tbuckley/cabot-search huggingface dataset:
Abstract 17655: Cost-effectiveness of Ivabradine as a Treatment for Systolic Chronic Heart Failure in the United States
Authors: Anuraag R Kansal, Martin Cowie, Adrian Kielhorn, Stanimira Krotneva, Ali Taffazzoli, Ying Zheng, Nicole Yurgin
Journal: Circulation (2015)

Introduction: To compare the long-term clinical, cost and quality of life outcome of ivabradine+ standard of care (SoC) versus SoC and assess the cost-effectiveness of ivabradine as a treatment to systolic chronic HF, a cost effectiveness model was developed from the perspective of US payers. Hypothesis: Ivabradine+SoC is a cost-effective treatment for systolic chronic HF compared to SoC in the US. Methods: A state-transition model was developed modeling the risk of death and HF-, non-HF CV-, and non-CV- related hospitalization and mortality over 10 years in a cohort of patients receiving ivabradine+SoC. As patients experienced more HF and non-HF CV hospitalizations in the model, they were subject to higher future risk of HF and non-HF CV hospitalization and lower quality of life. Hospitalization rates and costs by hospitalization type were taken from US claims data for patients in commercial and Medicare Advantage insurance plans. Mortality, utility inputs, and ivabradine treatment effect were derived from analyses of the pivotal randomized placebo-controlled SHIFT study. Both health and cost outcomes were discounted at 3% per year. One-way and multi-way sensitivity analyses were conducted. Results: In the commercially insured population based on a cost of $4,500 per year for ivabradine, the total costs over 10 years were $355,080 for a patient treated on ivabradine+SoC and $361,516 for a patient on SoC alone. The total lifetime drug cost of ivabradine ($27,201) was more than offset with cost-savings from reduction in hospitalization. Patients on ivabradine+SoC also had better health outcomes with an incremental improvement of 0.21 life-years and 0.24 quality-adjusted life years (QALYs) compared to SoC. Similar incremental health benefit was seen in the Medicare Advantage (0.20 QALYs) population, but the lower cost per hospitalization led to a modest increase in cost ($7,284). The incremental cost-effectiveness ratio was $36,944/QALY in the Medicare Advantage population. Conclusions: The results of this model indicate that ivabradine+SoC may be a less costly and more effective option compared to SoC in the commercial population and a cost-effective treatment option among Medicare Advantage patients.
Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1
Authors: Yehudi Bloch, Laura Bouchareychas, Romain Merceron, Katarzyna Składanowska, Lien Van den Bossche, Sammy Detry, Srinath Govindarajan, Dirk Elewaut, Filomeen Haerynck, Melissa Dullaers, Iannis E. Adamopoulos, Savvas N. Savvides
Journal: Immunity (2017)
P01.03 Telomere length, allergies and risk of glioma
Authors: U. Andersson, S. Degerman, A. S. Dahlin, T. Brännström, G. Roos, B. S. Melin
Journal: Neuro-Oncology (2017)

Background: In glioma, a malignant brain tumour with poor prognosis, the etiology is largely unkown. Rare inherited syndromes, and high doses of ionising radiation are associated with increased risk of glioma. Common genetic variants have been associated with risk of glioma, and familial glioma have been associated with genetic variants in genes functionally important in telomere regulation (e.g. RTEL, TERT and POT1). The association between telomere length and risk of cancer is complex and seems to be tumour type dependent. Patients with asthma have significantly shorter telomeres than those of control subjects, and a protective effect has been observed with an inverse association with allergies and asthma and glioma risk. Methods: We investigated population based glioma case-control series (431 cases and 672 controls) from Sweden at diagnosis with a quantitative PCR method for relative leukocyte telomere length measured in blood confirming with direct measurement of the association between telomere length and risk of glioma. We also explored the relationship between, age, gender, allergies and asthma, as these are established factors associated both with telomere length and glioma. Results: Longer relative leukocyte telomere length was significantly associated with increased risk of glioma, adjusting for age and gender (OR=2.23, CI: 1.11–4.47). As expected, for patients with allergies there was a protective effect with an inverse association with glioma risk, adjusting for age and gender (OR=0.64, CI; 0.48–0.85). Nevertheless, when analysing specific types of allergy, eczema (OR=0.66, CI; 0.41–1.08) and water eyes (OR=0.52, CI; 0.31–0.88) appeared to be more protective against glioma, compared to asthma (OR=0.92, CI; 0.59–1.41), and respiratory symptoms (OR=1.14, CI; 0.71–1.84) which showed no protective effect against glioma. Additionally adjusting for allergies did not markedly change the OR between relative leukocyte telomere length and glioma risk, indicating that the protective effect having allergies seems not to be coupled to telomere length. Conclusions: The adverse association of longer telomere and risk of glioma displays the complexity in understanding the biological role of telomere length and risk of developing cancer.
Police in Xinjiang province gather biometric data under guise of health programme
Authors: Owen Dyer
Journal: BMJ (2017)

