tbuckley/cabot-search huggingface dataset:
Phase II study of oral topotecan plus bevacizumab (topo-bev) for second-line treatment of small cell lung cancer (SCLC).
Authors: D. M. Waterhouse, S. K. Morgan, D. R. Spigel, S. Shankar, B. Dharan, D. E. Foose, K. Bhatt
Journal: Journal of Clinical Oncology (2010)

7055 Background: Topotecan has been FDA-approved for second-line treatment of relapsed SCLC. Alteration in tumor vasculature by addition of bevacizumab could increase delivery of topotecan to tumor cells and enhance its efficacy. Methods: This is an open-label, multicenter, single-arm phase II study of oral topotecan 2.3 mg/m2/dx5 + IV bevacizumab 15 mg/kg/d1 q21d for second-line treatment in adults with first relapse of SCLC, adequate organ function, and ECOG PS ≤ 2. Treatment was planned for 8 cycles or until disease progression or the development of unacceptable toxicity. The primary efficacy endpoint was PFS rate at 3 months. The study had 90% power with 5% type 1 error to detect a 40% relative improvement in 3-month PFS rate from 50% for topotecan (historical control) to 70%. Secondary endpoints included ORR, PFS, OS, and safety evaluation. Results: Fifty subjects were enrolled from July 2008 to April 2009. Mean age was 61 y (28-80); 52% female; 98% Caucasian. 92% of patients had ECOG PS 0 or 1 and 86% had extensive disease at baseline. 57% of subjects had sensitive disease (TTP > 90 d from end of prior chemotherapy). Six subjects were on treatment and 44 had discontinued, most commonly for progression (24) and adverse events (AEs) (10). 3-month PFS rate was 60.3% (95% CI, 44.6, 72.9). Median PFS and OS were 17.4 and 31.6 weeks, respectively. ORR was 10% (CR+PR 95% CI, 3.3, 21.8). Gr3, 4 or 5 AEs were reported in 58% of patients. Gr3/4 neutropenia and thrombocytopenia occurred in 44% and 50% of patients. No grade 3/4 proteinuria or hypertension were reported. Nonhematologic toxicity was primarily nausea, diarrhea, vomiting, asthenia, and fatigue. There were 5 non-disease-related deaths: thrombocytopenia, upper GI hemorrhage, respiratory distress/failure, pneumonia, sepsis. Conclusions: The primary efficacy endpoint of improvement in 3-month PFS was not met. A marginal benefit of this combination cannot be ruled out. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Abstract 8789: Serial Measurements of C-Reactive Protein in Predicting Clinical Outcomes in Patients with Acute Aortic Intramural Hematoma
Authors: Takeshi Kitai, Shuichiro Kaji, Atsushi Yamamuro, Kitae Kim, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Tomoko Tani, Toru Kita, Yutaka Furukawa
Journal: Circulation (2011)

