tbuckley/cabot-search huggingface dataset:
Association of core needle biopsies with increase in metastatic dissemination of breast cancer.
Authors: Carman A. Giacomantonio, Cheryl A. Dean, Edward G. Mathenge, Amber A. Black, Wendy Schulte, Desmond B. Pink, Paola Marcato, Patrick W. Lee, Andries Zijlstra, John D. Lewis
Journal: Journal of Clinical Oncology (2012)

e21090 Background: Given the reported association between incisional procedures performed on cancer patients and subsequent increases in metastasis, as well as the established inverse relationship between metastasis and patient survival, this study establishes the extent to which incisional core needle biopsies (CNB) affects tumor growth and metastatic dissemination in two distinct breast cancer animal models. Methods: Using the chick embryo system (CES) and murine breast cancer model (MuBC)the impact of CNB on cancer metastases was evaluated. Human MDA-MB-231 and MDA-MB-435 cancer cells were used in the xenograft / CES, and murine 4T1 Breast cancer cells for the syngeneic MuBC . In each model, tumors were biopsied in half of the animals while the other half were left undisturbed (CES:n=40, MuBC:n=40). The impact of CNB on tumor growth, necrosis and metastases was assessed. Metastases levels in the CES was determined by quantitative PCR for human alu sequence DNA in chick tissue extracts. Metastatic burden in the MuBC model was evaluated by microscopic quantification of metastatic areas in sectioned and H-E stained mouse organs. Results: When biopsied and un-biopsied groups were compared, both models showed significant difference in pulmonary metastasis. MDA-MB-435 CES (p=0.025) and 4T1 MuBC (p=0.026). MDA-MB-231 CES showed no significant change in lung metastases in the CES but did however show increased Chorioallantoic Membrane (CAM) metastasis (p=0.018) and both cell lines showed statistically significant alteration in Liver metastasis, (MDA-MB-231 CES (p=0.006); MDA-MB-435 CES (p=0.004)). Interestingly only MDA-MB-435 (CES) tumor growth was significantly increased after CNB (p=0.002). Conclusions: These results offer the first experimental evidence that core needle biopsies result in an increased risk of metastatic dissemination and affect metastatic tropic behavior. They also reinforce the concept of a multi-step metastatic pathway and suggest involvement of extrinsic factors that influence the extravastion and intravasation steps. The clinical implications are considerable and follow-up studies examining potential mechanisms and countermeasures are urgently required
PMO-172 Direct non-invasive serum markers of liver fibrosis predict fibrosis evolution in chronic hepatitis C but are increased by interferon-based therapy: Abstract PMO-172 Figure 1
Authors: S Tanwar, P M Trembling, E Ellis, J Parkes, C Herold, D Schuppan, W M C Rosenberg
Journal: Gut (2012)

<h3>Introduction</h3> Liver biopsy remains the reference standard for the detection of liver fibrosis. While non-invasive markers of liver fibrosis have been validated in chronic hepatitis C, their performance during interferon-based therapy is not established. <h3>Methods</h3> 70 previous non-responders to interferon based therapy for chronic hepatitis C (40 male, age range 24–67, mean 48.7) were recruited from five centres. Patients were randomised to receive pegylated interferon with or without silymarin for 24 months as an exploratory antifibrotic therapy. All patients underwent a liver biopsy and ELF tests (HA, P3NP, TIMP-1) prior to, and after treatment (month 0 and 24). Changes in histological fibrosis stages before and after therapy (0 to 24 months) were compared with changes in marker scores before, during and after therapy (0 to 24 months). <h3>Results</h3> Mean ELF score prior to therapy was 9.32 (SD 1.10), during therapy 9.91 (SD1.18) and after therapy 9.53 (SD 1.27). ELF scores were significantly higher during therapy than when compared to both before therapy (p&lt;0.00001) and after therapy (p=0.0002) but levels before therapy were not significantly different from post therapy. Elevated scores on therapy were attributable to an increase in mean HA (p&lt;0.0002) and P3NP (p&lt;0.01) levels on therapy, whereas a significant change in mean TIMP-1 during therapy was not seen. These elevations were seen in all patients regardless of changes in histological fibrosis after therapy (n=20 decrease, n=25 no change, n=35 increase in Ishak stage). However, individual changes in TIMP1 (r=0.239, p=0.04) and changes in ELF (r=0.315, p=0.004) from pre- to post-therapy levels were found to correlate with the change of Ishak fibrosis stage before and during treatment. <h3>Conclusion</h3> During interferon-based therapy, levels of HA and P3NP and the ELF score rise globally and subsequently fall to values similar to those seen prior to therapy regardless of fibrosis evolution, while TIMP1 levels remained unaffected. However, ELF scores pre and post therapy did accurately reflect changes in histology. This suggests that ELF scores and non-invasive panels incorporating HA and P3NP should be interpreted with caution during interferon-based therapy. <h3>Competing interests</h3> None declared.
An Open-Label, Single-Arm, Phase 1 Study of the Pharmacokinetics (PK) and Safety of Carfilzomib in Patients with Relapsed Multiple Myeloma and End-Stage Renal Disease (ESRD)
Authors: Hang Quach, Darrell White, Andrew Spencer, P. Joy Ho, Divaya Bhutani, Mike White, Sandeep Inamdar, Chris Morris, Ying Ou, Martin Gyger
Journal: Blood (2016)
Abstract 17441: The Clinical Factors Agreed Upon by Pediatric Cardiac Intensivists to Define Low Cardiac Output Syndrome
Authors: Melissa Smith-Parrish, Kurt Schumacher, Larry Gruppen, Robert B Stansfield, John Charpie, Dennis Crowley, Robert Gajarski, Michael G Gaies
Journal: Circulation (2013)

