tbuckley/cabot-search huggingface dataset:
G-CSF Starting Day +1 after Autologous Transplant Is Safer Than Day +5 or Day +7 in Patients with Multiple Myeloma
Authors: Francesca Cottini, Douglas Sborov, Yu Kyoung Cho, Misty Lamprecht, Karen Tackett, Junan Li, Steven M. Devine, Ming Poi, Mitch A. Phelps, Craig C Hofmeister
Journal: Blood (2016)
Roar: A Phase Ib Trial of Oral Azacitidine (CC-486) in Combination with Lenalidomide and Dexamethasone (Rd) for Patients with Relapsed and/or Refractory (R/R) Multiple Myeloma Who Have Failed a Prior Lenalidomide-Containing Regimen
Authors: Anna Kalff, Kate Reed, Tiffany T. Khong, Sridurga Mithraprabhu, Malarmathy Ramachandran, John Reynolds, Krystal Bergin, Anjan Thakurta, Maria Wang, Andrew Spencer, Roberto Guzman, Suzana Cuoto, Yan Ren
Journal: Blood (2016)
Abstract 21363: Improving Glycemic Control is Associated with A Beneficial Impact on Progression of Coronary Atherosclerosis: Insights From Intravascular Ultrasound
Authors: Kiyoko Uno, Julie Thornton, Kathy Wolski, Ayman Hussein, Paul Schoenhagen, Samir Kapadia, E. Murat Tuzcu, Steven E Nissen, Stephen J Nicholls
Journal: Circulation (2010)

Background: Measures of glycemic control and insulin sensitivity are associated with cardiovascular outcome in patients with diabetes. However, there is currently no data suggesting that favorable ...
Factors associated with <i>BRCA 1/2</i> testing among young women from hereditary breast and ovarian cancer families.
Authors: Erin Elizabeth Roesch, Beth N. Peshkin, Andrea Johnson, Sarah Murphy, Rebekah Hamilton, Sue Friedman, Claudine Isaacs, Kenneth Tercyak, Suzanne C. O'Neill
Journal: Journal of Clinical Oncology (2016)

e13122 Background: A positive BRCA 1/2 test result can provide young women from hereditary breast cancer (HBC) families with essential information about future cancer risk. While test results can inform life planning, 5-year breast cancer risks for young women are low. Little is known about what motivates testing for young women. While the likelihood of testing should increase as women age, it might also increase with the familial burden of disease (more affected relatives and relatives diagnosed at younger ages). We predicted the likelihood of testing would increase with age and greater familial disease burden. Methods: Sixty-one young women (Mean age 23 yrs) who were 1st or 2nd degree relatives of BRCA 1/2 carriers provided cancer family histories. Participants ages 18-30 were recruited through research registries and a national non-profit. Using logistic regression, we examined the association between self-reported receipt of BRCA 1/2 genetic testing and the young woman’s age (18-24, > 25 years), her number of relatives affected with breast/ovarian cancer, and the age at which her youngest relative was affected. Results: Thirty-eight women (61%; 6 of 20 women < 25 yrs (30%); 32 of 41 women > 25 yrs (78%)) received genetic testing. The odds of testing were higher among women > 25 (OR = 6.78, 95% CI = 1.27-36.36, p < .05). The odds of testing decreased marginally for each cancer-affected family member (OR = 0.77, 95% CI = .56-1.05, p = .09) and as the age of the youngest affected relative’s age increased (OR = 0.88, 95% CI = .78-1.01, p = .06). Conclusions: Few studies have examined predictors of testing in young women who are members of HBC families. Our results support a high rate of testing among these women. The finding that the odds of testing increases with age concurs with current guidelines as screening and prevention recommendations only commence at age 25. The significance of cancer family history in young women’s test use remains to be elucidated with the goal of continually improving risk counseling for patients.
Survival impact of initial local therapy selection for men under 60 with high risk prostate cancer.
Authors: Adeel Kaiser, Soren Bentzen, Minhaj Siddiqui, Michael J Naslund, Young Kwok, Pradip P. Amin, Zeljko Vujaskovic, Mark Vikas Mishra, Shahed Nicolas Badiyan
Journal: Journal of Clinical Oncology (2017)

