tbuckley/cabot-search huggingface dataset:
Abstract 12830: Circulating Thrombospondin-2 Reflects Disease Severity and Provides Prognostic Information in Patients with Reduced Left Ventricular Ejection Fraction
Authors: Shinsuke Hanatani, Yasuhiro Izumiya, Yuichi Kimura, Taku Rokutanda, Satoshi Araki, Hisao Ogawa
Journal: Circulation (2013)

Introduction: Thrombospondin-2 (TSP-2) is a matricellular protein found in human serum. Recent work suggests that deletion of TSP-2 causes age-dependent dilated cardiomyopathy. Hypothesis: TSP-2 could be a useful biomarker for disease severity and cardiovascular mortality in patients with left ventricular (LV) systolic dysfunction. Methods and results: We measured serum TSP-2 levels in 101 patients with LV systolic dysfunction. LV systolic dysfunction was defined as LV ejection fraction of 50% or less. Serum TSP-2 concentrations were measured by ELISA. The endpoint of this study was a composite of total mortality and cardiovascular hospitalization. These patients were divided into 2 groups according to TSP-2 levels. Median TSP-2 levels in each group were 13.28 ng/ml and 22.95 ng/ml, respectively. High TSP-2 group revealed significantly higher BNP (median 324.8, interquartile range [179.9-641.3] vs. 105.5, [46.7-199.4] pg/ml, p≤0.0001), high sensitive C-reactive protein (0.12, [0.04-0.52] vs. 0.035, [0.02-...
SPEAR-Bladder (Study informing treatment Pathway dEcision in bladder cAnceR): Influence of treatment sequencing on time to treatment failure and overall survival in the United States.
Authors: Gurjyot K. Doshi, Mairead Kearney, Murtuza Bharmal, Hemant Phatak, Marley Boyd, Kathleen Aguilar, Ruth Kim, Abhijeet Bhanegaonkar
Journal: Journal of Clinical Oncology (2019)

453 Background: With the introduction of immunotherapy (IO) for locally advanced or metastatic urothelial carcinoma (mUC), optimal treatment sequence should be considered. This study aimed to compare time to treatment failure (TTF) and overall survival (OS) among these patients (pts) treated with first-line (1L) systemic chemotherapy followed by second-line (2L) IO ( C-IO) vs 1L and 2L chemotherapy ( C-C) sequence within the US community oncology Network (USON). Methods: This was a retrospective study of adult locally advanced or mUC pts who initiated systemic therapy between 1/1/15 – 4/30/17 within USON and had a minimum of two-month follow-up. Descriptive analyses were performed, with Kaplan-Meier used for comparisons between pts who received C-IO vs C-C sequence. Pts considered for this analysis did not receive a third-line treatment. Regression analyses were performed to assess variables associated with TTF and OS. Results: 117 pts were included in the analysis ( C-IO n = 79, C-C n = 38). Median age (range) was 69 years (38, 90+), with 74.4% male. Baseline demographic and clinical characteristics were similar between the groups. The median (range) duration between start of 1L and start of 2L therapy was significantly longer among C-IO vs C-C pts (29.0 [4.1, 102.1] vs 20.0 [0.1, 63.1] weeks; P = 0.0047). Median TTF and OS were longer among C-IO vs C-C pts but the trends were not significant (Table). The duration between initial diagnosis and advanced disease status was associated with TTF (P = 0.0124) in univariate analysis. Conclusions: These results suggest that patients receiving C-IO demonstrated greater (&gt;30 weeks) but statistically non-significant improvement in OS versus those receiving C-C. Considering these OS trends, future research should explore prognostic characteristics of IL chemotherapy treated pts who may benefit from an earlier switch to IO therapy. [Table: see text]
Lymph node involvement pattern and survival differences of FIGO IIIC[1] and FIGO IIIA1[2] ovarian cancer patients after primary complete tumor debulking surgery: A ten years retrospective analysis of the Tumor Bank Ovarian Cancer Network (TOC). [1] According to FIGO classification of 1985 [2] According to revised FIGO classification of 2013.
Authors: Khayal Gasimli, Elena Ioana Braicu, Mani Nassir, Ralf Richter, Aygun Babayeva, Radoslav Chekerov, Silvia Darb-Esfahani, Jalid Sehouli, Mustafa Zelal Muallem
Journal: Journal of Clinical Oncology (2015)

