tbuckley/cabot-search huggingface dataset:
Cost-effectiveness analysis based on neurocognitive function of a randomized study with stereotactic radiosurgery (SRS) alone versus SRS plus whole-brain radiation therapy (WBRT) for patients with one to three brain metastases.
Authors: L. Lal, J. S. Wefel, C. A. Meyers, E. L. Chang, L. Franzini, L. G. Reasonda, C. Feng, J. M. Swint
Journal: Journal of Clinical Oncology (2010)

e16528 Background: This paper illustrates the incremental cost-effectiveness ratio (ICER) of SRS alone versus SRS plus WBRT for brain metastases with neurocognitive scores as the primary outcome. Methods: A decision analysis model, including subsequent treatment for recurrences, was developed and populated with data from patients randomized to either SRS alone (SA) versus SRS plus WBRT (SW), using costs from the healthcare institution perspective and outcomes based the raw function score and standardized score of the Hopkins Verbal Learning Test- Revised (HVLT-R) Total Recall variable at the last study visit. Tornado diagrams and one-way sensitivity analyses were conducted to determine robustness of the model. Results: Fifty-eight patients were included in the final analysis, with 31 patients in the SA arm and 27 patients in the SW arm. The average cost of the SA arm is $119,000 versus $74,000 for the SW arm. The average HVLT-R raw score for the SA arm was 23.28 points versus 20.94 points for the SW arm. The ICER for total cost was $19,528 per unit of increase in raw score. The average standardized HVLT-R score was - 0.876 for the SA arm and -1.335 for the SW arm. The ICER for the total costs per unit of change in the standardized score was $99,691. Tornado diagrams revealed that the following variable had the highest impact on the ICER in both analyses: probability of being alive with SA in recursive partitioning analysis (RPA) class 2 and being treated for recurrence. Assuming the probability of being alive after treatment for recurrence is 1.0, a one-way sensitivity analysis demonstrated the ICER favoring SRS alone over SRS plus WBRT would $5,000 per unit raw score and $22,000 per unit of standardized score. Conclusions: Compared to other interventions in the $50,000 to $100,000 per QALY cost- effectiveness range, from an economic perspective the application of SA, with subsequent management of recurrences, is shown to be a reasonable treatment modality for brain metastases, in terms of cost per unit of change in neurocognitive function. No significant financial relationships to disclose.
Quarter of patients think it's fine to use friend or family member's antibiotics, survey finds
Authors: A. Gulland
Journal: BMJ (2015)

Doctors have been urged to treat antibiotics as a “precious commodity” in the wake of a World Health Organization survey showing widespread confusion among the general public about their correct use.1

At the launch of a new WHO campaign to encourage good practice among the public, health workers, policy makers, and the agricultural sector, the organisation’s director general, Margaret Chan, urged doctors to play their part. She said, “Doctors need to treat antibiotics as a precious commodity and must try to resist the pressure from individual patients who come in with a cold or flu or viral infection asking for antibiotics.”

Keiji Fukuda, Chan’s special representative …
Prolonged Survival in Bronchogenic Carcinoma Associated With HL-A Antigens W-19 and HL-A5: A Preliminary Report
Authors: A. L. Dellon, G. N. Rogentine, P. B. Chretien
Journal: JNCI Journal of the National Cancer Institute (1975)

The HL-A antigens were determined retrospectively in a group of 14 surgically cured bronchogenic carcinoma patients and prospectively in another group of 100 untreated patients. In the retrospective group, the frequencies of antigens W-19 and HL-A5 were significantly increased when compared with the noncancer control and the prospective lung cancer populations. In the latter group, 60% of the patients with W-19 and 58% with HL-A5 survived without evidence of tumor for at least 1 year after treatment compared with 15% of patients with neither of these antigens, P less than 0.01 and 0.005, respectively. These comparisons were for adenocarcinoma and squamous carcinoma. The patient groups for oat cell and undifferentiated carcinoma were too small for valid statistical comparisons. This preliminary study suggests that the presence of HL-A antigens W-19 and HL-A5 confers resistance to dissemination of bronchogenic carcinoma.
Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa
Authors: Gareth J. Padfield, Carolina A. Escudero, Astrid M. DeSouza, Christian Steinberg, Karen Gibbs, Joseph H. Puyat, Pei Yoong Lam, Shubhayan Sanatani, Elizabeth Sherwin, James E. Potts, George Sandor, Andrew D. Krahn
Journal: Circulation (2016)

Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia.Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026).Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa.
HER2-neu status as a predictor of survival in patients with brain metastases from primary breast adenocarcinoma
Authors: S. M. Sawrie, R. F. Meredith, S. A. Spencer, J. M. Markert, J. B. Fiveash
Journal: Journal of Clinical Oncology (2007)

