrease in respiratory function is commonly assessed by the FVC or slow VC (1), depending on the magnitude of skeletal muscle denervation (2).Complications of functional decline include hypoventilation, pneumonia, and respiratory failure, necessitating initiation of assisted ventilation (3).There have been few descriptions of the different patterns of respiratory function decline in ALS.In this issue of the Journal, Ackrivo and colleagues (pp.1513-1521) describe the creation of a group-based trajectory model (GBTM) that identified three distinct trajectory groups of FVC in ALS, termed "stable low," "rapid progressor," and "slow progressor" (4).Patients were followed until they developed respiratory insufficiency, were lost to follow-up, or completed the study.Five variables were found to have a significant association with the trajectory groups: diagnosis delay, body mass index, bulbar-onset disease, ALS Functional Rating Scale-Revised (ALSFRS-R) orthopnea score, and ALSFRS-R total score.The authors found that compared with the slow progressors group, rapid progressors tended to have longer diagnosis delays, a lower body mass index, more bulbar-onset disease, lower ALSFRS-R total scores, and an orthopnea score.The potential clinical value of this analysis of functional decline is that it can predict the initiation of noninvasive ventilation or tracheostomy, or death.The study is based on an earlier investigation in which Ackrivo and colleagues created and validated a model to be used at baseline "at the bedside" to discriminate patients at high risk of developing respiratory insufficiency at 6 months (5).A few points regarding the computational model used by the authors should be noted.GBTM involves a procedure in which individuals are gathered into meaningful subgroups that show statistically similar trajectories (6).It is facilitated by use of the Bayesian information criterion, a criterion for model selection among a finite set of models that is based, in part, on the likelihood function.In this study, the authors selected the model in which all groups had stable or declining FVC values while following significantly different trajectories.This strategy left out groups with increasing FVC values (which would be highly unlikely in ALS) while it preserved the least number of groups,
Psychiatric Practice Patterns and Barriers to the Adoption of Esketamine
Authors: Samuel T. Wilkinson, David H. Howard, Susan H. Busch
Journal: JAMA (2019)

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Abstract 4374: The role of glycine decarboxylase in neuroblastoma
Authors: Ahmet Alptekin, Jane Ding, Bingwei Ye, Han-Fei Ding
Journal: Cancer Research (2019)

Abstract Neuroblastoma is the most common cancer in infants. While the low and intermediate risk groups of neuroblastoma patients have ≥90% five-year-survival rates, the high-risk group has only 40-50% five-year-survival rates despite multimodal therapies. Genomic amplification of the oncogene MYCN (a member of the MYC family of transcription factors) is a major cause of high-risk neuroblastoma and is strongly correlated with poor prognosis. A key function of MYCN is to promote cell growth and proliferation, which requires increased cellular metabolism to meet the biosynthetic demand for growth. Serine-Glycine-One-Carbon (SGOC) metabolism is particularly important in sustaining cell proliferation by producing amino acids for protein synthesis and one-carbon units for nucleotide production. We investigated the role of glycine decarboxylase (GLDC) in neuroblastoma. GLDC catalyzes the first reaction in glycine cleavage, which generates one-carbon unit and reduced NADH. Analysis of gene expression data from two cohorts of neuroblastoma patients showed that GLDC expression is correlated with advanced stages, high-risk disease and poor prognosis in neuroblastoma. We found that GLDC is required for neuroblastoma cell proliferation as silencing GLDC expression by shRNA induced G1 cell cycle arrest. Consistent with this observation, microarray gene expression profiling revealed that GLDC knockdown resulted in a significant decrease in the expression of E2F target genes. In addition, we obtained evidence that GLDC is a direct target gene of MYCN. Knockdown of MYCN expression reduced GLDC mRNA and protein expression, and overexpression of MYCN increased GLDC mRNA and protein levels. Moreover, chromatin immunoprecipitation with quantitative PCR demonstrated that MYCN binds to the GLDC promoter region. These findings suggest an important role of GLDC in driving neuroblastoma cell proliferation, which could be exploited as a therapeutic strategy against high-risk neuroblastoma with MYCN amplification. Citation Format: Ahmet Alptekin, Jane Ding, Bingwei Ye, Han-Fei Ding. The role of glycine decarboxylase in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4374.
HER2/neu (HER2) specific T-cell immunity in patients with HER2+ inflammatory breast cancer (IBC) and prognosis
Authors: L. G. Salazar, D. Wallace, P. Mukherjee, D. Higgins, J. Childs, N. Bates, A. L. Coveler, M. L. Disis
Journal: Journal of Clinical Oncology (2009)

