tbuckley/cabot-search huggingface dataset:
Protecting young children from influenza
Authors: Peter J. Gill, Kay Wang
Journal: European Respiratory Journal (2017)

Influenza is a major global cause of childhood morbidity and mortality [1, 2], and puts a strain on healthcare resources, particularly during epidemics and pandemics [3, 4]. Annual seasonal influenza vaccination programmes were launched to help reduce the burden of influenza but there is variation between countries on which children are targeted. Certain national programmes (for example, in Canada and the USA) recommend universal influenza vaccination [5, 6] while most European countries still focus mainly on groups considered to be at greater risk of influenza-related complications [7]. These include children with certain known underlying medical conditions and those under 2 years of age [8, 9]. Evidence-based strategies are needed to ensure children targeted by influenza programmes are vaccinated <http://ow.ly/qap430evC7y>
Induction chemotherapy followed by concurrent chemotherapy and proton beam for sinonasal undifferentiated carcinoma.
Authors: Yue Christine Lu, Judith A. Adams, John Ross Clark, Norbert Liebsch, Annie W Chan
Journal: Journal of Clinical Oncology (2017)

e17557 Background: The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains to be defined given its aggressiveness and dismal outcome with traditional treatment. We examined the treatment outcomes of SNUC treated with combined proton beam with concurrent chemotherapy +/- induction chemotherapy. Methods: Between 2005 and 2016, 15 patients with SNUC were treated at our institution. All patients had T4 disease, with 20% had nodal involvement and 87% with orbital invasion. Forty-seven percent of patients underwent induction chemotherapy followed by concurrent chemoradiotherapy (sequential group) and 53% underwent or concurrent chemoradiotherapy alone. All patients underwent proton beam for the primary site and upper neck, and photon irradiation for the lower neck. The median dose to the primary site was 70Gy(RBE). Locoreigonal control, freedom from distant metastasis, disease-free survival, and overall survival were estimated by the Kaplan-Meier method. Results: With a median follow-up of 25 months, there were 2 local, 2 regional, 4 distant, and 5 dural-leptomeningeal failures. The 2-year locoregional control rates were 100% and 60% (95%CI:33%-100%) for the sequential and concurrent alone groups, respectively, (p=0.10). The 2-year overall survival was 100% for the sequential group and 58% (95%CI:31%-100%) for the concurrent group (p=0.03). The 2-year distant-metastasis-free survival was 83% (95%CI:58%-100%) and 31% (95%CI:10%-96%) for the sequential and concurrent group, respectively (p= 0.03). Furthermore, the sequential group has a 2-year disease-free survival rate of 100% compared with 58% (95%CI:31%-100%) for the concurrent group (p=0.02). Conclusions: Induction chemotherapy followed by concurrent chemotherapy and proton beam results in promising outcome in patients with SNUC.
A randomized, phase II efficacy assessment of multiple MET kinase inhibitors in metastatic papillary renal carcinoma (PRCC): SWOG S1500.
Authors: Sumanta K. Pal, Catherine M. Tangen, Ian Murchie Thompson, Brian M. Shuch, Naomi B. Haas, Daniel J. George, Mark N. Stein, John Joseph Wright, Melissa Plets, Primo Lara
Journal: Journal of Clinical Oncology (2017)