Background: Inflammation is involved in the pathogenesis and progression of acute aortic dissection, and a high circulating C-reactive protein (CRP) level may be a risk factor for adverse events in patients with aortic dissection. However, there is no data regarding time course in CRP levels during acute phase in patients with aortic intramural hematoma (IMH). The aim of this study was to evaluate the prognostic relevance of serial CRP measurements in patients with IMH. Methods: A total of 180 IMH patients (age; 70±11 years, male/female; 105/75) who were admitted to our institution within 48 hours from the onset, were evaluated. CRP data were obtained at admission, 2 days, 1 week, 2 weeks from the onset and maximal values during hospitalization. Patients who underwent surgery within 2 weeks from the onset were excluded. Clinical outcomes were evaluated with a mean follow-up of 5.1±3.9 years. Results: CRP levels were 3.0±4.6, 8.7±5.9, 9.0±5.5, and 5.7±4.5 mg/dL at admission, 2 days, 1 week and 2 weeks, respectively. Maximal value of CRP was 12.4±6.3 mg/dL. There were 23 deaths including 9 cases of aortic rupture, and 23 patients underwent surgical or percutaneous repair during follow-up and 19 patients showed progression to classic aortic dissection or aortic aneurysm without surgery. CRP levels at 2 weeks of patients with aorta-related events were significantly higher than that of patients without the events (8.8±5.2 vs 4.5±3.6; P&lt;0.001). Receiver-operating characteristic curve analysis identified CRP level of 5.0 mg/dL at 2 weeks as a cut off for predicting aorta-related events, with sensitivity, specificity, and positive and negative predictive values of 71%, 66%, 35%, and 86%, respectively. The aorta-related event free survival was significantly higher in patients with lower CRP (≤5.0) at 2 weeks (P&lt;0.001,Figure). Conclusions: Sustained high levels of CRP at 2 weeks from the onset were associated with a progressive disease course in patients with IMH.
Abstract 12233: Variability in the Recovery Rate of Platelet Cyclooxygenase Activity During Chronic Therapy With Low-Dose Aspirin in Type 2 Diabetes
Authors: Bianca Rocca, Francesca Santilli, Dario Pitocco, Luciana Mucci, Giovanna Petrucci, Ester Vitacolonna, Stefano Lattanzio, Domenico Mattoscio, Francesco Zaccardi, Rossella Liani, Natale Vazzana, Adriana Del Ponte, Elisabetta Ferrante, Francesca Martini, Giovanni Ghirlanda, Giovanni Davi, Carlo Patrono
Journal: Circulation (2010)

Aspirin is currently recommended for cardiovascular prevention in type 2 diabetes (T2DM). However, two primary prevention trials failed to substantiate its efficacy in T2DM and incomplete platelet inhibition has been reported. We hypothesized that faster recovery of platelet cyclooxygenase (COX)-1 activity may explain incomplete thromboxane (TX) A2 inhibition by low-dose aspirin during the 24-hour dosing interval. One-hundred T2DM patients on chronic therapy with aspirin 100 mg daily were studied. Serum TXB2, an index of platelet COX-1 activity, was measured every 3 hours, between 12 and 24 hours after a witnessed aspirin administration, to characterize the kinetics of platelet COX-1 recovery (phase 1). Thirty-three patients with the steepest COX-1 recovery slopes were randomized to receive aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily for 28 days (phase 2). On day 29, COX-1 recovery was reassessed over the 12 to 24 hour dosing interval. COX-1 activity displayed linear kinetics with l...
Abstract 2061: High Velocity Penetrating Thoracic Trauma with Suspected Cardiac Involvement in Combat During Operation Iraqi Freedom
Authors: Francisco Dominguez, Alec C Beekley, Linda L Huffer, Philip J Gentlesk, Robert E Eckart
Journal: Circulation (2008)