3057 Background: IBC is rare, highly aggressive, and associated with worse prognosis when compared to non-IBC tumors. Moreover, multimodality treatment has had little impact on overall prognosis. HER2 is overexpressed in about 40% of IBC tumors and is associated with worse overall survival (OS). We have developed vaccines that elicit both HER2-specific CD4+ and CD8+ T-cell immunity in HER2+ cancer patients. Generation of HER2-specific T-cell immunity could (1) target immunogenic and biologically relevant proteins such as HER2 in IBC, (2) result in immunogenic eradication of HER2+ tumor cells, and (3) potentially prevent disease relapse when used in the adjuvant setting after standard therapy. A retrospective analysis of IBC patients immunized with HER2 vaccines was conducted to better understand the development of HER2-specific T-cell immunity and its possible impact on overall prognosis in IBC. Methods: Clinical and immunological data of IBC patients enrolled in University of Washington IRB approved HER2 vaccine trials was collected and reviewed. 27 patients immunized between 1996–2008 were identified; and 24/27 subjects who received vaccines designed to elicit both CD4+/CD8+ immunity were included in immunologic and survival analysis. The 24 subjects received either a HER2 DNA or HER2 peptide-based vaccine that were admixed with GM-CSF and given intradermally monthly for a total of 3 DNA or 6 peptide vaccines. Immune responses were assessed via IFN-γ ELISPOT at baseline and post-vaccination. Results: All 24 subjects had stage III IBC and median age was 48 (range 34–77). 10/24 (42%) patients had ER/PR+ tumors, 9/24 (37%) had received trastuzumab, and 15/24 (62%) had received multimodality treatment (chemotherapy, mastectomy, radiotherapy). 12/18 subjects (66%) evaluable for immunologic response developed HER2-specific T-cell immunity post-vaccination. Median OS for patients (n=6) not generating HER2-specific immunity was 31 months and median OS for the 12 patients who developed HER2-specific immunity has not been reached at median follow-up of 46 months, (p=0.026). Conclusions: Patients with IBC are able to generate HER2-specific T-cell immunity after HER2 vaccination, and development of HER2-specific immunity may impact survival. No significant financial relationships to disclose.
Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial
Authors: Stefan Groeneweg, Robin P Peeters, Carla Moran, Athanasia Stoupa, Françoise Auriol, Davide Tonduti, Alice Dica, Laura Paone, Klara Rozenkova, Jana Malikova, Adri van der Walt, Irenaeus F M de Coo, Anne McGowan, Greta Lyons, Femke K Aarsen, Diana Barca, Ingrid M van Beynum, Marieke M van der Knoop, Jurgen Jansen, Martien Manshande, Roelineke J Lunsing, Stan Nowak, Corstiaan A den Uil, M Carola Zillikens, Frank E Visser, Paul Vrijmoeth, Marie Claire Y de Wit, Nicole I Wolf, Angelique Zandstra, Gautam Ambegaonkar, Yogen Singh, Yolanda B de Rijke, Marco Medici, Enrico S Bertini, Sylvia Depoorter, Jan Lebl, Marco Cappa, Linda De Meirleir, Heiko Krude, Dana Craiu, Federica Zibordi, Isabelle Oliver Petit, Michel Polak, Krishna Chatterjee, Theo J Visser, W Edward Visser
Journal: The Lancet Diabetes & Endocrinology (2019)
Investigation of the diagnostic precision and utility of sentinel lymph node biopsy in the treatment of patients with Merkel cell carcinoma (MCC).
Authors: Elena Mantas Paulus, Fawwaz Ridwan Shaw, Martin D. Fleming
Journal: Journal of Clinical Oncology (2013)

