tbuckley/cabot-search huggingface dataset:
Older patients should take PPIs to cut risk of bleed from aspirin, study says
Authors: Susan Mayor
Journal: BMJ (2017)

Elderly people who take long term daily aspirin have a higher than expected risk of disabling or fatal upper gastrointestinal bleeding, a major UK study has found.1 The researchers recommend prescribing proton pump inhibitors (PPIs) to prevent bleeds in older patients undergoing aspirin based antiplatelet treatment.

An estimated 40-66% of people aged over 75 in Europe and the US currently take daily aspirin or other antiplatelet drugs, often for secondary prevention of vascular disease. But guidelines recommending this treatment are based on trials carried out in younger people.

Peter Rothwell, from the Centre for Prevention of Stroke and Dementia …
Surgeon Variation in Complications With Minimally Invasive and Open Colectomy
Authors: Mark A. Healy, Scott E. Regenbogen, Arielle E. Kanters, Pasithorn A. Suwanabol, Oliver A. Varban, Darrell A. Campbell, Justin B. Dimick, John C. Byrn
Journal: JAMA Surgery (2017)

<h3>Importance</h3> Minimally invasive colectomy (MIC) is an increasingly common surgical procedure. Although case series and controlled prospective trials have found the procedure to be safe, it is unclear whether safe adaptation of this approach from open colectomy (OC) is occurring among surgeons. <h3>Objective</h3> To assess rates of complications for MIC compared with OC among surgeons. <h3>Design, Setting, and Participants</h3> We analyzed 5196 patients who underwent MIC or OC from January 1, 2012, through December 31, 2015, by 97 surgeons in the Michigan Surgical Quality Collaborative, with each surgeon performing at least 10 OCs and 10 MICs. Hierarchical regression was used to assess surgeon variation in adjusted rates of complications and the association of these outcomes across approaches. <h3>Main Outcomes and Measures</h3> Primary study outcome measurements included overall 30-day complication rates, variation in complication rates among surgeons, and surgeon rank by complication rate for MIC vs OC. <h3>Results</h3> Of the 5196 patients (mean [SD] age, 62.9 [14.4] years; 2842 [54.7%] female; 4429 [85.2%] white), 3118 (60.0%) underwent MIC and 2078 (40.0%) underwent OC. Overall, 1149 patients (22.1%) experienced complications (702 [33.8%] in the OC group vs 447 [14.3%] in the MIC group;<i>P</i> &lt; .001). For MIC, the rates of complications varied from 8.8% to 25.9% among surgeons. For OC, rates of complications were higher but varied less (1.7-fold) among surgeons, ranging from 25.9% to 43.8%. Among the 97 surgeons ranked, the mean change in ranking between OC and MIC was 25 positions. The top 10 surgeons ranged in rank from 6 of 97 for OC to 89 of 97 for MIC. <h3>Conclusions and Relevance</h3> Surgeon-level variation in complications was nearly twice as great for MIC than for OC among surgeons enrolled in a statewide quality collaborative. Moreover, surgeon rankings for OC outcomes differed substantially from outcomes for those same surgeons performing MIC. This finding implies a need for improved training in adoption of MIC techniques among some surgeons.
Human papillomavirus-related oropharyngeal cancer
Authors: M. Taberna, M. Mena, M.A. Pavón, L. Alemany, M.L. Gillison, R. Mesía
Journal: Annals of Oncology (2017)

