tbuckley/cabot-search huggingface dataset:
Presentation of non-small cell lung cancer (NSCLC) in octogenarians
Authors: V. Velcheti, A. Viswanathan, N. Sainani, L. Grove, R. Suresh, M. Q. Baggstrom, R. Govindan
Journal: Journal of Clinical Oncology (2006)

18555 Background: Lung cancer is the most common cause of cancer related death in the United States. Non-small cell lung cancer (NSCLC) accounts for over 80% of all new cases of lung cancer. Lung cancer is a disease of the elderly. There are only limited data available on NSCLC in octogenarians. Methods: From our institutional tumor registry, we identified all patients with NSCLC from 1995 to 2002 who were 80 years or older at the time of initial presentation. Data regarding overall stage, histology, date and extent of surgery, and co-morbidities were analyzed. Co-morbidity determination was based on the Adult Co-morbidity Evaluation (ACE-27) test, which ranges from 0 to 3 depending on severity of co-existing conditions. Results: At the time of initial presentation with NSCLC, 236 pts were 80 years or older. The distribution of stages were: stage I in 93 pts (39.5%), stage II in 15 pts (6.5%), stage III in 66 pts (28%) and stage IV in 62 pts (26%). Of the 236 patients the co-morbidity score was known for 223 pts. The distribution of the known scores was: 0, 39 pts (17.5%); 1, 79 pts (35%); 2, 68 pts (30.5%); and 3, 37 pts (17%). Only 35 patients in this cohort underwent surgery. Conclusions: 1. Despite a high proportion (46%) of early stage NSCLC, only a few elderly patients 80 years or older undergo surgical resection, likely because of co-morbid conditions. 2. Innovative non-surgical local modalities of therapy need to be studied in this population. No significant financial relationships to disclose.
The Wrestlers
Authors: G. V. Chelvapilla
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I was pleased to see the cover picture ofThe Journal's April 8 issue. However, your cover story did not fully explain the picture. For the information of your esteemed readers, may I mention a few things that I know about the incident depicted? It was a wrestling match all right. The two wrestlers getting ready were the famed wrestlers of their time (Chanura and Mustika). They were meant to kill the two young boys in an unequal fight. The two boys were Krishna and Balarama, shown standing beside them. The presiding King Kamsa, who was afraid of these youngsters, arranged the fight; however, contrary to his expectations, both the wrestlers and the evil king himself get killed in the ensuing contest. These and other pastimes of the Lord Krishna form the subject matter of<i>Bhagavad Gita</i>, a book of stories of god that have been
A T315I Gate Keeper Mutation Responding To Pegylated Interferon Alfa-2a (Peg-IFN) Monotherapy With Major Molecular Response (MMR4) At 12 Months In An Imatinib-Resistant Chronic Myeloid Leukemia (CML) Patient
Authors: Hyacinthe Johnson-Ansah, Dina Naguib, Hervé Mittre, Seyefeddine Kadi, Xavier Troussard
Journal: Blood (2013)
구연 : TGF-β1유전자의 codon 10의 다형성과 HBV에 의한 간경변, 간세포암과의 관계
Authors: 권오상, 우덕수, 임도윤, 권광안, 정문기, 박동균, 김선숙, 김연석, 권소영, 구양서, 김유경, 최덕주, 박효주, 황유진, 양달모, 김주현
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 바이러스성 및 알코올성 간질환에서 간경변으로 진행하는 정도는 개인에 따라 차이가 많아 이에 영향을 미치는 숙주인자의 하나로 TGF-β1유전자의 codon 10의 유전적 다형성이 관련이 있음을 저자들이 보고하였으며, 간세포암에서는 암의 모양과 codon 10의 유전형이 연관이 있음을 시사하였다. 그러나 대조군과 환자의 예가 충분치 못하고 간질환의 원인이 동일하지 않아 본 연구에서는 대상군을 좀더 확보하고 원인도 HBV에 국한하여 TGF-β1유전자의 codon 10의 유전형과 간경변, 간세포암과의 관계를 알아보고자 하였다. 대상과 방법: 간기능이 정상이고 바이러스성 간질환이 없는 119예를 대조군으로 하고 HBsAg(＋)인 간경변 환자 52예와 간세포암 환자 77예을 대상으로 전혈을 채취하여 genomic DNA를 분리하고 TGF-β1 유전자의 codon 10을 포함하는 부위를 중합효소연쇄반응으로 증폭한 후 SSCP를 시행하였다. 직접염기서열법을 통해 codon 10의 유전형에 따른 SSCP의 양상을 분석하여 환자군의 유전형을 대조군과 비교하였다. 결과: 대조군의 평균 연령은 48±13세, 남/여 59/60, 간경변군의 평균 연령은 53±11세, 남/여 32/20, 그리고 간세포암군의 평균 연령은 56±11세, 남/여 56/21이었다. 간경변의 원인은 HBV 43예, HBV＋알코올 9예였고 간세포암의 원인은 HBV 54예, HBV＋알코올 23예였다. 간세포암 중 10예는 간경변을 동반하고 있지 않았다. 대조군에서 codon 10의 유전형은 proline homozygous genotype은 31예(26%), proline/leucine heterozygous genotype은 53예(45%), 그리고 leucine homozygous genotype은 35예(29%)였다. 간경변이 없는 간세포암 10예를 제외한 전체 간경변 119예에서 proline homozygous genotype은 21예(18%), proline/leucine heterozygous genotype은 51예(43%), 그리고 leucine homozygous genotype은 47예(39%)로 대조군에 비해 leucine homozygous genotype의 비율이 증가하는 경향을 보였다(p=0.054). 알코올이 원인으로 겹친 예를 제외한 HBV 단독에 의한 간경변 87예에서 proline homozygous genotype은 10예(11%), proline/leucine heterozygous genotype은 39예(45%), 그리고 leucine homozygous genotype은 38예(44%)로 대조군에 비해 leucine homozygous genotype의 비율이 높았다(p=0.005). 간세포암의 모양별로 codon 10의 leucine homozygous genotype의 비율은 uninodular type에서는 47%, multinodular type에서는 41%, 그리고 massive type에서는 13%로 massive type에서 다른 type에 비해 leucine homozygous genotype의 비율이 낮았다(p=0.003). 결론: HBV 단독원인에 의한 간경변 환자들에서 TGF-β1유전자의 codon 10의 유전형이 leucine homozygous genotype이 많아 간섬유화로의 진행에 관여하는 중요한 숙주인자로 생각되며, 만성 B형 간질환 환자에서 codon 10의 유전형에 대한 선별검사가 유용하리라 생각된다. HBV에 의한 간세포암에서는 암의 진행에 codon 10의 유전형이 영향을 미치는 것으로 생각되어 유전형에 따른 간세포암의 진행에 관한 전향적 연구가 필요하다.
Non-medical risk factors of underdiagnosis of childhood asthma in Upper Silesia, Poland
Authors: Jan Zejda, Malgorzata Farnik, Irena Smolka
Journal: European Respiratory Journal (2013)

