tbuckley/cabot-search huggingface dataset:
S107 Disease progression modelling in idiopathic pulmonary fibrosis: a prediction of time to disease progression and life expectancy with pirfenidone
Authors: M Fisher, T Maher, C Hill, J Marshall
Journal: Thorax (2015)

<h3>Objectives</h3> Currently, clinical trials in idiopathic pulmonary fibrosis (IPF) are not designed to estimate disease progression and survival over a long period. The objective of this study was to develop a disease progression model in IPF to predict the extent to which treatment with pirfenidone could extend the time to disease progression and improve life expectancy versus best supportive care (BSC) over a patient’s lifetime. <h3>Methods</h3> A disease progression model was developed categorising disease progression into four health states: progression free; progressed (≥10% decline in FVC or ≥50 m decrease in 6-minute walking distance); lung transplant; and dead. Two cohorts entered the model in the progression-free state: one cohort received pirfenidone (n = 1000), the other received BSC (n = 1000). The proportion of patients in each health state was calculated every 3 months based on parametric survival distributions fitted to data from clinical trials and registries. Distributions calculating progression-free survival (PFS) and overall survival (OS) for pirfenidone were fitted to data from randomised controlled trials (RCTs; Studies 004, 006, 016) and a long-term open-label extension study (Study 012). Distributions calculating PFS and OS for BSC were fitted to data from the RCTs and a US-based IPF registry. Mean PFS and OS were determined for pirfenidone and BSC. Uncertainty was explored by deterministic and probabilistic sensitivity analysis. <h3>Results</h3> The model calculated mean PFS as 3.28 years and 2.18 years with pirfenidone and BSC, respectively (Figure). Hence, pirfenidone extended the estimated mean time to disease progression by 1.10 years. Mean OS was calculated as 9.29 years and 6.10 years with pirfenidone and BSC, respectively (Figure 1). Therefore, pirfenidone improved estimated life expectancy by 3.19 years. The extent to which pirfenidone improved PFS and OS was sensitive to choice of parametric survival distribution and method of extrapolation. <h3>Conclusions</h3> This disease progression model suggests that treatment with pirfenidone extends the time to disease progression and improves life expectancy, thus preventing early morbidity and deaths in IPF. These conclusions are consistent with expectations for a therapy that has been shown to reduce disease progression and mortality, as measured by a pooled analysis of outcomes in Phase 3 clinical trials.
Manifestation of Huntington’s disease pathology in human induced pluripotent stem cell-derived neurons
Authors: Evgeny D. Nekrasov, Vladimir A. Vigont, Sergey A. Klyushnikov, Olga S. Lebedeva, Ekaterina M. Vassina, Alexandra N. Bogomazova, Ilya V. Chestkov, Tatiana A. Semashko, Elena Kiseleva, Lyubov A. Suldina, Pavel A. Bobrovsky, Olga A. Zimina, Maria A. Ryazantseva, Anton Yu. Skopin, Sergey N. Illarioshkin, Elena V. Kaznacheyeva, Maria A. Lagarkova, Sergey L. Kiselev
Journal: Molecular Neurodegeneration (2016)

Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons (GMSLNs) under defined culture conditions. The generated HD GMSLNs recapitulated disease pathology in vitro, as evidenced by mutant huntingtin protein aggregation, increased number of lysosomes/autophagosomes, nuclear indentations, and enhanced neuronal death during cell aging. Moreover, store-operated channel (SOC) currents were detected in the differentiated neurons, and enhanced calcium entry was reproducibly demonstrated in all HD GMSLNs genotypes. Additionally, the quinazoline derivative, EVP4593, reduced the number of lysosomes/autophagosomes and SOC currents in HD GMSLNs and exerted neuroprotective effects during cell aging. Our data is the first to demonstrate the direct link of nuclear morphology and SOC calcium deregulation to mutant huntingtin protein expression in iPSCs-derived neurons with disease-mimetic hallmarks, providing a valuable tool for identification of candidate anti-HD drugs. Our experiments demonstrated that EVP4593 may be a promising anti-HD drug.
Case 68-1963
Authors: Roman W. DeSanctis, Robert E. Scully
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A seventy-four-year-old woman entered the hospital because of dyspnea.The patient had been well and active until the evening of admission, when she suddenly complained of a "painful gas bubble" in the epigastrium accompanied by dyspnea and profuse sweating. The pain subsided within three hours, but the dyspnea persisted. There was no history of previous heart disease or use of medications.Physical examination revealed a sallow, dyspneic, elderly woman sitting upright in bed. The chest was kyphotic, and crackling inspiratory rales were heard over the lower two thirds of both lung fields. The heart . . .
179P: Nivolumab monotherapy in patients with previously treated advanced non-small cell lung cancer (NSCLC) in routine clinical practice in a Spanish center
Authors: X. Mielgo, P. Toro, L. Ruiz-Giménez, C. Olier, M. Pérez, A. Rosero, J.C. Cámara, S. Hernando, A. Hurtado, C. Jara
Journal: Journal of Thoracic Oncology (2016)
AB0153 Prevalence of HLA-B27 in Yakut Children with Seronegative Spondyloarthropathy
Authors: V. Chasnyk, F. Vinokurova, L. Grigorieva, V. Argunova, A. Golderova, T. Burtseva, V. Nikolaev, S. Efremova, O. Tikhonova
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The term seronegative spondyloarthropathies (SpA) is used to define a specific group of disorders with certain common features, an increased incidence of HLA-B27, as well as negative rheumatoid factor and ANA being among them. The association of HLA-B27 within the group of SpA varies significantly, ranging from &lt;50% in psoriatic, enteropathic, and inflammatory bowel disease-associated SpA, to 80% in reactive arthritis, to $&gt;&lt;$ 50% in psoriatic, enteropathic and inflammatory bowel disease-associated SpA, to &gt;95% in ankylosing spondilitis. The frequency of the HLA-B27 allele also varies widely across populations. The North-South and the East-West gradients are known with HLA-B27 high prevalence in Northern Eurasia and North America (10–16% of Scandinavians, 25–50% of Indigenous Northern Americans), and lower (2–6%) in Mediterranean regions, and decreasing prevalence from Southeast Asia (&gt;12%) to China (1-6%) [1]. <h3>Objectives</h3> To determine the prevalence of HLA-B27 in Yakut children with SpA and in the population of healthy Yakuts <h3>Methods</h3> The prevalence of HLA-B27 was studied among 75 unrelated Yakut children with SpA (mean age 10.2±0,5 years, 41 boys and 34 girls, otherwise healthy) and among unrelated healthy adult Yakuts (mean age 39.5±1,2, 56 men and 36 women) reflecting the general population of Yakutia. HLA typing was performed by means of a standard single specific primer - polymerase chain reaction (Amplikit-27, Russia). <h3>Results</h3> In children association of SpA with HLA-B27 was revealed (p=0,022), 46,67% of them being HLA-B27 positive (OR =2, 22, CI<sub>OR</sub>: 1,17-4,22). Prevalence of HLA-B27 in total Yakut population was found to be 28.26%. <h3>Conclusions</h3> Our results show low prevalence of HLA-B27 haplotype in Yakut children with SpA and rather high prevalence in the total population of Yakuts, being at the level of prevalence in Koriaks and Cukchi [2,3]. HLA-B27 is known to encompass many different alleles while SpA has thus far been documented in subjects possessing any one of the first several subtypes. Low prevalence of HLA-B27 in children with SpA makes it important to investigate which of them are specific for Yakut population <h3>References</h3> Khan MA: HLA-B27 and its subtypes in world populations. Curr Opin Rheumatol 1995, 7:263–269. Pereverzeva VV. Prevalence of HLA-antigenes, genes and haplotypes in alien and native population of North-Eastern Russia. Diss. PhD. Tomsk, 2002: 191 pp. (in Russian) Krylov M., Erdesz S., Alexeeva L., Benevolenskaya L., Arnett F.C., J.D.Reveille. HLA Class II and HLA-B27 oligotyping in two native Siberian population groups. Tissue Antigens, 1995;46(5):382-6 <h3>Disclosure of Interest</h3> None declared
ELN 2013 Response Status Criteria: Relevance For De Novo imatinib Chronic Phase Chronic Myeloid Leukemia Patients?
Authors: Gabriel Etienne, Stephanie Dulucq, Axelle Lascaux, Anna Schmitt, Audrey Bidet, Marie-Pierre Fort, Eric Lippert, Caroline Bureau, Didier Adiko, Sandrine Hayette, Josy Reiffers, Franck E. Nicolini, Francois-Xavier Mahon
Journal: Blood (2013)
Rhinovirus C Infections Are Associated with Treatment Failure in Preschool Children with Recurrent Wheezing
Authors: Alalia W. Berry, David Mauger, Leonard B. Bacharier, Theresa W. Guilbert, Fernando D. Martinez, Kristine Grindle, Tressa Pappas, James E. Gern, Robert F. Lemanske, Daniel J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2016)
Cystic Emphysema in Premature Infants
Authors: Joseph Butterfield, Carlo Moscovici, Cameron Berry, C. Henry Kempe
Journal: New England Journal of Medicine (1963)