Introduction: The most common cardiac injuries in the U.S. are either blunt trauma from motor vehicle accidents, or low-velocity injuries from stabbings. High-velocity injury is less common, and survival to presentation is rare. During military conflict, high-velocity injury, including gunshot wounds (GSW) and fragment injury from improvised explosive devices (IED) are relatively more common. Methods: Retrospective review of cases with high-velocity penetrating injury and suspected myocardial involvement. We sought to describe the role of varying diagnostic modalities during a 6 month period in Baghdad, Iraq at a U.S. Army hospital during Operation Iraqi Freedom. Results: There were 11 cases who survived to admission (GSW in 5, IED in 6). The mean age of the all male cohort was 27 years (range 3 to 54). Eight of the eleven patients (73%) were victims of polytrauma. The entrance involved the right ventricle (n=3), right atrium (n=2), left ventricle (n=1) or mediastinum and pericardial reflections (n=5). Echocardiography was performed in all eleven patients. All patients had preserved or hyperdynamic myocardial contractility. In seven patients, no foreign body was identifiable, in two patients the foreign body was identified as being within the pericardial fat pad. Three patients were identified as having a suspected ventricular septal defect, ranging in size from 2 to 8 mm. The most common ECG abnormality was conduction delay, both atrioventricular block and right bundle branch block. Plain film radiography and CT scanning were routinely performed, but definitive localization was frequently limited by metallic streak artifact. In four patients, the management of the chest injury was non-surgical, and in one patient the treatment was a chest tube only. Four of the patients underwent median sternotomy, one underwent emergent lateral thoracotomy, and one underwent an infra-diaphragmatic approach. Conclusions: While this case series is too small to draw definitive conclusions, it does demonstrate that a multidisciplinary approach to high-velocity injuries with potential for cardiac involvement augments pre-operative assessment for myocardial injury and may allow selective non-operative management.
Insights Into Echo-Attenuated Plaques, Echolucent Plaques, and Plaques With Spotty Calcification
Authors: Jun Pu, Gary S. Mintz, Sinan Biro, Jin-Bae Lee, Stephen T. Sum, Sean P. Madden, Allen P. Burke, Pei Zhang, Ben He, James A. Goldstein, Gregg W. Stone, James E. Muller, Renu Virmani, Akiko Maehara
Journal: Journal of the American College of Cardiology (2014)
Abstract 1611: Remote Ischemic Preconditioning Improves 6-month Outcome after Elective Percutaneous Coronary Intervention: A Single-Center Randomized Controlled Trial
Authors: Stephen Hoole, Patrick Heck, Sadia Khan, Linda Sharples, Michael O’Sullivan, David Dutka
Journal: Circulation (2008)

Endogenous “early” protection by remote ischemic preconditioning (rIPC) attenuates infarct size in animals but improvement in infarct size and clinical outcome in humans undergoing percutaneous coronary intervention (PCI) has not been documented. We hypothesized that rIPC would attenuate procedure-related cardiac troponin (cTnI) release during elective PCI and improve clinical outcome at 6-months. We randomized 242 patients undergoing elective PCI to either rIPC (n = 125): three 5-minute blood pressure cuff inflations to 200mmHg around the upper arm with 5-minutes of cuff deflation between, or control (n = 117): a deflated cuff throughout, before PCI. Patients taking nicorandil or glibenclamide and those with raised cTnI at baseline were excluded. Interventional cardiologists were blinded to the pretreatment protocol. Post-PCI serum cTnI level at 24-hours was recorded and major adverse cardiac and cerebral event (MACCE) rate determined at 6-months. The two groups were matched demographically. Interval between rIPC and first coronary balloon inflation was 66 ± 30 minutes. Median 24-hour cTnI was significantly lower in the rIPC group (0.06ng/mL vs. 0.16ng/mL, p=0.04). Subjects in the rIPC group experienced less chest pain (p=0.0006) and ST-segment deviation (p=0.005) during PCI than control subjects. MACCE free survival at 6-months was significantly higher in the rIPC group (Figure ), predominantly due to less acute coronary syndromes in the rIPC group (Hazard Ratio (95%CI): 0.28 (0.12– 0.82)). rIPC attenuates procedure-related cTnI release after elective PCI, and reduces 6-month MACCE rate.
Abstract 3276: Assessment of Predictive Accuracy of Centers for Medicare and Medicaid Services’ Method to Risk Adjust Patients for Interhospital Comparison of 30-day Mortality Rates
Authors: Todd M Koelling, Sara Saberi, Anthony C DeFranco, Stephen Skorcz, Cecelia K Montoye, Cameron Shultz, Kirk D Smith, Andrew Fotenakes, Pete A Levine, Keith D Aaronson
Journal: Circulation (2007)

