tbuckley/cabot-search huggingface dataset:
P09.48 Residual contrast enhancement and residual 5-ALA fluorescence are independent negative surgical prognostic factors in GBM
Authors: W. Sage, M. Guilfoyle
Journal: Neuro-Oncology (2017)

BACKGROUND: Intraoperative 5-ALA fluorescence-guided resection and local chemotherapy using carmustine wafers (Gliadel) are recent advances in the surgical management of glioblastoma (GBM) that have been independently shown to improve survival in clinical trials. The benefit of carmustine wafers has not been examined in combination with 5-ALA guided resection followed by a temozolomide-based chemotherapy protocol. Materials and Methods: Single centre retrospective cohort study of 260 patients who underwent 5-ALA resection of confirmed WHO Grade IV glioma between July 2009 and December 2014. Propensity score matched analysis was used to compare survival between groups whilst controlling for baseline characteristics. A cox proportional hazards regression was performed to identify variable predicting survival. Results: Carmustine wafers showed no significant survival benefit over 5-ALA resection alone on propensity-matched analysis (median survival 14.2 vs 12.9 months; HR 0.97 [0.68-1.26], p=0.836). There was a trend towards higher incidence of wound infection requiring revision surgery in those who received carmustine. Cox regression analysis indicated that residual enhancement (HR 1.66 [1.25-2.22], p <0.001) and residual fluorescence (HR 1.57 [1.17-2.10], p = 0.003) were independently associated with reduced survival. In a substantial proportion (40.1%) of patients the intraoperative and post-operative assessment of residual disease differed. Conclusions: Carmustine wafers do not appear to offer additional survival benefit over 5-ALA fluorescence guided resection of GBM. Both residual 5-ALA fluorescence and residual contrast enhancing tumour on post-operative MRI are independent negative prognostic factors following resection of GBM. Residual enhancement should be considered when stratifying GBM patients for drug trials.
Occupational Fatalities Resulting from Falls in the Oil and Gas Extraction Industry, United States, 2005–2014
Authors: Krystal L. Mason, Kyla D. Retzer, Ryan Hill, Jennifer M. Lincoln
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

During 2003-2013, fatality rates for oil and gas extraction workers decreased for all causes of death except those associated with fall events, which increased 2% annually during 2003-2013 (1). To better understand risk factors for these events, CDC examined fatal fall events in the oil and gas extraction industry during 2005-2014 using data from case investigations conducted by the Occupational Safety and Health Administration (OSHA). Sixty-three fatal falls were identified, accounting for 15% of all fatal events. Among fatal falls, 33 (52%) workers fell from a height of >30 feet (9 meters), and 22 (35%) fell from the derrick board, the elevated work platform located in the derrick (structure used to support machinery on a drilling rig). Fall fatalities occurred most frequently when drilling rigs were being assembled or disassembled at the well site (rigging up or rigging down) (14; 22%) or when workers were removing or inserting drill pipe into the wellbore (14; 22%). Measures that target derrickmen and workers engaged in assembling and disassembling drilling rigs (rigging up and down) could reduce falls in this industry. Companies should annually update their fall protection plans and ensure effective fall prevention programs are in place for workers at highest risk for falls, including providing trainings on proper use, fit, and inspection of personal protective equipment.
Recent Advances in Endocrinology.
Journal: Annals of Internal Medicine (1934)

This splendid little book contains more than merely the recent advances in endocrinology. It is really a small textbook. The subject is treated in a scholarly way and is supplemented with an extensive bibliography, photographs and charts. One is surprised to find how much important material has been compressed into a brief space. The book should be equally useful to the physiologist and to the clinician.
Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome
Authors: John Bian, Brian Chen, Dawn L. Hershman, Norman Marks, LeAnn Norris, Richard Schulz, Charles L. Bennett
Journal: Journal of Clinical Oncology (2017)

Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction ( P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.
P04.03 Extent of surgery improves the overall survival independently of imaging characteristics in newly diagnosed glioblastoma
Authors: J. Capellades, J. Puig, S. Domenech, R. Diaz, L. Oleaga, T. Pujol, A. Camins, C. Majos, C. de Quintana, C. Balana
Journal: Neuro-Oncology (2017)