A public health initiative called “Physicals for All” in China’s Xinjiang autonomous region is actually part of a police operation to collect DNA samples, iris scans, and blood type data from all of its 22 million citizens, according to Human Rights Watch.1

“Xinjiang authorities should rename their physical examinations project ‘Privacy Violations for All,’ as informed consent and real choice do not seem to be part of these programmes,” said Sophie Richardson, China director for the human rights organisation. “The mandatory databanking of a whole population’s biodata, including DNA, is a gross violation of international human rights norms, and it’s even more disturbing if it is done surreptitiously, under …
HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma
Authors: Qiuran Xu, Jianfeng Tu, Changwei Dou, Jun Zhang, Liu Yang, Xin Liu, Kefeng Lei, Zhikui Liu, Yufeng Wang, Lijie Li, Hangxing Bao, Jiahui Wang, Kangsheng Tu
Journal: Molecular Cancer (2017)

Heat shock protein 90 (HSP90) functions as a well-known onco-protein to regulate protein conformation, stability and degradation. Pyruvate kinase M2 (PKM2), a critical regulator of the metabolism, growth and metastasis of cancer cells, has been confirmed to be overexpressed in various human cancer including hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the oncogenic functions of HSP90 and PKM2 overexpression in HCC remain unknown.The expression of HSP90 and PKM2 in HCC specimens and cells were detected by immunoblotting and immunostaining. The interaction between HSP90 and PKM2 was confirmed by tandem affinity purification, co-immunoprecipitation and Glutathione S transferase (GST)-pulldown assay.In this study, we found that HSP90 could bind to PKM2 and subsequently increased PKM2 abundance in HCC cells. Immunohistochemistry (IHC) staining showed that HSP90 level was positively correlated with PKM2 level in HCC tissues. Mechanistically, HSP90 was found to increase the phosphorylation of PKM2 at Thr-328. Protein kinase glycogen synthase kinase-3β (GSK-3β) formed a protein complex with HSP90 and PKM2, and directly mediated Thr-328 phosphorylation of PKM2 induced by HSP90. Thr-328 phosphorylation was critical for maintaining PKM2 stability and its biological functions in regulating glycolysis, mitochondria respiration, proliferation and apoptosis. Functionally, we found that HSP90 promoted the glycolysis and proliferation and inhibited apoptosis of HCC cells in a PKM2 dependent manner. In vivo experiments disclosed that PKM2 was required for the promoting effects of HSP90 on the growth of HCC cells in mice. Furthermore, we demonstrated that positive expression of HSP90 and PKM2 was correlated with poor clinicopathological features including high alpha fetoprotein (AFP) level, large tumor size, portal vein tumor thrombus (PVTT) and advanced tumor-node-metastasis (TNM) stage. Furthermore, we demonstrated that positive expression of HSP90 and PKM2, and a combination of these proteins could strongly predict the poor prognosis of HCC patients.We suggest that HSP90 potentiates the glycolysis and proliferation, reduces the apoptosis and thus enhances the growth of HCC cells through PKM2.
Tailoring the colorectal cancer disease assessment to the treatment strategy
Authors: Dustin A Deming
Journal: Gut (2017)

The treatment options for metastatic colorectal cancer (CRC) continue to evolve with over 10 therapies now approved by the Food and Drug Administration for this indication. These include cytotoxic chemotherapeutics, biologics targeting vascular endothelial growth factor (VEGF) and epidermal growth factor receptor, and most recently the approval of the immunotherapeutic agents pembrolizumab and nivolumab for mismatch repair-deficient cancers. Additional agents targeting the BRAF mutant subtype of CRC are likely to be approved in the near future. This growing number of treatment options for patients increases the demand for accurate disease assessments to allow for further treatment in the setting of benefit, and also discontinuation or change in the treatment strategy in the setting of resistance.

