tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C
Authors: Jake R. Jacobs, Raymond S. Koff
Journal: Hepatology (2000)

To the Editor: I read with great interest and more than a little dismay the article by Myers, Gregor, and Marotta 1 on the cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C. While I found the article to be very well written and thorough, I find the premise for the article to be totally unacceptable.Are we to withhold a simple vaccination from our patients, knowing that they run the risk of severe morbidity or death simply because it may not be "cost effective" in a population study?This article calls to mind a story that was recently played out in the courts in the United States.There was once a large automobile manufacturer that produced a vehicle it knew was unsafe.Not only did they know that it was unsafe, they also knew how to fix the problem to render the vehicle safe.However, rather than do the right thing and fix the vehicle (at a cost of $11 per vehicle), they embarked on a course similar to Myers et al.They first calculated the cost of correcting the defect and then compared it with the cost they may incur if the defect was not corrected.They used data from the federal government and that the National Highway Traffic Safety Administration made available to them.They calculated the average damage per person killed by their vehicle.They added medical costs, property damage, insurance administration, legal and court costs, employer losses, victim pain and suffering, and funeral bills as well as "other costs."When they found that this cost would be less than the cost of correcting the defect on the vehicle, they elected to take their chances in court.Their strategy ultimately landed them in court and resulted in one of the largest settlements in the American legal system.The ethics involved in their decision-making process was headline news throughout the nation.The parallels between this story and the conclusions drawn from this article I find to be quite remarkable.I can see myself in the future consoling Mrs. X upon the death of her husband from hepatitis A superimposed on hepatitis C, a disease that could have been prevented by a simple vaccination, by handing her the article and saying, "but as you can see here, clearly it would not have been cost effective for me to have given your husband a simple vaccine."I was surprised that this article did not provoke more editorial comments from the editors of HEPATOLOGY and I certainly hope that the ACIP does not reconsider its stance on vaccinating all patients with hepatitis C with the hepatitis A vaccine.
Clinical Outcomes in Pediatric Mixed Phenotype Acute Leukemia (MPAL) Differ Depending on Disease Classification Criteria; A Multi-Center Cohort Study
Authors: Matthew J. Oberley, Gerald Wertheim, Sunil S. Raikar, Jemily Malvar, Richard Sposto, Jyotinder N. Punia, Karen R. Rabin, Alix E. Seif, Reuven J. Schore, Dragos C. Luca, Terri Guinipero, William G. Woods, Maurice R.G. O'Gorman, Etan Orgel
Journal: Blood (2018)
Prediction of Prognosis of Intermediate-Stage HCC Patients: Validation of the Tumor Marker Score in a Nationwide Database in Japan
Authors: Atsushi Hiraoka, Kojiro Michitaka, Takashi Kumada, Namiki Izumi, Masumi Kadoya, Norihiro Kokudo, Shoji Kubo, Yutaka Matsuyama, Osamu Nakashima, Michiie Sakamoto, Tadatoshi Takayama, Takashi Kokudo, Kosuke Kashiwabara, Susumu Eguchi, Tatsuya Yamashita, Masatoshi Kudo
Journal: Liver Cancer (2019)

&lt;b&gt;&lt;i&gt;Background/Aim:&lt;/i&gt;&lt;/b&gt; Adequate assessment of transcatheter arterial chemoembolization (TACE)-refractory status has become more important for switching treatment in intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) patients treated with TACE. The usefulness of a previously proposed tumor marker score for predicting prognosis of BCLC-B HCC patients treated with TACE was investigated. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Using a nationwide database, we examined the records of 1,306 naïve BCLC-B HCC with Child-Pugh A who were treated from 2001 to 2007, after excluding those with missing data (hepatic function or tumor markers) or cases with a single large tumor. Alpha-fetoprotein (AFP) ≥100 ng/mL, fucosylated AFP (AFP-L3) ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL were markers used to define positive cases. The number of positive tumor markers was used as a prognostic score, and its predictive value was evaluated in a retrospective manner. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Median survival time became shorter along with increased score (0, 1, ≥2 = 4.8, 3.8, 3.2 years, respectively; &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.01). Tumor marker score (≥2; hazard ratio [HR] 1.675, 95% confidence interval [CI] 1.372–2.044, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001), serum levels of albumin (≥3.5 g/dL; HR 0.726, 95% CI 0.528–0.997, &lt;i&gt;p&lt;/i&gt; = 0.048), and up-to-7 criteria (HR 1.673, 95% CI 1.400–2.000, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001) were significant prognostic factors for death in the Cox hazard multivariate analysis. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Tumor marker score had a useful predictive prognostic value in BCLC-B HCC treated with TACE. Especially in patients with a tumor marker score of 2 or greater, a poor therapeutic response should be expected, and appropriate judgement of TACE-refractory status is necessary.
Reverse signaling via PD-L1 supports malignant cell growth and survival in classical Hodgkin lymphoma
Authors: Shahrzad Jalali, Tammy Price-Troska, Cole Bothun, Jose Villasboas, Hyo-Jin Kim, Zhi-Zhang Yang, Anne J. Novak, Haidong Dong, Stephen M. Ansell
Journal: Blood Cancer Journal (2019)