Introduction: In glioblastoma, the extent of surgery affects neurological condition, survival, and the efficacy of postsurgical systemic treatment. We analyzed the impact of surgical extent on overall survival in function of baseline tumor radiological characteristics (size, eloquence of adjacent brain, and location) and known prognostic factors. Material and Methods: Patients received standard radiotherapy and concomitant/adjuvant temozolomide (GLIOCAT Study). We used an MRI-based topographical glioblastoma staging system (stages I, II, and III) integrating tumor location (A, B, C), size (≤5 cm or >5cm), and eloquence of adjacent brain. Evaluations were accepted when kappa was near 1; only evaluations of T1Gd sequences are reported. Surgery was classified as complete resection (CR=disease-free postoperative MRI), partial resection (PR), or biopsy (B). Age, Karnofsky performance score (KPS), Mini-Mental State (MMS), isocitrate dehydrogenase mutations (mIDH), and O6-methylguanine-DNA methyltransferase promoter methylation (methMGMT) were recorded. Results: In 280 patients, Location: A = 133 (47.5%) // B = 110 (39.3%) // C = 37 (13.2%); Eloquence: NO=196 (70%)//YES= 84(30%); size: ≤5cm: 150(54.5%) // > 5cm: 125(45.5%); Stage: I: 100(43.9%)//II: (22.8%)//III: 76(33.3%). Clinical factors KPS (<70, ≥70), age (<50, ≥50), MMS (<27, ≥27), mIDH, and methMGMT were uniformly distributed across stages. Surgical type: CR 16%//PR 65.7%//B 14.6%. CR was more frequent in stage I (80%) and biopsy in stage III (46.3%) (p=0.000). Univariate analyses found type of surgery (p=0.000), KPS ≥70 (p=0.02), methMGMT (P=0.01), mIDH (P=0.03), stage I vs II vs III (P=0.000), location A vs B vs C (P=0.000), and size (P=0.005) but not brain eloquence (P=0.39) were associated with longer overall survival. In multivariate analyses, methMGMT, KPS≥70% and resection (CR or PR) were independent prognostic factors, and eloquence, size, and location lost their prognostic value. Conclusions: In glioblastoma, PR or CR improves overall survival independently of size, eloquence, or tumor location. Overall survival is best in patients with good KPS and methMGMT. The present study is supported by a Grant of the Fundació TV3 (Project: 665/C/2013). The radiological platform is supported by a citizens initiative: Associació Mongat en Acció.
P16.10 An Unusual cyst wall enhancement in a patient with cerebellar hemangioblastoma
Authors: J. Hwang, K. Park
Journal: Neuro-Oncology (2017)

OBJECT: Hemangioblastomas(HGBLs) are the most common primary brain tumors of adult posterior fossa. Solid mural nodule associated with peritumoral cyst is the common radiological finding in HGBLs of cerebellar hemisphere. The cyst wall usually reveals no enhancement with paramagnetic contrast media and regarded as reactive gliosis devoid of tumor cells. Surgical excision of nodule and drainage of cyst could achieve good long-term outcome. A nodule with enhanced peritumoral cyst wall after contrast injection is extremely rare and can be source of misdiagnosis and recurrence. METHODS: The authors present an unusual case of hemangioblastoma showing radiographic cyst wall enhancement in cerebellar hemisphere.A 25-year-old man without evidence of von Hippel-Lindau disease presented with a cerebellar hemispheric lesion. Neurological examination showed mild headache and dizziness. Magnetic resonance (MR) imaging showed a large cystic lesion with an enhancing mural nodule and atypical strong linear enhancement throughout the whole cyst wall. Results: At surgery, vascular reddish tumor nodule was found at inferolateral corner of the cyst. The entire peritumoral cyst wall was thickened by highly vascular, friable red tissue showing copious bleeding. A tiny portion of cyst wall remained on postoperative MR imaging. Gamma-Knife radiosurgery was performed for small remnant, 6 months after surgery. Regular MR imaging follow-up revealed tumor regrowth at 5 years after radiosurgery.Conclusions: HGBLs with peritumoral enhanced cyst wall is exceedingly rare and could be considered as tumor cells within the cyst wall. Additionally, enhanced thick cyst wall causes not only surgical difficulty with abundant bleeding, but also tumor recurrences by preventing complete excision of cyst wall.
Abstract 20427: Activation of Large Conductance Ca++ Activated K+ Channels (BK) During Ischemic Cardioplegic Arrest (CP) Promotes Formation of Mitochondrial Supercomplexes and Enhanced Mitochondrial Respiration
Authors: Brenda Cordeiro, Richard T Clements
Journal: Circulation (2014)