5082 Background: The impact of initial local therapy selection on survival for high risk prostate cancer (PCa) patients remains uncertain. We sought to assess this effect, while limiting competing causes of death, through the examination of a younger PCa patient cohort within the National Cancer Database. Methods: We evaluated the overall survival (OS) of men under 60 with high risk PCa receiving either radiation therapy (RT) or radical prostatectomy (RP). All men in this age group were treated between 2004 and 2013, harbored cN0M0 disease, and presented with Gleason Scores (GS) of 8 to 10. The RT group included patients who received external beam radiation (EBRT) alone or EBRT in combination with brachytherapy (BT). Overall survival and covariates were evaluated using multivariable Cox regression analysis. Results: A total of 16,944 patients met inclusion criteria of which 12,155 underwent RP and 4,789 received RT as initial therapy. 82.5% of RT patients received hormonal therapy, and the median dose was 77.4 Gy. In the RP group, 17.2% of patients received postoperative radiation, and 87% of these cases received a dose exceeding 64.80 Gy. The RP group had a higher proportion of cases with Charlson-Deyo comorbidity score &gt; 0 (15.2% v. 11.2%, p &lt; 0.000001). At a median follow-up of 50 months (0 - 131 months), RP was associated with improved OS in comparison to RT (hazard ratio = 0.52; 95% CI (0.47, 0.58); p &lt; 0.000001). The estimated 8-year OS (±1 standard error of the estimate) was 85.1±0.7% and 74.9±0.7%, after RP and RT, respectively. This benefit remained present when adjusting for age, year of treatment, race, comorbidity score, Gleason score, T stage, hormonal therapy, chemotherapy, form of radiation, PSA, or insurance status. Conclusions: Compared to RT, initial treatment of men under 60 with high risk PCa with RP results in a large, statistically significant improvement in overall survival that remains consistent over time and remains significant in a multivariable model adjusting for known prognostic variables. These results are limited by the retrospective nature of the database analysis, and the lack of cancer specific survival information.
Abstract 168: Drp1 Accumulates in Mitochondria and Plays a Protective Role in the Heart in Response to Pressure Overload
Authors: Akihiro Shirakabe, Yoshiyuki Ikeda, Toshiro Saito, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2015)

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining the quality control of mitochondria through mitochondrial (Mt) fission and mitophagy. We investigated how Mt function, autophagy and Drp1 are regulated in the heart during pressure overload (PO) and whether endogenous Drp1 plays an important role in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 6 hours and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 5 (TAC vs Baseline; 6.21 ± 0.28 vs 4.59 ± 0.36, p&lt;0.05). Ejection fraction (EF) was maintained at Day 5 (79±5 vs 82±7%), but gradually decreased thereafter (30 days; 51±12%, p&lt;0.05). LC3-II was decreased (-40.0%, p&lt;0.05) while p62 accumulated (1.84 fold, p&lt;0.05) significantly at Day 5. Both Mt ATP content (-65.6%, p&lt;0.05) and production (-90.3%, p&lt;0.05) were reduced significantly at Days 7 and 14, respectively, and thereafter. Mt mass, evaluated by electron microscopy, was also reduced (-19.9%, p&lt;0.05) at Day 7. Drp1 accumulated in mitochondria at Day 7, and S616 phosphorylation of Drp1, associated with increased activity, was increased at Day 7. Thus, PO suppresses autophagy and induces Mt dysfunction by Day 7, at which time Drp1 accumulates in mitochondria and Mt mass is decreased. To examine the functional significance of endogenous Drp1 during PO, cardiac-specific heterozygous Drp1 knock out (Drp-hetCKO) mice were subjected to TAC. At Day 7, decreases in EF (57± 11 vs 80 ± 7%, p&lt;0.05) and increases in LVW/TL (7.22 ± 0.26 vs 5.86 ± 0.65, p&lt;0.05) and lung weight/TL (13.03 ± 1.09 vs 7.00 ± 1.31, p&lt;0.05) were exacerbated in Drp-hetCKO compared to in control mice. LV end diastolic pressure was significantly higher (20.0 ± 5.7 vs 7.4 ± 3.1 mmHg, p&lt;0.05) and myocardial fibrosis (14.1 ± 2.5 vs 6.2 ± 4.3 %, p&lt;0.05) was greater, and Mt mass was also significantly greater in Drp-hetCKO than in control mice (relative Mt mass, 1.21 ± 0.46 vs 1.00 ± 0.02, p&lt;0.05). These results suggest that PO inhibits autophagy and induces mitochondrial dysfunction by Day7, which coincides with Mt accumulation of Drp1. Drp1 plays an adaptive role in this condition, mediating decreases in Mt mass and protecting the heart from dysfunction.
New Concepts in the Treatment of Malignant Pleural Mesothelioma
Authors: Ori Wald, David J. Sugarbaker
Journal: Annual Review of Medicine (2017)