Background

Our recent study of 4535 children aged 7-17 years in Upper Silesia (PL) yielded 186 cases (4.1%) of asthma diagnosed before the survey. Children without that diagnosis but with asthmatic symptoms were examined by a chest physician who found 44 new asthma cases.

Objective

The goal of the study was to identify non-medical factors that could explain why children with newly diagnosed asthma were not diagnosed in the past.

Methods

A case-control analysis included a group of 44 'new-asthma' children and a group of 184 children with asthma diagnosed in the past. Their parents answered questionnaires on socio-economic and family-related factors. Correlates of underdiagnosed asthma were explored using odds ratios and their 95% confidence intervals (logOR, 95%CI) yielded by logistic regression.

Results

New diagnoses were more frequent in younger children, who had less parental attention and who were not registered with specialized health care. Logistic regression included variables for which OR>1.5: age, gender, farm residence, parental education, asthma, chronic bronchitis, allergy in siblings, dampness in house, registration with specialized health care, distance to health center, economic standing, time spent with child. The following variables reached the criterion p  5 km - logOR = 3.45 (95%CI: 1.05-11.36), time spent with child < 1 hour/day - logOR = 6.28 (95%CI: 1.98-19.91).

Conclusion

Among non-medical determinants of underdiagnosis of asthma low age of a child plays a major role. Other important factors were a large distance from home to health center and a low parental attention (time spent with child).
Abstract 14680: Loss of Intercalated Disc Protein mXin{beta} Leads to Atrioventricular Conduction Defects and Channel Remodeling
Authors: Qinchuan Wang, Kuo-Ho Wu, Pei-Hsiu Jiang, Ching-I Lin, Jenny L Lin, Eric A Adams, Jim J Lin
Journal: Circulation (2013)