High-risk human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world. The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into an OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability. Patients affected by HPV-related OPSCC tend to be younger and have better outcomes. This observation has lead current research to evaluate treatment de-escalation options to reduce long-term associated morbidity. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new options for targeted therapy and immunotherapy approaches. This paper comprehensively reviews our accumulated knowledge regarding the role of HPV in OPSCC spanning from infection to cancer development, including its clinical diagnosis, management and preventive strategies.
The transcription factor Runx3 guards cytotoxic CD8+ effector T cells against deviation towards follicular helper T cell lineage
Authors: Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M Hartwig, Jodi A Gullicksrud, Samarchith P Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D Martin, Steven M Varga, Ichiro Taniuchi, John T Harty, Weiqun Peng, Vladimir P Badovinac, Hai-Hui Xue
Journal: Nature Immunology (2017)
Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction
Authors: Sebastian J. Reinstadler, Thomas Stiermaier, Johanna Liebetrau, Georg Fuernau, Charlotte Eitel, Suzanne de Waha, Steffen Desch, Jan-Christian Reil, Janine Pöss, Bernhard Metzler, Christian Lücke, Matthias Gutberlet, Gerhard Schuler, Holger Thiele, Ingo Eitel
Journal: JACC. Cardiovascular imaging (2017)
Agreement Between R2 and R2* Liver Iron Estimates Is Independent of the Type of Iron Removal Therapy: Results from the Twitch Trial
Authors: John C Wood, Tim St Pierre, Banu Aygun, Nicole Mortier, William H Schultz, Connie M. Piccone, Jane Hankins, Zora R. Rogers, William Owen, Isaac Odame, Sharada A. Sarnaik, Lee Hilliard, Alan R. Cohen, Russell E. Ware
Journal: Blood (2016)
Assessment and Treatment of Syncope
Authors: Win-Kuang Shen, Robert S. Sheldon
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
Human Insulin for Type 2 Diabetes
Authors: Kasia J. Lipska, Irl B. Hirsch, Matthew C. Riddle
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Biweekly Bendamustine Monotherapy for Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma and Mantle Cell Lymphoma: A Rabbit-14 Trial
Authors: Tadahiko Igarashi, Hisashi Wakita, Hideki Tsujimura, Nobuyuki Aotsuka, Shinichi Masuda, Yoshikazu Utsu, Naoya Murata, Hiroyuki Irisawa, Kunihiro Tsukasaki, Kuniaki Itoh
Journal: Blood (2016)
Umbilical cord mesenchymal stem cells for the treatment of autoimmune diseases: beware of cell-to-cell contact
Authors: Alessia Alunno, Onelia Bistoni, Pia Montanucci, Giuseppe Basta, Riccardo Calafiore, Roberto Gerli
Journal: Annals of the Rheumatic Diseases (2017)

We have read with great interest the article from Deng and colleagues1 reporting on the results of a randomised, controlled clinical trial of allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) for lupus nephritis. The study demonstrated that the administration of intravenous UC-MSCs does not provide additional benefit to conventional immunosuppression.

Over the last decade, increasing evidence has indicated that UC-MSCs are multipotent cells with promising applications to regenerative medicine2 and also a powerful tool to modulate the immune system. UC-MSCs can interact with most immune cell types via both cell–cell contact and secretion …
Correlation between Oncotype DX recurrence score and classical risk factors in early breast cancer.
Authors: Fernando Namuche, Rossana Esther Ruiz Mendoza, Claudio J. Flores, Alfredo Aguilar, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2017)

e12011 Background: OncotypeDx(ODX) predicts the likelihood of estrogen receptor (ER) positive breast cancer (BC) recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy. Many clinical scores that estimate the risk category of ODX are being tested. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use. Methods: We retrospectively reviewed the electronic medical files of 190 patients with early stage ER+ BC for whom ODX recurrence score (RS) was available from 2014 to 2016. Our objective was to find out the degree to which classical clinicopathological variables -as defined by St. Gallen(SG) 2015- could predict ODX risk category, also to determine an optimal Ki67 cut-off in order to establish an accurate classification. Chi square test was used. Results: Mean age at diagnosis was 59 years (28-89). Mean tumor diameter was 15mm, 84.2% were intermediate grade. Mean expression of ER, PR and Ki67 were 87%, 53% and 22%, respectively. According to ODX 62.1% patients were low risk, 30.5% intermediate risk and 7.4% high risk. An overall concordance of 46.8% (73/190) was found between SG 2015 and the risk category of ODX (75.7% for low, 33.3% for intermediate and 23.9% for high RS). When changing SG Ki67 cutoffs to ≤20% (for low Ki67) and ≥30% (for high Ki67), an overall concordance of 56.3% (107/190) was found (69.6% for low, 47.3% for intermediate and 23.9% for high RS, with p=0.00) (Table 1). Conclusions: In best-case scenario, SG classical clinicopathological variables correctly classified 56.3% of patients of our series. Despite being a specialized center, the utility of classical clinicopathological variables for predicting ODX risk category is limited. [Table: see text]
EGFR signal pathways selectively activated in lung adenocarcinoma.
Authors: Miyako Hiramatsu, Hironori Ninomiya, Kentaro Inamura, Michiyo Okui, Yukitoshi Satoh, Mutsunori Fujiwara, Takao Yamori, Tomoyuki Kitagawa, Yuichi Ishikawa
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5038 

Back ground:

It is well known that mutations in the EGFR tyrosine kinase domain gene and the KRAS oncogene play key roles in acquiring growth advantage and that the products of these genes are necessary to maintain the viability of tumor cells in a certain population of lung adenocarcinoma. PI3K/Akt and Ras/Raf/MAPK are the two main signal transduction pathways triggered by EGFR and mediate their upstream effects on proliferation, survival or malignant transformation. Activations of these two pathways are dependent on the phosphorylation status of these components.