IN 1960 Wilson and Mikity1 reported the sporadic occurrence of a new form of respiratory disease in premature infants, characterized by an insidious course of hyperpnea and cyanosis, progressive pulmonary and cardiac symptoms and striking x-ray evidence of a diffuse pulmonary infiltrate.Since the isolation of the prototype ECHO virus Type 19 in 19552 , 3 only 2 cases of the association of that virus with human illness have been recorded,4 , 5 neither of which was fatal. This report describes an outbreak of a respiratory illness among 8 premature infants and records the isolation of that virus from the tissues in the only . . .
The impact of large lesions on the RECIST assessment criteria
Authors: G. R. Oliveira, R. L. Zondervan, A. D. Van Den Abbeele, M. A. Barish, T. Urban, M. Braschi, V. Frenkel, W. B. Hanlon, M. G. Harisinghani, G. J. Harris
Journal: Journal of Clinical Oncology (2008)

17560 Background: Since 2000 the Response Evaluation Criteria in Solid Tumors (RECIST) has been the standard measurement criteria for calculating tumor response. Although RECIST includes a minimun target lesion size to minimize errors in estimating the change in size of small lesions, RECIST does not provide a maximum size for target lesion selection. Previous research has shown that a tumor's rate of growth decreases at is approaches maximum volume. Furthermore, large lesions have the ability to greatly impact the overall assessment, which could result in the misclassification of response. The purpose of this study was to determine if the inclusion of a maximum target lesion size in the RECIST guidelines would significantly impact the response assessment. Methods: We reviewed 29 patients from the Tumor Imaging Metrics Core (TIMC) database who had 1 or more lesions > 7 cm at baseline and had a minimum of 3 time points. Previous research has shown that as a tumor approaches its maximum size its growth rate decreases. Therefore, we chose a diameter of 7 cm to study the impact of large lesions on response assessment. In order to test our hypothesis, were reviewed all scans using both standard and modified RECIST guidelines. The modified criteria included a maximum lesion diameter of 7 cm for selecting target lesions at baseline. We tracked tumor response using both criteria and determined if there was a difference in response assessment. Results: For standard RECIST the mean lesion diameter was 4.5 cm (n = 150) versus 2.5 cm (n = 121) for modified RECIST. Overall, response rates were significantly different when comparing the two criteria (p=.019). Additionally, according to the modified RECIST criteria, 20.7% of the patients would have had partial response (n = 3) or progressive disease (n = 3) one time point earlier. Conclusions: Our results suggest that the inclusion of a maximum lesion size in baseline target selection criteria has the ability to reduce the impact of a single large lesion on the overall response. Furthermore, in some cases, the implementation of a maximum target lesion size will improve RECIST's diagnostic ability. No significant financial relationships to disclose.
Case 35-1965
Authors: William C. Bostic, Jonas Hallgrimsson
Journal: New England Journal of Medicine (1965)

Presentation of CaseA seventeen-year-old Negro boy entered the hospital because of a swelling in the leg.Four years previously the right shin was lacerated by broken glass and healed, without apparent infection. Three years later an ache in the right shin developed, and he noticed a lump in the region of the scar. Six months before admission he came to the clinic, where examination disclosed a firm, fusiform mass, 5 by 8 cm., in the anteromedial aspect of the right tibia, 9 cm. below the knee joint, with minimal tenderness on palpation; there was no soft-tissue mass or local . . .
Case 38-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Stephen L. Hauser, Bhagwan Shahani, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 32-year-old woman was admitted to the hospital because of a sensorimotor neuropathy with eosinophilia and asthma.The patient was well until three years earlier, when asthma developed. Ten months before entry she had pneumonia, with left-sided pleuritic pain. Six months before admission hepatitis occurred, and she entered another hospital. A white-cell differential count showed 30 percent eosinophils and 9 percent atypical lymphocytes; the bilirubin rose as high as 436 μmol per liter (25.5 mg per 100 ml), and the serum aspartate aminotransferase (ASAT) increased to 589 U per liter; tests for hepatitis B and hepatitis A . . .
Tumor-Promoting Activity of Cigarette Tar in Rat Skin Exposed to Irradiation
Authors: John F. McGregor
Journal: JNCI Journal of the National Cancer Institute (1976)