9042 Background: Merkel cell carcinoma (MCC) is a relatively uncommon and aggressive cutaneous neuroendocrine neoplasm with a high incidence of local recurrence and regional and distant metastasis. The management and identification of prognostic factors remains of value in the treatment of these patients. Although the optimal multidisciplinary treatment of MCC has yet to be determined, the purpose of this study was to investigate whether sentinel lymph node biopsy confers a lower risk of recurrent disease in patients with Merkel cell carcinoma at our institution. Methods: After obtaining institutional review board approvals, all patients with a diagnosis of MCC from 2002-2012 were obtained from our tumor registries. Clinical features, pathologic characteristics, management modalities, and patient outcomes were retrospectively reviewed. Results: Of 20 patients with MCC, nine patients underwent sentinel lymph node biopsy, another four received therapeutic lymph node dissections, and seven patients did not have lymph node evaluation at the initial operation. The most common nodal basins involved were cervical and axillary. Recurrent disease was observed in seven patients (35%). Three patients underwent complete regional lymph node dissection after developing clinically positive nodal disease subsequent to only wide local excision at the index operation (15%). Three patients developed locoregional recurrence and the seventh patient developed metastatic disease to the liver. Of these seven patients with recurrent disease, only two (28.57%) had initial lymph node evaluation. Twelve patients (60%) received adjuvant therapy with chemotherapy (carboplatin/etoposide) and/ or radiation therapy. Conclusions: Merkel cell carcinoma continues to demonstrate its propensity for high rates of recurrence and metastatic disease. Of the seven patients with recurrent locoregional and/or nodal disease in our study, only two patients had initial lymph node evaluation, which was statistically significant with a p value of 0.01175. Further analysis focusing on additional prognostic factors is necessary to optimize our management algorithms and patient outcomes.
Non-linear relationship between HER-2 expression and response to trastuzumab in breast cancer cells
Authors: G. Valabrega, F. Montemurro, S. Giordano, M. Aglietta
Journal: Journal of Clinical Oncology (2006)

13083 Background: Currently, eligibility for treatment with the mAb trastuzumab (T) in breast cancer patients is assessed by semiquantitative immunohistochemical (IHC) analysis of HER-2 expression, where 3+ score represents overexpression, and/or by Fluorescence In Situ Hybridization (FISH), which detects HER-2 gene amplification. However, both methods do not measure small but potentially significant differences in protein expression. Methods: We modulated HER-2 expression by RNA interference (siRNA) in the human HER-2-overexpressing breast cancer cell line SKBR3. Protein expression was measured by Western Blot analysis. Cells expressing different levels of HER-2 protein were then treated with T, to assess the mAb effect on cell proliferation and apoptosis. Results: Compared with the parental cell line, SKBR3 cells transfected with 10, 20, and 30 nM HER2 specific siRNAs, showed a reduction of HER-2 protein levels of 40%, 55% and 70%, respectively. Despite up to a 70% decrease in HER-2 expression, transfected cells still scored 3+ at IHC (Dako HercepTest®). Interestingly, this reduction rendered cancer cells more sensitive to T treatment. In fact, we found that sensitivity to T follows a bell shaped curve, depending on different amounts of HER-2. When T was administered at the standard dose of 10 μg/mL, cells showing a 40% reduction of the HER-2 resulted more sensitive to the growth inhibitory effect of T, compared with parental SKBR3 cells and with cells showing lower levels of receptor. Furthermore, these cells were sensitive to T concentrations lower than standard (6 vs 10 μg/mL), which were markedly less effective in cells expressing higher or lower levels of HER-2 receptor. Conclusions: The observation that cells expressing significantly different amounts of HER-2 protein are all scored as “overexpressors” by conventional IHC suggests that quantitative analysis of HER-2 receptor in breast cancer might be more appropriate for the selection of candidates to T treatment. Moreover, we showed that the inhibitory effect of T depends in a non-linear manner on the quantity of HER-2 protein and that the level of HER-2 expression can influence the sensitivity to T, which requires an optimal drug/receptor ratio. No significant financial relationships to disclose.
Disease control with a second epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after failure of a first TKI in Asian patients with non-small cell lung cancer (NSCLC)
Authors: A. Wong, S. W. Lim, T. M. Chin, R. Soong, R. A. Soo
Journal: Journal of Clinical Oncology (2007)

