tbuckley/cabot-search huggingface dataset:
The treatment of primary and metastatic renal cell carcinoma (RCC) with stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS)
Authors: B. S. Teh, C. Bloch, A. C. Paulino, L. Doh, S. Chiang, S. Shen, D. Baskin, J. Jac, R. J. Amato
Journal: Journal of Clinical Oncology (2006)

14572 Background: RCC is often regarded as a radio-resistant tumor. However, brain metastases from RCC have been successful treated with SRS. Therefore, metastases to extra-cranial sites may be treated with similar success using stereotactic body radiation therapy (SBRT), where image-guidance allows for the delivery of precise high dose radiation in a few fractions. We report our experience with SRS/SBRT in the management of primary and metastatic RCC. Methods: The image-guided Novalis radiation therapy system was used. Thirty patients with brain metastases were treated with SRS (16–22 Gy in a single fraction). Five of these patients underwent resection of their metastatic lesions after SRS and their pathology were reviewed. Twenty patients with extra-cranial metastatic lesions (orbits, head and neck, lung, mediatinum, sternum, clavicle, scapula, humerus, rib, spine, abdomen) and 2 patients with biopsy proven primary RCC (not surgical candidates), were treated with SBRT (24–32 Gy in 3–4 fractions over 1–2 weeks). All patients were immobilized in body cast and image-guidance was used for all fractions. 4D-CT was utilized in the treatment planning to assess tumor motion. Results: Of the 30 patients who received SRS to brain metastases, 25 showed decreasing or stable lesion size. Five patients showed an increase in size and underwent resection. Their pathology revealed necrosis in &gt;99% of the specimen, with no viable RCC. Nineteen patients who received SBRT to extra-cranial metastases achieved symptom relief. One patient had local progression, yielding a local control rate of 95%. In the 2 patients with primary RCC, tumor size remained unchanged but their pain improved, and their renal function was unchanged post SBRT. There was no significant treatment related side-effect. Conclusions: Precise high dose radiation can cause significant tumor cell death in “radio-resistant” metastases from RCC. It also offers excellent local control and symptom palliation, without significant toxicity. Therefore, SBRT may represent a novel non-invasive, nephron-sparing option for the treatment of primary RCC as well as extra-cranial metastatic RCC. A prospective clinical trial using SBRT for primary and metastatic RCC is on-going. No significant financial relationships to disclose.
Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential surrogate biomarker in patients with <i>isocitrate dehydrogenase</i> mutant (<i>IDH</i>m) intrahepatic cholangiocarcinoma (ICC).
Authors: Lipika Goyal, Darrell R. Borger, Thomas Yau, Ronnie Tung Ping Poon, Marek Ancukiewicz, David C. Christiani, Hannah M. Liebman, Katharine Yen, Kimberly Straley, Samuel V. Agresta, Jason Edward Faris, Eunice Lee Kwak, Jeffrey W. Clark, David P. Ryan, Kenneth Tanabe, Vikram Deshpande, Rakesh K. Jain, Anthony John Iafrate, Dan G. Duda, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2013)