The Response Evaluation Criteria in Solid Tumors (RECIST v1.1)1 is the standard response criteria used in oncology clinical trials and is loosely followed in standard clinical practice. For CRC, this is most commonly done with oral and intravenous contrast enhanced CT imaging. These criteria use changes in the cross-sectional diameter to quantify whether cancers are …
Current status of multiple personality disorder in India
Authors:  Adityanjee, G S Raju, S K Khandelwal
Journal: American Journal of Psychiatry (1989)

Three consecutive cases of multiple personality disorder seen over a period of 3 years at a psychiatric clinic in India are reported. The prevalence of this disorder at the clinic is about 0.15/1,000 patients per year. The authors discuss the infrequency of this diagnosis in India in contrast to the frequent diagnosis of possession syndrome for patients who have many of the same symptoms. Transcultural differences in diagnostic practices are also discussed.
Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to methotrexate
Authors: Hiroaki Matsuno, Masato Tomomitsu, Atsushi Hagino, Seonghye Shin, Jiyoon Lee, Yeong Wook Song
Journal: Annals of the Rheumatic Diseases (2017)

To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment.This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated.In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were -3.01 (95% CI -3.198 to -2.820) in the LBEC0101 group and -2.86 (95% CI -3.051 to -2.667) in the ETN-RP group. The estimated between-group difference was -0.15 and its 95% CI was -0.377 to 0.078, which was within the prespecified equivalence margin of -0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs.The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP.NCT02357069.
Association of Coronary Vessel Characteristics With Outcome in Patients With Percutaneous Coronary Interventions With Incomplete Revascularization
Authors: Edward L. Hannan, Ye Zhong, Peter B. Berger, Alice K. Jacobs, Gary Walford, Frederick S. K. Ling, Ferdinand J. Venditti, Spencer B. King
Journal: JAMA Cardiology (2017)

Many studies have compared outcomes for incomplete revascularization (IR) among patients undergoing percutaneous coronary interventions (PCI), but little is known about whether outcomes are related to the nature of the IR.To determine whether some coronary vessel characteristics are associated with worse outcomes in patients with PCI with IR.New York's PCI registry was used to examine mortality (median follow-up, 3.4 years) as a function of the number of vessels that were incompletely revascularized, the stenosis in those vessels, and whether the proximal left anterior descending artery was incompletely revascularized after controlling for other factors associated with mortality for patients with and without ST-elevation myocardial infarction (STEMI). This was a multicenter study (all nonfederal PCI hospitals in New York State) that included 41 639 New York residents with multivessel coronary artery disease undergoing PCI in New York State between January 1, 2010, and December 31, 2012.Percutaneous coronary interventions, with complete and incomplete revascularization.Medium-term mortality.For patients with STEMI, the mean age was 62.8 years; 26.2% were women, 11.9% were Hispanic, and 81.5% were white. For other patients, the mean age was 66.6 years, 29.1% were women, 11.3% were Hispanic, and 79.1% were white. Incomplete revascularization was very common (78% among patients with STEMI and 71% among other patients). Patients with IR in a vessel with at least 90% stenosis were at higher risk than other patients with IR. This was not significant among patients with STEMI (17.18% vs 12.86%; adjusted hazard ratio [AHR], 1.16; 95% CI, 0.99-1.37) and significant among patients without STEMI (17.71% vs 12.96%; AHR, 1.15; 95% CI, 1.07-1.24). Similarly, patients with IR in 2 or more vessels had higher mortality than patients with completely revascularization and higher mortality than other patients with IR among patients with STEMI (20.37% vs 14.39%; AHR, 1.35; 95% CI, 1.15-1.59) and among patients without STEMI (20.10% vs 12.86%; AHR, 1.17; 95% CI, 1.09-1.59). Patients with proximal left anterior descending artery vessel IR had higher mortality than other patients with IR (20.09% vs 14.67%; AHR, 1.31; 95% CI, 1.04-1.64 for patients with STEMI and 20.78% vs 15.62%; AHR, 1.11; 95% CI, 1.01-1.23 for patients without STEMI). More than 20% of all PCI patients had IR of 2 or more vessels and more than 30% had IR with more than 90% stenosis.Patients with IR are at higher risk of mortality if they have IR with at least 90% stenosis, IR in 2 or more vessels, or proximal left anterior descending IR.
Abstract 13576: Concomitant Valve Intervention During Left Ventricular Assist Device Implantation Improves Mid-term Hemodynamics and Survival
Authors: Akiko Tanaka, David Onsager, Daniel Cozadd, Gene Kim, Sirtaz Adatya, Nitash Sarswat, Gabriel Sayer, Savitri Fedson, Nir Uriel, Valluvan Jeevanandam, Takeyoshi Ota
Journal: Circulation (2015)