Malignant pleural mesothelioma (MPM) is a highly aggressive and generally incurable cancer. Current anti-MPM chemotherapy-based treatments are only marginally effective, and long-term survival remains an unmet goal. Nonetheless, in selected cases, personalized surgery-based multimodality treatments (MMT) have been shown to significantly extend survival. The design of MMT and selection of patients are challenging, and optimal results require accurate presurgical diagnosis, staging, and risk stratification. Further, meticulous surgical techniques and advanced radiation protocols must be applied. We review key principles and evolving concepts in the care of MPM patients with a focus on the expanding role of MMT in MPM.
Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints
Authors: Annalisa Pianta, Sheila L. Arvikar, Klemen Strle, Elise E. Drouin, Qi Wang, Catherine E. Costello, Allen C. Steere
Journal: Journal of Clinical Investigation (2017)

In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels. FLNA did not show the same results. The HLA-DR-presented GNS peptide has marked sequence homology with epitopes from sulfatase proteins of the Prevotella sp. and Parabacteroides sp., whereas the HLA-DR-presented FLNA peptide has homology with epitopes from proteins of the Prevotella sp. and Butyricimonas sp., another gut commensal. Patients with T cell reactivity with each self-peptide also had responses to the corresponding microbial peptides, and the levels were directly correlated. Furthermore, HLA-DR molecules encoded by shared-epitope (SE) alleles were predicted to bind these self- and microbial peptides strongly, and these responses were more common in RA patients with SE alleles. Thus, sequence homology between T cell epitopes of 2 self-proteins and a related order of gut microbes may provide a link between mucosal and joint immunity in patients with RA.
Assessment of EGFRvIII and PTEN profiles on routine histologic material from astrocytic tumors for patient selection for anti-EGFR treatment.
Authors: Vassiliki Kotoula, Despoina Televantou, Elpida Charalambous, Emily Daskalaki, Athanasios Fassas, George Karkavelas
Journal: Clinical Cancer Research (2008)

B32  Based on the reported predictive value of the EGFRvIII+/PTEN+ profile for targeted therapeutic approaches with EGFR kinase inhibitors in patients with glioblastoma, we started assessing this profile prospectively, when patient re-evaluation was mandatory in routine clinical practice, in order to select those who would benefit from such targeted treatment. Herein, we present our experience with this testing during the last 2 years. In order to evaluate the methods to be used, we initially assessed available archived tissue material (paraffin blocks) from 106 previously diagnosed astrocytic tumors (66 glioblastomas [GBM], 19 anaplastic astrocytomas [AA], 21 diffuse fibrillary astrocytomas [DFA]) for EGFR gene amplification (real time PCR), EGFRwt and EGFRvIII expression (semiquantitative RT-PCR, strong and low expression), as well as PTEN protein presence (immunohistochemistry [IHC]). Semiquantitative EGFRvIII determination was used in order to exclude cases where vIII would be expressed by only a minority of neoplastic cells. EGFR gene dosage assessment was used as a control for EGFRvIII expression in GBMs, where vIII expression has been repeatedly observed exclusively in cases with EGFR gene amplification. The cutoff for PTEN protein positivity was set at 75% with 2+ intensity. By using the same methods, diagnostic tissue material from 17 patients with GBM who suffered relapse upon initial treatment failure (mostly temozolomide and radiotherapy) was prospectively evaluated for new treatment assessment. EGFRvIII expression was observed in 34% of all tumors tested, including AAs and DFAs. Low EGFR vIII expression was also found in low grade astrocytomas (50% of AAs), where it was unrelated to EGFR gene amplification. Strong EGFRvIII expression was observed in only 15% of all tumors, almost exclusively GBMs (p
Green living environment protects against allergy, or does it?
Authors: Lasse Ruokolainen
Journal: European Respiratory Journal (2017)