Treatment with programmed death-1 (PD-1) blocking antibodies results in high overall response rates in refractory and relapsed classical Hodgkin lymphoma (cHL) patients, indicating that PD-1/PD-1 ligand interactions are integral to progression of this disease. Given the genetically driven increased PD-L1/2 expression in HL, we hypothesized that reverse signaling through PD-1 ligands may be a potential mechanism contributing to the growth and survival of Hodgkin Reed-Sternberg (HRS) cells in cHL. Our data show that engagement of PD-L1 using an agonistic monoclonal antibody increases cell survival and proliferation and reduces apoptosis in HL cell lines. We show that HL patients have significantly higher serum levels of soluble PD-1 than healthy controls, and find that both membrane-bound and soluble forms of PD-1 are able to induce PD-L1 reverse signaling in HL cell lines. PD-L1 signaling, which is associated with activation of the MAPK pathway and increased mitochondrial oxygen consumption, is reversed by PD-1 blockade. In summary, our data identify inhibition of reverse signaling through PD-L1 as an additional mechanism that accounts for clinical responses to PD-1 blockade in cHL.
PTPN14 phosphatase and YAP promote TGFβ signalling in rheumatoid synoviocytes
Authors: Angel Bottini, Dennis J Wu, Rizi Ai, Michelle Le Roux, Beatrix Bartok, Michele Bombardieri, Karen M Doody, Vida Zhang, Cristiano Sacchetti, Martina Zoccheddu, Ana Lonic, Xiaochun Li, David L Boyle, Deepa Hammaker, Tzu-Ching Meng, Lin Liu, Maripat Corr, Stephanie M Stanford, Myles Lewis, Wei Wang, Gary S Firestein, Yeesim Khew-Goodall, Costantino Pitzalis, Nunzio Bottini
Journal: Annals of the Rheumatic Diseases (2019)

We aimed to understand the role of the tyrosine phosphatase PTPN14-which in cancer cells modulates the Hippo pathway by retaining YAP in the cytosol-in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Gene/protein expression levels were measured by quantitative PCR and/or Western blotting. Gene knockdown in RA FLS was achieved using antisense oligonucleotides. The interaction between PTPN14 and YAP was assessed by immunoprecipitation. The cellular localisation of YAP and SMAD3 was examined via immunofluorescence. SMAD reporter studies were carried out in HEK293T cells. The RA FLS/cartilage coimplantation and passive K/BxN models were used to examine the role of YAP in arthritis.RA FLS displayed overexpression of PTPN14 when compared with FLS from patients with osteoarthritis (OA). PTPN14 knockdown in RA FLS impaired TGFβ-dependent expression of MMP13 and potentiation of TNF signalling. In RA FLS, PTPN14 formed a complex with YAP. Expression of PTPN14 or nuclear YAP-but not of a non-YAP-interacting PTPN14 mutant-enhanced SMAD reporter activity. YAP promoted TGFβ-dependent SMAD3 nuclear localisation in RA FLS. Differences in epigenetic marks within Hippo pathway genes, including YAP, were found between RA FLS and OA FLS. Inhibition of YAP reduced RA FLS pathogenic behaviour and ameliorated arthritis severity.In RA FLS, PTPN14 and YAP promote nuclear localisation of SMAD3. YAP enhances a range of RA FLS pathogenic behaviours which, together with epigenetic evidence, points to the Hippo pathway as an important regulator of RA FLS behaviour.
Lenalidomide As Maintenance Treatment for Patients with Newly Diagnosed Multiple Myeloma Post-Autologous Stem Cell Transplantation: A Pharmacoeconomic Assessment in the Netherlands
Authors: Carin A. Uyl-de Groot, Rachel Ramsden, Janneke Boersma, Sonja Zweegman, Sujith Dhanasiri
Journal: Blood (2018)
Abstract 5506: Anti-angiogenic effects of zoledronic acid on osteotropic breast cancer cells
Authors: Cynthia Jackson, William Whalen, Shana Morshedian, Jason A. Bush
Journal: Cancer Research (2015)

