tbuckley/cabot-search huggingface dataset:
Changing landscape of immunosuppression in ANCA-associated vasculitis
Authors: Sergey V Moiseev, Ilya Smitienko, Nikolai Bulanov, Ekaterina Karovaikina, Pavel I Novikov
Journal: Annals of the Rheumatic Diseases (2019)

Table 1 Possible tailored regimens of remission induction treatment in patients with AAV Non-severe AAV Severe AAV Proteinase-3 ANCA Methotrexate* or rituximab Rituximab † or cyclophosphamide MPO-ANCA Methotrexate* or MMF or rituximab Cyclophosphamide or rituximab † or MMF † ANCA-negative Methotrexate* or cyclophosphamide Cyclophosphamide Immunosuppressive medications should be used in combination with glucocorticoids (at least 40 mg daily of prednisone in non-severe AAV and at least 60 mg daily of prednisone in severe AAV).*Only in patients with estimated glomerular filtration rate >30 mL/min/1.73m 2 .†Preferably in younger patients as well as in patients with relapsing disease.AAV, ANCA-associated vasculitides; ANCA, antineutrophil cytoplasmic antibody; MMF, mycophenolate mofetil; MPO, myeloperoxidase.
Impact of the distance from the root of the splenic artery to the tumor in patents with the pancreatic body/tail cancer.
Authors: Takuya Minagawa, Yukiyasu Okamura, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Ryo Ashida, Katsuhisa Ogi, Katsuhiko Uesaka
Journal: Journal of Clinical Oncology (2019)

221 Background: The impact of the distance from the root of the splenic artery to the tumor (DST) on prognosis and selection of operative procedures in patients with pancreatic body/tail cancer remains to be unclear. Methods: Between 2008 and 2018, 98 and 17 patients who underwent distal pancreatectomy (DP) and DP with celiac axis resection (DP-CAR) for conventional pancreatic ductal carcinoma were retrospectively analyzed. DST (mm) was measured by preoperative CT scan images. The indications for DP-CAR are the following: tumor involvement of the common hepatic artery and/or the celiac artery or difficulty in keeping surgical margin at the stump of the splenic artery. Results: Patients with DST = 0 had longer operation time ( p = 0.005), greater amount of blood loss ( p= 0.002), and higher morbidity rate ( p= 0.010) than those with DST &gt; 0. The rate of introducing adjuvant chemotherapy in the DST = 0 group was significantly lower than that in the DST &gt; 0 group (50% vs. 82%, p= 0.012). The median survival time (MST) of the DST = 0 group was significantly worse than that of the DST &gt; 0 group (20 vs. 56 months, p&lt; 0.001). In contrast, there was no significant difference of MST between the groups of 0 &lt; DST≤10 and DST &gt; 10 ( p= 0.499). Multivariate analyses revealed that DST = 0 (HR 4.51, p= 0.001), preoperative CA19-9 ≥40 U/mL (HR 2.91, p= 0.032) and preoperative neutrophil-to-lymphocyte ratio ≥2.3 (HR 2.49, p= 0.001) were independent prognostic factors. Regarding to the operative procedures, DP-CAR was performed 12 out of 14 patients with DST = 0, and 5 out of 16 patients with 0 &lt; DST≤10. In the DST = 0 group, DP-CAR presented greater amount of dissected lymph nodes, higher rate of R0 resection, and lower rate of recurrence despite they were not identified statistically significant. In the 0 &lt; DST≤10 group, DP-CAR tended to need longer operative time and higher rate of blood transfusion compared to DP, while there was no difference of prognosis. Conclusions: Multidisciplinary treatment including DP-CAR should be warranted for patients with DST = 0, which was a prognostic indicator. If surgical margin at the root of the splenic artery is secured in patients with DST &gt; 0, DP should be an acceptable procedure.
Abstract 18770: Dysregulation of miR-301b Contributes to Diabetic Cardiomyopathy via Upregulation of AMP Deaminase in the Vicinity of the Sarcoplasmic Reticulum
Authors: Yuki Tatekoshi, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Toshiyuki Yano, Wataru Ohwada, Koki Abe, Yusuke Igaki, Yugo Fujita, Tetsuji Miura
Journal: Circulation (2017)