4125 Background: Mutations in the genes encoding for IDH1 and IDH2 occur in ~20% of ICC patients (pts), and they lead to the production of the oncometabolite 2HG. We examined whether serum 2HG levels in IDHm ICC pts may 1) serve as a surrogate biomarker for IDH status, 2) correlate with tumor burden, and 3) correlate with circulating proangiogenic biomarkers. Methods: Blood samples from 33 ICC pts [11 IDHm, 22 IDH wild-type (IDHwt)] of different AJCC stages from MGH and 39 surgically resected ICC patients (7 IDHm, 32 IDHwt) from HKU were analyzed for serum 2HG concentration by reverse-phase liquid chromatography coupled to mass spectrometry. Eight circulating proangiogenic biomarkers were measured in plasma using multiplex ELISA. Results: In the MGH cohort, median serum 2HG levels were significantly elevated in IDHm (478 ng/ml [interquartile range 174–643]) versus IDHwt ICC pts (118ng/ml [68–160])(p&lt;0.001). Similarly, in the HKU cohort, the pre-resection median serum 2HG levels were significantly elevated in IDHm (343ng/ml [192–596]) versus IDHwt ICC pts (56ng/ml [42–81]) (p&lt;0.0001). The area under ROC curve for prediction of an IDH mutation using 2HG was 93%; with a threshold of 2HG≥170ng/ml, the sensitivity was 83% and specificity was 90%. IDH2 mutations were more frequent in the HKU cohort (3/7, 43%) compared with the MGH cohort (0/11, 0%) (p&lt;0.05), but 2HG levels did not differ among the specific IDH1 or IDH2 allelic variants. 2HG levels correlated directly with tumor burden (Spearman’s rho=0.89; p&lt;0.05) in the HKU cohort. Median plasma levels of PlGF—a growth factor from the VEGF-family—were higher in IDHm (35pg/ml [33–40]) versus IDHwt ICC pts (median 26pg/ml [24–34]) from the HKU cohort (p&lt;0.05). No other associations were seen between proangiogenic biomarkers and IDH status. Conclusions: IDHm ICC pts had significantly higher serum 2HG levels compared to IDHwt ICC pts. High serum 2HG correlated with increased tumor burden. Pre-resection circulating PlGF levels were higher in IDHm ICC versus IDHwt pts. These data support further exploration of circulating 2HG as potential surrogate and response biomarker in IDHm ICC.
Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis Patients Undergoing Chronic Dialysis
Authors: Yohei Ohno, Guilherme F. Attizzani, Marco Barbanti, Paola D’Errigo, Claudio Grossi, Remo Daniel Covello, Francesco Onorati, Francesco Santini, Marco Ranucci, Stefano Rosato, Gennaro Santoro, Danilo Fusco, Corrado Tamburino, Fulvia Seccareccia
Journal: Journal of the American College of Cardiology (2015)
Scoring criteria for portable monitor recordings: a comparison of four hypopnoea definitions in a population-based cohort
Authors: Sopharat Vat, Jose Haba-Rubio, Mehdi Tafti, Nadia Tobback, Daniela Andries, Raphael Heinzer
Journal: Thorax (2015)

<h3>Rationale</h3> Limited-channel portable monitors (PMs) are increasingly used as an alternative to polysomnography (PSG) for the diagnosis of obstructive sleep apnoea (OSA). However, recommendations for the scoring of PM recordings are still lacking. Pulse-wave amplitude (PWA) drops, considered as surrogates for EEG arousals, may increase the detection sensitivity for respiratory events in PM recordings. <h3>Objectives</h3> To investigate the performance of four different hypopnoea scoring criteria, using 3% or 4% oxygen desaturation levels, including or not PWA drops as surrogates for EEG arousals, and to determine the impact of measured versus reported sleep time on OSA diagnosis. <h3>Methods</h3> Subjects drawn from a population-based cohort underwent a complete home PSG. The PSG recordings were scored using the 2012 American Academy of Sleep Medicine criteria to determine the apnoea–hypopnoea index (AHI). Recordings were then rescored using only parameters available on type 3 PM devices according to different hypopnoea criteria and patients-reported sleep duration to determine the 'portable monitor AHIs' (PM-AHIs). <h3>Main results</h3> 312 subjects were included. Overall, PM-AHIs showed a good concordance with the PSG-based AHI although it tended to slightly underestimate it. The PM-AHI using 3% desaturation without PWA drops showed the best diagnostic accuracy for AHI thresholds of ≥5/h and ≥15/h (correctly classifying 94.55% and 93.27% of subjects, respectively, vs 80.13% and 87.50% with PWA drops). There was a significant but modest correlation between PWA drops and EEG arousals (r=0.20, p=0.0004). <h3>Conclusion</h3> Interpretation of PM recordings using hypopnoea criteria which include 3% desaturation without PWA drops as EEG arousal surrogate showed the best diagnosis accuracy compared with full PSG.
Pleurodesis for malignant pleural effusions: A comparison of bleomycin or tranexamic acid alone versus a combination of both
Authors: Essam Mohamed, Elsayed Ali, Hamdy Mahmoud
Journal: European Respiratory Journal (2013)

BACKGROUND and OBJECTIVE:

Searching for the ideal pleurodesis agent still continues, Bleomycin is one of the most commonly used agents for pleurodesis. Tranexamic acid have been reported as a cheap pleurodesis agent by many authors. In this study, we evaluate the efficacy, safety and cost of using a combination of bleomycin and Tranexamic acid versus each agent alone.