e16554 Background: FIGOstaging system for ovarian cancer was introduced in 1964 and revised in 2013 due to critics regarding survival disparities of subgroups in the same stage of the previous version which was established in 1985. Survival differences in FIGO IIIC of patients with lymph node positivity only were proved and in the recently revised FIGO classification considered as IIIA1. Methods: A total number of 218 patients with primary ovarian cancer who received complete cytoreductive surgery were included to the current retrospective analysis of validated TOC-Database, which covers the periods January 2002 until December 2012. According to their tumor spread pattern patients were divided into 3 groups; A (peritoneum only), B (peritoneum and lymph nodes) and C (lymph nodes only). Results: The vast majority of patients were classified in group B. Lymph node involvement was detected in 70.5% of the cases where peritoneal implants presented ≥ 2 cm beyond pelvis (group A+B). The estimated 5-year overall survival rates were 47.4 % in group A, 45.1% in group B and 91.7 % in group C (p< 0.01). The median overall survival differed significantly between patients with paraaortic lymph node affection only versus patients with both pelvic and paraaortic affection (68.5 vs. 46.7 months, respectively, p= 0.02). 3-year progression-free survival was 90.0% in FIGOIIIA1(i) and 62.6% in FIGOIIIA1(ii) (HR = 2.30, 95%CI = 0.45-11.58). Conclusions: Patients in FIGO IIIC stage with lymph node affection only have the best clinical outcome compared to patients of the same stage with peritoneal affection only. Furthermore, involvement of both pelvic and paraaortic lymph nodes are the same infrequency and involvement of only paraaortic lymph node in this stage has better survival chance than pelvic only or simultaneous of them.
Abstract 20375: Physicians Disagree on Team Leadership and Have Limited Knowledge of Task Allocation on the Cardiac Arrest Team - A Nationwide Study
Authors: Kasper Glerup G Lauridsen, Anders S Schmidt, Philip G Caap, Rasmus S Aagaard, Bo Løfgren
Journal: Circulation (2016)

Introduction: In-hospital resuscitation is performed by an ad hoc cardiac arrest team. Team members generally change daily. Lack of task allocation and delayed team leader identification may compro...
Abstract P152: A Personalised Home-Based Physical Activity Intervention for Chronic Heart Failure: Do Physiological Changes Correspond with Patient Experiences?
Authors: Nduka C Okwose
Journal: Circulation (2019)

Background: Referrals to physical activity and exercise programmes for patients with heart failure is suboptimal with high dropout rates in hospital-based programmes. Home-based programmes have gained popularity and help address this issue. The aim of the present study was to explore patients’ experiences of participating in a personalised homebased physical activity intervention programme and to explore whether experiences corresponded with physiological changes post intervention. Methods: Twenty patients (68±7 years) with chronic heart failure (13±11 years) due to reduced ejection fraction underwent a 12-week personalised home-based physical activity programme. This involved increasing daily pedometer step count by 2000 steps from baseline. Patients completed exercise, cardiac function and quality of life tests pre-post intervention. Sixteen of the 20 patients attended one of three focus group discussions to provide their views around the decision to participate in the programme and their experience of the programme when enrolled. Results: Seventeen patients (85%) completed the intervention, and 15 patients achieved the daily target step count which increased from baseline to 3 weeks by 2546 (5108±3064 to 7654±3849, p=0.03), and maintained until week 12 (9022±3942). On completion of the intervention, quality of life improved by 15% (26±18 vs. 22±19), cardiac index and stroke volume increased by 11% and 19% respectively (6.8±1.5 vs. 7.6±2.0 L/min/m2; and 127 ± 34 vs 151 ± 34, P=0.05). Workload and O2 consumption at anaerobic threshold increased by 16% (49±16 vs. 59±14 watts, p=0.01) and 10% (11.5±2.9 vs 12.8±2.2 ml/kg/min). Thematic analyses identified 10 themes influencing participation and maintenance. These included patient’s fear of engaging in physical activity, family influences on engagement with physical activity, support from clinicians and research staff, and increased confidence as a result of participating in a personalised programme. Conclusion: A personalised home-based physical activity intervention programme is feasible and for patients with stable chronic heart failure and led to improved quality of life and submaximal exercise capacity. However, qualitative findings suggest that outcomes are likely to be contingent on personalised feedback and support from suitably trained team members to increase confidence and self-efficacy, family support, and endorsement of the programme from a clinician.
Synergistic effect of simvastatin plus radiation in gastric cancer and colorectal cancer: Implications of BIRC5 and connective tissue growth factor.
Authors: Taekyu Lim, Won Ki Kang
Journal: Journal of Clinical Oncology (2015)