1016 Background: Recent data suggests that Her2-neu positivity predicts for development of brain metastases in patients with breast cancer. However, there now exists a targeted agent, trastuzumab, that provides excellent systemic control of Her2-positive (Her2 +) disease. We therefore explore the course of this disease as a function of Her2 status in patients with primary breast cancer who have developed brain metastases. Method: We retrospectively analyzed data from 50 consecutive patients with primary breast cancer who subsequently developed brain metastases. Factors evaluated included Her2-neu, ER/PR, T stage, nodal stage, use of whole brain radiotherapy (WBRT) as initial management of CNS disease, initial number of metastases, hormonal therapy, use of trastuzumab, and Karnofsky Performance Status (KPS). Overall survival (OS) was modeled using Cox proportional hazard. Kaplan-Meier analysis was used for significant predictors. Results: Median age was 49 years (28–78 y). Fifty-four percent of patients were Her2 +, whereas only 15% were ER +. All but one Her2 + patient received trastuzumab. Seventy-two percent were node positive, and only 5 patients were metastatic at time of diagnosis. T stage was as follows: T1 = 24%, T2 = 36%, T3 = 8%, and T4 = 16%. Adjuvant chemotherapy was administered to 90% of the sample, and 94% underwent radiation to the primary site. Sixty-six percent had &lt;= 3 initial brain metastases, and 38% underwent WBRT as part of their initial CNS management. Median followup was 55 weeks. A Cox multivariate model of OS yielded two independent predictors. Her2 positivity (p = 0.007) and &lt;= 3 initial brain metastases (p = 0.003) were associated independently with OS from time of initial diagnosis of CNS disease. Median survival and actuarial one year survival for Her2 + patients were 65 weeks and 87%, respectively, versus 33 weeks and 44% for Her2 negative patients (Mantel Cox p = 0.025). Conclusions: Although Her2 + patients appear to have a greater risk of developing brain metastases, overall survival from time of initial diagnosis of brain metastasis appears to be better in this cohort. This may be a function of the improved extracranial control provided by trastuzumab in patients with Her2+ disease. No significant financial relationships to disclose.
Diagnostic usefulness of T-cell based assays for tuberculous meningitis in HIV-uninfected patients
Authors: Ki-Ho Park, Mi Suk Lee, Sun-Mi Kim, Su-Jin Park, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Joong Koo Kang, Sang-Ahm Lee, Sung-Han Kim
Journal: Journal of Infection (2016)
Prognostic Impact of Cytarabine Pathway Gene Polymorphisms in Acute Myeloid Leukemia Adults Undergoing Induction Chemotherapy
Authors: Juan Eduardo Megías, Pau Montesinos, Virginia Bosó, Federico Moscardo, Marí­a José Herrero, David Martínez-Cuadrón, Rebeca Rodríguez-Veiga, Luis Rojas, Blanca Boluda, Jesus Martinez, Jaime Sanz, Francisca López, Isabel Cano, Carmen Alonso, Aima Lacharro, José Cervera, José Luis Poveda, Salvador Aliño, Miguel Ángel Sanz
Journal: Blood (2014)
Obinutuzumab (GA101) Significantly Inhibits Cell Proliferation and Induces Programmed Cell Death in Primary Mediastinal B-Cell Lymphoma (PMBL): Obinutuzumab May be a Future Targeted Agent for the Treatment of PMBL
Authors: Changhong Yin, Sanghoon Lee, Timmy O'Connell, Janet Ayello, Carmella van de Ven, Mitchell S. Cairo
Journal: Blood (2014)
ERCC1 immunohistochemical expression and cancer-specific survival in patients with locally advanced squamous-cell carcinoma of the head and neck treated by cisplatin-based induction chemotherapy
Authors: G. Mountzios, A. Handra-Luca, J. Hernandez, E. Taranchon, J. Lacau-St Guily, J. Soria, P. Fouret
Journal: Journal of Clinical Oncology (2007)