Background: Low cardiac output syndrome (LCOS) is a frequent complication following congenital heart surgery (CHS), but there is no consensus on how best to define the condition. We aimed to empiri...
エピジェネティクス:ショウジョウバエ(Drosophila)のクロマチン状態は複数世代にわたり安定してポリコーム依存的に継承される
Authors: Ciabrelli Filippo, Bonev Boyan, Szabo Quentin, Bantignies Frederic, Cavalli Giacomo, Comoglio Federico, Paro Renato, Fellous Simon, Xuereb Anne, Ninova Maria, Aravin Alexei, Klopp Christophe
Journal: Nature Genetics (2017)
ADVL1315: A phase 1 study of the VEGF receptor tyrosine kinase inhibitor axitinib (INLYTA, IND# 123101) in children with recurrent or refractory solid tumors—A Children's Oncology Group study.
Authors: James I. Geller, Elizabeth Fox, Brian Turpin, Joel M. Reid, Xiaowei Liu, Charles G. Minard, Stuart Goldstein, Brenda Weigel
Journal: Journal of Clinical Oncology (2016)

10558 Background: Axitinib is a small molecule that inhibits receptor tyrosine kinases VEGFR1-3. A phase I trial evaluating dose limiting toxicities (DLT), the maximally tolerated dose (MTD) and the pharmacokinetics (PK) of axitinib was conducted in children with refractory solid tumors. Methods: Oral axitinib tablets were administered bid, continuously in 28-day cycles. Dose levels 2.4 and 3.2 mg/m2/dose were evaluated using a rolling 6 design. Serial PK were obtained in Cycle 1. Results: As of December 11, 2015, 17 patients were enrolled with 1 ineligible (inadequate time from prior therapy). The median age was 14 yrs (range 5-17 yrs); 9 were male. Patients received a median 3 prior chemotherapy regimens (range 1-8). Cancer diagnoses included soft tissue sarcomas (7), Ewing (2) and osteosarcoma (1), neuroblastoma (2), Wilms tumor (1), hepatoblastoma (1), hepatocellular carcinoma (1), medullary carcinoma (1), and epithelial-myoepithelial carcinoma (1). Toxicity data are available for 15 patients (6 at dose level 1, 5 at dose level 2, and 4 on an expanded PK cohort). One patient was inevaluable for toxicity due to inadequate drug exposure. DLTs occurred in 0/6 and 2/5 patients treated at dose level 1 and 2 respectively (palmar-plantar erythrodysesthesia syndrome (1); intratumoral hemorrhage (1)). Cycle 1 hematologic toxicities included grade 3 lymphopenia (1) and grade 1 or 2 anemia (4), lymphopenia (3), elevated hemoglobin (3), leukopenia (2), neutropenia (1), thrombocytopenia (1), and lymphocytosis (1). Non-hematologic toxicities included grade 1 or 2 nausea (5), hypertension (4), anorexia (3), creatinine elevation (2), diarrhea (2), fatigue (2), headache (2), lipase elevation (2), proteinuria (2), and acneiform rash (2). The most common subsequent cycle grade 3 or 4 toxicities included neutropenia (grade 3 (3), grade 4 (1)) and lymphopenia (grade 3 (1), grade 4 (1)). Further analyses await completion of the expanded PK cohort. Conclusions: Axitinib is tolerated in pediatric patients. The MTD of axitinib given to children with solid tumors is 2.4 mg/m2/dose, corresponding to 4 mg bid (or 80%) of the adult dose. Clinical trial information: NCT02164838.
Efficient Site-Specific Multi-Gene Engineering of Renewable Pluripotent Cells for Generation of Off-the-Shelf Hematopoietic Immunotherapeutics
Authors: Ramzey Abujarour, Weijie Lan, Tom Tong Lee, Greg Bonello, Miguel Meza, Megan Robinson, Raedun Clarke, Christopher Truong, Chris Lynn, David Robbins, Betsy Rezner, Stewart E. Abbot, Daniel Shoemaker, Bahram Valamehr
Journal: Blood (2016)
ETHNIC DIFFERENCES IN LOWER EXTREMITY DYNAMIC POSTURAL MEASURES AS POTENTIAL RISK FACTOR FOR ANTERIOR CRUCIATE LIGAMENT (ACL) INJURY
Authors: Chang-Young Kim, Young Min Chun, Sae Yong Lee
Journal: British Journal of Sports Medicine (2017)