Methods:

190 evaluable cases with primary lung adenocarcinomas surgically resected between 1998 and 2001 were selected for this study. We explore the phosphorylation pattern of Akt and MAPK by means of immunohistochemistry to elucidate the selectively activated pathways in each case. Both positive and negative controls were prepared using mouse xenografts of PC-3 (pAkt+/pMAPK-) and HTB26 (pAkt-/pMAPK+) cell lines. Association of these downstream activated pathways with clinicopathological factors were determined by univariate analysis.

EGFR mutations and KRAS mutations were also examined in consecutive 93 cases out of the 190 cases and relationships between these mutation status and phosphorylation of downstream peptides were also analyzed.

Results:

Of the 190 cases, 59 (31%) were strongly positive for pAkt, and 147 (77%) for pMAPK. pMAPK immunoreactivity showed association with female (p=0.015), well differentiated characteristics (p=0.004), and fewer smoking index (p=0.01).

Among the 93 cases with mutational status , cases with EGFR mutations (n=54) showed higher positive rates for both pAkt (mutation+: 44% / mutation-: 28%, p=0.132) and pMAPK (mutation+: 85% / mutation-: 69%, p=0.066) but failed to show statistical significance. All the cases with KRAS mutations (n=7) were strongly positive for pMAPK. Among the cases without both EGFR and KRAS mutations, pMAPK immunoreactivity correlates with early stage (Stage I) (p=0.032) and TTF-1-positivity (p=0.006).

Conclusion:    >Exploration of activated EGFR downstream pathways in clinical lung adenocarcinoma reveals the associations of the two main signal pathways (PI3K/Akt and Ras/Raf/MAPK ) with certain clinicopahtological factors and mutation status ( EGFR and KRAS ). The results of this study support the relation of pMAPK activation to early stage tumors, not advanced ones, although there are some controversies in clinical and in vitro works.
Identification of genes targeted by 6p-amplification in retinoblastoma
Authors: Corinna Grasemann, Sandrine Gratias, Harald Stephan, Andreas Schueler, Angelika Eggert, Dietmar R. Lohmann
Journal: Cancer Research (2004)

1682   Mutations in both alleles of the RB-gene are required for development of retinoblastoma, a childhood cancer of the eye. Additional genetic alterations occur during progression of this tumor including, most prominently, gains of genetic material on chromosomes 1q31-q32 and on 6p22-p23. Recently, the minimal region of amplification on 6p was narrowed to a region of 0.6 Mb that contains  RBKIN , a kinesin-like gene, and  DEK , which is a known oncogene. To narrow down the region of interest we used quantitative multiplex PCR to investigate DNAs from 69 retinoblastomas. We determined relative gene doses of 14 STS loci in a 2 Mb region on 6p22-23, and of 2 control loci on 6q and 10q. Six of these STS-loci were located in the 0.6 Mb region of interest, one marker in the  RBKIN  and two markers in the  DEK  gene. In addition, we analyzed 3 primary retinoblastoma cell lines ( RBL13, RBL15, and RBL 30). In 29 tumors, an increase in gene dosage is detected for all STS-loci on chromosome 6p, a finding that is consistent with the presence of an i6p (isochromosome). 24 tumors show no increase in gene dosage for any of the loci investigated. In 16 tumors, gains are detected only for some of the 6p-loci. In these tumors the minimal region of gain is restricted to the two STS loci located within the DEK gene. In the RB cell lines, an increase of gene dosage was observed for all STS-loci. Strong expression of DEK protein was confirmed by Western blot analysis. RNA expression profiles using affymetrix U133A chips from 16 tumors are being analyzed. Our results narrow down the minimal region of amplification on 6p22 in retinoblastoma to a region that contains the known oncogene  DEK  but not  RBKIN . This finding is consistent with strong expression of  DEK  protein in retinoblastoma cell lines and suggests that DEK is a functional target of 6p-gains in this tumor.
A phase 1B/ phase 2A study of TRC105 (Endoglin Antibody) in combination with pazopanib (P) in patients (pts) with advanced soft tissue sarcoma (STS).
Authors: Steven Attia, Kamalesh Kumar Sankhala, Richard F. Riedel, Steven Ian Robinson, Robert Martin Conry, Patrick McKay Boland, Minal A. Barve, Karen Fritchie, Ben K. Seon, Delia Alvarez, Bonne J. Adams, Ronald L. Shazer, Charles P. Theuer, Robert G. Maki
Journal: Journal of Clinical Oncology (2016)