Introduction: This is a retrospective single-institutional study to investigate safety and efficacy of concomitant valve procedures in patients undergoing left ventricular assist device (LVAD) implantation. Methods: From July 2008 to December 2014, 254 patients underwent LVAD implantation. 165 patients had concomitant valve intervention (aortic valve [A], N=3; mitral valve [M], N=78; tricuspid valve [T], N=131; multiple valve intervention, N=67, A+M=3, A+T=11, M+T=44, A+M+T=9). Patients were divided into two groups: Group D, with residual diseased valve, N=97; and Group C, with no-diseased valve, N=157) (see details in figure) and short-/mid-term outcomes were compared. Results: Intraoperative and postoperative outcomes did not differ in two groups except for significantly more concomitant valve procedures (Group D=54 [56%], Group C=111 [70%], P&lt;.0001) and longer cardio-pulmonary bypass time (Group D=125 min vs Group C=148min, P = 0.003) in Group C compared to Group D. There was no statistically significant difference in two groups in In-hospital mortality with a tendency to be favorable to Group C (Group D=19.6% vs Group C=11.6%, P=0.09). Concomitant valve intervention did not increase in-hospital mortality (LVAD+valve=15.7%, isolated LVAD=14.1%, P=0.73). During mid-term follow up, mean pulmonary artery pressure (mmHg)(Group D=27, Group N=22, P=0.012) and wedge pressure (Group D=15, Group C=12,P=0.038) were significantly lower in Group C compared to Group D. Post-LVAD implant survival and freedom from heart failure readmission rate at 1 year were significantly higher in Group C compared to Group D (survival, Group D=59 ± 5%, Group C=72 ± 3%, P=0.035; admission, Group D=79 ± 5%, Group C=88±3%, P=0.034) Conclusions: Concomitant valve procedure during LVAD implantation did not increase operative morbidity and mortality. Aggressive valve intervention during LVAD implantation may contribute to improved mid-term hemodynamics and survival.
Oncogenic RAS-Induced Perinuclear Signaling Complexes Requiring KSR1 Regulate Signal Transmission to Downstream Targets
Authors: Sandip K. Basu, Sook Lee, Jacqueline Salotti, Srikanta Basu, Krisada Sakchaisri, Zhen Xiao, Vijay Walia, Christopher J. Westlake, Deborah K. Morrison, Peter F. Johnson
Journal: Cancer Research (2017)

The precise characteristics that distinguish normal and oncogenic RAS signaling remain obscure. Here, we show that oncogenic RAS and BRAF induce perinuclear relocalization of several RAS pathway proteins, including the kinases CK2 and p-ERK1/2 and the signaling scaffold KSR1. This spatial reorganization requires endocytosis, the kinase activities of MEK-ERK and CK2, and the presence of KSR1. CK2α colocalizes with KSR1 and Rab11, a marker of recycling endosomes, whereas p-ERK associates predominantly with a distinct KSR1-positive endosomal population. Notably, these perinuclear signaling complexes (PSC) are present in tumor cell lines, mouse lung tumors, and mouse embryonic fibroblasts undergoing RAS-induced senescence. PSCs are also transiently induced by growth factors (GF) in nontransformed cells with delayed kinetics (4-6 hours), establishing a novel late phase of GF signaling that appears to be constitutively activated in tumor cells. PSCs provide an essential platform for RAS-induced phosphorylation and activation of the prosenescence transcription factor C/EBPβ in primary MEFs undergoing senescence. Conversely, in tumor cells, C/EBPβ activation is suppressed by 3'UTR-mediated localization of Cebpb transcripts to a peripheral cytoplasmic domain distinct from the PSC region. Collectively, our findings indicate that sustained PSC formation is a critical feature of oncogenic RAS/BRAF signaling in cancer cells that controls signal transmission to downstream targets by regulating selective access of effector kinases to substrates such as C/EBPβ.Significance: In addressing the long-standing question of the difference between normal and oncogenic RAS pathway signaling, this study shows that oncogenic RAS specifically triggers constitutive endocytosis-dependent movement of effector kinases to a perinuclear region, thereby creating connections to unique downstream targets such as the core prosenescence and the inflammatory regulatory transcription factor C/EBPβ. Cancer Res; 78(4); 891-908. ©2017 AACR.
Cytokine diagnosis of pleural TB: will it stand the test of time?
Authors: Marc Tebruegge, Paul T Elkington
Journal: Thorax (2017)