Introduction : The Centers for Medicare and Medicaid Services (CMS) will initiate public reporting of 30 day death rates for hospitals caring for patients with heart failure (HF). While hospital specific rates will be adjusted for medical comorbidities, it is not known if this method is adequate to allow direct hospital comparisons. Hypothesis : More accurate risk adjustment of patients can be accomplished by including variables that have previously been described to be predictors of mortality in HF. Methods : We assessed the CMS HF risk adjustment model in a population of 3639 patients studied in the Guidelines Applied in Practice (GAP) - HF study. Probabilties for 30 day mortality were calculated for the CMS model. Multivariable logistic regression analysis was then performed with other models including variables (no mVO 2 ) from the Heart Failure Survival Score (HFSS), ADHERE Registry model (ARM), body mass index categories (BMI), pre-admission origin of patient (PAO), and admission in the previous 6 months (AP6). Probabilities of mortality were tabulated. Backward selection was then used to derive the best model from all candidate variables from a derivation data subset, followed by testing of the model on a validation data subset. Area under the curve (AUC) was then compared for each model. Results : The AUCs and 95% CI are shown in the table below. Calculated AUCs for the CMS model and separate models were similar. The best model was defined by the following variables: admission in the previous 6 months, BUN &gt; 43, systolic blood pressure &gt; 115, 35 ≤ BMI &lt; 40, BMI ≥ 40, mean arterial pressure, serum sodium, and PAO as well as the CMS model variables. The AUCs for the derivation and validation sets were both significantly greater than that provided by the CMS model alone. Conclusions : Risk adjustment for the purpose of interhospital comparison of 30-day mortality rates is best performed with models that include clinical admission variables in addition to the medical comorbidites. Comparison of AUCs for 30 day mortality prediction
Abstract 5663: Intracardiac Echocardiography From Within the Left Atrium Improves the Accuracy of Image Integration During Catheter Ablation of Atrial Fibrillation
Authors: Sheldon M Singh, E. Kevin Heist, David M Donaldson, Theofanie Mela, Jeremy N Ruskin, Moussa C Mansour
Journal: Circulation (2008)

Background: Intracardiac echocardiography (ICE) can be integrated with pre-procedural CT or MR imaging to direct catheter ablation of atrial fibrillation (AF). Prior work has described ICE imaging of the left atrium (LA) with the ICE probe in the RA, but it is feasible to image the LA from an ICE probe placed directly into the LA via a trans-septal puncture performed for the mapping/ablation procedure. The purpose of this study was to determine whether direct LA imaging with ICE results in improved image integration during AF ablation compared with LA imaging indirectly from the RA. Methods: Twenty-five consecutive patients undergoing an AF ablation procedure with the CARTO-Sound system were studied. A 10 French phased array catheter with an embedded CARTO navigation sensor was employed to provide 2D echocardiogram images of the LA - 13 patients underwent imaging from the RA alone and 12 patients from the LA. The accuracy of the image integration was assessed by the average integration error after surface registration and the requirement to take supplementary electroanatomic mapping points to obtain acceptable image integration. Results: Twenty-five patients (56% paroxysmal AF, average LA size = 42±8 mm, average EF = 63±10 %) were examined. There was no difference in the time or number of ultrasound contours required to create a LA anatomic map with ICE imaging from the RA versus the LA (24±17min vs. 24±25min, P=1.0, 24±16 contours vs. 29±18 contours, P=0.5). The average integration error for all patients was 2.19±0.59mm. Direct LA imaging was associated with improved integration error compared to indirect LA imaging from the RA (1.85±0.33mm versus 2.51±0.62mm, P=0.004). Image integration using RA acquired LA images had a tendency to be less accurate resulting in the primary operator acquiring additional registration points to supplement the registration process (patients requiring additional registration points for registration: 3/12 for LA imaging versus 9/13 for RA imaging of the LA, P=0.05). Conclusion: Direct ICE imaging from within the LA is feasible and associated with improved accuracy of image integration during AF ablation.
Improved Igh-Based MRD Detection By Using Droplet Digital PCR: a Comparison With Real Time Quantitative PCR In MCL and MM
Authors: Daniela Drandi, Lenka Kubiczkovà, Nadia Dani, Simone Ferrero, Luigia Monitillo, Barbara Mantoan, Elisa Genuardi, Daniela Barbero, Manuela Gambella, Davide Barberio, Paola Ghione, Guglielmo Guarona, Elona Saraci, Paola Omedè, Roberto Passera, Roman Hajek, Sergio Cortelazzo, Antonio Palumbo, Mario Boccadoro, Giorgio Inghirami, Marco Ladetto
Journal: Blood (2013)
Treatment of patients with ibandronate and correlation with serum carboxy-terminal telopeptide of type I collagen levels
Authors: A. Galanopoulos, P. Arseni, E. Michalis, T. Marinakis, G. Gortzolidis, A. Zomas, M. Tsipra, M. Ragousi, N. I. Anagnostopoulos
Journal: Journal of Clinical Oncology (2004)