Background: Diabetic cardiomyopathy is a major risk factor of HFpEF, which often decompensates under increased afterload. We recently found that excessive degradation of ATP by upregulated AMP deaminase (AMPD) contributes to marked enhancement of diastolic dysfunction at the time of increased afterload in a rat model of type 2 diabetes (T2D), OLETF. Upregulation of AMPD by T2DM appears to be shared with other animal models of T2D according to the Gene Expression Omnibus, a public genomics data repository. Here we examined the mechanism by which the activity of AMPD is upregulated by T2D. Methods and Results: AMPD activity in the ventricular tissue of OLETF was higher by 60% than that in LETO, non-diabetic control rats. Factors known to regulate AMPD activity, including PKC-mediated phosphorylation, were similar in OLETF and LETO. Western blot analysis revealed that protein level of the 90-kDa full-length form AMPD3 (a dominant isoform in rat hearts), but not that of the 78-kDa N-terminus truncated form AM...
Phase I Results of a Multicenter Clinical Trial Combining Guadecitabine, a DNA Methyltransferase Inhibitor, with Atezolizumab, an Immune Checkpoint Inhibitor, in Patients with Relapsed or Refractory Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Authors: Casey L. O'Connell, Patricia L. Kropf, Nathan Punwani, Dan Rogers, Richard Sposto, Kirsten Grønbæk
Journal: Blood (2018)
Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release
Authors: Shijie Li, Cai Yuan, Jincan Chen, Dan Chen, Zhuo Chen, Wenlie Chen, Shufeng Yan, Ping Hu, Jinping Xue, Rui Li, Ke Zheng, Mingdong Huang
Journal: Theranostics (2019)

Cancer cell expresses abundant surface receptors. These receptors are important targets for cancer treatment and imaging applications. Our goal here is to develop nanoparticles with cargo loading and tumor targeting capability. Methods: A peptide targeting at cancer cell surface receptor (urokinase receptor, uPAR) was expressed in fusion with albumin (diameter of ~7 nm), and the fusion protein was assembled into nanoparticles with diameter of 40 nm, either in the presence or absence of cargo molecules, by a novel preparation method. An important feature of this method is that the nanoparticles were stabilized by hydrophobic interaction of the fusion protein and no covalent linking agent was used in the preparation. The stability, the cargo release, in vitro and in vivo properties of such formed nanoparticles were characterized by transmission electron microscopy, dynamic light scattering, gel shift assay, laser scanning confocal microscopy and 3D fluorescent molecular tomography. Results: The nanoparticles were stable for more than two weeks in aqueous buffer, even in the buffer containing 10% fetal bovine serum. Interestingly, in the presence of urokinase receptor, the uPAR-targeting nanoparticle disintegrated into 7.5 nm fragments and released its cargo, but not the non-targeting nanoparticles made from albumin by the same preparation method. Such nanoparticles also showed higher uptake and cytotoxicity to the receptor-expressing cancer cells in vitro and higher tumor accumulation in xenografted tumor-bearing mice in vivo compared to the non-targeting nanoparticles. Conclusion: Our results demonstrate a new function of cell surface receptor as a responsive trigger to disassemble nanoparticles, besides its common use to enrich targeting agents. Such nanoparticles were thus named receptor-responsive nanoparticles (RRNP).
Persistent sore throat may be a warning sign for laryngeal cancer, study suggests
Authors: Susan Mayor
Journal: BMJ (2019)

Persistent sore throat, particularly when combined with other apparently low risk symptoms, is a previously overlooked clinical risk factor for cancer of the larynx, a UK case control study in UK general practice1 has found.

“This research matters. When the National Institute for Health and Care Excellence (NICE) guidance for cancer investigation was published there was no evidence from GP practices to guide this—nor to inform GPs,” said study author Willie Hamilton, from the University of Exeter Medical School, UK.