Abstract Emerging data suggest the bisphosphonate, zoledronic acid (ZOL), exerts both indirect and direct anti-tumor effects by decreasing tumor cell proliferation, increasing apoptosis, and inhibiting angiogenesis. Recent data indicate that antiangiogenic factors exert cellular effects via suppression of mitochondrial oxidative phosphorylation/respiration and elevation of intracellular ROS levels. This project intended to define proteins involved in response to ZOL-treatment of an osteotropic breast cancer cell line, MDA-231BO. Results demonstrate that MDA-231BO cells are more sensitive to ZOL cytotoxicity and salutary effects are both media- and calcium-dependent. This cytotoxicity was more pronounced in spheroid cultures. To investigate pro-apoptotic mechanisms of ZOL, total RNA, whole cell protein lysates, or mitochondrial-enriched fractions were isolated from MDA-231BO cells and using a combination of RT-PCR, 1D/2D-PAGE separation and MALDI-MS/MS, we identified several angiogenesis inhibitors that were upregulated and pro-angiogenic factors that were downregulated after ZOL treatment. Functional studies demonstrate the improved efficacy of ZOL on MDA-231BO compared to MDA-MB-231 controls. However, when the cells were challenged in a hypoxic environment, these effects were mitigated. Taken together, these results further support a model that ZOL tips the ‘angiogenic switch’ in favor of anti-angiogenic factors in cancer cells with a propensity for bone metastases. Citation Format: Cynthia Jackson, William Whalen, Shana Morshedian, Jason A. Bush. Anti-angiogenic effects of zoledronic acid on osteotropic breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5506. doi:10.1158/1538-7445.AM2015-5506
Predicting Postoperative Liver Dysfunction Based on Blood‐Derived MicroRNA Signatures
Authors: Patrick Starlinger, Hubert Hackl, David Pereyra, Susanna Skalicky, Elisabeth Geiger, Michaela Finsterbusch, Dietmar Tamandl, Christine Brostjan, Thomas Grünberger, Matthias Hackl, Alice Assinger
Journal: Hepatology (2019)

There is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery and thereby determine the optimal time point of liver resection, specifically as current markers are often expensive, time consuming, and invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic, and treatment‐response biomarkers for several diseases. Using next‐generation sequencing as an unbiased systematic approach, 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative liver dysfunction (LD) after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature—consisting of miRNAs 151a‐5p, 192‐5p, and 122‐5p—that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real‐time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a‐5p to 192‐5p and 122‐5p to 151a‐5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stays, and even mortality before an operation with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Our data demonstrate the clinical utility of an miRNA‐based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in individualized patient treatment. Thereby, our data might help to tailor surgical strategies to the specific risk profile of patients.
Complete Remission with Incomplete Count Recovery (CRi) Prior to Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia Is Associated with a High Non-Relapse Mortality without Increased Relapse Risk
Authors: Andrew James Innes, Philippa Woolley, Richard Szydlo, Sara Lozano, Fiona Fernando, Divya Bansal, Renuka Palanicawandar, Elisabet Nadal-Melsio, Eva Yebra-Fernandez, Jane Apperley, Eduardo Olavarria, Jiri Pavlu
Journal: Blood (2018)
Changing trends in coding for depression among the UK IBD population: reply from authors
Authors: Isabelle Vallerand, Alexandra D Frolkis, Scott Patten, Gilaad G Kaplan
Journal: Gut (2019)

We thank Blackwell  et al 1 for raising an important question about the classification of depression in a population of IBD patients in the UK. In our study,examining depression as a risk factor for the development of IBD,2 we chose to use a more restrictive case definition of depression based closely on a definition of major depressive disorder (MDD) as a clinically significant form of depression recognised in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)3 and known to be associated with a significant degree of morbidity and mortality.4 5 In …
Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap
Authors: Nicolas Louarn, Aurélie Dauta, Emmanuèle Lechapt-Zalcman, Paul Kauv, Emmanuel Itti
Journal: Clinical Nuclear Medicine (2019)