Introduction:  Activation of mitochondrial BK channels is cardioprotective in response to ischemic insults. Activation of BK channels enhances cardiac function and reduces ROS generation in cell and rodent models of ischemic cardioplegic arrest. Recent advances demonstrate that components of the mitochondrial electron transport chain can organize into respiratory supercomplexes yielding more efficient respiration and reduced ROS generation.   Hypothesis:  BK channel activation during ischemic CP may enhance cardioprotection through mitochondrial supercomplex formation and respiration.   Methods:  H9c2 cells were subjected to in vitro CP (3 hrs) under hypoxic, hypothermic (20C), conditions with or without the BK channel activators rottlerin (500 nM) or NS11021 (100 nM), followed by 30 minute reoxygenation. Cell respiration was measured using a Seahorse XFe analyzer and mitochondria were isolated to assess supercomplex formation using Blue-Native electrophoresis (BN-PAGE). Complexes were identified via mass spectrometry.   Results:  Treatment with rottlerin caused a robust increase (>2 fold) in large mitochondrial supercomplexes (~1.2 mD) in both control and CP cells (n=3, p   Conclusions:  Activation of BK channels during ischemic insults promotes enhanced mitochondrial respiration which associates with enhanced mitochondrial supercomplex formation. To our knowledge this is the first report of therapeutically enhanced formation of respiratory supercomplexes following ischemic insults.
POLO: A randomized phase III trial of olaparib tablets in patients with metastatic pancreatic cancer (mPC) and a germline <i>BRCA1/2</i>mutation (g<i>BRCA</i>m) who have not progressed following first-line chemotherapy.
Authors: Hedy Lee Kindler, Gershon Y. Locker, Helen Mann, Talia Golan
Journal: Journal of Clinical Oncology (2015)

TPS4149 Background: Germline mutations in BRCA1/2 define a molecular subgroup of PC that in some populations has a prevalence as high as 15%. gBRCAm-defective tumors are intrinsically sensitive to platinum and PARP inhibitors. In a Phase II trial (NCT01078662), 23 previously-treated gBRCAm mPC patients received the PARP inhibitor olaparib (Lynparza) as monotherapy. The tumor response rate was 22%, progression-free survival (PFS) was 4.6 months and overall survival (OS) was 9.8 months (Kaufman, JCO 2014). These data led to a double-blind, placebo-controlled Phase III trial (NCT02184195; POLO) of olaparib 'switch maintenance' monotherapy in patients with gBRCAm-associated mPC who have not progressed on first-line platinum chemotherapy. Methods: Eligible mPC patients must have documented disease control after completing at least 16 weeks of a first-line platinum-based regimen and must have a known or suspected deleterious gBRCAm, which will be confirmed by Integrated BRACAnalysis (Myriad Genetic Laboratories) during the trial. Patients are randomized (3:2) to olaparib (300 mg orally bid) or placebo. The primary endpoint is PFS, determined by blinded independent central review using RECIST 1.1. Disease will be assessed by CT scans at baseline, every 8 weeks for 40 weeks and every 12 weeks thereafter. Patients will receive treatment until objective disease progression unless toxicity is unacceptable. The primary PFS analysis will be performed after ~89 PFS events (~60% maturity) using a log-rank test. Secondary endpoints include OS, time from randomization to second progression (PFS2), HRQoL, safety and tolerability. Enrollment began in Q4 2014. The target number for randomization is ~145 patients across ~80 centers worldwide. Clinical trial information: NCT02184195.
Abstract P232: Cardiac Excitation Contraction Coupling Stimulates Mitochondrial Respiration and Superoxide Flash Activity
Authors: Wang Wang, Xiaoyun Liu, Guohua Gong
Journal: Circulation Research (2011)

Normal cardiac excitation-contraction (EC) coupling relies on highly coordinated intracellular calcium (Ca2+) handling and adequate mitochondrial energy metabolism. Whether mitochondria can sense the oscillating Ca2+ signals during EC coupling to adjust its respiration status and other functions is largely unknown. Recently, we discovered stochastic and transient mitochondrial superoxide production events, named superoxide flashes, in resting cardiac myocytes. Superoxide flashes are coupled with mitochondrial respiration and triggered by physiological relevant transient permeability transition pore (mPTP) openings. Using superoxide flash as the optical determination of mitochondrial respiration status in living myocytes, we found that EC coupling promotes mitochondrial respiration and reactive oxygen species (ROS) production as evidenced by the significantly increased superoxide flash activity by electrical stimulation (pacing frequency 0.5 - 2 Hz). Pre-incubation with Ru360 (50-100 uM), a mitochondrial Ca2+ uniporter inhibitor, or cyclosporine A (1 uM), an mPTP blocker, prevented this increase. Simultaneous monitoring of mitochondrial Ca2+ (by rhod-2) and superoxide (by mt-cpYFP, a mitochondrial targeted superoxide indicator) revealed step-wise accumulation of mitochondrial Ca2+ during cytosolic Ca2+ transients in individual mitochondria, which is followed by superoxide flash production and matrix Ca2+ release. Importantly, mitochondrial respiration only responds to transient Ca2+ signals (acute addition of ionophore or pacing) but not chronic manipulations of steady state Ca2+ (depleting or elevating resting cytosolic Ca2+). Through spatiotemporal mapping of superoxide flash and local sarcoplasmic reticulum (SR) Ca2+ releasing events, Ca2+ sparks, we found that significant amount of Ca2+ sparks clustered near the flashing mitochondria. Antioxidant pretreatment attenuated the superoxide flash associated Ca2+ sparks. In summary, mitochondrial Ca2+ uptake during cardiac EC coupling leads to stochastic acceleration of mitochondrial respiration, mPTP activity and free radical production, which in turn modulate local Ca2+ signaling through promoting SR Ca2+ release.
P18.08 Does functional disorder after awake surgery reduce quality of life in patients with glioma?
Authors: R. Nakajima, M. KInoshita, H. Okita, T. Yahata, Y. Hayashi, M. Nakada
Journal: Neuro-Oncology (2017)