Intercalated discs (ICDs) transmit mechanical force and electrical impulses, organize assembly of certain ion channels and transduce signals. The mouse orthologs (mXinα and mXinβ) of human cardiomyopathy-associated genes (CMYA1 and CMYA3, respectively) encode proteins localized to ICDs. Ablation of mXinα leads to late-onset cardiomyopathy with conduction defects. Our recent reports that mXinα interacts with KChIP2 and cortactin, which influence surface expression of Ito and IK, slow1, provide a novel mechanism for the reduced Ito and IK in mXinα-null cardiomyocytes. On the other hand, mXinβ is required for the postnatal maturation of ICDs and the localization of mXinα to ICDs. Therefore, we hypothesized that mXinβ also plays a role in cardiac electrophysiology. Supporting this hypothesis, surface ECG recording showed significantly prolonged PR, QT and QTc in 14-17 day-old mXinβ-null mice. Furthermore, 18-day-old mXinβ-null mice had 100% incidence of second or third degree AV block, while wildtype controls...
Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB 100104.
Authors: P. L. McCarthy, K. Owzar, K. C. Anderson, C. C. Hofmeister, H. Hassoun, D. D. Hurd, E. A. Stadtmauer, S. Giralt, V. Hars, C. A. Linker
Journal: Journal of Clinical Oncology (2010)

8017 Background: Disease relapse/progression is the primary cause of treatment failure after ASCT for MM. Methods: The primary objective of CALGB 100104 was to investigate if maintenance lenalidomide would prolong time to progression (TTP) following single ASCT. Eligibility included: Stage I-III disease, ≤ 1 year from diagnosis, ≥ 2 months of induction with Stable Disease or better (≥ SD) and age < 70 years. ASCT regimen was melphalan 200 mg/m2. Patients (pts) with ≥ SD were randomized double-blind at day 100-110 post-ASCT to lenalidomide or placebo until disease progression, after stratification by diagnostic β-2 microglobulin (β-2M) level and prior thalidomide or lenalidomide therapy. Starting dose was 10 mg/day, escalated to 15 mg/day after 3 months. Drug was held for ≥ Gr 3 toxicity, restarted at resolution to ≤ Gr 2 and was de- escalated by 5 mg or maintained at 5, 10 or 15 mg/day as tolerated. Results: 568 pts were enrolled (04/15/05 - 07/03/09). The second interim analysis, based on 418 randomized pts occurred on 09/09 after 28% of the required number of events (progression or death before progression) had been observed. The median follow-up was 12 months. The number of events among 210 pts randomized to lenalidomide was 29 compared to 58 among 208 pts randomized to placebo. The one-sided unadjusted P-value was < 0.0001. The estimated hazard ratio was 0.42 (95% CI=0.27,0.67) corresponding to a 58% reduction in event risk in the lenalidomide arm. The estimated median TTP was 25.5 months for the placebo arm. The median TTP has not been reached for the study arm. Deaths in the study and placebo arms were 11 and 17 respectively (P=0.2). Significant delay in TTP in the lenalidomide arm was observed regardless of β-2M level or prior thalidomide or lenalidomide therapy. For 285 reported pts, the post-randomization, highest grade, overall AEs were Gr 3 (n=19), Gr 4 (n=111) and Gr 5 (n=1) for the lenalidomide arm and Gr 3 (n=4) Gr 4 (n=115) and Gr 5 (n=1) for placebo. The majority of AEs were hematologic in both arms. Conclusions: Lenalidomide initiated at day 100-110 post-ASCT in MM patients significantly delays TTP and has a similar AE profile when compared to placebo. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Millennium, Novartis Celgene, Genzyme, Millennium, Novartis Celgene, Millennium, Novartis
Omalizumab Can be Effective in Patients with Allergic Bronchopulmonary Aspergillosis
Authors: John W. O'Quinn, Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, Stephanie Santucci, William H. Yang
Journal: Journal of Allergy and Clinical Immunology (2016)
Correlation of N-telopeptide of type I collagen (NTX) with survival and fractures in patients (pts) with bone metastases from renal cell carcinoma (RCC)
Authors: J. E. Brown, A. Lipton, R. J. Cook, D. Michaelson, R. E. Coleman, F. Saad
Journal: Journal of Clinical Oncology (2009)