A threefold increase (P=0.006) in the number of skin tumors induced by beta irradiation was demonstrated in rats after surface applications of cigarette tar. The effect appeared due to a tumor-promoting activity of the cigarette tar rather than to an additive tumorigenic effect of the two agents.
Efficacy of Novel Glutaminase Inhibitor CB-839 in Acute Myeloid Leukemia
Authors: Polina Matre, Maryam Shariati, Juliana Velez, Yuan Qi, Sergej Konoplev, Xiaoping Su, Courtney D. DiNardo, Naval Daver, Ravi Majeti, Michael Andreeff, Steven M. Chan, Marina Konopleva
Journal: Blood (2014)
Abstract 14157: Periodontal Microbiome Induces Inflammation and Atherosclerosis in Hyperlipidemic Atherogenic Apoe <sup>Null</sup> Mice
Authors: Sasanka Chukkapalli, Irina Velsko, Mercedes Rivera-Kweh, Donghang Zheng, Alexandra Lucas, Kesavalu Lakshmyya
Journal: Circulation (2015)

Introduction: Periodontal disease (PD) is a polymicrobial dysbiotic chronic inflammatory disease produced by a complex subgingival microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). American Heart Association supported the association between PD and ASVD but not causal association. Prior reports investigated the associations between these two diseases PD and ASVD. But the complex signaling molecules and mechanisms establishing a causal association are not well defined. Methods: To investigate how polybacterial infections initiate atherosclerotic plaque growth, ApoE null mice were orally infected with a polybacterial consortium of 4 well-characterized periodontal pathogens Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum . We assessed PD characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Results: Polybacterial infections have enhanced gingival colonization and significantly induced alveolar bone loss ApoE null mice. Polybacterial infections were found to be invasive with hematogenous dissemination into heart and aorta. Polybacterial infection-induced significantly higher levels of serum risk factors (oxidized LDL, nitric oxide), altered lipid profiles (cholesterol, triglycerides, chylomicrons, VLDL) as well as accelerated aortic plaque formation in ApoE null mice. Polybacterial infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Gingival infections after 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. At 24 weeks of chronic infection additional changes in inflammatory molecules were induced with reduced KC, MCSF, and enhanced GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, and RANTES. Conclusions: This is the first study demonstrating differences in the host immune response to a polybacterial infection with atherosclerotic lesion progression in a mouse model.
The Route of Antibiotic Administration in Superficial Impetigo
Authors: Joseph Warren Burnett
Journal: New England Journal of Medicine (1963)

A GREAT variety of therapeutic measures are advocated for the treatment of impetigo in different clinics in this country. They range from mechanical removal of the crusts and cleansing of the lesions with soap to systemic administration of antibiotics. A previous report‡ stressed the need for antibiotic medication in the treatment of impetigo and deeper pyodermas. The study reported below was made in the outpatient departments of the Massachusetts General Hospital, the Children's Hospital Medical Center and the Boston City Hospital between November, 1961, and June, 1962. It was designed to permit comparison of the effectiveness of topically administered antibiotics . . .
Case 31-2009
Authors: Hasan B. Alam, Gregory L. Fricchione, Alexander S.R. Guimaraes, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2009)

A 26-year-old man was admitted to this hospital because of abdominal distention and shock. He had been well until the previous evening, when mild abdominal pain developed; the next day, the pain became severe, and he was unresponsive. In the emergency department, he was hypotensive, with a rigid, distended abdomen. Imaging revealed marked distention of the colon, without focal obstruction. He had a history of schizophrenia and was taking several medications.
Philosophical Oncology: Calling on the Principle of Double Effect
Authors: Frank J Brescia
Journal: Journal of the National Comprehensive Cancer Network (2003)