Introduction: Goals of awake surgery are maximum resection and prevention of postoperative functional deficits to maintain patients’ quality of life (QOL). Recent studies revealed that some factors influence on QOL, including overall survival, post-operative treatment, and social communication. Since whether functional disorders actually induce reduction of QOL is not known, we investigated the influence of functional disorders on QOL after awake surgery. METHODS: Patients with glioma (n=28) who underwent awake surgery participated in this study. Patients background were: age, 44.8 +/- 11.6 years; focus of tumor, left 13, right 15; post-operative treatment, 18 (64%); and return to work, 17 (61%). At 6 months after surgery health-related QOL was assessed using SF-36, which consists of 36 items of self-reported questionnaire. Using total scores we could calculate 3 summary scores of physical (PCS), mental (MCS), and role and social (RCS) components. Motor function and following neuropsychological function were also assessed, which included language, fluency, attention, inhibition, working memory, emotion, social cognition, and visuospatial cognition. To examine the relationship between SF-36 and background factors, and motor and neuropsychological function, multiple linear regression analysis with stepwise method was used. Results: As for the component summary scores, only RCS was significantly lower than standard score of healthy Japanese (p < 0.0001). Using multiple linear regression analysis, factors of return to work and age caused reduction of PCS (adjusted R2 = 0.34, p=0.0012). Moreover, we found positive correlation between PCS and the scores of attention, inhibition, emotion, social cognition, and motor function (adjusted R2 = 0.66, p < 0.0001). Notably, the score of emotion had negative effect on PCS (β= -0.66, p = 0.0011). DISCUSSION: Since awake surgery could preserve basic function required for daily life, high-level motor and cognitive function, which are essential for social life, affected QOL. Emotional function, however, had negative effect on QOL maybe due to its association with social and/or cultural background. Considering optimal onco-functional balance, preserving functions related to QOL may be required during awake surgery. CONCLUSION: In patients with glioma who underwent awake surgery, factors related to social life such as motor function, attention, inhibition, social cognition and emotion affected postoperative QOL.
Epidemic Tracking Tool Wins Open Science Prize
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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Corrigendum re: “Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group” [Eur Urol 2017;71:723–6]
Authors: Justin W. Collins, Abolfazl Hosseini, Christofer Adding, Tommy Nyberg, Anthony Koupparis, Edward Rowe, Matthew Perry, Rami Issa, Martin C. Schumacher, Carl Wijburg, Abdullah E. Canda, Mevlana Balbay, Karel Decaestecker, Christian Schwentner, Arnulf Stenzl, Sebastian Edeling, Saša Pokupić, Fredrik D’Hondt, Alexander Mottrie, Peter N. Wiklund
Journal: European Urology (2017)
P15.04 Treatment results of combination chemotherapy with high-dose methotrexate and procarbazine for primary CNS lymphoma: A single institution experience
Authors: K. Makino, H. Nakamura
Journal: Neuro-Oncology (2017)

BACKGROUND: This retrospective single-center study assessed the feasibility, outcomes, and side effects of high-dose methotrexate (HD-MTX) plus procarbazine in the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL). METHODS: One-hundred twelve patients diagnosed with PCNSL between January 2001 and December 2014 were treated with HD-MTX (3.5 g/m2) plus procarbazine (60 mg/m2) To reduce neurotoxicity in patients aged ≥ 60 years, only those not responding to chemotherapy and patients with relapse underwent whole-brain irradiation. RESULTS: All 112 consecutive patients were scheduled to receive HD-MTX. Their median age was 67 years (range, 32-88 years) and their median Karnofsky performance score was 40 (range, 20-100). While 69 patients (61.6%) completed 3 cycles of HD-MTX chemotherapy and 60 (53.6%) showed a complete response, treatment was stopped in 14 patients (12.5%) due to toxicity. The median overall survival and progression-free survival were 51.1 and 7.6 months, respectively. Overall survival was significantly improved in patients who completed 3 cycles of chemotherapy compared with those did not (56.6 vs. 29.4 months; p = 0.03 by univariate- and p = 0.037 by multivariate analysis). Conclusions: Initial treatment with HD-MTX plus procarbazine was effective in patients with PCNSL. ­Completion of 3 cycles of HD-MTX chemotherapy was a significant independent prognostic factor for patient survival.