TPS4599 Background: PRCC constitutes approximately 15% of RCC cases, and no standard of care exists for metastatic disease. Approved VEGF- and mTOR-directed therapies for clear cell RCC in metastatic PRCC (mPRCC) have generally been ineffective. Trials assessing sunitinib and everolimus in non-clear cell RCC show a numerical advantage in progression-free survival (PFS) with sunitinib therapy. Prospective studies evaluating sunitinib in mPRCC show a broad range of efficacy, with PFS ranging from 1.6-6.6 months. Another possible approach to treating mPRCC is to target the MET protooncogene, which is frequently altered across both type I and type II disease. SWOG 1500 is a randomized, phase II study which will compare sunitinib to three MET-directed therapies in pts with mPRCC. Methods: Eligible pts will have PRCC (type I, type II or NOS), Zubrod performance status 0-1, and measurable metastatic disease. Pts may have received up to 1 prior systemic therapy, with the exception of prior VEGF-directed treatments. Treated brain metastases are allowed. Tissue must be available for central pathologic review of papillary subtype. Pts will receive either oral sunitinib, cabozantinib, crizotinib or savolitinib in a 1:1:1:1 randomization, with stratification by (1) prior therapy (0 vs 1) and (2) PRCC subtype (type I vs type II vs NOS). The primary endpoint of the study is to compare PFS with sunitinib to PFS with MET-directed therapies. Secondary endpoints in the study include comparison of response rate, overall survival and safety profile. Translational aims of the study include correlation of clinical outcome with MET mutation, copy number and other markers of MET signaling. Radiographic assessment will be performed every 12 wks. Interim analyses are planned for each arm. A total of 275 pts will be enrolled, with 26 pts registered as of Jan 30, 2017. Clinical trial information: NCT02761057.
Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia
Authors: Aatur D Singhi, Kevin McGrath, Randall E Brand, Asif Khalid, Herbert J Zeh, Jennifer S Chennat, Kenneth E Fasanella, Georgios I Papachristou, Adam Slivka, David L Bartlett, Anil K Dasyam, Melissa Hogg, Kenneth K Lee, James Wallis Marsh, Sara E Monaco, N Paul Ohori, James F Pingpank, Allan Tsung, Amer H Zureikat, Abigail I Wald, Marina N Nikiforova
Journal: Gut (2017)

Objective DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS / GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53 / PIK3CA / PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing. Design Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS / GNAS mutations by Sanger sequencing. Results KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively). Conclusions In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS / GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53 / PIK3CA / PTEN alterations is a useful preoperative marker for advanced neoplasia.
Treatment and outcomes of primary pericardial mesothelioma: A systematic review.
Authors: Elizabeth McGehee, Joan Reisch, Jonathan Dowell, David E. Gerber
Journal: Journal of Clinical Oncology (2017)

e20027 Background: Primary pericardial mesothelioma (PPM) is a rare cancer, for which there is no consensus on treatment. We performed a retrospective systematic review of recently published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Methods: Published literature from 2000-2016 was searched using the terms “primary pericardial mesothelioma”, “pericardial mesothelioma” and “malignant pericardial mesothelioma”. T-tests, Chi-square, and multivariable stepwise logistic regression were employed to correlate demographics, disease characteristics, and treatment with mortality. Results: We identified 6 case series and 84 case reports for a total of 103 PPM cases. Median age at diagnosis was 55; age range was 19 to 87. 39% were female and 61% were male. The mean time from diagnosis to death was 5.6 months. Tobacco exposure and asbestos exposure were reported in 15% and 25%, respectively. Neither exposure was predictive of mortality. 46% of patients underwent surgery, 8% received radiation, 37% received chemotherapy and 23% received no treatment. For 13% of patients, the treatment received, if any, was unknown. Radiation treatment was not associated with a mortality benefit (p = 0.54). A mortality benefit was seen for patients who had resection of their tumor (46% alive at last follow-up, p = 0.0061) but not in patients who had pericardiectomy (25% alive at last follow-up, p = 0.44). A mortality benefit was noted in those who received chemotherapy (p = 0.0022), specifically pemetrexed (p = 0.0038) or platinum agents (p = 0.003). Gemcitabine was not associated with a mortality benefit (p = 0.101). Conclusions: To the authors’ knowledge, this is the first comprehensive analysis of published PPM cases in the modern era. In this retrospective systematic review, a mortality benefit was seen with tumor resection and chemotherapy. Selection bias may account for some of this effect. However, given the inability to perform prospective studies in this population due to small patient numbers, it seems reasonable to offer surgical and medical therapy to eligible patients with PPM.
Molecular targets involved in the antiangiogenic activity of a polytherbal chemopreventive agent brahma rasayana
Authors: Rajesh L. Thangapazham, Jaya P. Gaddipati, Anuj Sharma, Anoop K. Singh, Radha K. Maheshwari
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5875 