METHODS:

Sixty three patients with massive malignant pleural effusions were divided in 3 equal groups in a simple randomized manner. Tranexamic acid (30 mg/kg [maximum of 2 g] in 50 mL of normal saline) was administered through a chest tube in Group 1. Group 2 received bleomycin (1 U/kg [maximum of 60 U] in 70 mL of normal saline). Group 3 received the above 2 preparations (tranexamic acid, 30 mg/kg [maximum of 2 g] in 40 mL of normal saline and bleomycin, 1 U/kg [maximum of 60 U] in 50 mL of normal saline) instilled one following the other by 15 minutes. Follow-up CXR examinations were performed at 7 days, 30 days, 60 days and 90 days.

RESULTS:

There was no significant difference in the complete response rate of the 3 groups during the first 60 days days. At the end of the study at 90 days, Group 3 had a significantly higher complete response rate (65 %) compared with Groups 1 and 2 (27 % and 35 %, respectively).The rate of complications was nearly equal in the three groups. The most common complications were chest pain, fever and worsening dyspnea.

CONCLUSIONS:

Using a combination of bleomycin and tranexamic acid for pleurodesis in patients with malignant pleural effusion is more efficient than using each agent alone without significant increase in the cost or complications.
The AMPK-related kinase SNARK regulates muscle mass and myocyte survival
Authors: Sarah J. Lessard, Donato A. Rivas, Kawai So, Ho-Jin Koh, André Lima Queiroz, Michael F. Hirshman, Roger A. Fielding, Laurie J. Goodyear
Journal: Journal of Clinical Investigation (2015)

The maintenance of skeletal muscle mass is critical for sustaining health; however, the mechanisms responsible for muscle loss with aging and chronic diseases, such as diabetes and obesity, are poorly understood. We found that expression of a member of the AMPK-related kinase family, the SNF1-AMPK-related kinase (SNARK, also known as NUAK2), increased with muscle cell differentiation. SNARK expression increased in skeletal muscles from young mice exposed to metabolic stress and in muscles from healthy older human subjects. The regulation of SNARK expression in muscle with differentiation and physiological stress suggests that SNARK may function in the maintenance of muscle mass. Consistent with this hypothesis, decreased endogenous SNARK expression (using siRNA) in cultured muscle cells resulted in increased apoptosis and decreased cell survival under conditions of metabolic stress. Likewise, muscle-specific transgenic animals expressing a SNARK dominant-negative inactive mutant (SDN) had increased myonuclear apoptosis and activation of apoptotic mediators in muscle. Moreover, animals expressing SDN had severe, age-accelerated muscle atrophy and increased adiposity, consistent with sarcopenic obesity. Reduced SNARK activity, in vivo and in vitro, caused downregulation of the Rho kinase signaling pathway, a key mediator of cell survival. These findings reveal a critical role for SNARK in myocyte survival and the maintenance of muscle mass with age.
Sequential changes in platelet function and coagulation in leukemic children treated with L-asparaginase, prednisone, and vincristine.
Authors: C H Pui, C W Jackson, C Chesney, S A Lyles, W P Bowman, M Abromowitch, J V Simone
Journal: Journal of Clinical Oncology (1983)

Coagulation and platelet function in 13 children with acute lymphoblastic leukemia were studied sequentially during a remission induction with L-asparaginase, prednisone, and vincristine. In the first weeks of therapy, which included four doses of L-asparaginase coagulation was characterized by significant decreases in plasma concentrations of plasminogen, antithrombin III alpha 2-macroglobulin, and fibrinogen. All measures gradually returned to normal after complication of L-asparaginase therapy. In the latter part of induction treatment, clotting times, especially partial Thromboplastin time, decreased significantly, while levels of factors V and VIII increased with recovery of platelet counts. At this time, 6 patients had an increased in vitro platelet aggregation response to adenosine diphosphate, and their partial thromboplastin times were significantly shorter than those of patients without increased aggregation. Concurrent abnormalities in coagulation and platelet function may account for the thrombotic complications that develop in some children receiving induction therapy with these agents.
Rituximab, gemcitabine, vinorelbine, and methylprednisone (R-GVM), a hematopoietic cell (HC) mobilizing and salvage regimen for malignant lymphoma (ML)
Authors: A. Rezazadeh, G. Herzig, R. Herzig
Journal: Journal of Clinical Oncology (2007)