Background ACL injury rate for female is as much as eight times higher than male in the United States. However, based upon Korean Health Insurance Corporation, higher injury rate was reported in male compared to female. Objective To determine whether ethnic differences exist in lower extremity dynamic postural measures between Caucasian female and Asian female. Design Case controlled study. Setting Controlled laboratory. Patients (or Participants) 15 Caucasian female (age: 21.3±1.58 yrs; weight: 63.9±7.42 kg; height: 169.6±4.60 cm) and 15 Asian female (age: 20.4±1.20 yrs; weight: 57.8±3.86 kg; height: 164.0±2.72 cm) were recruited as subjects for this study. Interventions (or Assessment of Risk Factors) All subjects performed Drop jump from a 30 cm-box, which was set at the half of their height distance away from the force plate. Main Outcome Measurements Three dimensional knee joint kinematics were extracted from motion analysis system (Vicon Inc, Oxford, UK; BTS Bioengineering, Milano, Italy). All joint kinematics were analyzed at one discrete point which was 30° knee flexion. Independent sample t-test was performed to analyze mean differences between ethnicity. Results Caucasian female had significantly greater knee valgus (t=−3.293, p=0.03, Caucasian: −3.15°±6.12°; Asian: 3.19°±3.94°) and knee internal rotation (t=2.143, p=0.41, Caucasian: 12.58°±9.54°; Asian: 5.05°±9.35°) compared to Asian female in Drop jump. Conclusions Our results showing signiﬁcantly greater knee valgus and internal rotation in Caucasian female may support the difference of ACL injury rates between Caucasian and Asian. Possibly reducing knee valgus and internal rotation may drop the injury rate of female to similar with male as found in South Korea.
Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition
Authors: Michail Mamantopoulos, Francesca Ronchi, Filip Van Hauwermeiren, Sara Vieira-Silva, Bahtiyar Yilmaz, Liesbet Martens, Yvan Saeys, Stefan K. Drexler, Amir S. Yazdi, Jeroen Raes, Mohamed Lamkanfi, Kathy D. McCoy, Andy Wullaert
Journal: Immunity (2017)
Late mortality after acute hypoxic respiratory failure
Authors: Hallie C Prescott, Michael W Sjoding, Kenneth M Langa, Theodore J Iwashyna, Daniel F McAuley
Journal: Thorax (2017)

Background Acute hypoxic respiratory failure (AHRF) is associated with significant acute mortality. It is unclear whether later mortality is predominantly driven by pre-existing comorbid disease, the acute inciting event or is the result of AHRF itself. Methods Observational cohort study of elderly US Health and Retirement Study (HRS) participants in fee-for-service Medicare (1998–2012). Patients hospitalised with AHRF were matched 1:1 to otherwise similar adults who were not currently hospitalised and separately to patients hospitalised with acute inciting events (pneumonia, non-pulmonary infection, aspiration, trauma, pancreatitis) that may result in AHRF, here termed at-risk hospitalisations. The primary outcome was late mortality—death in the 31 days to 2 years following hospital admission. Results Among 15 075 HRS participants, we identified 1268 AHRF and 13 117 at-risk hospitalisations. AHRF hospitalisations were matched to 1157 non-hospitalised adults and 1017 at-risk hospitalisations. Among patients who survived at least 30 days, AHRF was associated with a 24.4% (95%CI 19.9% to 28.9%, p&lt;0.001) absolute increase in late mortality relative to adults not currently hospitalised and a 6.7% (95%CI 1.7% to 11.7%, p=0.01) increase relative to adults hospitalised with acute inciting event(s) alone. At-risk hospitalisation explained 71.2% of the increased odds of late mortality, whereas the development of AHRF itself explained 28.8%. Risk for death was equivalent to at-risk hospitalisation beyond 90 days, but remained elevated for more than 1 year compared with non-hospitalised controls. Conclusions In this national sample of older Americans, approximately one in four survivors with AHRF had a late death not explained by pre-AHRF health status. More than 70% of this increased risk was associated with hospitalisation for acute inciting events, while 30% was associated with hypoxemic respiratory failure.
Racial Differences in In-Hospital Cardiac Arrest
Authors: Myron Weisfeldt, Lance Becker
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
アトルバスタチンの脳室内注入はSHRSPにおけるRac1/NAD(P)Hオキシダーゼの阻害とMn‐SODのアップレギュレーションにより交感神経活性を低下させる
Authors: Kishi Takuya, Hirooka Yoshitaka, Koga Yasuaki, Araki Syuitiroh, Konno Satomi, Itoh Koji, Sunagawa Kenji
Journal: Circulation (2009)
Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes
Authors: Samuel M Brown, Emily L Wilson, Angela P Presson, Victor D Dinglas, Tom Greene, Ramona O Hopkins, Dale M Needham
Journal: Thorax (2017)

With improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding survivors' posthospitalisation outcomes is increasingly important. However, little is known regarding associations among physical, cognitive and mental health outcomes. Identification of outcome subtypes may advance understanding of post-ARDS morbidities.
08.42 Dna accumulations in the peripheral blood and salivary gland tissues fuel inflammasome activation in patients with severe primary sjögren’s syndrome
Authors: Aglaia G Vakrakou, Sorina Boiu, Panagiotis Ziakas, Menelaos N Manoussakis
Journal: Annals of the Rheumatic Diseases (2017)

<h3></h3> Sjögren's syndrome patients manifest impaired serum DNase1 activity and increased serum levels of cell-free genomic DNA (cfDNA). Such circulating cfDNA may accumulate in tissues and may act as danger signal able to activate the intracellular inflammasomes. Herein, we sought to investigate the occurrence of defective nuclease activity, as well as of inflammasome activation in various tissues of SS patients. The mRNA levels of inflammasome-related and nuclease-encoding genes were evaluated in PBMC by q-PCR. Serum and salivary gland (SG) tissue expression of inflammasome-related proteins were assessed by ELISA and confocal microscopy. DNase-II activity in PBMC was measured by the SRED-assay. Indicative of inflammasome activation, SS patients exhibited elevated serum levels of ASC (n=56; p=0.002), IL-1β (n=37; p=0.003) and IL18 (n=33; p&lt;0.0001), compared to healthy controls (HC; n=20). The serum ASC protein levels were higher in SS patients at high risk for lymphoma development (SStype I; n=17) and in SS patients with lymphoma (n=28), compared to SS at low risk for lymphoma development (SS-type II; n=11, for p=0.030 and p=0.004, respectively). ASC and IL-18 serum levels correlated positively with cumulative ESSDAI score (p=0.005 and p=0.006, respectively), whereas ASC correlated with C4 hypocomplementemia, RF positivity and purpura. Compared to HC-PBMC (n=16), SS-PBMC expressed significantly higher levels of ASC, NLRP3, IL-1β, IL-18 and pro-caspase-1 transcripts (n=39, p&lt;0.05). In CD68+macrophages of SS-SG, ASC protein localised in perinuclear aggregates (specks), also suggesting inflammasome activation. SS patients (but not controls) manifested extranuclear DNA accumulations in PBMC and SG macrophages, as well as extracellular dsDNA strands in the SG tissues. cfDNA from SS patients sera was able to serve as a priming signal for inflammasome activation in healthy monocytes. Among various nucleases tested, DNase-II transcriptional levels and enzymatic activity were diminished in SS-PBMC. DNase-II mRNA silencing in healthy monocytes led to upregulation of inflammasome-related genes and fueled caspase-1 activation. Overall, SS patients manifest inflammasome activation in peripheral blood and SG, which associates with deficient nuclease activity and the presence of extranuclear DNA accumulations. Several indices of inflammasome activation were found to correlate with the occurrence of severe SS manifestations, including lymphoma development, and may constitute valuable clinical biomarkers.
Comparison of long-term outcome between doublet versus triplet neoadjuvant chemotherapy in nonmetastatic osteosarcoma of extremity
Authors: S. Hong, S. Rha, J. Jeong, Y. Lee, S. Shin, K. Shin, J. Roh
Journal: Journal of Clinical Oncology (2009)