The current therapy for prostate cancer includes radical prostatectomy, radiation therapy and hormonal ablation. Chemotherapy also provides beneficiary results for some patients with advanced prostate cancer but with several harmful side effects. Hence there is a need to identify and develop alternate therapies, which can reduce the disease progression with minimal or few side effects. Earlier studies from our laboratory have shown a Polyherbal mixture, Brahma rasayna (BR) rich in anti-oxidant principles has a potential to be an anti-tumor agent. BR treatment of MAT-LyLu cell inoculated Copenhagen rats resulted in a decrease of palpable tumor incidence, delay in tumor occurrence and lower mean tumor volumes. Also a significant reduction in tumor weight and lung metastasis was observed in rasayana treated animals in comparison to untreated controls. As we observed a reduction in tumor volume and metastasis, we focused our present study to examine the effect of BR on angiogenesis and regulation of molecular markers involved in angiogenesis. Analysis included estimation of micro vessel density by Factor VIII staining and expression of angiogenic regulators such as VEGF, MMP-9 and MMP-2 by Western blotting and zymograms, in tumor tissues from rasayana treated and untreated animals. We also conducted in vitro angiogenesis assays to study the effect of BR on cell migration, invasion and differentiation in human umbilical vein endothelial cells (HUVEC). BR treatment showed a significant reduction in Factor VIII expression compared to control indicating reduced angiogenesis. BR treated tumor specimens showed a decrease in the proangiogenic factors like VEGF, MMP-9 and MMP-2. Methanolic extract of BR was found to inhibit the proliferation, tube formation, cell migration and attachment of HUVEC on matrigel in a dose dependant manner. These findings suggest the possible mechanism(s) of action of Brahma rasayana in the reduction of tumor growth and metastatic spread.
Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission
Authors: Margherita Zen, Luca Iaccarino, Mariele Gatto, Francesca Saccon, Maddalena Larosa, Anna Ghirardello, Leonardo Punzi, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2017)

To evaluate the prevalence, duration and effect on damage accrual of the 'Lupus Low Disease Activity State' (LLDAS) in a monocentric cohort of patients with systemic lupus erythematosus (SLE).We studied 293 Caucasian patients with SLE during a 7-year follow-up period. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SELENA-SLEDAI physician global assessment (PGA), and damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We considered the following definition of LLDAS: SLEDAI-2K ≤4 without major organ activity, no new disease activity, PGA (0-3)≤1, prednisone ≤7.5 mg/day and well-tolerated immunosuppressant dosages. The effect of LLDAS on SDI was evaluated by multivariate regression analysis. We also evaluated remission defined as clinical SLEDAI-2K=0 and prednisone ≤5 mg/day in patients treated with/without stable immunosuppressants and/or antimalarials.LLDAS lasting 1, 2, 3, 4 or ≥5 consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%) and 109 (37.2%) patients, respectively. Patients who spent at least two consecutive years in LLDAS had significantly less damage accrual compared with patients never in LLDAS (p=0.001), and they were significantly less likely to have an increase in SDI (OR 0.160, 95% CI 0.060 to 0.426, p<0.001). On average, 84% of patients in LLDAS also fulfilled the criteria for remission.LLDAS was associated with a decrease in damage progression in Caucasian patients with SLE. The majority of patients in LLDAS were in remission, which can largely contribute to the protective effect of LLDAS on damage accrual.
Just 3% of patients with long term conditions have a written care plan, study finds
Authors: Abi Rimmer
Journal: BMJ (2017)

Just 3% of patients with long term conditions have a written care plan and large numbers of people are not as involved in their healthcare decisions as they want to be, a study has found.

A study by National Voices, a coalition of over 160 health and care charities, collated patient and service user reported data from 19 England-wide surveys.