“These results expand current NICE guidance by identifying new symptom combinations that are associated with laryngeal …
Investigation of aberrant DNA methylation in association with cisplatin-resistant hepatoblastoma.
Authors: Sunao Fujiyoshi, Shohei Honda, Eiso Hiyama, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2019)

258 Background: Cisplatin (CDDP) is a key-drug of mainstream treatment for hepatoblastoma (HB), but 22.3% of HB patients have resistance to CDDP, and their prognoses are poor. We investigated methylation status of HB patients and identified CDDP resistant candidate genes in HB. Methods: First, we performed a genome-wide methylation array analysis of 11 resected HB tumors. These cases included six cases of RECIST (Response Evaluation Criteria In Solid Tumors) CR or PR (S group) and five cases of SD or PD (R group). We analyzed methylation status of these patients, comparing with clinical course, and selected significant differentially methylated genes. Next, We made CDDP-resistant HepG2 cells by repeated CDDP treatments for a year, then compared expression levels between the CDDP-resistant cells and original cells, using cDNA microarray analysis. We selected CDDP resistant candidate genes from these data. Results: In methylation array analysis data, unsupervised hierarchical clustering analysis showed that methylation profiles were separable into 2 groups in accord with clinical S group and R group. In principal component analysis, the S group also showed a different methylation pattern to the R group. We compared survival rates using Kaplan-Meier method, and results showed that the R group had poorer prognosis significantly. The R group showed 336 hypermethylated genes and 106 hypomethylated genes around the transcriptional start site compared with S group significantly. And in cDNA microarray analysis, 1271 genes were downregulated and 1571 genes were upregulated significantly in CDDP-resistant cells. From among these genes, we selected 15 suppressor and 8 promoter candidate genes that could be related to CDDP-resistance. Conclusions: We identified methylation status associated with CDDP resistance and poor prognosis, and 23 candidates genes in HB. Further refining might lead us to find out the pathogenesis of chemoresistance or new target of therapies and biomarkers in HB.
Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab
Authors: P.F. Ferrucci, P.A. Ascierto, J. Pigozzo, M. Del Vecchio, M. Maio, G.C. Antonini Cappellini, M. Guidoboni, P. Queirolo, P. Savoia, M. Mandalà, E. Simeone, S. Valpione, M. Altomonte, F. Spagnolo, E. Cocorocchio, S. Gandini, D. Giannarelli, C. Martinoli
Journal: Annals of Oncology (2017)
EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains
Authors: Maria C. Donaldson-Collier, Stephanie Sungalee, Marie Zufferey, Daniele Tavernari, Natalya Katanayeva, Elena Battistello, Marco Mina, Kyle M. Douglass, Timo Rey, Franck Raynaud, Suliana Manley, Giovanni Ciriello, Elisa Oricchio
Journal: Nature Genetics (2019)
Abstract 16340: Association Between Smokeless Tobacco Use and Circulating Concentrations of Cardiac Troponin I in the General Population: The Hunt Study (Nord-Trøndelag Health Study)
Authors: Julia B Skranes, Magnus N Lyngbakken, Ståle Nygård, Håvard Dalen, Oddgeir L Holmen, Kristian Hveem, Helge Røsjø, Torbjørn Omland
Journal: Circulation (2017)

Background: Consumption of moist oral tobacco (snus) has increased in Scandinavia during the last decades, and in recent years snus has been aggressively marketed in the United States. While smoking is a well-established cardiovascular risk factor, the association between snus and cardiovascular risk is unclear. Current smoking is associated with lower concentrations of cardiac troponin I (cTnI). We examined the association between snus and smoking tobacco, respectively, and circulating concentrations of cTnI in the general population. Methods: We used a high-sensitivity assay to detect cTnI in 5483 subjects enrolled in the prospective, population-based HUNT Study (Nord-Trondelag Health Study). Self-reported tobacco habits (snus user/smoker) were reported as: never (n=4662/2193), former (n=229/1937) and current (n=390/1230). The association between self-reported tobacco use and cTnI was assessed by linear regression, and adjusted for traditional cardiac risk factors, C-reactive protein and estimated glome...
Activating MAPK Pathway Mutations Mediate Primary Resistance to PI3K Inhibitors in Chronic Lymphocytic Leukemia (CLL)
Authors: Ishwarya Murali, Siddha Kasar, Emily M. McWilliams, Gilad Itchaki, Svitlana Tyekucheva, Dimitri Livitz, Ignaty Leshchiner, Shuai Dong, Stacey M. Fernandes, Gad Getz, Amy J. Johnson, Jennifer R. Brown
Journal: Blood (2018)
Inappropriate Use of the Term <i>Autism</i> as Analogy
Authors: Georgina Perez Liz, Lauren Bradstreet, Sherira Fernandes
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
Disagreement between high confidence endoscopic adenoma prediction and histopathological diagnosis in colonic lesions ≤ 3 mm in size
Authors: Prasanna Ponugoti, Amit Rastogi, Tonya Kaltenbach, Margaret MacPhail, Andrew Sullivan, John Thygesen, Heather Broadley, Douglas Rex
Journal: Endoscopy (2019)