10542 Background: Multimodal approach had improved outcomes of non-metastatic osteosarcoma. This study was to compare outcomes between doublet (AP; doxorubicin and cisplatin) and triplet (IAP; AP and ifosfamide) neoadjuvant chemotherapy for non-meteastatic osteosarcoma of extremity in a single institute. Methods: A total of 124 osteosarcoma patients were enrolled. In AP group, doublet regimen was given to 77 patients from 1991 to 1999, who received intra-arterial cisplatin(120mg/m 2 ) at day 1 and intravenous doxorubicin (25mg/m 2 ) for 3 days. In IAP group, triplet regimen was given to 49 patients from 2000 to 2007, who received ifosfamide additionally at a dose of 2.5g/m 2 /day for 3 days. After completion of 3 cycles of chemotherapy, patients underwent limb-salvage surgery. We assessed tumor response according to pathologic tumor necrosis, and treated further adjuvant chemotherapy. In AP group, responder received 3 more cycles of AP, while non-responders received 6 cycles of ifosfamide-contaning regimens. In IAP group, all patients had 3 more cycles of IAP chemotherapy. Results: The median follow-up duration was 5.2 years (0.4–16.7). The most frequent site and histology were distal femur and osteoblastic type. Overall pathologic response was more than 90% tumor necrosis in 74.8% of patients. Total necrosis of tumor was also found in 46 patients (37.4%). There was no difference between two groups in pathologic response (76.3% vs. 72.3%; p=0.62) or other clinico-pathologic parameters. Tumor recurrence was occurred in 31.5% of patients with the most common site of lung (84.6%). There was no difference between two groups in recurrence (p=0.17) or lung metastasis (p=0.53). There were no statistical differences in disease free survival (p=0.75) and overall survival (p=0.07) between two groups. In toxicity profiles, there were more hematologic toxicity in IAP group (febrile neutropenia,p&lt;0.001; thrombocytopenia,p&lt;0.05), while there were no statistical differences in treatment related death. Conclusions: The addition of ifosfamide to doxorubicin and cisplatin in neoadjuvant chemotherapy did not show improved outcomes in this study. Further trials are required to elucidate optimal neoadjuvant chemotherapy and effective salvage regimens. No significant financial relationships to disclose.
08.33 Treatment of rheumatoid arthritis patients: comparative efficacy of four treatment regimens
Authors: Evgeniya Fedorenko, Galina Lukina, Yakov Sigidin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To compare efficacy and safety of 4 treatment regimens in early (&lt;2 years duration) RA including methotrexate (MTX), leflunomid (LEF) and combinations of MTX with glucocorticoids (GC). <h3>Methods</h3> One hundred eighteen pts with early RA (100 women, mean age 55, mean disease duration 7 months, mean DAS28 5,83) were randomly assigned to receive one of the 4 treatment regimens for one year: MTX 10–20 mg/week (30 pts); MTX (10–20 mg/week) + GC (equivalent of 10 mg/day prednisolone, 31 pts); MTX (10–20 mg/week) + GC (equivalent of 10 mg/day prednisolone) + one single intravenous infusion of 1000 mg methylprednisolone (MP) at the first day of treatment (31 pts); LEF 20 mg/day (26 pts). According to clinical and demographic data all groups were comparable. Efficacy of therapy was assessed by EULAR criteria. <h3>Results</h3> By now seventy one pts completed one-year course of treatment. Results of the therapy by that time are shown in the table (%). In the MTX group 19% of the pts reached clinical remission (DAS28 &lt;2,6); in the MTX+GC group, 46%; in the MTX+GC+MP group, 47%; in the LEF group, 28%. Side effects of the treatment were as follows: MTX, skin depigmentation (1 pt) and hair loss (1); MTX+GC, increase of ALT and AST level (1) and hair loss (1); MTX+GC+MP, hair loss (1); LEF, urticaria (3), leucopenia (1) and increase of ALT and AST level (1). <h3>Conclusion</h3> All 4 treatment regimens proved to be effective in early RA but the most promising results were obtained in groups with the combination of MTX and GC. The total amount of remissions in the whole group of early RA after one year of therapy was 34% which can be considered as satisfactory. Tolerability of all regimens was good.
Impact of Nutrition on Non-Relapse Mortality and Acute Graft Versus Host Disease during Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies
Authors: Julie Beckerson, Richard M Szydlo, Mary Hickson, Catriona E Mactier, Andrew Innes, Ian H Gabriel, Renuka Palanicawandar, Edward J Kanfer, Donald Macdonald, Dragana Milojkovic, Amin Rahemtulla, Aristeidis Chaidos, Anastasios Karadimitris, Eduardo Olavarria, Jane F. Apperley, Jiří Pavlů
Journal: Blood (2016)