6011 Background: The excision repair cross-complementation group 1 (ERCC1) enzyme is a key element of the nucleotide excision repair (NER) pathway which removes cisplatin-induced DNA adducts and has been associated with resistance to platinum-based chemotherapy. We assessed the correlation of ERCC1 immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) treated with cisplatin-based induction chemotherapy (CBIC). Methods: The initial cohort comprised 107 patients who had received CBIC (modified Al Saraf protocol) from 1992 to 1996 for locally advanced HNSCC. P53 mutations had been previously studied. Pre-therapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 expression using the H-score protocol. The median H-score value was a priori selected as the cutpoint in order to dichotomize ERCC1 expression for statistical analysis. Results: In 68 cases [71%, 95% CI: 61% - 79%] tumors expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 patients [29 %, 95% CI:21%-39%] with tumors expressing ERCC1 at lower levels had a four time greater odds of benefiting from an objective response to chemotherapy [OR 4.3, 95% CI: 1.4 - 13.4; p = 0.01]. ERCC1 and p53 status, but not their association, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on well-established prognosticators including age, T, N, M, tumor differentiation and localization, ERCC1 low expression was associated with a lower risk of cancer death [RR 2.13, 95% CI: 1.03 - 4.43; p=0.04], while p53 status had no prognostic value. Conclusions: Patients with ERCC1 negative tumors are more likely to derive a substantial benefit from CBIC, translated to a lower risk for cancer-related death compared to patients with ERCC1 positive tumors. Large prospective trials should evaluate ERCC1 and other critical biomarkers involved in DNA damage repair process as molecular predictors of responsiveness to chemotherapy in patients with HNSCC. No significant financial relationships to disclose.
Prospective FDG-PET and CT assessment of discontinuation of erlotinib (E) or gefitinib (G) in patients with EGFR TKI sensitive non-small cell lung cancer (NSCLC) who subsequently progress radiographically on E or G (“acquired resistance”) followed by re-initiation of E or G and the subsequent addition of everolimus (RAD001)
Authors: G. J. Riely, M. G. Kris, L. H. Schwartz, T. Akhurst, B. Zhao, D. T. Milton, E. Moore, L. Tyson, W. Pao, V. A. Miller
Journal: Journal of Clinical Oncology (2006)

7065 Background: About 10% of patients (pts) with NSCLC have a radiographic response to E or G. A dependence on signaling through the epidermal growth factor receptor (EGFR) is thought to underlie this response. Despite initial regression, these pts invariably develop acquired resistance to E or G. Optimal management of these patients is unknown. In patients with acquired resistance, we sought to evaluate changes in tumor metabolism by PET and size by CT after discontinuation of E or G, resumption of E or G, and then the addition of the mTOR inhibitor everolimus to E or G. Methods: Pts with stage IV NSCLC with exon 19 or 21 EGFR mutation or previous radiographic response after treatment with E or G and then radiographic progression after &gt; 6 months of treatment were eligible. All pts had 4 FDG-PET/CT and helical CT scans: baseline, 3 weeks after discontinuation of E or G, 3 weeks after restarting E or G, and 3 weeks after combined treatment with everolimus (5 mg daily) and E or G. CT measurements were uni-dimensional. Results: To date, 9 pts (5 on G, 4 on E) have enrolled with 6 pts completing all 4 PET/CT and CT assessments. Within 3 weeks of discontinuation of E or G, 7 of 9 (77%, 95% CI 40–97%) developed symptomatic disease progression. Three of 6 pts had an increase in SUV of &gt;50% and increase in CT measurements &gt;15% 3 weeks after discontinuation of E or G. Three of 6 pts had decrease in SUV of &gt;10% 3 weeks after resumption of E or G. Two of 6 pts had further reduction of SUV &gt; 50% and &gt;10% decrease in CT measurements 3 weeks after everolimus was added to E or G. Conclusions: In EGFR TKI-sensitive patients who develop acquired resistance: 1) Discontinuation of E or G results in rapid symptomatic progression and increases in SUV on PET of indicator lesions. 2) Both symptoms and SUV values improve on re-initiation of E or G, suggesting that some tumor cells remain sensitive to EGFR blockade. 3) We saw further improvement when everolimus was combined with E or G. Based on these data we now recommend continuing E or G in similar patients. Support: Novartis, CA05826, MSKCC “Steps for Breath.” [Table: see text]
Screening in women at genetic risk of breast cancer: Results of the UK multicentre study of magnetic resonance imaging (MRI) and X-ray mammography (XRM)
Authors: M. O. Leach
Journal: Journal of Clinical Oncology (2005)

