tbuckley/cabot-search huggingface dataset:
Why Are Private Health Insurers Losing Money on Obamacare?
Authors: Uwe Reinhardt
Journal: JAMA (2016)

every doctor, can understand that this opportunity exists.It needs money, however.So whether through philanthropy, business, or government, we all need to contribute to make this happen.In addition, I'm most interested in making sure that this kind of technology is not only limited to the rich.I was born in South Africa and grew up in apartheid.I understand how the black community suffered, and we need to make sure that whether you're rich or poor, these opportunities exist.Whether that's considered a business or not, I don't know.All I know is that we are here to help people and patients.
Factors Associated With Tyrosine Kinase Inhibitor Initiation and Adherence Among Medicare Beneficiaries With Chronic Myeloid Leukemia
Authors: Aaron N. Winn, Nancy L. Keating, Stacie B. Dusetzina
Journal: Journal of Clinical Oncology (2016)

Purpose There is substantial concern surrounding affordability of orally administered anticancer therapies, particularly for Medicare beneficiaries. We examined rates of initiation and adherence to tyrosine kinase inhibitors (TKIs) among Medicare beneficiaries with chronic myeloid leukemia (CML) with and without cost-sharing subsidies. We selected TKIs given their effectiveness and strong indication for use among patients diagnosed with CML. Patients and Methods Using SEER-Medicare data, we identified individuals diagnosed with CML from 2007 to 2011. We used Cox proportional hazards regression to assess time from diagnosis to TKI initiation. We used generalized estimating equations to examine treatment initiation within 180 days and TKI adherence among initiators. We defined adherence as at least 80% of days covered during the 6 months after TKI initiation. Results Among 393 individuals diagnosed with CML from 2007 to 2011, 68% initiated TKI treatment within 180 days after diagnosis. In multivariate analysis, individuals with cost-sharing subsidies, younger age, lower comorbidity, and later year of diagnosis were significantly more likely to initiate TKIs. Among TKI initiators, 61% were adherent; adherence was lower for individuals age 80 years or older versus 66 to 69 years. Conclusion Only 68% of Medicare beneficiaries with CML initiated TKI therapy within 6 months of diagnosis. Delayed initiation among individuals without cost-sharing subsidies suggests that out-of-pocket costs may be a barrier to timely initiation of therapy among individuals diagnosed with CML.
Algorithm to Rule-Out Clinically Significant Portal Hypertension Combining Shear-Wave Elastography of Liver and Spleen: A Prospective Multi-Center Study
Authors: C. Jansen, C.K.-P. Bogs, W. Verlinden, M. Thiele, P. Moeller, J. Goertzen, J. Lehmann, M. Praktiknjo, J. Chang, A. Krag, C. Strassburg, S. Franque, J. Trebicka
Journal: Journal of Hepatology (2016)
Comprehensive Genetic Characterization of 17p Deleted CLL Identifies Predictors of Overall Survival
Authors: Lijian Yu, Haesook T. Kim, Siddha Kasar, Parul Benien, Wei Du, Kevin Hoang, Reina Improgo, Stacey M. Fernandes, Josephine L. Klitgaard, Charles Lee, Gady Getz, Sunita R Setlur, Jennifer R. Brown
Journal: Blood (2015)
Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric H,K-ATPase
Authors: Jin-Young Min, Christopher J. Ocampo, Whitney W. Stevens, Caroline P.E. Price, Christopher F. Thompson, Tetsuya Homma, Julia H. Huang, James E. Norton, Lydia A. Suh, Kathryn L. Pothoven, David B. Conley, Kevin C. Welch, Stephanie Shintani-Smith, Anju T. Peters, Leslie C. Grammer, Kathleen E. Harris, Kathryn E. Hulse, Atsushi Kato, Nikolai N. Modyanov, Robert C. Kern, Robert P. Schleimer, Bruce K. Tan
Journal: Journal of Allergy and Clinical Immunology (2016)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by tissue eosinophilia that is associated with poor prognosis. Recent findings that proton pump inhibitors (PPIs) directly modulate the expression of eotaxin-3, an eosinophil chemoattractant, in patients with eosinophilic diseases suggest therapeutic potential for PPIs in those with CRSwNP.We assessed the effect of type 2 mediators, particularly IL-13 and eotaxin-3, on tissue eosinophilia and disease severity in patients with chronic rhinosinusitis (CRS). Further investigation focused on PPI suppression of eotaxin-3 expression in vivo and in vitro, with exploration of underlying mechanisms.Type 2 mediator levels in nasal tissues and secretions were measured by using a multiplex immunoassay. Eotaxin-3 and other chemokines expressed in IL-13-stimulated human sinonasal epithelial cells (HNECs) and BEAS-2B cells with or without PPIs were assessed by using ELISA, Western blotting, real-time PCR, and intracellular pH imaging.Nasal tissues and secretions from patients with CRSwNP had increased IL-13, eotaxin-2, and eotaxin-3 levels, and these were positively correlated with tissue eosinophil cationic protein levels and radiographic scores in patients with CRS (P < .05). IL-13 stimulation of HNECs and BEAS-2B cells dominantly induced eotaxin-3 expression, which was significantly inhibited by PPIs (P < .05). Patients with CRS taking PPIs also showed lower in vivo eotaxin-3 levels compared with those without PPIs (P < .05). Using intracellular pH imaging and altering extracellular K+, we found that IL-13 enhanced H+,K+-exchange, which was blocked by PPIs and the mechanistically unrelated H,K-ATPase inhibitor, SCH-28080. Furthermore, knockdown of ATP12A (gene for the nongastric H,K-ATPase) significantly attenuated IL-13-induced eotaxin-3 expression in HNECs. PPIs also had effects on accelerating IL-13-induced eotaxin-3 mRNA decay.Our results demonstrated that PPIs reduce IL-13-induced eotaxin-3 expression by airway epithelial cells. Furthermore, mechanistic studies suggest that the nongastric H,K-ATPase is necessary for IL-13-mediated epithelial responses, and its inhibitors, including PPIs, might be of therapeutic value in patients with CRSwNP by reducing epithelial production of eotaxin-3.
Prevalence of Cardiac and Hepatic Siderosis in Australian Patients with Transfusion-Dependent Anemias or Non-Transfusion-Dependent Thalassemia, As Assessed By MRI (the TIMES study)
Authors: Phoebe Joy Ho, Devendra Hiwase, Raj Ramakrishna, Nicholas Viiala, David M Ross, Evren Zor, Othon L Gervasio, Donald Bowden
Journal: Blood (2015)
Abstract 18061: Supplementation to Treat Antithrombin Deficiency Improves Sensitivity to Heparin, Anticoagulation and Decreased Thrombogenecity in Neonates and Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass
Authors: Brian W McCrindle, Cedric Manlhiot, Helen M Holtby, Anthony K Chan, Leonardo R Brandao, Martha Rolland, Lia Stenyk, Lynn Crawford-Lean, Celeste Foreman, Glen S Van Arsdell, Colleen E Gruenwald
Journal: Circulation (2015)

Introduction: Preoperative antithrombin (AT) deficiency is common in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB), and is associated with heparin resistance, difficulties achieving optimal intraoperative anticoagulation and post-operative thrombosis. Methods: We performed a pilot randomized trial of pooled human AT supplementation for children &lt;1 year with preoperative AT &lt;0.85U/ml. Subjects received a split (patient and CPB prime) dose of AT before heparinization. AT was dosed to reach a predicted AT activity of 1.2U/ml during CPB calculated from preoperative AT level and patient weight. Results: We randomized 18 subjects; 17 completed the study (9 controls, 8 AT). Mean preoperative AT level was similar between groups (Control: 0.65±0.10 vs. AT: 0.68±0.15 U/mL, p=0.66). AT group subjects had higher AT than controls immediately after start of CPB (Control: 0.44±0.10 vs. AT: 1.15±0.20 U/mL, p&lt;0.001) and at the end of CPB (Control: 0.67±0.14 vs. AT: 1.19±0.16 U/mL, p&lt;0.001). AT supplementation was associated with increased activated clotting time (ACT) post-heparinization (Control: 500±72 vs. AT: 639±172 seconds, p=0.02), increased heparin sensitivity (Control: 89±23 vs. AT: 114±22 ACT seconds per 100U/kg heparin, p=0.02), and decreased heparin dose given during CPB (Control: 1126±344 vs. AT: 845±165 U/kg, p=0.03). After primary heparinization, 56% of control subjects did not achieve ACT target vs. 25% of AT subjects. At the end of CPB, AT group subjects had lower prothrombin levels (Control: 746±372 vs. AT: 460±102 ng/mL, p=0.02) and lower levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8 and TNFα). Supplementation with AT was not associated with increased chest tube volume loss or blood product requirements. One subject in each group had severe bleeding, and one in each group had post-operative infection. Thrombosis was noted for 3 controls and 1 AT subjects. Conclusions: AT supplementation to treat preoperative AT deficiency in young children is associated with decreased heparin resistance, improved anticoagulation and decreased thrombogenecity. Safety profile regarding bleeding and infections appears favorable. Equipoise exists for a larger definitive outcome trial.
P1241 : JAK/STAT pathway and susceptibility to hepatitis B virus infection and related liver diseases
Authors: Hoang T.V., N.X. Hoan, A. Clark, F. Gerlach, N.L. Toan, L.H. Song, C.-T. Bock, P.G. Kremsner, T.P. Velavan
Journal: Journal of Hepatology (2015)
Indirect Comparisons to Assess the Relative Efficacy of Carfilzomib + Lenalidomide + Dexamethasone Versus Panobinostat + Bortezomib + Dexamethasone and Bortezomib + Dexamethasone: A Matching Adjusted Indirect Comparison
Authors: Michael Rael, Agnes Benedict, Jack Ishak, Sarah Cadarette, Marco Campioni, Sumeet Panjabi
Journal: Blood (2015)
A randomized trial comparing mesorectal excision with or without lateral lymph node dissection for clinical stage II, III lower rectal cancer: Primary endpoint analysis of Japan Clinical Oncology Group study JCOG0212.
Authors: Shin Fujita, Junki Mizusawa, Yukihide Kanemitsu, Masaaki Ito, Yusuke Kinugasa, Koji Komori, Masayuki Ohue, Mitsuyoshi Ota, Yoshihiro Akazai, Manabu Shiozawa, Takashi Yamaguchi, Hiroyuki Bandou, Kenji Katsumata, Kohei Murata, Yoshito Akagi, Nobuhiro Takiguchi, Yoshihisa Saida, Takayuki Akasu, Yoshihiro Moriya
Journal: Journal of Clinical Oncology (2016)