It found that just over half (54%) of the 808 332 respondents to the 2017 General Practice Patient Survey identified themselves as having one or more long term conditions and, of these, 3% said they had a written care …
Underwater endoscopic mucosal resection for superficial nonampullary duodenal adenomas
Authors: Yasushi Yamasaki, Noriya Uedo, Yoji Takeuchi, Koji Higashino, Noboru Hanaoka, Tomofumi Akasaka, Minoru Kato, Kenta Hamada, Yusuke Tonai, Noriko Matsuura, Takashi Kanesaka, Masamichi Arao, Sho Suzuki, Taro Iwatsubo, Satoki Shichijo, Hiroko Nakahira, Ryu Ishihara, Hiroyasu Iishi
Journal: Endoscopy (2017)

Abstract Background and study aim Underwater endoscopic mucosal resection (UEMR) was recently developed in a Western country. A prospective cohort study to investigate the effectiveness of UEMR was conducted in patients with small superficial nonampullary duodenal adenomas. Patients and methods Patients with duodenal adenomas ≤ 20 mm were enrolled. After the duodenal lumen had been filled with physiological saline, UEMR was performed without submucosal injection. Endoclip closure was attempted for all mucosal defects after UEMR. Follow-up endoscopy with biopsy was performed 3 months later. The primary end point was the complete resection rate, defined as neither endoscopic nor histological residue of adenoma at the follow-up endoscopy. Results 30 patients with 31 lesions were enrolled. The mean (SD) tumor size was 12.0 mm (7.3). The complete resection rate was 97 % (90 % confidence interval, 87 % – 99 %). The en bloc resection rate was 87 %. All mucosal defects were successfully closed by endoclips. No adverse events occurred except for one case of mild aspiration pneumonia. Conclusions UEMR is efficacious for the treatment of small duodenal adenomas, but further large-scale trials are warranted to confirm these results. Trial registered at University Hospital Medical Network Clinical Trials Registry (UMIN 000018710).
CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma
Authors: Tony Avril, Amandine Etcheverry, Raphaël Pineau, Joanna Obacz, Gwénaële Jegou, Florence Jouan, Pierre-Jean Le Reste, Masumeh Hatami, Rivka R. Colen, Brett L. Carlson, Paul A. Decker, Jann N. Sarkaria, Elodie Vauléon, Dan Cristian Chiforeanu, Anne Clavreul, Jean Mosser, Eric Chevet, Véronique Quillien
Journal: Clinical Cancer Research (2017)

Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear.Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90high primary GSC lines.Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients. Clin Cancer Res; 23(23); 7360-74. ©2017 AACR.
Multi-institutional European single-arm phase II trial of pazopanib in advanced malignant/dedifferentiated solitary fibrous tumors (SFT): A collaborative Spanish (GEIS), Italian (ISG), and French (FSG) sarcoma groups study.
Authors: Javier Martin Broto, Silvia Stacchiotti, Antonio Lopez-Pousa, Andres Redondo, Daniel Bernabeu, Paolo Giovanni Casali, Antoine Italiano, Giovanni Grignani, Sarah Dumont, Xavier Garcia del Muro, Antonio Gutierrez, Javier Martinez Trufero, Emanuela Palmerini, Nadia Hindi, Enrique de Alava, Paola Collini, Dominique Ranchère-Vince, Jean-Yves Blay, Josefina Cruz
Journal: Journal of Clinical Oncology (2017)