6734 Background: Ibandronate (IB) is found to reduce, significantly, the occurrence of osteolytic bone lesions in a murine model of myeloma bone disease. The carboxy-terminal telopeptide of type I collagen (ICTP) is a serum marker of bone metastasis in patients (pts) with solid tumors and can be used as a serum marker of bone metabolism in multiple myeloma (MM). Methods: Sixteen MM pts with osteolytic lesions, 6 M and 10 F, with a median age of 72 years (range 47–86 ) were treated with IB at a dose of 4 mg, administrated by IV infusion over 1 hour, every 4 weeks for at least 12 months. Pts were clinically evaluated before, during and after IB administration for possible occurrence of side effects. Routine serum chemical screening including beta-2 microglobulin (β2-m), calcium and alkaline phosphate and radiographic evaluation of osteolytic lesions were performed during the study. Serum samples were taken before each IB administration and stored frozen until used for measurement of ICTP levels with b-CrossLaps/serum immunoassay. Results: Clinical improvement of skeletal pains was observed after the first cycle of IB treatment. There were no major side effects after IB administration. Haematologic, hepatic or renal dysfunction were not detected except for transient hypocalcaemia and hypophosphataemia in 5 pts (31%). High mean serum ICTP levels were documented only in 3/16 pts ( 1,513 ± 0,31 ng/ml ) while the remainder of pts had levels within normal limits ( 0,392 ± 0,31 ng/ml). High serum ICTP levels were correlated with progressive osteolytic bone disease and elevated serum levels of β2-m, hypercalcaemia, bad performance status and stage of disease. Treatment with IB, in these fore mentioned 3 pts, resulted in reducing the high ICTP levels in normal limits even after the first cycle of treatment (pre: 1,513 ± 0,31 ng/ml, post: 0,881 ± 0,38 ng/ml ). If the decrease of serum ICTP levels caused by IB treatment is confirmed, in future trials, with a greater number of pts, serum ICTP levels can be used as a prognostic index in MM. Conclusions: Treatment of MM pts with osteolytic lesions with ΙΒ is well tolerated and probably may decrease serum ICTP levels. No significant financial relationships to disclose.
Two memorable patients: Teaching myself lessons
Authors: D W Sarll
Journal: BMJ (2002)

In the 1950s we scaled and cleaned teeth mainly by hand—ultrasonic scalers and efficient aspirators of particulate matter and spray had yet to appear. We dislodged calculus and plaque from tooth surfaces manually and completed cleaning with paste, rotating brushes, and rubber cups. Operators sometimes impelled this bacteria-laden mixture into their own eyes, and after one such event my right eye became inflamed; it led to lesson one.

Salt eyebaths did not help, and, although a dentist who treats himself has a fool for a patient, I prescribed more radical care for myself. Thus, when everyone had gone home, I locked the doors in case the cleaners came early, drew the curtains, and injected penicillin into my left quadriceps. Repeating the process on following days cured the …
Abstract 3560: Obstructive Sleep Apnea Exacerbates Endothelial Dysfunction In Patients With Metabolic Syndrome
Authors: Masahiro Akishita, Yumiko Ohike, Masayoshi Hashimoto, Katsuya Iijima, Masato Eto, Shinji Teramoto, Yasuyoshi Ouchi
Journal: Circulation (2007)