17537 Background: The prognosis of pts with recurrent ML remains poor. High-dose therapy (HDT) with HC rescue can cure a proportion of such pts. HC mobilization can be adversely affected by number and duration of prior treatments, interval from diagnosis to HC collection, prior radiotherapy and marrow involvement. There remains a need for more effective and less toxic salvage regimens, capable of mobilizing HCs. Methods: The mobilizing potential of R-GVM salvage regimen with hematopoietic growth factor (HGF) support (G- and GM-CSF) was evaluated in 6 pts with relapsed (n=5) or primary refractory (n=1) ML. Pts received R-GVM salvage therapy [rituximab (375 mg/m 2 , day 1), gemcitabine (1 g/m 2 , day 1, 8), vinorelbine (30 mg/m 2 , day 1, 8) and methylprednisone (1 g/m 2 , day 1, 8)] with HGF administration and subsequent HC collection. The HGF support was started on day 9 and was continued through apheresis which started when the CD34+ cell count ≥ 20/μl (median day of R-GVM cycle: 15, range 14–19). Pts had daily apheresis with continued HGF support until at least 5 x 10 6 CD34+ cells/kg were collected. The hematologic and non-hematologic toxicity were tolerable in all pts; no pt required hospitalization. Results: 6 pts (age range 20–45 years) with Hodgkin (n =3) and non- Hodgkin lymphoma (n =3) were evaluated in this study. Pts had received 1–3 previous treatment regimens. The median number of R-GVM courses given before HC collection was 2.5 (range 1–5). Effective HC mobilization (≥5x10 6 CD34+ cells/kg) was obtained in all ps. A single apheresis resulted in satisfactory HC collection in 4 pts (range 8.2–17.7 x 10 6 CD34+ cells/kg); 2 pts required 3 aphereses to collect an adequate number of cells (6.7 and 7.4 x 10 6 CD34+ cells/kg). One pt was heavily pretreated and had failed two previous attempts of HC mobilization (one with HGF alone and one with cyclophosphamide and HGF); the other pt was HIV+ treated with HAART and had prior marrow involvement. As a salvage regimen, one pt had progressive disease, 1 had stable disease, 1 had a partial response, and 3 had a complete response before proceeding with HDT with HC rescue. Conclusions: R-GVM regimen is feasible, tolerable and effective in mobilizing HPC in patients with relapsed and refractory lymphoma. No significant financial relationships to disclose.
Nestin-expressing vascular wall cells drive development of pulmonary hypertension
Authors: Farhan Saboor, Ansgar N. Reckmann, Claudia U.M. Tomczyk, Dorothea M. Peters, Norbert Weissmann, Andre Kaschtanow, Ralph T. Schermuly, Tatyana V. Michurina, Grigori Enikolopov, Dieter Müller, Andrea Mietens, Ralf Middendorff
Journal: European Respiratory Journal (2015)

Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension. The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs). Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor β and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima. Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension.
Immunomodulatory Maintenance Therapy with Tlr-9 Agonist Mgn1703 in Patients with Metastatic Colorectal Carcinoma–The Randomized Phase 3 Impala Study
Authors: D. Arnold, A. Zurlo, R. Salazar, M.P. Ducreux, T. Waddell, A. Stein, C. Tournigand, W. Scheithauer, A. Sobrero, E. Van Cutsem, D. Cunningham
Journal: Annals of Oncology (2014)
Educating the health workforce in China: a commentary
Authors: John S Ji, Lincoln Chen
Journal: The Lancet (2015)