3508 Background: Mesorectal excision (ME) is the standard surgery for lower rectal cancer. However, lateral pelvic lymph node metastasis is occasionally found, and ME with lateral lymph node dissection (LLND) is the standard procedure in Japan. We conducted a randomized trial to confirm the non-inferiority of ME alone to ME with LLND in terms of efficacy and reported the ME group tended to show lower postoperative morbidity than the ME+LLND group. This is the primary analysis of the relapse-free survival (RFS) as the primary endpoint. Methods: Eligibility criteria included histologically proven rectal cancer; clinical stage II/III; main lesion located in the rectum and the lower margin below the peritoneal reflection; no lateral pelvic lymph node swelling; PS of 0 or 1; patient age 20-75 years. After surgeons had confirmed R0 resection by the ME procedure, patients were randomized intraoperatively to ME alone or ME with LLND. The primary endpoint was RFS and the non-inferiority margin of the hazard ratio (HR) was 1.34. The planned sample size was 700 with a power of 75% and a one-sided alpha of 5%. Results: A total 701 patients enrolled from 33 institutions were randomized to ME+LLND (n=351) or ME (n=350) between June 2003 and August 2010. The 5-year RFS was 73.4% and 73.3% in the ME+LLND group and the ME group, respectively. The HR was 1.07 [90.9% CI 0.84-1.36 (>1.34)]; thus the non-inferiority of ME was not confirmed (p=0.055). The 5-year overall survival (OS) and the 5-year local-recurrence-free survival (LRFS) were shown in the Table. The numbers of patients with local recurrence were 25 (7.1%) and 44 (12.6%) in the ME+LLND group and the ME group, respectively (p=0.02). Conclusions: The non-inferiority of ME to ME with LLND was not confirmed. ME with LLND significantly reduced local recurrence after surgery compared with ME alone. Clinical trial information: C000000034. ME+LLND (95% CI) ME (95% CI) HR (95% CI) 5-year RFS 73.4% (68.5-77.7%) 73.3% (68.3-77.6%) 1.07 (0.81-1.41) 5-year OS 92.6% (89.3-94.9%) 90.2% (86.5-92.9%) 1.25 (0.85-1.84) 5-year LRFS 87.7% (83.8-90.7%) 82.4% (78.0-86.1%) 1.37 (0.98-1.93)
長期の胎児母性マイクロキメリズムにリンクされるHLA‐ハブロタイプ一致非遺伝性母系抗原(NIMA)不一致家族間の非T細胞減少造血幹細胞移植の結果
Authors: Ichinohe T, Uchiyama T, Shimazaki C, Tamaki S, Watanabe A, Hamaguchi M, Hino M, Adachi S, Endoh M, Uoshima N, Yoshihara T, Hatanaka K, Fujii H, Kawa K, Gondo H, Kawanishi K, Maruya E, Saji H, Kodera Y
Journal: Blood (2003)
Randomized phase II trial of erlotinib (E) versus temozolomide (TMZ) or BCNU in recurrent glioblastoma multiforme (GBM): EORTC 26034
Authors: M. J. Van Den Bent, A. Brandes, R. Rampling, M. Kouwenhoven, J. M. Kros, A. F. Carpentier, P. Clement, B. Klughammer, T. Gorlia, D. Lacombe
Journal: Journal of Clinical Oncology (2007)