e16016 Background: The osteolysis marker NTX has shown prognostic significance in pts with bone metastases from a broad range of solid tumors, but its potential in pts with RCC has not been investigated. Methods: This was an exploratory correlative analysis of NTX levels and outcomes in the RCC subset of pts treated with zoledronic acid (ZOL) in a 21-month phase III trial (Rosen et al. J Clin Oncol. 2002). In North American pts in this study, urinary NTX was measured approximately every 3 mo and was expressed per mmol creatinine (CR). Endpoints included overall survival (OS), disease progression in bone, and pathologic fractures. Relative risks and 95% confidence intervals for pts with elevated NTX (NTX ≥ 64 nmol/mmol CR) versus normal NTX (&lt; 64 nmol/mmol CR) were calculated by Cox regression for baseline and most recent (≤ 6 mo prior) NTX assessments. Results: Among 55 ZOL-treated RCC pts, 29 had baseline NTX data (median = 60 nmol/mmol CR). Whereas baseline NTX levels showed trends for outcomes, recent NTX levels profoundly correlated with outcomes ( Table ). An elevated recent NTX measurement correlated with a &gt; 13-fold increased risk of death and a &gt; 11-fold increased risk of progression in bone. Correlations were also significant for first and all on-study fractures. Conclusions: In pts with RCC receiving ZOL, serial NTX assessments may provide important prognostic insight. Although based on a small sample size, correlations between recent NTX levels and outcomes in RCC pts are more profound than those previously reported in pts with other solid tumors (Brown et al. J Natl Cancer Inst. 2005). Elevated NTX could alert physicians to the need to more closely monitor bone lesions and intervene to prevent fractures in RCC pts. This may be especially important in the context of new systemic therapies that are improving the outlook in the advanced RCC setting. [Table: see text] [Table: see text]
The effect of interleukin-1β on lung ventilation and central CO2 chemoreception
Authors: Nina P. Aleksandrova, Galina A. Danilova
Journal: European Respiratory Journal (2011)

Oxidative stress developed at many respiratory diseases associated with significant increase in inspiratory resistive loading (such as asthma, COPD, sleep apnea) leads to elevation of the plasma and cerebral levels of pro-inflammation cytokines. On the other hand resistive breathing has influence on the central chemoreception by decreasing the ventilatory response to hypercapnic stimulation. Little is known about mechanisms of this influence.  The aim of the present study was to examine the hypothesis that elevation of pro-inflammatory cytokine level in liquor may decrease the ventilatory response to carbon dioxide.  For this purpose intracerebroventricular microinjections of human recombinant interleukin-1β (IL-1β) were used in tracheostomized anaesthetized rats during the resting and hypercapnic stimulated breathing. The hypercapnic ventilatory response was measured by using rebreathing techniques before and after 10 μl intracerebroventricular injection of ether saline (placebo) or IL-1β (0,5 μg/rat).  It was sown that when the resting breathing the intracerebroventricular injections of IL-1β evoke the significant increase in minute ventilation and mean inspiratory flow. During the hypercapnic rebreathing experiments it was obtained that the increase of IL-1β in liquor weakens the ventilatory, tidal volume and mean inspiratory flow responses to carbon dioxide.  We concluded that the elevation of pro-inflammatory cytokine level in liquor intensifies ventilation during the resting breathing but weakens chemoreflex sensitivity to hypercapnia that suggests participation of pro-inflammatory cytokines in mechanisms of central breathing control and central chemoreception.
Estimated Lifetime Medical and Work-Loss Costs of Fatal Injuries — United States, 2013
Authors: Curtis Florence, Thomas Simon, Tamara Haegerich, Feijun Luo, Chao Zhou
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Injury-associated deaths have substantial economic consequences. In 2013, unintentional injury was the fourth leading cause of death, suicide was the tenth, and homicide was the sixteenth; these three causes accounted for approximately 187,000 deaths in the United States. To assess the economic impact of fatal injuries, CDC analyzed death data from the National Vital Statistics System for 2013, along with cost of injury data using the Web-Based Injury Statistics Query and Reporting System. This report updates a previous study that analyzed death data from the year 2000, and employs recently revised methodology for determining the costs of injury outcomes, which uses the most current economic data and incorporates improvements for estimating medical costs associated with injury. Number of deaths, crude and age-specific death rates, and total lifetime work-loss costs and medical costs were calculated for fatal injuries by sex, age group, intent (intentional versus unintentional), and mechanism of injury. During 2013, the rate of fatal injury was 61.0 per 100,000 population, with combined medical and work-loss costs exceeding $214 billion. Costs from fatal injuries represent approximately one third of the total $671 billion medical and work-loss costs associated with all injuries in 2013. The magnitude of the economic burden associated with injury-associated deaths underscores the need for effective prevention.
Cost-effectiveness of lenalidomide in treating patients with transfusion-dependent myelodysplastic syndromes (MDS) in the United States
Authors: T. F. Goss, A. Szende, C. P. Schaefer, P. J. Totten, M. Y. Wang, A. F. List
Journal: Journal of Clinical Oncology (2006)