Reasonable human behavior is based on doing something for a consequence that is perceived as good. Ethical medical decision-making is based on prioritizing values after understanding the relevant facts. There is an ethical obligation to do no harm. This is especially true in relieving the pain and suffering of dying patients; in these cases, treatment has the risk of contributing to a patient's death. The principle of double effect has been helpful as a moral guide in troubling cases to discern what actions are acceptable, even though the action could lead to an end that would seem as immoral as if the effect were directly intended. This principle, though, is not without problems and critics, and some have pointed out its shortcomings as an ethical guide.
A Novel Function of Stat1α and Stat3 Proteins in Erythropoietin-Induced Erythroid Differentiation of a Human Leukemia Cell Line
Authors: Keita Kirito, Mie Uchida, Masaaki Takatoku, Koichi Nakajima, Toshio Hirano, Yasusada Miura, Norio Komatsu
Journal: Blood (1998)
The Success of Medicare's End-Stage Renal-Disease Program
Authors: Edmund G. Lowrie, C. L. Hampers
Journal: New England Journal of Medicine (1981)

The 92nd Congress extended Medicare benefits to patients with end-stage renal disease (ESRD), sparing patients the financial burden of treating this catastrophic illness. The costs of the ESRD program have been contained better than those of health care generally; payment was originally limited by a screen of $138 per dialysis but could be higher if higher cost was documented. About 48 per cent of patients receive dialysis in units outside hospitals. The majority of these units are operated for profit, in which physicians share. The payment to these facilities has remained constant while payment to the nonprofit hospitals' unit has increased markedly. Physicians in for-profit units have a strong incentive to learn about costs and control them. They are involved in medical economic management as well as clinical management; this results in integrated administration of health care. The success of the ESRD program in expanding service to meet demand while controlling costs and maintaining quality has been due primarily to the combined effect of setting a price and creating a system of incentives that involves physicians in the medical marketplace.
Efficacy of the Anti-CD22 Recombinant Immunotoxin BL22 in Chemotherapy-Resistant Hairy-Cell Leukemia
Authors: Robert J. Kreitman, Wyndham H. Wilson, Karen Bergeron, Miranda Raggio, Maryalice Stetler-Stevenson, David J. FitzGerald, Ira Pastan
Journal: New England Journal of Medicine (2001)

Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells.
Randomized, Placebo-Controlled Trial of Inactivated Poliovirus Vaccine in Cuba
Journal: New England Journal of Medicine (2007)

After poliomyelitis has been eradicated, access to live polioviruses will be highly restricted and the use of oral poliovirus vaccine (OPV) will probably be discontinued. Countries using OPV must decide whether to switch to inactivated poliovirus vaccine (IPV) or stop polio vaccination. Because data on the immunogenicity of IPV in tropical developing countries are limited, we conducted a randomized, controlled trial of IPV in Cuba.The study population consisted of healthy infants born in Havana. A total of 166 infants were randomly assigned to two groups. Group A received a combination of the diphtheria-pertussis-tetanus (DPT) vaccine, the Haemophilus influenzae type b (Hib) vaccine, and IPV (DPT-Hib-IPV) at 6, 10, and 14 weeks of age. Group B, the control group, received a combination of the DPT vaccine and the Hib vaccine at 6, 10, and 14 weeks of age. Another group (group C, 100 infants), which did not undergo randomization at the same time as groups A and B, received the DPT-Hib-IPV combination at 8 and 16 weeks of age. Serum samples were collected before vaccination and at least 4 weeks after the last dose. Stool samples were obtained before and 7 days after challenge with OPV.The seroconversion rates in group A were 94%, 83%, and 100% for types 1, 2, and 3 poliovirus, respectively. There were no seroconversions in group B. The seroconversion rates in group C were 90%, 89%, and 90% for poliovirus types 1, 2, and 3, respectively. For groups A, B, and C, the virus isolation rates after challenge with OPV were 94%, 91%, and 97%, respectively, and the mean log10 viral titers of any serotype were 3.46, 3.89, and 3.37, respectively. There was one major adverse event, an episode of hypotonia.Vaccination with two or three doses of IPV resulted in a rate of seroconversion of at least 90%, except for seroconversion against type 2. The viral titer of OPV shed in the stool after OPV challenge was reduced in both groups receiving IPV. (ClinicalTrials.gov number, NCT00260312 [ClinicalTrials.gov].).