520 Background Genetically predisposed women have an increased risk of breast cancer at an earlier age where dense breasts may reduce the sensitivity of XRM. A multicentre study to evaluate the sensitivity of MRI compared to XRM commenced in the UK in 1997. Methods Women at high risk (>0.9%pa) of breast cancer, based on testing, family history or affected relatives, were recruited from 22 centres. Women were enrolled aged 35 to 49 and offered annual MRI and XRM. Exclusion criteria included previous breast cancer or symptoms of breast cancer. MRI measurement and evaluation followed a published protocol with a defined scoring scheme. Cancers were verified histologically. The 2-view XRM followed national standards. MRI and XRM were independently double read. 838 women were screened for between 2 and 7 years. Results A total of 1861 women-years with both MRI and XRM resulted in 35 detected cancers: 19 by MRI, 6 by XRM, 8 by both, 2 interval. Significantly more cancers were detected by MRI than by XRM (P=0.01). The difference was most marked for women with a BRCA1 mutation (P=0.004). Adding MRI to XRM increases the sensitivity from 40% to 94%. Average invasive tumour size was 15 mm. The number with DCIS and with grades 1–3 were 6, 3,7 and 19 respectively. Biopsy rates per 1000 woman-years were 12.9 (benign) and 17.7 (malignant). Cancer detection rates were 27.1 (prevalence) and 13.0 (incidence). 5/26 were node positive. Conclusions MRI was significantly more sensitive than XRM in cancer detection in both the entire cohort and specifically in the sub-group of BRCA1 carriers. Specificity for both procedures was acceptable. Despite a high proportion of grade 3 tumours, tumours were small and few women were node positive. Annual screening combining MRI and XRM would detect most tumours in this risk group. The high biopsy rates reflect the cancer detection rate and the high level of concern in this population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Specialty Scanners PLC Specialty Scanners PLC
Systematic vs hit-and-run endosonographic staging of lung cancer
Authors: Laurence Crombag, Jos Stigt, Christophe Dooms, Kurt Tournoy, Jouke Annema
Journal: European Respiratory Journal (2014)

Introduction:  Guidelines recommend endosonography for mediastinal nodal staging. The value of a systematic nodal evaluation vs targeted sampling of the suspected nodes based on CT-PET findings is unknown.  Aim:  To investigate whether systematic endosonographic staging (assessment of all nodal regions) results in improved loco-regional nodal staging compared to PET-CT directed assessment (ie targeted approach).  Methods:  A prospective, international multicenter study in patients with (suspected) Non-Small Cell Lung Cancer (NSCLC) and an indication for mediastinal nodal staging. Prior to endoscopy, nodal target(s) were defined based on CT-PET reports.  Intervention:  A systematic EBUS evaluation followed by systematic EUS-B (EBUS scope in esophagus). Both target nodes as well as sonographically suspected and/or nodes with a short axis greater than 8 mm were sampled. Surgery with nodal dissection was the reference standard.  Results:  80 patients with (suspected) NSCLC (mean age 65 years, 50 male) were investigated according to protocol. Final diagnosis was NSCLC, SCLC, benign and other in 68, 6, 4 and 2 patients, respectively. The prevalence of mediastinal nodal metastases was 33/80 (41%). In 7 patients (9%) systematic nodal staging resulted in an added value in comparison to the targeted approach (1 N1, 5 N2, 1 N3 disease). False negative findings were present in 6 patients.  Conclusion and implications:  Systematic endosonographic staging (assessment of all nodal regions) results in improved loco-regional staging compared to PET-CT directed hit-and-run approach and should be the preferred endoscopic staging strategy of NSCLC.
Intranuclear Inclusions in &lt;italic&gt;Rattus (Mastomys) Natalensis&lt;/italic&gt; Infected With Rat Virus
Authors: A S RABSON, L KILHAM, R L KIRSCHSTEIN
Journal: JNCI Journal of the National Cancer Institute (1961)

Newborn mastomys inoculated with rat virus (RV), an agent originally isolated from tumor-bearing rats, develop an acute fatal disease characterized histopathologically by Feulgen-positive intranuclear inclusions in reticuloendothelial cells in the liver, heart, lungs, kidneys, spleen, and gastrointestinal tract. The inclusions resemble those seen in cells infected with polyoma virus in vitro. Although polyoma virus and RV have a number of common biological properties, including the ability of both agents to infect mastomys with involvement of Kupffer cells in the liver, no evidence of proliferative or oncogenic activity has been observed in mastomys inoculated with RV.
Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering
Authors: Colin R. Butler, Robert E. Hynds, Kate H. C. Gowers, Dani Do Hyang Lee, James M. Brown, Claire Crowley, Vitor H. Teixeira, Claire M. Smith, Luca Urbani, Nicholas J. Hamilton, Ricky M. Thakrar, Helen L. Booth, Martin A. Birchall, Paolo De Coppi, Adam Giangreco, Christopher O’Callaghan, Sam M. Janes
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Stem cell–based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell–seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts.Objectives: To define a scalable cell culture system to deliver airway epithelium to clinical grafts.Methods: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation-dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air–liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air–liquid interface cultures.Measurements and Main Results: 3T3-J2 feeder cells and ROCK inhibition allowed rapid expansion of airway basal cells. These cells were capable of multipotent differentiation in vitro, generating both ciliated and goblet cell lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated tracheal scaffolds in a heterotopic transplantation xenograft model.Conclusions: Our method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction.