tbuckley/cabot-search huggingface dataset:
BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults
Authors: A Craig Davidson, Stephen Banham, Mark Elliott, Daniel Kennedy, Colin Gelder, Alastair Glossop, Alistair Colin Church, Ben Creagh-Brown, James William Dodd, Tim Felton, Bernard Foëx, Leigh Mansfield, Lynn McDonnell, Robert Parker, Caroline Marie Patterson, Milind Sovani, Lynn Thomas
Journal: Thorax (2016)

### Principles of mechanical ventilation #### Modes of mechanical ventilation Recommendation 1. Pressure-targeted ventilators are the devices of choice for acute NIV (Grade B). Good practice points #### Choice of interface for NIV Recommendation 2. A full face mask (FFM) should usually be the first type of interface used (Grade D). Good practice points #### Indications for and contra-indications to NIV in AHRF Recommendation 3. The presence of adverse features increase the risk of NIV failure and should prompt consideration of placement in high dependency unit (HDU)/intensive care unit (ICU) (Grade C). Good practice points #### Monitoring during NIV Good practice points #### Supplemental oxygen therapy with NIV Recommendations 4. Oxygen enrichment should be adjusted to achieve SaO2 88–92% in all causes of acute hypercapnic respiratory failure (AHRF) treated by NIV (Grade A). 5. Oxygen should be entrained as close to the patient as possible (Grade C). Good practice points
Alk and Ros1-Positive Lung Adenocarcinoma (La) Patient Outcomes: a Mono-Istitutional Experience
Authors: R. Chiari, G. Metro, C. Bennati, D. Iacono, D. Giannarelli, V. Minotti, L. Marcomigni, M. Meacci, L. Crinò
Journal: Annals of Oncology (2014)
AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma
Authors: Alba A Brandes, Gaetano Finocchiaro, Vittorina Zagonel, Michele Reni, Claudia Caserta, Alessandra Fabi, Matteo Clavarezza, Evaristo Maiello, Marica Eoli, Giuseppe Lombardi, Marta Monteforte, Emanuela Proietti, Raffaele Agati, Vincenzo Eusebi, Enrico Franceschi
Journal: Neuro-Oncology (2016)

Few prospective studies have assessed the role of bevacizumab and included a control arm with standard treatments for recurrent glioblastoma. We conducted a noncomparative phase II trial (AVAREG) to examine the efficacy of bevacizumab or fotemustine in this setting.Eligible patients were randomized 2:1 to receive bevacizumab (10 mg/kg every 2 weeks) or fotemustine (75 mg/m(2) on days 1, 8, and 15, then 100 mg/m(2) every 3 weeks after a 35-day interval). The primary endpoint was 6-month overall survival (OS) rate (OS-6). No formal efficacy comparison was made between the treatment arms.Ninety-one patients were enrolled (bevacizumab n = 59; fotemustine n = 32). Median age was 57 years (range, 28-78 y), and patients had Eastern Cooperative Oncology Group performance status of 0 (n = 42), 1 (n = 35), or 2 (n = 14). OS-6 rate was 62.1% (95% confidence interval [CI], 48.4-74.5) with bevacizumab and 73.3% (95% CI, 54.1-87.7) with fotemustine. OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors (50% and 85%, respectively), but higher in fotemustine-treated patients (87.5% and 50%, respectively). OS rates at 9 months were 37.9% (95% CI, 25.5-51.6) and 46.7% (95% CI, 28.3-65.7) with bevacizumab and fotemustine, respectively, and median OS was 7.3 months (95% CI, 5.8-9.2) and 8.7 months (95% CI, 6.3-15.4), respectively. Toxicity was as expected with the 2 agents.Single-agent bevacizumab may have a role in patients with recurrent glioblastoma.
Therapy of chronic lymphocytic leukemia and cutaneous T-cell lymphoma with T101 monoclonal antibody.
Authors: R O Dillman, D L Shawler, J B Dillman, I Royston
Journal: Journal of Clinical Oncology (1984)

The findings accompanying the administration of 50 intravenous courses of monoclonal antibody to human T-cell (T101) in eight patients, four with chronic lymphocytic leukemia and four with cutaneous T-cell lymphoma are reported. Infusion rates of 0.7 to 1 mg/min were associated with unacceptable toxicity in the presence of circulating target cells, but slower rates were well-tolerated. Immunofluorescence techniques confirmed that circulating cells did bind the antibody in vivo and were subsequently removed from the circulation. Modulation of the antigen on target cells in the bone marrow and skin has important implications for the schedule of administration of such antibodies, and points out the possible limitation of effector cell-mediated cytotoxicity at the tissue level. Production of anti-mouse antibodies resulted in neutralization of therapy in two patients with cutaneous T-cell lymphoma, and suggests that whether such an anti-mouse response is produced may be secondary to the underlying immune status of the patient or the amount of mouse protein to which immunocompetent cells are exposed. The relative specificity and efficacy of monoclonal antibody therapy is encouraging, but the limited clinical benefit and problems of modulation and anti-mouse antibody production underscore the need for continued research into passive therapy and suggest that cytotoxic conjugates may be of more clinical value.
FDA Approval of Gefitinib for the Treatment of Patients with Metastatic <i>EGFR</i> Mutation–Positive Non–Small Cell Lung Cancer
Authors: Dickran Kazandjian, Gideon M. Blumenthal, Weishi Yuan, Kun He, Patricia Keegan, Richard Pazdur
Journal: Clinical Cancer Research (2016)

Abstract On July 13, 2015, the FDA approved gefitinib (Iressa; AstraZeneca UK Limited) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Concurrently, a labeling expansion of the therascreen EGFR RGQ PCR Kit (Qiagen) as a companion diagnostic test was approved. The approval was based on the results of a multicenter, single-arm, open-label clinical study of 106 treatment-naïve patients with metastatic EGFR mutation–positive NSCLC who received gefitinib, 250 mg daily, until disease progression or intolerable toxicity. The major efficacy outcome was RECIST v1.1 objective response rate (ORR). The blinded independent central review (BICR) ORR was 50% [95% confidence interval (CI), 41–59] with a median duration of response (DoR) of 6.0 months. Efficacy results were supported by a retrospective exploratory analysis of a subset of a randomized, multicenter, open-label trial on 1,217 patients with metastatic NSCLC. Of the patients randomized, 186 (15%) were retrospectively determined to be EGFR positive and evaluable for a BICR assessment. The HR for progression-free survival (PFS) was 0.54 (95% CI, 0.38–0.79), favoring gefitinib over platinum-doublet chemotherapy. The most common (≥20%) adverse reactions were skin reactions, increased aspartate and alanine aminotransferase, proteinuria, and diarrhea. Approximately 5% of patients discontinued treatment due to an adverse reaction. Given the safety profile and clinically meaningful ORR, DoR, and PFS, the benefit–risk analysis was deemed favorable for FDA approval. Clin Cancer Res; 22(6); 1307–12. ©2016 AACR.
US insurers are denying women access to care guaranteed by health law, report finds
Authors: M. McCarthy
Journal: BMJ (2015)

Many US insurance companies are routinely denying women access to services guaranteed by the 2010 Affordable Care Act, a report by the National Women’s Law Center, a non-profit organization based in Washington, DC, has found.

Before the passage of the Affordable Care Act insurers could legally charge women higher premiums or even deny them coverage simply on the basis of their being women, and plans did not have to cover such services as contraceptive or maternity care. “In fact, the vast majority of individual market plans did not cover maternity care at all, while a limited number of insurers sold separate maternity riders for an additional premium,” the report noted.1

The Affordable Care Act contains a number of provisions requiring insurers …
Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites.
Authors: Ozge Gumusay, Mustafa Benekli, Ozgur Ekinci, Meltem Baykara, Ahmet Ozet, Ugur Coskun, Aytug Uner, Ayse Dursun, Ecine Yesim Atak, Suleyman Buyukberber
Journal: Journal of Clinical Oncology (2015)

25 Background: Determination of HER2 status in advanced gastric cancer (GC) is important in clinical decision making. In the ToGA trial, trastuzumab based therapy demonstrated a significant OS benefit in patients with HER2 positive advanced GC. HER2 discordance in GC primary and its metastases has been long debated. The aim of the study was to evaluate the rate of HER2 discordance and its effect on treatment decisions in advanced GC. Methods: A total of 74 patients with advanced GC were included in the study. Both immunohistochemical staining (IHC) and dual-color silver in situ hybridization (SISH) were performed in all patients to evaluate the HER2 status of the primary lesion and paired metastasis. Results: The assessment of HER2 status with the IHC staining method and SISH revealed a discordance rate of 9.5% and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a HER2 negative status in primary tumor (IHC=0, SISH=negative), the HER2 status was positive for liver metastasis (IHC=2+, SISH=positive). Trastuzumab was added to the chemotherapy regimen. Conclusions: In this study, we found a higher rate of HER2 discordance between primary gastric tumor and metastatic lesions compared to the rates reported in previous studies. Detection of a HER2 positive metastasis with a HER2 negative primary tumor suggests that investigation of HER2 is also required for the metastatic lesion and that trastuzumab could be administered in case of a positive result.
Updated efficacy and safety assessment of first-line therapy with lapatinib, trastuzumab, and paclitaxel in HER2+ metastatic breast cancer.
Authors: F. J. Esteva, S. Franco, M. K. Hagan, A. Brewster, W. Williams, A. M. Florance, K. Koch, S. J. Turner, M. Ridderheim, A. T. Perez
Journal: Journal of Clinical Oncology (2010)

1046 Background: Although concomitant trastuzumab and paclitaxel is an established treatment for metastatic breast cancer (MBC), 30% to 40% of HER2-positive patients show no response to this combination. Lapatinib, with a differing mechanism of action, may increase efficacy when given concurrently with trastuzumab and paclitaxel. Methods: This is an open-label phase I study with the primary objective of assessing the safety and tolerability of lapatinib when administered with paclitaxel and trastuzumab. The secondary objective was to determine the efficacy of lapatinib via overall response rate (ORR), duration of response and time to response. Patients were enrolled sequentially into 1 of 3 cohorts. Cohort 1 received lapatinib (1,000 mg/d), paclitaxel (80 mg/m2 weekly for 3 weeks of a 4-week cycle), and the standard weekly dose of trastuzumab (2 mg/kg). Cohort 2 received lapatinib (1,000 mg/d), paclitaxel (70 mg/m2), and trastuzumab. Cohort 3 received lapatinib (750 mg/d), paclitaxel (80 mg/m2), and trastuzumab. Patients were IHC 3+ or FISH-amplified for HER2, had stage IV disease, and had no prior treatment for metastatic disease. Treatment continued until progression or toxicity. Patients received prophylactic loperamide per protocol amendment. Results: Safety data and preliminary efficacy data are available for all 63 patients when the last patient enrolled completed 12 weeks on study. The commonly reported adverse events for all cohorts were diarrhea (86%), rash (75%), and nausea (62%). No grade 4 or 5 diarrhea events were reported. The proportion of patients with grade 3 diarrhea was 62% in cohort 1, 50% in cohort 2, and 20% in cohort 3. The ORR was 68% for all patients, with an ORR of 79%, 71%, and 50%, respectively, in cohorts 1, 2, and 3. Updated safety and efficacy including 8 months of additional data will be reported. Conclusions: Previously reported preliminary efficacy data showed a similar ORR for trastuzumab plus paclitaxel when given in combination with lapatinib. A high incidence of grade-3 diarrhea was seen in cohorts 1 and 2, and was significantly reduced in cohort 3. Results from a pharmacokinetics analysis and updated efficacy and safety data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Memorial Health Care Systems Celgene, Cepahlon, Genomic Health, GlaxoSmithKline, Millennium, Novartis, sanofi-aventis GlaxoSmithKline Celgene, Cepahlon, Genomic Health, GlaxoSmithKline, Millennium, Novartis, sanofi-aventis GlaxoSmithKline
Immunotherapy with the trifunctional antibody removab leads to significant elimination of tumor cells from malignant ascites in ovarian cancer: Results of a phase I/II study
Authors: M. Jaeger, M. A. Stroehlein, A. Schoberth, A. Burges, M. M. Heiss, H. Lindhofer
Journal: Journal of Clinical Oncology (2004)

2504 Background: Malignant ascites is the abnormal accumulation of fluid within the peritoneal cavity due to the peritoneal spread of the tumor. It is associated with a poor prognosis and low quality of life. Currently available treatment methods are of limited success. In a phase I/II study we investigated a new concept of ascites treatment based on the intraperitoneal application of the trifunctional antibody removab. Via its two binding arms specific for EpCAM and CD3, and its Fc region, removab binds simultaneously to tumor cells, T cells and antigen-presenting cells resulting in a significant tumor cell killing. Methods: For evaluation of treatment success, we developed an immunofluorescence detection method for monitoring effects on tumor cells within the ascites fluid. Cytospins were prepared from fresh ascites samples before, during and after removab treatment. Tumor cell reduction was monitored with a fluorescence double staining (EpCAM; CK8, 18,19). In addition, tumor cell/leukocyte ratio was determined by EpCAM/CD45 double staining. Results: 23 women with ascites in ovarian cancer (stage IIIb, IIIc and IV) were treated with up to 5 intraperitoneal removab infusions within 13 days using increasing dosages of 5–200 μg. During the treatment, a drastic and continuous decrease of tumor cells within the ascites fluid from 540,000 /10e6 total cells to a mean of 35 /10e6 total cells was observed. Remarkably, the tumor cell/leukocyte ratio was completely reversed after the first low-dose (10 μg) removab infusion. After the last removab infusion, all patients had tumor cell counts below 0.1% to 0%. These findings were associated with a strong reduction of ascites flow from a median of 105 ml/h to 23 ml/h. By the end of observation (day 37), 22/23 patients had no need for further paracentesis. Conclusions: The trifunctional antibody removab may provide a promising tumor targeted option for treatment of malignant ascites. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Trion Research GmbH Trion Pharma GmbH
Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression
Authors: Trevelyan R. Menheniott, Louise O’Connor, Yok Teng Chionh, Jan Däbritz, Michelle Scurr, Benjamin N. Rollo, Garrett Z. Ng, Shelley Jacobs, Angelique Catubig, Bayzar Kurklu, Stephen Mercer, Toshinari Minamoto, David E. Ong, Richard L. Ferrero, James G. Fox, Timothy C. Wang, Philip Sutton, Louise M. Judd, Andrew S. Giraud
Journal: Journal of Clinical Investigation (2016)

Chronic mucosal inflammation is associated with a greater risk of gastric cancer (GC) and, therefore, requires tight control by suppressive counter mechanisms. Gastrokine-2 (GKN2) belongs to a family of secreted proteins expressed within normal gastric mucosal cells. GKN2 expression is frequently lost during GC progression, suggesting an inhibitory role; however, a causal link remains unsubstantiated. Here, we developed Gkn2 knockout and transgenic overexpressing mice to investigate the functional impact of GKN2 loss in GC pathogenesis. In mouse models of GC, decreased GKN2 expression correlated with gastric pathology that paralleled human GC progression. At baseline, Gkn2 knockout mice exhibited defective gastric epithelial differentiation but not malignant progression. Conversely, Gkn2 knockout in the IL-11/STAT3-dependent gp130F/F GC model caused tumorigenesis of the proximal stomach. Additionally, gastric immunopathology was accelerated in Helicobacter pylori–infected Gkn2 knockout mice and was associated with augmented T helper cell type 1 (Th1) but not Th17 immunity. Heightened Th1 responses in Gkn2 knockout mice were linked to deregulated mucosal innate immunity and impaired myeloid-derived suppressor cell activation. Finally, transgenic overexpression of human gastrokines (GKNs) attenuated gastric tumor growth in gp130F/F mice. Together, these results reveal an antiinflammatory role for GKN2, provide in vivo evidence that links GKN2 loss to GC pathogenesis, and suggest GKN restoration as a strategy to restrain GC progression.
Outside the scope of our practice: an unexpected thoracoscopy and pleurocentesis during gastroscopy
Authors: Sern Yeoh, Christopher Middleton
Journal: Endoscopy (2016)

A 56-year-old man described 2 weeks of regurgitation of ingested liquids, dyspnea, and chest pain. He had undergone laparoscopic esophagectomy with cervical anastomosis 1 year previously for esophageal adenocarcinoma; this had been complicated by a stricture at the esophagogastric anastomosis that required serial endoscopic dilations. Shortly after admission, a computed tomography (CT) scan demonstrated a dilated, fluid-filled intrathoracic stomach. There was obstruction to the passage of oral contrast at the level of the intrathoracic duodenum, and a left-sided pleural effusion was seen ([Fig. 1]).
Risk factors for recurrent biliary obstruction following placement of self-expandable metallic stents in patients with malignant perihilar biliary stricture
Authors: Shin Miura, Atsushi Kanno, Atsushi Masamune, Shin Hamada, Seiji Hongou, Naoki Yoshida, Eriko Nakano, Tetsuya Takikawa, Kiyoshi Kume, Kazuhiro Kikuta, Morihisa Hirota, Hiroshi Yoshida, Yu Katayose, Michiaki Unno, Tooru Shimosegawa
Journal: Endoscopy (2016)

Self-expandable metallic stents (SEMSs) are used for palliation in patients with malignant perihilar biliary strictures. However, recurrent biliary obstruction occasionally causes cholangitis and jaundice. This study aimed to identify risk factors for recurrent biliary obstruction in such patients.Data from consecutive patients with malignant perihilar biliary strictures treated with endoscopic placement of SEMSs between 2007 and 2014 in Tohoku University Hospital were retrospectively reviewed. Risk factors for recurrent biliary obstruction were calculated using the Cox proportional hazards models (with hazard ratios [HRs] and 95 % confidence interval [95 %CIs]), and SEMS patency period was examined using the Kaplan - Meier method. SEMS patency was defined as the period between SEMS insertion and the development of recurrent biliary obstruction.104 patients were included. Median survival time was 281 days; and 85 patients died during a median follow-up period of 320 days. Recurrent biliary obstruction occurred in 35 patients. Median SEMS patency period was 549 days. Multivariable analyses showed that: compared with bile duct carcinoma, gallbladder carcinoma was associated with shorter SEMS patency (HR 8.18, 95 %CI 2.41 - 26.83); patency of left-sided SEMS was inferior to that of bilateral (HR 0.5, 95 %CI 0.32 - 0.93) and right-sided SEMS (HR 0.1, 95 %CI 0.02 - 0.65). Cholangitis before SEMS placement increased the risk of recurrent biliary obstruction (HR 11.44; 95 %CI 4.48 - 32.35) and reduced the SEMS patency period (746 vs. 210 days).Gallbladder carcinoma, left-sided stent placement, and cholangitis before SEMS placement are risk factors for recurrent biliary obstruction after SEMS placement.
Efficacy of 300IR 5-Grass Pollen Sublingual Tablet in the Treatment of Rhinitis Symptoms in Polysensitized Subjects with Grass Pollen-Induced Allergic Rhinoconjunctivitis
Authors: Robert K. Zeldin, Yann Amistani, Josiane Cognet-Sicé, Kathy Abiteboul
Journal: Journal of Allergy and Clinical Immunology (2016)
Use of ERCC1 polymorphism and extreme drug resistance assay to predict overall non-small cell lung cancer survival and responsiveness to platinum-based chemotherapy agents
Authors: M. Romkes, R. J. Landreneau, M. J. Schuchert, S. C. Buch, J. D. Luketich, J. M. Siegfried
Journal: Journal of Clinical Oncology (2008)

8092 Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Increased ERCC1 mRNA levels are related directly to platinum resistance in various cancers. A previous study demonstrated the utility of in vitro tumor resistance drug testing in predicting poor clinical outcome when platinum based therapy is utilized to treat patients with evidence of extreme drug resistance (EDR). Here, we evaluated the role of genetic variation in the ERCC1 gene on non- small cell lung cancer (NSCLC) survival in 81 cases that were also evaluated for EDR. Methods: The Extreme Drug Resistance (EDR) Assay is a clinically validated in vitro assay used to test tumors for chemotherapy drug resistance. Based on response in the EDR assay, tumors specimens from 81 stage I-IV NSCLC patients were segregated into three groups: extreme drug resistant (EDR), intermediate drug resistant (IDR), and low drug resistant (LDR). Tumor recurrence and patient survival were evaluated following platinum based chemotherapy. Kaplan-Meier survival curves were generated to evaluate the impact of the polymorphisms on progression-free and overall survival. ERCC1 polymorphisms were screened using the Illumina Bead Station GX. Results: The median follow-up time among these patients was 11.4 months and a total of 25 deaths (19 with disease) were observed. The EDR group had significantly reduced survival times as compared to the IDR and LDR groups (p<0.08). Furthermore, in the EDR group, the ERCC1 T19007C (rs11615) was significantly associated with decreased survival times among cases (p<0.027). Median survival time was 2.4 months (0.6–4.2) for the ERRC1 variant allele carriers vs. 7.6 (1.7–37.7) months for non-variant carriers in the EDR group. Conclusions: These findings suggest that genetic polymorphisms in the ERCC1 gene may modulate overall NSCLC prognosis as well as response to platinum-based chemotherapy agents. The identification of extreme drug resistance profiles in conjunction with polymorphisms in the ERCC1 gene and other genes in the NER pathway may better predict response to platinum-based therapies. No significant financial relationships to disclose.
Deforestation Clears Way for Zoonotic Malaria in Malaysia
Authors: M. J. Friedrich
Journal: JAMA (2016)

Intensive deforestation in Malaysia’s rainforests is exposing more humans to a type of malaria previously found only in long-tail and pig-tail macaques, report an international team of investigators (Fornace KM et al. Emerg Infect Dis. 2016;22[2]:201-209).
Abstract 17072: Mortality Outcomes Following Inter-Hospital Transfer (IHT) for Acute Myocardial Infarction (AMI)
Authors: Isuru Ranasinghe, Federica Barzi, David Brieger, Martin Gallagher
Journal: Circulation (2012)

Background: IHT is common in AMI yet there are limited population studies evaluating its effect upon mortality. Methods: All patients (n=40,028) with a principle ICD10 diagnosis of AMI (14,115 STEM...