11016 Background: P, a VEGFR TKI, is approved for advanced STS based on median PFS (mPFS) in the absence of CR. Endoglin is a receptor expressed on tumor vessels that is overexpressed in certain STS, particularly angiosarcoma (AS). It is upregulated following VEGF inhibition and may mediate resistance to P. We performed a phase 1B/2A study of TRC105, an endoglin antibody, in combination with P in pts with advanced STS. Methods: The phase 1 was a dose escalation to determine the RP2D. The phase 2 was a single arm evaluation of TRC105 at the RP2D with P at 800 mg/day PO, with a primary endpoint of increasing PFS beyond that expected with P (HR = .667, power = 86%, one-sided α = 0.05). Secondary endpoints included PFS stratified by histology and tumor endoglin expression. Both phases required progression on chemotherapy, and excluded adipocytic STS and GIST. Results: The RP2D of TRC105 10 mg/kg/week IV was well tolerated with P 800mg/day. 18 pts were enrolled in phase 1B and 63 in phase 2A, (leiomyosarcoma (35); undifferentiated pleomorphic sarcoma (UPS) (18); synovial sarcoma (7); myxofibrosarcoma (6); epithelioid sarcoma (5); AS (5); epithelioid hemangioendothelioma (2)). Median age = 57, M:36 F:45; median prior lines of systemic therapy = 2. mPFS in phase 2 pts was 3.91 mo. (95%CI = 2.53, 5.69) and in all 81 pts was 3.95 mo. (95%CI = 3.72, 5.92), and was not significantly different from mPFS expected with P. mPFS will be stratified by histology and tumor endoglin expression. Three pts have ongoing CR (treatment duration = 44, 51, 75 wks), including 2 of 5 with AS, all of whom had tumor reductions, and 1 pt with multiorgan UPS. Adverse events (AEs) characteristic of each drug were not increased in frequency or severity. Common TRC105 related AEs included grade (g) ≤ 2 telangiectasia (with epistaxis and gingival bleeding) and headache, and g ≤ 3 anemia; common P related AEs included g ≤ 3 fatigue, diarrhea, and hypertension. Conclusions: TRC105 combined with P was well tolerated and exhibited activity, including durable CR in AS, a STS known to densely express endoglin, and UPS. A Phase 3 study in AS is planned. Stratification of PFS by tumor endoglin expression may direct TRC105 treatment in other STS histologies. Clinical trial information: NCT01975519.
Interleukin-10 Mediates Suppression of Host Anti-Tumour Responses in Hepatic Malignancy
Authors: AM Kelly, L Golden-Mason, O Traynor, G McEntee, JE Hegarty, C O'Farrelly
Journal: Endoscopy (2004)

The immune response to hepatic malignancy is likely to be determined by several factors, including cytotoxic T-cells and the local cytokine profile. A predominantly proinflammatory-IFN-γ (Th1) response promotes tumour rejection, while an anti-inflammatory-IL-10(Th2) response promotes tolerance and tumour progression. It has also been suggested that T-regulatory cells producing large amounts of IL-10, TGF-β and IL-13 suppress the inflammatory response. We examined levels of regulatory cytokines; TGF-β, IL-10 and IL-13 and the Th1 cytokine IFN-γ in tumour-bearing and normal liver. Normal controls obtained from donor organs (n=11) and tumour-bearing liver (n=12) obtained at the time of resection of colorectal metastases, were snap frozen, powdered, protein was extracted and cytokine levels were quantified using a modified ELISA. Relatively high levels of both TGF-β and IL-13 were detected in normal liver tissue compared to IL-10 (25.03, 54.87 and 1.73ng/100mg protein respectively). This may contribute to the tolorogenicity seen in the liver transplant setting. The Th2/regulatory cytokine, IL-10, was significantly raised in hepatic malignancy (12.74 vs. 2.31ng/100mg protein, p<0.0001). Despite a large amount of IFN-γ in tumour-bearing liver, the IFN-γ:IL-10 ratio was 1.37:1, as compared to 4.35:1 in normal liver reflecting the greater IL-10 levels in tumour samples. TGF-β and IL-13 levels were significantly reduced in tumour-bearing compared to normalliver (p<0.05). Our results suggest a shift towards a Th2-response in tumour-bearing liver. IL-10 but not TGF-β/IL-13 is involved in the suppression of host antitumour responses, facilitating tumour progression. Anti-IL-10 may be a useful therapeutic strategy in the treatment of colorectal metastatic disease.
Timing of Aspirin and Other Nonsteroidal Anti-Inflammatory Drug Use Among Patients With Colorectal Cancer in Relation to Tumor Markers and Survival
Authors: Xinwei Hua, Amanda I. Phipps, Andrea N. Burnett-Hartman, Scott V. Adams, Sheetal Hardikar, Stacey A. Cohen, Jonathan M. Kocarnik, Dennis J. Ahnen, Noralane M. Lindor, John A. Baron, Polly A. Newcomb
Journal: Journal of Clinical Oncology (2017)

Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( P