A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.
P023 Tenosynovitis and HLA-SE predict arthritis onset in ACPA-positive individuals at risk of developing rheumatoid arthritis
Authors: AH Hensvold, Y Kisten, M Hansson, A Cîrciumaru, M Sun, G Fei, E af Klint, H Rezaei, A Antovic, AI Catrina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow <h3>Introduction</h3> Anti-citrullinated protein antibodies (ACPA) are predictive markers with pathological effects in rheumatoid arthritis (RA). Previous prospective studies have used a clinical definition of arthritis. Thus, we aimed to investigate risk factors of developing arthritis in ACPA-positive subjects with musculoskeletal complaints who did not have any of clinical and ultrasound signs of arthritis. <h3>Methods</h3> Subjects with positive ACPA-test referred from primary care to rheumatology clinic, lacking arthritis in hands and feet by clinical and ultrasound examination (according to EULAR-OMERACT synovitis definition), were recruited into the Risk-RA research program. Patient included between years 2015–2016 with clinical data up to 2017 were analysed. Blood samples from inclusion were analysed for 13 specific ACPA reactivities using a custom made ImmunoCAP ISAC microarray. Presences of HLA-SE risk gene were analysed using DR low-resolution kit. <h3>Results</h3> 41% (27 out of 66) of the Risk RA subjects developed arthritis during a median follow up of 8 months. The rest was followed 25 months in median without any signs of arthritis. Subjects developing arthritis tended to have a higher concentration of anti-CCP, more tender joints and rheumatoid factor positivity at inclusion compared to those not developing arthritis. The number of ACPA-reactivities (mean 6 vs 3), the presence of HLA-SE (89% vs 56%) and the occurrence of ultrasound detected tenosynovitis (44% vs 5%) at inclusion were significantly increased in subjects developing arthritis compared to those not developing arthritis. Univariate cox proportional hazards regression showed a hazard ratio (HR) for arthritis development of 1.1 for every increase in number of ACPA reactivities (95% CI 0.99 to 1.2, p 0.07); HR: 4.4 (95% CI 2.0 to 9.5, p 0.0002) for tenosynovitis and for HR: 4.9 (95% CI 1.5 to 16, p 0.01) for HLA-SE carriers. All subjects with tenosynovitis (n=14) prior to arthritis development were carriers of HLA-SE, except for one subject but similar to the majority this HLA-SE no-carrier also progressed to arthritis. <h3>Conclusions</h3> Subjects with ACPA-positive musculoskeletal complaints lacking any clinical and ultrasound signs of arthritis are at high risk of developing arthritis, especially carriers of HLA-SE with tenosynovitis. The role of inflammatory spreading from tendons (synovial sheath) to synovial tissue within joints need to be further investigated. <h3>Disclosure of Interest</h3> None declared
Survival in Patients with Relapsed/Refractory Multiple Myeloma: Outcomes after 4 Years of the Ongoing Multinational Observational Preamble Study
Authors: Gordon Cook, David Cella, Clara Chen, Catherine Davis, Brian GM Durie, Hartmut Goldschmidt, David J. Kuter, Philippe Moreau, Ravi Vij
Journal: Blood (2018)
Vinorelbine-Based Hematopoietic Stem-Cell Mobilization: A More Effective, Low-Cost Alternative to Conventional Chemotherapy
Authors: Bruno Kosa Lino Duarte, Marcos Paulo Colella, Fernando Vieira Pericole Souza, Gabriela G Yamaguti-Hayakawa, Jose Francisco Comenalli Marques, Afonso Celso Vigorito, Erich Vinicius De Paula, Margareth C Ozelo
Journal: Blood (2018)
Reply to Maurizio Serati, Stefano Uccella and Stefano Salvatore's Letter to the Editor re: Annette Kuhn, Caroline Eggeman, Fiona Burkhard and Michael D. Mueller. Correction of Erosion after Suburethral Sling Insertion for Stress Incontinence: Results and Related Sexual Function. Eur Urol. In press. Doi:10.1016/j.eururo.2008.09.016
Authors: Annette Kuhn
Journal: European Urology (2008)
Deaths from Anaesthetics in 1884
Authors: E. H. Jacob
Journal: BMJ (1885)

__A __an but I have.elsewharepointed qubow, from the nature of t4e particles embSdded, it is not'alwEys etjyafiy applicable.CASE XV. -A man, aged S4, was tok* in the right eye by a piece of steel from-a chise4 with which: he was cutting some iron.A dark mark was noticed under the co6njunctiva, on the outer'side of the globe, a4d, on applying the electro-magnet, it was noticed to move, and'it, was readily e*tracted through a small incision in the con- junetiva.The particle was about one-eighth of an inch long.In both these instantees, the fracrments of steel were removed by Mr.J.,R.Turner, And to him and' to Mr. P. Priestley, I ata, indebted for many of the notes df the cases,here related.The fifteen dases now recorded make, together with those previously publibhed by 'me-nineteen in number-a 'total of thirty-four.Now, a8 'preibusly, I make no record of the numerous instances in which w0unds, in shomewhat doubtful 'cases, have been " probed " by the electro-magnet'; if these were calculated, the aggregate number would perhaps be doubled.Of the cases themselves, 1 would merely remark that they illustrate the wide applicability of the electro-mag'net to the various parts of the eye; of course, they vary much in value and in-
Needed: Antimicrobial Development
Authors: Edward Cox, Sumathi Nambiar, Lindsey Baden
Journal: New England Journal of Medicine (2019)

Antimicrobial resistance continues to erode our therapeutic armamentarium for treating patients with bacterial infections. Clinicians are now encountering infections that are susceptible to few or even (although rarely) none of the available drugs. One of the multiple components of a strategy to effectively respond to antimicrobial resistance — the development of new antibacterial agents — is particularly challenging because of the nature of serious acute bacterial infections and the economic realities in this field. The initiation of antimicrobial therapy is urgently needed in patients with serious acute bacterial infections. Initiation is often recommended within an hour after presentation,1 despite the . . .