Background: Both obstructive sleep apnea (OSA) and metabolic syndrome (MS) are well known as the risk factor of cardiovascular diseases, and are prevalent among obese patients. However, whether OSA deteriorates endothelial dysfunction in MS patients has not been determined. We therefore examined flow-mediated vasodilation (FMD) in MS patients with or without OSA. Methods: We enrolled 49 overweight patients (body mass index ≥25, aged 35–69 years) and categorized into the 3 groups; patients with MS but not OSA (MS group, n=21), Group 2: patients with both MS and OSA (MS+OSA group, n=14), Group 3: patients with no risk factors but overweight (control group, n=14). MS was defined using the IDF criteria and OSA using polysomnography. FMD was measured using ultrasound as the percent change of the brachial artery diameter. Results: Compared with the control group, MS group showed significantly lower %FMD (6.8±2.4 [mean±SD] vs 5.0±2.7, p&lt;0.001) and HDL cholesterol, and higher triglycerides and hemoglobin A1c. Although there were no significant differences in classical risk factors between MS group and MS+OSA group, %FMD was significantly lower in MS+OSA group than in MS group (3.0±1.3 vs 5.0±2.7, p&lt;0.001). On multiple regression analysis, OSA was significantly related to %FMD, independent of age, body mass index, blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, fasting plasma glucose, and smoking (β=−0.328, p=0.02). Conclusion: OSA exacerbates endothelial dysfunction in patients with MS, possibly leading to the increased risk of cardiovascular disease.
Abstract 91: Influence of Early Return of Spontaneous Circulation and Early Induction of Cooling on Neurological Outcome in Patients Treated with Therapeutic Hypothermia After Out-of-Hospital Shockable Cardiac Arrest
Authors: Taketomo Soga, Ken Nagao, Hiroyuki Yokoyama, Naohiro Yonemoto, Hiroshi Nonogi
Journal: Circulation (2011)

BACKGROUND Therapeutic hypothermia is a helpful therapeutic approach in patients who remain comatose after return of spontaneous circulation (ROSC). However, optimal time window for therapeutic hypothermia have not been known. We hypothesized that early achievement of ROSC and early induction of therapeutic hypothermia would be associated with favorable outcome. METHODS The J-PULSE-Hypo was conducted a multi-center registry to investigate the effects of therapeutic hypothermia. In this study, we investigated the relationship between neurological outcome at hospital discharge and time intervals from collapse to ROSC and from ROSC to induction of cooling. We constructed a receiver-operating-characteristics (ROC) curve to illustrate the various cutoff values of those time intervals. RESULTS Of the 452 unconscious patients who were treated with hypothermia after out-of-hospital cardiac arrest due to cardiac etiology, 301 who were cooled from 32°C to 34 °C after witnessed shockable cardiac arrest were included. The cutoff value for identification of favorable outcome was 28.5 minutes in the collapse-to-ROSC interval and 48.0 minutes in the ROSC-to-cooling interval. Significant difference was seen in favorable outcome among the 4 groups of patients who were classified according to those cutoff values (81% in group 1 of collapse-to-ROSC interval≤28 minutes and ROSC-to-cooling≤48 minutes, 78% in group 2 of collapse-to-ROSC interval≤28 minutes and ROSC-to-cooling&gt;48 minutes, 46% in group 3 of collapse-to-ROSC interval&gt;28 minutes and ROSC-to-cooling≤48 minutes, and 36% in group 4 of collapse-to-ROSC interval&gt;28 minutes and ROSC-to-cooling&gt;48 minutes, p&lt;0.0001). In a logistic-regression model in which we adjusted for other independent predictors, those 4 groups remained associated with neurological outcome. The adjusted odds ratio for favorable outcome among those 4 groups was 10.8 (95%CI, 4.5-18.5) in groups 1, 8.5 (95%CI, 3.6-20.1) in group 2 and 2.0 (95%CI, 0.85-4.6) in group 3. CONCLUSION Early achievement of ROSC was associated with favorable outcome, but early induction of cooling did not influence on neurological outcome in unconscious patients treated with therapeutic hypothermia after out-of-hospital shockable cardiac arrest.