Increasing human populations impose enormous pressure on natural habitats. For example, forests around the world are being converted into timber, pastures, croplands and settlements. To put the rate of deforestation into context, an area equivalent of ∼50 football fields is destroyed every minute [1]. While this development is one of the most important threats to biological diversity, human health is also at stake. In 2011, it was suggested that the global loss of biodiversity might be related to the parallel increase in the incidence of inflammatory disorders [2]. This gave rise to the biodiversity hypothesis of allergic disease [3] proposing that contact with natural environments enriches the human microbiome, promotes immune balance and protects from inflammatory disorders. The biodiversity hypothesis enlarges the Old Friends mechanism, emphasising the co-evolutionary history between humans and immunoregulatory microbes [4]. We need more direct and accurate measures to assess the quality and amount of environmental exposure <http://ow.ly/McGd30c4Aww> I would like to thank Tari Haahtela and an anonymous reviewer for their comments to improve the manuscript.
Phase 1b study of WNT inhibitor vantictumab (VAN, human monoclonal antibody) with paclitaxel (P) in patients (pts) with 1st- to 3rd-line metastatic HER2-negative breast cancer (BC).
Authors: Monica M. Mita, Carlos Becerra, Donald A. Richards, Alain C. Mita, Elena Shagisultanova, Cynthia R. C. Osborne, Joyce O'Shaughnessy, Chun Zhang, Randall Henner, Ann M. Kapoun, Lu Xu, Jakob Dupont, Rainer Karl Brachmann, Azeez Farooki, Jennifer Robinson Diamond
Journal: Journal of Clinical Oncology (2016)

2516 Background: The WNT pathway is an important oncologic driver of BC. VAN is a first-in-class antibody that blocks canonical WNT signaling by interacting with 5 Frizzled receptors (1, 2, 5, 7, 8). In pt-derived BC xenografts, VAN inhibits growth, reduces cancer stem cell frequency, promotes differentiation and synergizes with taxanes. A 6-gene expression WNT biomarker, without prognostic value, predicts VAN efficacy in pt-derived BC xenografts. In Phase 1a, VAN was well tolerated except for bone toxicity mitigated with blood-based bone marker monitoring and zoledronic acid (ZA) administration. Target modulation was observed in tumor tissues at VAN ≥ 0.5 mg/kg every 2 weeks (q2w). Methods: Dose escalation started with intravenous VAN q2w using a standard 3+3 design, and was then pursued for q4w with 6-pt cohorts. P at 90 mg/m2 was given on Days 1, 8 and 15 of each 28-day cycle. Objectives were determination of maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, predictive biomarkers and efficacy. Results: 23 pts have been treated to date, the 1st 11 in 3 q2w cohorts (3.5, 7 & 14 mg/kg). After 2 Grade (G) 2 fragility fractures, 12 pts were treated with a revised safety plan in 2 q4w cohorts (3 & 5 mg/kg) without further fragility fractures. VAN-related adverse events (AEs) ≥ 10% were fatigue, constipation, neutropenia, diarrhea, nausea and abdominal pain. Only related G ≥ 3 AEs were G3 neutropenia (n = 3), leukopenia & pelvic pain. For q4w pts, baseline ZA, if indicated, increased monitoring and more sensitive bone marker triggers for ZA resulted in bone-protective ZA therapy by end of Cycle 1 in 100% of pts. Of 21 evaluable pts, 7 (33%) had a partial response and 6 (29%) stable disease. Conclusions: VAN is well tolerated in combination with paclitaxel. A revised safety plan appears to have addressed bone toxicity encountered early in the study. Updated results, including correlation of the 6-gene biomarker in pt tumors with progression-free and overall survival, will be presented Clinical trial information: NCT01973309.
Aclidinium bromide improves symptoms and sleep quality in COPD: a pilot study
Authors: Helgo Magnussen, Michael Arzt, Stefan Andreas, Tanja Plate, Anna Ribera, Beatriz Seoane, Henrik Watz, Anne-Marie Kirsten
Journal: European Respiratory Journal (2017)

In patients with chronic obstructive pulmonary disease (COPD), nighttime and early-morning symptoms are associated with an increased rate of exacerbation, hospital admission and reduced survival [1, 2]. Furthermore, patients with COPD frequently have poor sleep quality [3] and reduced physical activity [4, 5]. We hypothesised that nighttime airflow obstruction in patients with COPD is associated with impaired sleep quality, leading to early-morning symptoms and reduced physical activity. Aclidinium statistically improved symptoms, and sleep and physical activity in moderate COPD <http://ow.ly/2chV30adLbW> The authors would like to thank the patients, study staff and investigators at each of the participating centres for their contribution to this study. The authors thank Richard Knight, Complete Medical Communications, Macclesfield, UK for providing medical writing support, which was funded by AstraZeneca, Cambridge, UK in accordance with Good Publication Practice (GPP3) guidelines.
Wide Complex Tachycardia in an Elderly Woman
Authors: Andres Enriquez, David S. Frankel
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Immunohistochemistry as an aid to the diagnosis of HNPCC
Authors: R Geraghty, D Keegan, E Fox, D Leahy, A Green, JM Hyland, K Sheahan, DP O'Donoghue
Journal: Endoscopy (2006)