e14588 Background: In this study, we investigated the synergistic effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor plus radiation therapy, on the proliferation and survival of gastric cancer (GC) and colorectal cancer (CRC) cells. We also studied several genes involved in the simvastatin/radiation-induced effects. Methods: GC (AGS, SNU601, MKN1, and MKN28) and CRC (CoLo320, SW48, HT29, and HCT8) cell lines were treated with 0.2μM simvastatin alone, or in combination with 0 to 6 Gy of radiation, and subjected to clonogenic survival and proliferation assays in vitro. To assess the molecular mechanism of the combination treatment, we performed microarray analysis, immunoblot assays, siRNA knockdown experiments, and plasmid rescue assays. The antitumoral effects of simvastatin and radiation were evaluated in vivo using xenograft models. Results: The combination therapy of simvastatin plus radiation inhibited basal clonogenic survival and proliferation of GC and CRC cells in vitro. Combination indices were < 1 in all tested cancer cells. Simvastatin suppressed the expression of BIRC5 and CTGF genes in these cancer cells. In vivo, the combined treatment with simvastatin and radiation significantly reduced the growth of xenograft tumors compared with treatment with radiation alone. Conclusions: We suggest that simvastatin has a synergistic effect with radiation on GC and CRC through the induction of apoptosis, which may be mediated by a simultaneous inhibition of BIRC5 and CTGF expression. A clinical trial of simvastatin in combination with radiation in patients with GC or CRC is warranted.
Misclassification of Myocardial Injury as Myocardial Infarction
Authors: Cian McCarthy, Sean Murphy, Joshua A. Cohen, Saad Rehman, Maeve Jones-O’Connor, David S. Olshan, Avinainder Singh, Muthiah Vaduganathan, James L. Januzzi, Jason H. Wasfy
Journal: JAMA Cardiology (2019)

Similar to other patients with acute myocardial infarction, patients with type 2 myocardial infarction (T2MI) are included in several value-based programs, including the Hospital Readmissions Reduction Program and the Hospital Value-Based Purchasing Program. To our knowledge, whether nonischemic myocardial injury is being misclassified as T2MI is unknown and may have implications for these programs.To determine whether patients with nonischemic myocardial injury are being miscoded as having T2MI and if this has implications for 30-day readmission and mortality rates.Using the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code, we identified patients who were coded as having T2MI between October 2017 and May 2018 at Massachusetts General Hospital. Strict adjudication using the fourth universal definition of MI was then applied.Clinical adjudication of T2MI and 30-day readmission and mortality rates as a function of T2MI or nonischemic myocardial injury.Of 633 patients, 369 (58.3%) were men and 514 (81.2%) were white. After strict adjudication, 359 (56.7%) had T2MI, 265 (41.9%) had myocardial injury, 6 (0.9%) had type 1 MI, and 3 (0.5%) had unstable angina. Patients with T2MI had a higher prevalence of cardiovascular comorbidities than those with myocardial injury. Patients with T2MI and myocardial injury had high in-hospital mortality rates (10.6% and 8.7%, respectively; P = .50). Of those discharged alive (563 [88.9%]), 30-day readmission rates (22.7% vs 21.1%; P = .68) and mortality rates (4.4% vs 7.4%; P = .14) were comparable among patients with T2MI and myocardial injury.A substantial percentage of patients coded as having T2MI actually have myocardial injury. Both conditions have high 30-day readmission and mortality rates. Including patients with high-risk myocardial injury may have substantial implications for value-based programs.
Same-Day Discharge After Percutaneous Coronary Intervention—An Elusive Bargain
Authors: Mukta C. Srivastava, Christina Varricchio, Anuj Gupta
Journal: JAMA Cardiology (2019)