18104 Background: Asian NSCLC patients are known to have higher response rates to the EGFR TKI gefitinib (G) and erlotinib (E). Anecdotal reports suggest some activity for a second EGFR TKI after failure of the first. Methods: A retrospective review of the electronic pharmacy records, clinical and radiographic records of patients with advanced NSCLC at the National University Hospital who received both G and E in the previous 2 years was conducted. Objectives were to assess the disease control (response/stable disease) of the second TKI after failure of the first and characterize the clinical, pathological and molecular features of patients benefiting from a 2nd TKI. Results: 14 patients with advanced NSCLC who received a 2nd EGFR TKI after progression on the 1st TKI were identified. Patient characteristics: Chinese 12, female 10, and non-smokers 13. Histologic subtype: adenocarcinoma 7, bronchioloalveolar carcinoma (BAC) 3, squamous-cell carcinoma 1, NSCLC unspecified 3. 12 patients received cytotoxic chemotherapy with a median of 2 lines, (range 1–5). G and E was used as 1st/2nd/3rd/=4th line treatment in 8/2/2/2 and 0/4/2/8 patients respectively. G was used before E in 13 cases and disease control was seen in 8/14 (57%) patients. With a 2nd TKI after disease progression, disease control was seen 4/14 (28%) patients. Patient characteristics were: adenocarcinoma 3, BAC 1, all were never smokers and all received and responded to prior G. Median duration of control in these 4 patients for G was 8 (range 7–12) months, and subsequently to E was 2.5 (range 2–8) months. Disease control was associated with symptomatic improvement. Conclusion: This study documents disease control in 28% of Asian NSCLC patients treated with a second EGFR TKI after failure of a first. The molecular basis for these observations is currently being investigated. No significant financial relationships to disclose.
Comparative effectiveness of sphincter-sparing surgery (SSS) versus abdomino-perineal resection (APR) in rectal cancer: Patient-reported outcomes (PROs) from NSABP R-04.
Authors: Patricia A. Ganz, Samia H. Lopa, Greg Yothers, Clifford Y. Ko, Amit Arora, James Norman Atkins, Nathan Bahary, Gamini S. Soori, John M. Robertson, Janice F. Eakle, Benjamin T. Marchello, Timothy F. Wozniak, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

3545 Background: R-04 is a trial of pre-surgical RT and either capecitabine or 5-FU with or without oxaliplatin in patients (Pts) with resectable rectal cancer. PROs were measured before treatment, post-RT, and 1 yr post-op. We compare PROs at 1 yr by type of surgery with hypothesis that APR Pts would have worse quality of life (QOL). Methods: Pts completed the FACT-C and EORTC-CR38 at all times. Baseline and 1 yr were compared within groups (SSS and APR) with paired t-test, and between groups at 1 yr, with adjustment for covariates of age, gender, clinical stage, baseline score, and surgery intent in a general linear model. These secondary/exploratory hypotheses were significant if p &lt; 0.05. Results: 1,608Pts were randomized and 1405 completed baseline QOL form after consent, prior to treatment. 1,003 completed QOL form 1 yr post-op: 6 were ineligible, 10 did not have surgery, leaving 987 Pts. 615 had SSS and 372 had APR. 66.6% were male, 61.5% stage II, and almost all had post-surgical adjuvant chemotherapy. SSS Pts were significantly younger (60.3% vs. 53.5% &lt; 59 yr, p=0.04). FACT-C total and subscale scores were not significantly different by surgery type at 1 yr, with only minimal decline from baseline in both groups. For SSS Pts, EORTC-CR38 scores significantly worsened for body image, sexual function, sexual enjoyment (all p &lt;0.0001), while future perspective improved (p&lt;0.0001) at 1 yr from baseline. All symptom subscales except weight loss and micturition showed worsened symptoms (GI tract, chemo side effects, defecation problems, sexual problems) all p &lt; 0.0001 at 1 yr from baseline. Compared to APR Pts, SSS had less severe functional problems and symptoms, especially in sexual enjoyment, weight loss, GI symptoms, and body image, all significant. Conclusions: Contrary to prediction, there were no significant differences in FACT-C scores for SSS vs. APR. Symptoms and functional problems were detected by the EORTC-CR38, reflecting expected differences. The largest differences between the surgical treatments were for GI symptoms and body image. Information from these PROs may be useful in counseling Pts anticipating surgery for rectal cancer.
Mechanistic Insights into Lethal Lung Developmental Disorders. The Rare Informs the Common
Authors: Steven H. Abman, Xin Sun
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

predicting CHP progression and survival will be of major interest.Such findings could also be in the context of extrapulmonary (e.g., hematological) abnormalities of short-telomere syndrome.Whether telomeropathy and short telomeres represent the inciting events of immune deregulation of CHP or simply exacerbate the disease process remains to be determined.There is ongoing disagreement about what constitutes HP.In a previous study, agreement across multidisciplinary teams about an HP diagnosis was fair (k = 0.24), whereas agreement about IPF (k = 0.60) or connective tissue disease-associated interstitial lung disease (k = 0.64) was moderate to good (14).Large, prospective, collaborative studies in well-defined patients with CHP are sorely needed to overcome these limitations and allow firm conclusions to be drawn.