Aims: Assess the value of routine Immunohistochemistry (IHC) for loss of Mismatch Repair Proteins (MMR) in the detection of Hereditary Non Polyposis Colorectal Cancer (HNPCC).
Phase I/II Study of DFP-10917 in Relapsed/Refractory AML Demonstrates Efficacy and Safety Profile Suitable for Phase III Study
Authors: Hagop M. Kantarjian, Elias J. Jabbour, Guillermo Garcia-Manero, Tapan M. Kadia, Courtney D. DiNardo, Naval G. Daver, Gautam Borthakur, Nitin Jain, Jane Waukau, Monica Kwari, Barry Douglas Anderson, Kenzo Iizuka, Cheng Jin, Chun Zhang, Farhad Ravandi, William Plunkett
Journal: Blood (2016)
Epidemiology and outcomes of bloodstream infections in 177 severe burn patients from an industrial disaster: a multicentre retrospective study
Authors: C.Q. Tang, J.Q. Li, B.M. Shou, B.H. Pan, T.S. Chen, Y.Q. Xiao, X.P. Zheng, S.C. Xiao, Q. Tan, Z.F. Xia
Journal: Clinical Microbiology and Infection (2017)
Effect of Oncotype DX Recurrence Score (RS) on chemotherapy (CT) decision-making by providing information beyond intrinsic subtypes in both luminal A and B breast cancer (BC) patients (pts): A retrospective study in the Spanish population.
Authors: Laura Garcia-Estevez, Elena Hernandez, Daniel Acosta, Fernando Lopez-Rios, Mario Prieto, Isabel Calvo
Journal: Journal of Clinical Oncology (2016)

e12013 Background: St Gallen guidelines recommend the use of Ki67 by IHC as a surrogate marker for luminal A and B BC subtypes, such that pts with luminal B ( ≥ 14%) subtypes should be considered for adjuvant CT. Oncotype DX RS is a predictor of CT benefit. The aim of this study is to assess the distribution of the RS in luminal A and B BC subtypes as defined by Ki67 and to assess treatment changes based on RS. Methods: Data were collected from 210 pts with invasive breast cancer for which Oncotype DX results and pathology data were available. Estrogen (ER) and progesterone (PR) receptor was assessed by immunostaining (cut-off 10% nuclear staining). Ki67 was assessed by IHC [high ( ≥ 14%) and low ( < 14%)]. Grading was performed using the Nottingham grading system. Results: Median age: 50 years (35-78); premenopausal status: 122 pts (58.1%). Median tumor size: 1.7 cm (2-10); Overall, 65.7% of cases had grade II tumors, and 13.3% grade III. All pts had HER2 negative tumors, 90 were luminal A and 120 luminal B. Of those with positive lymph nodes (36.7%), 51.9% had macrometastasis. Median ER value was 95 (range: 35-100) and PR 85 (0-100). Median Ki67 index was 15 (2-63) and RS 16 (1-55). Luminal A and B subtypes showed statistical differences with respect to tumor size, grade III and levels of ER and PR (p = 0.027, p < 0.001, p < 0.001, and p = 0.009, respectively) in favor of luminal B. In the luminal A group, 56 (62.2%) pts presented low RS, 30 (33.3%) intermediate, and 4 (4.4%) high RS. Similar distribution in the luminal B group: 67 patients (55.8%), 41 (34.2%) and 12 (10%), respectively. Overall, 103 pts (49%) changed their treatment. In the luminal A group, RS results changed initial treatment recommendation in 43.3% vs 53.3% in the luminal B group, both groups in favor of hormonotherapy. Conclusions: A substantial number (55.8%) pts with luminal B BC subtype had a low RS, therefore preserving them from adjuvant CT treatment. According to this data, luminal subtyping by Ki67 is not always a reliable surrogate marker for receiving chemotherapy, confirming the important role of Oncotype DX in treatment decision-making.