Abstract Background Diminutive colorectal polyps resected during colonoscopy are sometimes histologically interpreted as normal tissue. The aim of this observational study was to explore whether errors in specimen handling or processing account in part for polyps ≤ 3 mm in size being interpreted as normal tissue by pathology when they were considered high confidence adenomas by an experienced endoscopist at colonoscopy. Methods One endoscopist photographed 900 consecutive colorectal lesions that were ≤ 3 mm in size and considered endoscopically to be high confidence conventional adenomas. The photographs were reviewed blindly to eliminate poor quality images. The remaining 644 endoscopy images were reviewed by two external experts who predicted the histology while blinded to the pathology results. Results Of 644 consecutive lesions ≤ 3 mm in size considered high confidence conventional adenomas by a single experienced colonoscopist, 15.4 % were reported as normal mucosa by pathology. The prevalence of reports of normal mucosa in polyps removed by cold snare and cold forceps were 15.2 % and 16.0 %, respectively. When endoscopy photographs were reviewed by two blinded outside experts, the lesions found pathologically to be adenomas and normal mucosa were interpreted as high confidence adenomas by endoscopic appearance in 96.9 % and 93.9 %, respectively, by Expert 1 (P = 0.15), and in 99.6 % and 100 %, respectively, by Expert 2 (P = 0.51). Conclusion Retrieval and/or processing of tissue specimens of tiny colorectal polyps resulted in some lesions being diagnosed as normal tissue by pathology despite being considered endoscopically to be high confidence adenomas. These findings suggest that pathology interpretation is not a gold standard for lesion management when this phenomenon is observed.
68Ga-PSMA-11 PET/MR Can Be False Positive in Normal Prostatic Tissue
Authors: Daniela A. Ferraro, Niels J. Rupp, Olivio F. Donati, Michael Messerli, Daniel Eberli, Irene A. Burger
Journal: Clinical Nuclear Medicine (2019)

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the cytosol of normal prostate tissue and highly overexpressed on the membrane of prostate cancer, therefore increasingly used to image prostate cancer. We report a case of a 65-year-old man with two focal PSMA-positive areas on a Ga-PSMA-11 PET/MR, one corresponding to a prostate carcinoma (Gleason score 4 + 3) and another region without any evidence of malignancy, but with corresponding high PSMA-expression on immunohistochemistry.
HIPEC scoring system: A preoperative model including clinical and radiographic parameters to improve patient selection.
Authors: Gabrielle Gauvin, Maxwell Kilcoyne, Kwan-Keat Ang, Leigh T Selesner, Brian L. Egleston, Jeffrey M. Farma, Elin R. Sigurdson, Sanjay S. Reddy
Journal: Journal of Clinical Oncology (2019)