The need for better diagnostics for TB has been repeated so frequently that there is a danger of message fatigue. However, the unfortunate return of TB as the number 1 cause of death due to an infectious disease must surely serve as a further call to action for researchers, clinicians and funders to redouble our efforts.1 The fundamental issues with TB diagnosis deserve repeating: standard diagnosis of pulmonary TB relies primarily on sputum smear tests, which have limited sensitivity and specificity, and have not significantly changed for over 100 years.2 Recent data show that staining for acid-fast bacilli remains the most commonly used diagnostic method globally.3 The development of interferon-gamma release assays (IGRAs) and molecular amplification tests such as Xpert MTB/RIF assays has improved the landscape somewhat, but both are critically limited by cost and the need for extensive infrastructure. In addition, IGRAs do not distinguish latent from active TB, have limited robustness and perform worse in children than in adults.4–6 Recent data suggest that the roll-out and scale-up of the Xpert MTB/RIF assays in resource-limited settings have been far slower than anticipated.7 Importantly, molecular assays require relatively high numbers of bacilli to achieve adequate sensitivity. The diagnosis of extrapulmonary TB is often more challenging than pulmonary TB, frequently with low bacterial loads in difficult-to-access locations. Therefore, the majority of TB diagnoses …
Tuberculose et BCG en Europe
Authors: J M Watson
Journal: Eurosurveillance (2006)

Le vaccin du BCG (Bacille de Calmette-Guerin) a ete developpe au debut du vingtieme siecle a partir d’une souche attenuee de Mycobacterium bovis. Ce vaccin a ete tres largement utilise d’abord en Europe, puis dans le monde, durant les 50 annees qui ont suivi. S’il reste l’un des vaccins les plus administres a l’echelle mondiale, il est egalement l’un des plus controverses. Les evaluations de son efficacite a proteger contre differentes formes de tuberculose dans divers sous-groupes de population en differents environnements montrent d’importantes variations [1]. Certains pays, de faible incidence de tuberculose, n’ont jamais adopte la vaccination BCG, d’autres l’ont abondonnee apres l’avoir utilisee. Par ailleurs, il existe d’importantes variations dans les programmes nationaux du BCG, en particulier en ce qui concerne l’âge (les âges) auquel le vaccin doit etre administre, ainsi que sur l’utilisation de tests de sensibilite a la tuberculine avant la vaccination et sur la question des rappels.
Identification of a KPC-9-producing Klebsiella pneumoniae ST258 cluster among KPC-2-producing isolates of an ongoing outbreak in Northwestern Greece: a retrospective study
Authors: K. Gartzonika, J.W.A. Rossen, H. Sakkas, S. Rosema, E. Priavali, A.W. Friedrich, S. Levidiotou, E. Bathoorn
Journal: Clinical Microbiology and Infection (2017)
Erythematous Velvety Plaque of the Scrotum and Penis
Authors: Yu Xi Terence Law, Valerie Huei Li Gan, Kae Jack Tay
Journal: JAMA Oncology (2017)

A 70-year-old Chinese man with a medical history of hypertension, hyperlipidaemia, and ischemic heart disease was referred to the urology clinic for 1 week of dysuria; there was a nonpruritic, erythematous, velvety plaque over the left base of his penis. What is your diagnosis?
Alternative VEGF splicing in WT1 mutants reveals SRPK1 to be a novel angiogenesis target
Authors: E M Amin, S Oltean, J Hua, M V Gammons, M K Cheung, L Ni, M Hamdollah Zadeh, S Kase, E S Rennel, G I Welsh, K E Symonds, D G Nowak, B Pokora-Royer, M A Saleem, M Hagiwara, V A Schumacher, S J Harper, D R Hinton, DO Bates, M R Ladomery
Journal: Cancer Cell (2011)