11003 Background: SFT is a rare soft tissue tumor. In advanced SFT chemotherapy has only limited activity. With the rationale of a rich vascular network &amp; VEGF (tumor cells and endothelium) and VEGFR1/2 (endothelial cells) expression in SFT, we designed an international, single-arm phase II trial to test pazopanib (P) in advanced SFT. Clinical and preclinical evidence suggesting that antiangiogenics was less effective in more aggressive compared with less aggressive SFT (Stacchiotti et al), led us to conduct the trial on two different cohorts: typical and malignant (M)/dedifferentiated (DD) SFT. Here we present the outcome of the latter cohort. Methods: Most relevant inclusion criteria were: unresectable or metastatic, M/DD SFT confirmed by central pathologic review with evidence of STAT6 (IHC and /or FISH or RT-PCR), ≥ 18 years, ECOG 0-2, progressive and measurable disease. Main endpoint was response rate (RR) according Choi criteria. Central radiological assessment was mandatory. P was administered at 800 mg/d continuously until progression or toxicity. Results: From June 2014 to November 2016, 34 patients (pts) were enrolled with a median age of 61 y (23-87). Median tumor size and mitosis at diagnosis were 77 mm and 8x10 HPF. Most relevant grade 3-4 toxicity were neutropenia (9%) and hypertension (12%). At the time of the present analysis, 31 pts are evaluable for response. RR according to Choi and RECIST were: PR 16 (52%), SD 7 (22%), PD 8 (26%) and PR 1 (3%), SD 19 (61%), PD 11 (35%) respectively. With a median follow-up of 15 months, the median PFS was 5.53 months (4.24-6.82), while 72% survived at 18 months. Size &gt; 5 cm, mitosis &gt; 8 and DD subtype showed significantly worse PFS. The 18-month OS was 90% for those with SD and PR and 25% for PD according to Choi (p &lt; 0.001), while 94% for SD and PR and 45% for PD according RECIST (p = 0.002). In multivariate analysis, only Choi was an independent prognostic factor for OS with PD showing a HR of 11.9 (2.3-63.1), p = 0.003 for the risk of death. Conclusions: Pazopanib showed activity in malignant SFT. Choi criteria exhibited a more accurate assessment of response than RECIST. Clinical trial information: NCT02066285.
Glutamine synthetase staining and CTTNB1 mutation in hepatocellular adenomas
Authors: Sanjay Kakar, Linda D. Ferrell
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. The excellent study by Rebouissou et al.1 demonstrates that different CTTNB1 mutations lead to different levels of β‐catenin activation in hepatocellular adenoma (HCA), providing a molecular basis for different glutamine synthetase (GS) staining patterns. This letter calls attention to two aspects of the study: Exceptions to reported correlation between CTTNB1 mutations and GS immunohistochemistry 1 (a) In this study, all HCAs with D32‐S37 deletions and T41 mutation in exon 3 of CTTNB1 had diffuse homogeneous GS and nuclear β‐catenin in >1% of tumor. Several exceptions to this result have been reported.2 2 (b) In this study, all HCA S45 mutation had diffuse heterogeneous GS. Staining can be highly variable with this mutation and diffuse homogeneous GS can be seen in some portions of the tumor.2 It would be of interest for the investigators to share their experience in light of the above‐noted exceptions. Correlation of GS staining and CTTNB1 mutation in hepatocellular carcinoma (HCC) would be of interest and was not stated in the article. 1 2. GS criteria Diffuse GS (moderate/strong in >50% of tumor) strongly correlates with β‐catenin activation3; currently followed criteria divide this into diffuse homogeneous (>90%) or diffuse heterogeneous (50%‐90%). In this study, the investigators have modified the criteria: 1 Pattern 1: Perivascular 2 Pattern 2: Weak diffuse heterogeneous 3 Pattern 3: Moderate diffuse heterogeneous 4 Pattern 4: Strong diffuse heterogeneous 5 Pattern 5: Strong diffuse homogeneous The new criteria raise several questions: 1 (a) "Diffuse GS staining" is understood as signifying β‐catenin activation; use of "weak diffuse GS" is potentially confusing given that most did not show exon 3 CTTNB1 mutation. Also, the image for pattern 2 shows staining of <50% of tumor, but is classified as "diffuse." 2 (b) Based on original GS criteria, pattern 2 would be GS "negative" (no β‐catenin activation) whereas pattern 3 would be "diffuse heterogeneous." Given that a minority of cases with GS patterns 2 and 3 show exon 3 CTTNB1 mutation, would the investigators recommend that patterns 2 and 3 be classified as "indeterminate for β‐catenin activation" for clinical purposes? The change in GS criteria can affect assessment of risk in hepatocellular neoplasms in diagnostic practice, which can influence management. The investigators have tremendous experience on this topic, and it would be useful to provide a rationale for changing the criteria and elucidate how the new criteria are better.