2005 Background: In 40–50% of GBM epidermal growth factor receptor (EGFR) is amplified, and often constitutively activated (EGFRvIII mutant). EGFR is therefore a potential therapeutic target. Previous studies suggested activity of EGFR tyrosine-kinase inhibitors in recurrent GBM, particularly in specific molecular subsets. This study explored erlotinib (E) activity in recurrent GBM. Methods: Randomized phase II trial. Eligibility criteria: histologically proven GBM, recurrent &gt;3 months after radiotherapy, Karnofsky performance status (KPS) =70, no prior chemotherapy for recurrent disease, tissue sample for EGFR studies. Patients (pts) received E 150mg/day (300mg/day if on enzyme inducing anti-epileptic drugs [EIAEDs]), or control (TMZ 150–200mg/m 2 , day 1–5 q4wk or BCNU 60–80mg/m 2 i.v., day 1–3 q8wk). If no significant toxicity, E was escalated to 200mg (500mg in patients on EIAEDs). The primary endpoint was 6 months’ PFS in =10/50 pts on E (20%); P0 was set at 15%, and P1 at 30%. Response was assessed with Macdonald’s criteria. EGFR amplification (FISH) and expression of EGFR, EGFRvIII and PTEN (immunohistochemistry [IHC]) were assessed. Results: 110 patients were randomized (54 E, 56 control: 27 TMZ; 29 BCNU). Median age 55 years; median KPS 90. All but 1 patient started treatment; median number of cycles was 2 for E, 4 for TMZ and 1 for BCNU. Grade 3/4 toxicities likely related to E: dermatological (5); hemorrhage (1). Grade 3/4 toxicities for control were mainly hematological (3 TMZ, 13 BCNU). Three pts discontinued E due to toxicity. Six-month PFS was 12% for E, 24% for control. Six and 12-month survival were 61% and 24% for E, and 63% and 26% for control. Two responses were seen on control; the best response on E was SD (n=6). Patients with EGFRvIII mutations (13 in E arm, 8 in control arm) had shorter PFS (p=0.007) and OS (p=0.004) regardless of treatment. Response to E was not correlated with EGFR expression, EGFR amplification or EGFRvIII mutation. Conclusions: This randomized, controlled phase II study did not find sufficient activity for erlotinib in the general population of recurrent GBM. The presence of EGFRvIII mutations was not predictive for response. No significant financial relationships to disclose.
Doctors warn of dangers of complementary medicine for children
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Doctors have warned of the dangers associated with complementary therapies after a 4 year old boy with autism was admitted to an emergency department after his parents followed advice to give him holistic supplements.

When he was admitted to hospital the young boy had symptoms including vomiting, constipation, weight loss, and loss of appetite, doctors from Barts Hospital in London have reported in BMJ Case Reports .1 Tests showed hypercalcaemia …
Validation of a Staging System for Acute Kidney Injury in Patients With Cirrhosis and Association With Acute-on-Chronic Liver Failure
Authors: Patricia Huelin, Salvatore Piano, Elsa Solà, Marialuisa Stanco, Cristina Solé, Rebeca Moreira, Elisa Pose, Silvano Fasolato, Nuria Fabrellas, Glòria de Prada, Chiara Pilutti, Isabel Graupera, Xavier Ariza, Antonietta Romano, Chiara Elia, Andrés Cárdenas, Javier Fernández, Paolo Angeli, Pere Ginès
Journal: Clinical Gastroenterology and Hepatology (2016)
Phase II study of sunitinib malate (SM) in subjects with metastatic and/or surgically unresectable non-GIST soft tissue sarcomas
Authors: C. E. Vigil, A. A. Chiappori, C. A. Williams, H. H. Shrager, B. L. Murray, D. G. Letson, D. M. Sullivan, C. R. Garrett, G. Z. D’Amato, S. V. Agresta
Journal: Journal of Clinical Oncology (2008)