BackgroundThe health of the Chinese people witnessed spectacular gains in the past half century. Life expectancy improved from 60 years in 1964 to 75 years in 2014. Infant and maternal mortality decreased substantially from 48 per 1000 children born in 1980 to 11 per 1000 children born in 2014, achieving benchmarks beyond those of Millennium Development Goals. The aim of this analysis is to examine three areas in China's development of its health workforce: improvements of the balance in the skill-mix amongst nurses and doctors, modernisation of medical education through reform of instructional content and purpose, and standardisation of post-graduate and continuing clinical education.FindingsChina has the largest production system of health professionals in the world. In 2012, China had 1·3 billion (18%) of 7 billion people in the world, 1·9 million (22%) of about 8·4 million doctors worldwide, and 1·9 million (11%) of 17·7 million nurses worldwide. However, the consequent doctor-nu rse ratio of 1:1 is highly imbalanced. Very rapid expansion of medical school student enrolment without corresponding expansion of faculty and infrastructure has compromised the quality of competence of graduating health professionals. Postgraduate education in China is currently ad hoc, fragmented, and suffering from the absence of quality standardisation. Currently, each institution is able to determine the content, duration, and quality of training of young physicians. There is inconsistency in the quality of physicians and specialists across all medical service institutions and between primary, secondary, and tertiary hospitals.InterpretationAlthough many people marvel at China's economic miracle, it has undergone slower progress in development of various social sectors such as health care. Continued progress and reform will require reform of undergraduate and postgraduate education, which are essential for cultivating health professionals who are trusted by patients to treat and prevent the growing burden of non-communicable diseases.FundingNone.
Nutritional Support and Outcomes in Malnourished Medical Inpatients
Authors: Martina R. Bally, Prisca Z. Blaser Yildirim, Lisa Bounoure, Viktoria L. Gloy, Beat Mueller, Matthias Briel, Philipp Schuetz
Journal: JAMA Internal Medicine (2015)

During acute illness, nutritional therapy is widely used for medical inpatients with malnutrition or at risk for malnutrition. Yet, to our knowledge, no comprehensive trial has demonstrated that this approach is effective and beneficial for patients.To assess the effects of nutritional support on outcomes of medical inpatients with malnutrition or at risk for malnutrition in a systematic review of randomized clinical trials (RCTs).The Cochrane Library, MEDLINE, and EMBASE. The study dates were October 5, 1982, to April 30, 2014, in various (mostly European) countries. The dates of our analysis were March 10, 2015, to September 16, 2015.Based on a prespecified Cochrane protocol, we systematically searched RCTs investigating the effects of nutritional support (including counseling and oral and enteral feeding) in medical inpatients compared with a control group.Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus.The primary study outcome was mortality. Secondary outcomes included hospital-acquired infections, nonelective readmissions, functional outcome, length of hospital stay, daily caloric and protein intake, and weight change.We included 22 RCTs with a total of 3736 participants. Heterogeneity across RCTs was high, with overall low study quality and mostly unclear risk of bias. Intervention group patients significantly increased their weight (mean difference, 0.72 kg; 95% CI, 0.23-1.21 kg), caloric intake (mean difference, 397 kcal; 95% CI, 279-515 kcal), and protein intake (mean difference, 20.0 g/d; 95% CI, 12.5-27.1 g/d) compared with control group patients. No differences between intervention group patients and control group patients were found with respect to mortality (9.8% vs 10.3%; odds ratio [OR], 0.96; 95% CI, 0.72-1.27), hospital-acquired infections (overall, 6.0% vs 7.6%; OR, 0.75; 95% CI, 0.50-1.11), functional outcome (mean Barthel index difference, 0.33 point; 95% CI, -0.88 to 1.55 points), or length of hospital stay (mean difference, -0.42 days; 95% CI, -1.09 to 0.24 days). Nonelective readmissions were significantly decreased by the intervention (20.5% vs 29.6%; risk ratio, 0.71; 95% CI, 0.57-0.87).In medical inpatients, nutritional support increases caloric and protein intake and body weight. However, there is little effect on clinical outcomes overall except for nonelective readmissions. High-quality RCTs are needed to fill this gap.