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Impact of sarcopenia on kidney function during neoadjuvant chemotherapy and post cystectomy complications in patients treated for localized muscle-invasive bladder cancer.
Authors: Pierre Regnier, Valeria De Luca, Serge Brunelle, Patrick Sfumato, Jochen Walz, Stanislas Rybikowski, Thomas Maubon, Nicolas Branger, Sami Fakhfakh, Matthieu Durand, Gwenaelle Gravis, Geraldine Pignot
Journal: Journal of Clinical Oncology (2019)

387 Background: Sarcopenia is suspected to influence the complication rates in patients undergoing radical cystectomy. The aim of our study was to assess variations in sarcopenia in patients scheduled for neoadjuvant cisplatin-based chemotherapy (NAC) and radical cystectomy for muscle invasive bladder cancer (MIBC) and to explore the impact of sarcopenia on complications linked to NAC and surgery. Methods: Between January 2012 and December2017, 82 consecutive patients who underwent NAC and RC for cT2-T4 N0 M0 MIBC were retrospectively selected. Using CT scan before and after NAC, Lumbar Skeletal Muscle Index (SMI) was assessed by two observers blinded to patient’s status. We defined severe sarcopenia as SMI &lt; 50 cm2/m2 for men and SMI &lt; 35 cm2/m2 for women. We evaluated pre- and post-NAC cisplatin-based chemotherapy renal function and post-operative complication rates after cystectomy using the Clavien-Dindo classification. We explored risk factors of complications by logistic regression models. Results: According to the SMI cut offs, 47 patients (57.3%) were classified as sarcopenic and 35 patients (42.7%) non-sarcopenic. Patients’ characteristics between sarcopenic and non-sarcopenic patients were not significantly different except for BMI (p &lt; 0.001). Among patients non-sarcopenic before NAC, 9 (19.1%) became sarcopenic after NAC. In multivariate analysis, sarcopenia was an independent significant predictor of renal impairment after NAC (OR 3.01; 95% CI 1.13–8.05; p = 0.02). There was a trend towards a higher rate of stage 3B kidney failure (GFR &lt; 45 mL/min/1.73m 2 ) after NAC in sarcopenic patients (OR 2.79; 95% CI 0.70–11.1) but the difference was not statistically significant (p = 0.14). Moreover, sarcopenia and ASA score were independent significant predictors of postoperative early complications ≤90 days (p = 0.01 and p = 0.02 respectively). Conclusions: We observed significant changes in sarcopenic status during NAC. Sarcopenia, estimated by the lumbar SMI measurement, was an independent predictor associated with the risk of renal impairment during NAC and early postoperative complications after RC.
A regimen of weekly nab-paclitaxel with weekly carboplatin in recurrent ovarian cancer: A retrospective analysis.
Authors: Amit Rauthan, Poonam Patil, S. P. Somashekhar, Shabber Zaveri
Journal: Journal of Clinical Oncology (2012)

e15516 Background: The standard of care for patients with recurrent platinum resistant ovarian cancer is treatment with non cross-resistant drugs. Carboplatin retreatment is usually not an option in the platinum resistant population. Weekly paclitaxel has been tried in recurrent patients. But paclitaxel can cause hypersensitivity reactions due to its Cremophor based solvent. nab-paclitaxel being a nano-particle albumin bound paclitaxel is devoid of this toxictity. Also, it is thought that nab-paclitaxel may have a higher intratumoral uptake leading to enhanced anti-tumor action. We looked at a regimen using weekly carboplatin with weekly nab-paclitaxel in platinum resistantrelapsed carcinoma ovary who had failed multiple lines of treatment. Methods: We treated 10 patients with recurrent platinum resistant ovarian cancer with measurable disease with nab-paclitaxel 100mg/m 2 on days 1,8,15 with carboplatin at AUC 1.5 on days 1,8,15 intravenously, repeated every 28 days for 4 cycles. All patients had received 3 or more lines of chemotherapy for recurrent disease. We looked for response rate, progression free survival and toxicities. Results: Three patients had complete response, 5 patients had partial response and 2 patients had disease progression. Median PFS was 6 months. There were no instances of paclitaxel induced hypersensitivity reactions. Two patients developed grade 3 neutropenia. One patient developed grade 3 thrombocytopenia. Three patients required blood transfusions. One patient developed grade 3 neuropathy. Conclusions: Weekly combination of nab-paclitaxel with weekly carboplatin is a safe and potentially active treatment in recurrent platinum resistant ovarian cancers who had failed multiple lines of treatment. Considering the efficacy and favorable toxicity profile, this weekly combination needs to be tested in a larger number of patients.
Anti–neurofascin-155 IgG4 antibodies prevent paranodal complex formation in vivo
Authors: Constance Manso, Luis Querol, Cinta Lleixà, Mallory Poncelet, Mourad Mekaouche, Jean-Michel Vallat, Isabel Illa, Jérôme J. Devaux
Journal: Journal of Clinical Investigation (2019)