10535 Background: Metastatic soft tissue sarcoma represents a diverse collection of disease types. Sunitinib malate is a multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor, with proven efficacy in imatinib mesylate-refractory or intolerant gastrointestinal stromal tumors (GIST). This study was designed to evaluate the efficacy and tolerability of sunitinib malate in four non-GIST sarcoma subytpes (liposarcoma, malignant fibrous histiocytoma, fibrosarcoma and leiomyosarcoma). Methods: Eligibility criteria included tissue documented metastatic soft tissue sarcomas, measurable disease (by RECIST criteria), and a maximum of three prior lines of therapy for metastatic disease. Treatment was with sunitinib malate 50 mg orally daily in 6 week cycles (4 weeks on/ 2 weeks off). Results: Thirty-six subjects have been accrued to date, 12 patients with leiomyosarcoma, 12 with liposarcoma, 11 with malignant fibrous histiocytoma (MFH) and one patient with fibrosarcoma. The median age was 64, range 42–86, male/female 18/18, ECOG performance status 0/1/2 24/11/1. The median number of cycles administered has been 3 (range 1 to 7). Tolerance of therapy has been acceptable with the only three serious drug-related adverse events being congestive heart failure and pulmonary emboli. One confirmed partial response was seen. 29 (80.6%) subjects have observed stable disease for at least 12 weeks. Conclusions: The data from the study to date demonstrate acceptable tolerability of sunitinib in metastatic soft tissue sarcomas of different histologies. A high percent of subjects with stable disease was observed. These finding support further evaluation of sunitinib malate in soft tissue sarcomas. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Margaret McCartney: Publishing doctors’ private earnings is not enough
Authors: Margaret McCartney
Journal: BMJ (2016)

The proposal to publish NHS consultants’ private earnings must have led to sharp intakes of breath all along Harley Street.1 We British are squeamish about money talk. And NHS England’s timing—right after the junior doctors’ strikes and before negotiations on the consultants’ contract—has prompted suspicion.

I was brought up in the era when consultants weren’t there to take ward rounds because they were “down at the mint” (seeing private patients). Then, also, private ambulances would deposit patients with no recordable blood pressure into NHS care. These were patients freshly wounded by private institutions that lacked intensive care facilities. Without doubt, there …
New Insights in the Pathogenesis of MGUS, Multiple Myeloma (MM) and Waldenström`s Macroglobulinemia (WM): Chronic Antigenic Stimulation by Autoantigenic Targets of Paraproteins Is Mediated by CD4+ t-Cells
Authors: Sandra Grass, Klaus-Dieter Preuss, Aleksandra Wikowicz, Natalie Fadle, Evi Regitz, Gerhard Held, Leon Bernal-Mizrachi, Sybille Raudies, Holger Thiele, Michael Pfreundschuh, Frank Neumann
Journal: Blood (2011)
Large tumor suppressor homologs 1 and 2 regulate mouse liver progenitor cell proliferation and maturation through antagonism of the coactivators YAP and TAZ
Authors: Jing Yi, Li Lu, Kilangsungla Yanger, Wenqi Wang, Bo Hwa Sohn, Ben Z. Stanger, Min Zhang, James F. Martin, Jaffer A. Ajani, Junjie Chen, Ju‐Seog Lee, Shumei Song, Randy L. Johnson
Journal: Hepatology (2016)

In the adult liver, the Hippo pathway mammalian STE20‐like protein kinases 1 and 2 and large tumor suppressor homologs 1 and 2 (LATS1/2) control activation of the transcriptional coactivators Yes‐associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ) in hepatocytes and biliary epithelial cells, thereby regulating liver cell proliferation, differentiation, and malignant transformation. Less is known about the contribution of Hippo signaling to liver development. We used conditional mutagenesis to show that the Hippo signaling pathway kinases LATS1 and LATS2 are redundantly required during mouse liver development to repress YAP and TAZ in both the biliary epithelial and hepatocyte lineages. In the absence of LATS1/2, biliary epithelial cells exhibit excess proliferation while hepatoblasts fail to mature into hepatocytes, defects that result in perinatal lethality. Using an in vitro hepatocyte differentiation assay, we demonstrate that YAP activity decreases and Hippo pathway kinase activities increase upon differentiation. In addition, we show that YAP activation in vitro , resulting from either depletion of its negative regulators LATS1/2 or expression of a mutant form of YAP that is less efficiently phosphorylated by LATS1/2, results in transcriptional suppression of genes that normally accompany hepatocyte maturation. Moreover, we provide evidence that YAP activity is repressed by Hippo pathway activation upon hepatocytic maturation in vitro . Finally, we examine the localization of YAP during fetal liver development and show that higher levels of YAP are found in biliary epithelial cells, while in hepatocytes YAP levels decrease with hepatocyte maturation. Conclusion: Hippo signaling, mediated by the LATS1 and LATS2 kinases, is required to restrict YAP and TAZ activation during both biliary and hepatocyte differentiation. These findings suggest that dynamic regulation of the Hippo signaling pathway plays an important role in differentiation and functional maturation of the liver. (H epatology 2016;64:1757‐1772).