695 Background: Most studies looking at long-term outcomes in patients undergoing cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CS/HIPEC) are based on scoring systems performed at the time of the operation. With a morbidity as high as 67%, it is crucial to carefully choose the patients who will benefit from this procedure. In this study, we evaluated preoperative factors that could impact patient outcomes. Results were used to create a predictive model for patients considered for CS/HIPEC. Methods: Patients assessed for CS/HIPEC at our tertiary cancer center between 2012 and 2017 were considered for this study. Postoperative complications, recurrence free survival (RFS) and overall survival (OS) were used as endpoints, and multivariable analysis accounting for demographics, clinical, bloodwork, radiologic and pathologic findings was performed. Results: Sixty-eight patients were considered for CS/HIPEC. Preoperative elements found to have an impact on OS were lymph node involvement (p = 0.001) and high extent of carcinomatosis (p &lt; 0.001) on computed tomography (CT) scan. Findings that impacted RFS were lymphovascular invasion (p = 0.042), lymph node involvement (p = 0.061) and omental caking (p = 0.010) on CT. Our preoperative predictive model is presented in table. An increased rate of complications was seen in smokers (p = 0.031), obese patients (p = 0.005) and carcinomatosis diagnosed ≤ 12 months from the primary diagnosis (p = 0.069). In our experience, performing CS/HIPEC did improve OS (p = 0.036) after adjustment for age, race, smoking, and BMI. Conclusions: Preoperative findings could help physicians in their discussions with patients prior to pursue CS/HIPEC. These interesting findings will be used to inform the next step of our study: a prospective clinical trial. [Table: see text]
A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation
Authors: Carlos M. Minutti, Rucha V. Modak, Felicity Macdonald, Fengqi Li, Danielle J. Smyth, David A. Dorward, Natalie Blair, Connor Husovsky, Andrew Muir, Evangelos Giampazolias, Ross Dobie, Rick M. Maizels, Timothy J. Kendall, David W. Griggs, Manfred Kopf, Neil C. Henderson, Dietmar M. Zaiss
Journal: Immunity (2019)

The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-αV activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.
Activity of EGFR inhibition in atypical (non-V600E) BRAF-mutated metastatic colorectal cancer.
Authors: Benny Johnson, Jonathan M. Loree, Van K. Morris, Arvind Dasari, Shubham Pant, Kanwal Pratap Singh Raghav, Scott Kopetz
Journal: Journal of Clinical Oncology (2019)

596 Background: Atypical BRAF mutations (a BRAF) represent a rare molecular subtype of metastatic colorectal cancer (mCRC), distinct from BRAF V600E (class I). Preclinical data categorizes a BRAF into class II (intermediate-high kinase activity without RAS dependency) and III (low kinase activity, RAS dependent), however the clinical impact regarding these functional classes is unknown. Methods: We retrospectively analyzed 2,084 mCRC patients (pts) at MD Anderson Cancer Center (MDACC) to identify a BRAF and BRAF V600E . Clinicopathologic features were compared by chi-square or fisher’s exact test. Overall survival (OS) calculated utilizing Kaplan-Meier method and log-rank test. Statistical tests were two-sided. Results: a BRAF occurred in 36 mCRC pts (1.7%; 95% CI 1.2-2.4): 22 class III, 10 class II, 4 unclassified. The most common class II and class III BRAF codons were 469 (60%) and 594 (59%), respectively . Median OS (mOS) for a BRAF mCRC was 39.4 months (mo), without difference between class III and II. 19/36 (53%) were left sided primary tumors and 24/36 (67%) were microsatellite stable. BRAF V600E occurred in 221 mCRC pts (10.6%; 95% CI 9.3-12.0) with a mOS of 21.0 mo. In contrast to BRAF V600E which is mutually exclusive with RAS mutations, 12 pts with a BRAF were RAS mutants (class III, 7/21 [33%], class II 5/10 [50%]). Among a BRAF RAS wt pts, 11 (50%) received anti-EGFR monoclonal antibodies (mAb) (class III 7/14 [50%], class II 3/5 [60%]). There were no responses, and only three pts (all class III) achieved stable disease as best response. Median time on therapy was 4 months. Class II RAS wt pts treated with anti-EGFR mAb had mOS of 31.7 mo versus 46.8 mo for those not exposed (HR 2.0; 95% CI 0.3-15.9). Class III RAS wt pts treated with anti-EGFR mAB had mOS of 44.2 mo versus 45.7 mo for those not treated (HR 0.80; 95% CI 0.2-2.6). Conclusions: a BRAF mCRC appear to manifest improved clinical outcomes as previously reported. Despite this, the efficacy of anti-EGFR therapy appears limited in class II and III patients. Future efforts are needed to establish the predictive impact of functional classes on anti-EGFR efficacy and to design novel therapeutic strategies for a BRAF mCRC.