Neurofascin-155 (Nfasc155) is an essential glial cell adhesion molecule expressed in paranodal septate-like junctions of peripheral and central myelinated axons. The genetic deletion of Nfasc155 results in the loss of septate-like junctions and in conduction slowing. In humans, IgG4 antibodies against Nfasc155 are implicated in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies are associated with an aggressive onset, a refractoriness to intravenous immunoglobulin, and tremor of possible cerebellar origin. Here, we examined the pathogenic effects of patient-derived anti-Nfasc155 IgG4. These antibodies did not inhibit the ability of Nfasc155 to complex with its axonal partners contactin-1/CASPR1 or induce target internalization. Passive transfer experiments revealed that IgG4 antibodies target Nfasc155 on Schwann cell surface, and diminished Nfasc155 protein levels and prevented paranodal complex formation in neonatal animals. In adult animals, chronic intrathecal infusions of antibodies also induced the loss of Nfasc155 and of paranodal specialization and resulted in conduction alterations in motor nerves. These results indicate that anti-Nfasc155 IgG4 perturb conduction in absence of demyelination, validating the existence of paranodopathy. These results also shed light on the mechanisms regulating protein insertion at paranodes.
Abstract P024: Hidden Risks: Relationship Among Visceral Adipose Tissue, Interleukin-18, and Adiponectin in the Development of Type 2 Diabetes in Filipino Americans
Authors: Julian L Gallegos, Ruth Taylor-Piliae, Thaddeus Pace, Matthew Gallek, Leslie Ritter
Journal: Circulation (2019)

Background and Aims: Filipino Americans (FAs) are at high risk for developing type 2 diabetes however little research exists as to why this occurs. There is evidence that pro-inflammatory Interleukin-18 (IL-18) and anti-inflammatory (adiponectin) markers associated with visceral adipose tissue (VAT) may explain this risk but this postulate has not yet been examined during the course of diabetes progression in FAs. Therefore, in FAs without diabetes, with pre-diabetes and with type 2 diabetes, the aims of this study were to: 1) Quantify VAT, IL-18, and adiponectin and describe the values in relation to known reference ranges (RR) for each group 2) Determine the relationships of VAT, IL-18, and adiponectin within each group and 3) Determine if VAT, IL-18, and adiponectin were different among groups. Methods: FAs were recruited from healthcare and community centers in Solano County, California. VAT was measured using the InBody 570 © body impedance analyzer. Blood was obtained for HgA1c and plasma was used to quantify IL-18 and adiponectin with ELISA. Correlation coefficients were conducted to determine the associations among VAT, IL-18 and adiponectin in the three groups. One-way ANOVAs were conducted for each biomarker to determine if there were statistically significant differences among groups. Results: Seventy-five participants enrolled (N=25 per group), 68% females with mean age=42 years. VAT values above the RR included 57% of women, but only 27% of men. Participants with an IL-18 above the RR used for this study was greater in the pre- diabetes (68%) and diabetes groups (64%) vs. the non-diabetes group (40%). Interestingly, 90- 100% of the adiponectin values in both men and women were well above the RR. There were no correlations among the biomarkers within any group. VAT and IL-18 were not significantly different among groups. Adiponectin was significantly different among groups (F 2 ,72 =3.789, p=0.03), with lower values in the diabetes group vs. the non-diabetes group (Post-hoc Tukey HSD test, p=0.02). Conclusions: This is the first time VAT, IL-18 and adiponectin have been examined in FAs without diabetes, with pre-diabetes and with diabetes. While a young, mostly female sample may have confounded the biomarker findings, the results point toward the potential usefulness of inflammation-related biomarkers to identify individuals in the FA population that may be at higher risk for type 2 diabetes and understand the mechanisms of diabetes development and progression in FAs.