6128 Background: Lenalidomide is approved for treatment of patients with transfusion-dependent Low- or Intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. We evaluated the cost-effectiveness (CE) of lenalidomide versus best supportive care (BSC) in these MDS patients. Methods: We used a decision analytic model to compare costs and outcomes of lenalidomide [with BSC, but no erythropoietin (EPO)] vs BSC (with EPO) over 1 year. Data were obtained from a phase II trial for lenalidomide (MDS-003). Data for BSC were based on a study that included TD MDS patients (efficacy and transfusion requirements) and the placebo arm of a randomized MDS trial (safety). The model compared results of MDS-003 and a theoretical cohort with similar characteristics (TD, EPO response and IPSS low or int-1 score). Outcome measures were rate and duration of response (TI time gained). The model incorporated costs (from Medicare schedules; 2005 US$) of meds, transfusions, lab tests, office visits and other resources. Results: Response rate (TI) was 67.0% in the lenalidomide group vs 32.8% for responders with no prior EPO experience in the BSC group. Lenalidomide therapy led to an estimated 0.53 transfusion-free and 0.23 quality-adjusted life year (QALY) gain compared to BSC at 1 year. The costs of lenalidomide therapy were largely offset by reduced blood transfusion and EPO costs with 1-year total treatment costs estimated at $62,138 vs $53,965 for BSC. We estimated incremental CE of lenalidomide vs BSC per TI year and QALY gained using one-way sensitivity analyses reflecting uncertainty in parameter estimates. The incremental CE ratio for lenalidomide vs BSC varied between $5,742 - $20,940 per TI year gained and $13,216 - $47,758 per QALY gained, suggesting acceptable ranges of CE for a new therapy. Conclusions: Results suggest that treating Low- or Int-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or w/o additional cytogenetic abnormalities with oral lenalidomide results in reduced transfusion requirements vs BSC. Research to confirm these results with data from ongoing randomized trials is warranted. [Table: see text]
Abstract 17911: Acute Cardiac Dysfunction by Adult-onset Cardiac Myosin Light Chain Kinase Ablation
Authors: Michael Massengill, Eileen Chang, Hasssan Ashraf, Stephen Chrzanowski, Rajib Chowdhury, Jeena Kar, Sonisha Warren, Glenn walter, Huadong Zeng, Byung-Ho Kang, Hideko Kasahara
Journal: Circulation (2014)

Introduction: Under sustained pressure overload, myocytes that initially remodel to become short and thick, eventually become elongated and maladaptive with little force for contraction. Mechanisms underlying this transition are largely unknown. We previously demonstrated that 1 week of transverse aortic constriction in wild-type mice reduced cardiac myosin light chain kinase (cMLCK) levels by ~85%. In cultured cardiomyocytes, cMLCK knockdown led to sarcomere disorganization. Germline Mylk3 (encoding cMLCK) knockout mice demonstrated moderate heart failure. Hypothesis: Acute cMLCK reduction is causative for reduced contractility and remodeling of cardiomyocytes during the transition from compensated to decompensated hypertrophy. Methods: To mimic acute cMLCK reduction, adult inducible Mylk3 gene knockout mice, Mylk3flox/flox/merCremer, were generated and compared to 2 control mice (Mylk3flox/flox and Mylk3+/+/merCremer) following tamoxifen injection (50 mg/kg/day, 2 consecutive days). We assessed cardiac function (MRI, echocardiogram) in addition to histopathologic (tissue sectioning, immunostaining, and EM), cellular (cell size and cell shortening and intracellular free Ca2+) and molecular analyses. Results: Reduction of cMLCK proteins was evident at day 4 following tamoxifen-injection in inducible Mylk3 knockout mice. At day 7, inducible Mylk3 knockout but not control mice demonstrated heart failure [%FS, 28.0% in flox/flox (n=6), 27.7% in +/+/merCremer (n=6), 19.8% in flox/flox/merCremer (n=8)]. Analysis of inducible Mylk3 knockout mice revealed unique, severely convoluted cell morphology; isolated cardiomyocytes were elongated and thinner with disorganized sarcomere and reduced contractility (%FS in sarcomere length, control 5.1% vs. inducible knockout 2.4%). Adenovirus encoding cMLCK enhanced organized sarcomere structures; this was not prevented by co-infection of adenovirus unphosphorylatable MLC2v(Ser14/15Ala) mutants incorporated into sarcomere. Conclusion: Results of acute cMLCK reduction in a novel mouse model suggest that cMLCK plays a pivotal role in transition from compensated to decompensated hypertrophy via sarcomere disorganization likely independent of MLC2 phosphorylation.
The radical prostatectomy series: apples are not oranges.
Authors: P W Kantoff, J A Talcott
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.11.2243 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7964938 The radical prostatectomy series: apples are not oranges. P W KantoffxP W KantoffSearch for articles by this author , J A TalcottxJ A TalcottSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.11.2243 First Page PDF © 1994 by American Society of Clinical Oncology