tbuckley/cabot-search huggingface dataset:
Supplement use in patients with hepatocellular carcinoma.
Authors: Valerie Lee, Abhishek Goyal, Christine Cho-Shing Hsu, Rosa D. Rodriguez, Abby B. Siegel
Journal: Journal of Clinical Oncology (2013)

e15037 Background: Vitamin and herbal supplement use has been steadily rising in the United States. Few data are available evaluating this use in patients with hepatocellular carcinoma (HCC). We analyzed our prospective database of patients with HCC to determine predictors of supplement use and associations with survival. Methods: We prospectively enrolled 146 patients with newly-diagnosed HCC between 10/2008 and 11/2012. Upon enrollment, patients completed an epidemiologic questionnaire and provided detailed demographic and lifestyle data including diet, exercise, smoking and use of vitamins and herbal supplements. Clinical characteristics and overall survival were collected from medical records. We assessed if socioeconomic, lifestyle, or clinical characteristics predicted vitamin and herbal supplement use in HCC patients. We also evaluated if use was predictive of overall survival. Results: The median age was 62, and 79% were men. 60% had underlying HCV and 38% had HBV; 64% were Child-Pugh A and 19% were metastatic. 71% of our cohort used vitamins and 45% used herbal supplements. Most commonly used were antioxidants (including vitamins C, E, A and selenium) (51%), multivitamins (46%), vitamin D (25%), and milk thistle (23%). Vitamin D use was higher in women and those without HCV. Use of vitamin C was associated with being HBV positive (OR = 3.01, P = 0.01) while HCV patients were more likely to use milk thistle (OR = 2.80, P = 0.03). In a univariable model, use of milk thistle at baseline was associated with a trend toward worse overall survival (HR = 1.78, P = 0.09), despite not being associated with other poor prognostic signs like higher stage or AFP, or worse Child-Pugh score. Use of other vitamin or herbal supplements did not predict survival. Conclusions: The majority of patients with newly-diagnosed HCC have used some form of vitamin or herbal supplement, with almost a quarter having used milk thistle in their lifetime. In our analyses, use of milk thistle may be associated with worse survival. Though our cohort is small, this emphasizes the prevalence of supplement use in patients with HCC and the need to further evaluate the safety and efficacy of these alternative treatments in various patient populations.
Chronic Lymphocytic Leukemia: Individualizing Treatment Approach
Authors: Andrew D. Zelenetz
Journal: Journal of the National Comprehensive Cancer Network (2017)

A host of new therapies are now available for treating patients with chronic lymphocytic leukemia (CLL) in both the upfront and relapsed or refractory settings. Although the optimal use of these agents is still being defined, established and emerging prognostic markers aid in the selection of appropriate treatment with the best chance of success. At the NCCN 22nd Annual Conference, Dr. Andrew Zelenetz discussed the role of the CLL-International Prognostic Index for risk stratification, reviewed optimal first-line therapy options, and then presented updated clinical trial data on the novel agents being used in the relapsed or refractory setting. The hope is that chronic therapy will be replaced by combinations that provide high rates of minimal residual disease negativity with durable remissions.
Clinical predictive model for brain metastasis at presentation in patients with non-small-cell lung cancer (NSCLC).
Authors: Carlos Rodrigo Acevedo-Gadea, Kathryn Trinkaus, Ramaswamy Govindan, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2013)

e19158 Background: There is limited data on the prevalence of brain metastases at presentation in NSCLC. Between 1988 and 1997, the Surveillance, Epidemiology, and End Results (SEER) database recorded the use of brain radiation in patients with lung cancer. We developed a predictive clinical model for brain metastases (BM) at presentation based on the use of brain radiation (BRT), which may be used as a surrogate since it is not indicated in NSCLC patients without BM. Methods: Patients with NSCLC diagnosed between 1988-1997, aged 21 or older were subdivided according to radiation data into none or indicated (given, refused or unknown if administrated). Since the database records only initial therapy, patients with indication for radiotherapy were assumed to have had early brain metastases. Frequencies and odds Ratio (OR) were calculated for each demographic factor and the most significant were included in the predictive model. Results: Among the 131,456 patients evaluated, 10,963 (8.4%) had BRT indicated. The most significant predictors in multivariate analysis were age &gt; 60 (HR 0.5; 95% CI 0.46-0.54), non-squamous histology (HR 0.53; 95% CI 0.48-0.59), size &gt; 5 cm (HR 1.27; 95% CI 1.16-1.39), grades III-IV (HR 2.04; 95% CI 1.82-2.27) and N2-3 involvement (HR 2.55; 95% CI 2.34-2.78). The 40,963 patients with known status of all 5 factors were used in the predictive model. The frequency of BM for patients with zero, 1, 2, 3, 4 and 5 factors were 0.7%, 1.8%, 4.7%, 8.9%, 13.7% and 20.2% respectively. Conclusions: Despite the limitations of this study, including indication for BRT as a surrogate for BM, older data and possible bias in the use of brain imaging according to demographic factors, our findings showed that the risk of BM at presentation may be stratified with the use of 5 clinical factors. These results may be used as a baseline for studies on clinical and molecular determinants of BM.
Task force on Research in Epidemiology and Prevention of Cardiovascular Diseases.
Authors: C Lenfant
Journal: Circulation (1994)

O ver the past two decades, the United States has witnessed noteworthy increases in life expect- ancy and major decreases in the death toll attributed to cardiovascular diseases (CVD).Age- adjusted death rates from coronary heart disease (CHD) are now half what they were 20 years ago, and death rates from stroke have declined even more sharply.It is well recognized that research in epidemiology and prevention of CVD has made major contri- butions to these favorable trends.Nonetheless, the public health and economic burden of CVD is still considerable, and much remains to be discovered if we are to achieve effective disease control and prevention.To identify new opportunities and chart a course for future research efforts, the National Heart, Lung, and Blood Institute (NHLBI) in 1992 convened a Task Force on Research in Epidemiology and Preven- tion of Cardiovascular Diseases.Composed of national experts, the task force was charged to review the state of knowledge in epidemiology and prevention of CVD over the past 5 years and develop a comprehensive plan, including scientific priorities, for NHLBI support of research in this area over the next several years.During a series of meetings that spanned nearly 2 years, the task force members worked to develop a detailed report of its findings and conclusions.
General practice needs ongoing commitment to training budgets
Authors: Catherine A O’Donnell, Joe Rosenthal, Michael Moore, Nick Francis, Debbie Sharp, Roger Jones, Christian Mallen, John Campbell
Journal: BMJ (2017)

The NHS is a key election issue.1 Patient demand for primary care rose by 10.5% between 2007 and 2014,2 while recruiting and retaining GPs is ever more challenging. The Royal College of General Practitioners’ election manifesto for NHS England includes a call to meet the health secretary’s pledge of an additional 5000 GPs by …
External validation of a nomogram predicting overall survival (OS) of women with uterine leiomyosarcoma (ULMS).
Authors: Alexia Iasonos, Emily Keung, Oliver Zivanovic, Rosanna Mancari, Michele Peiretti, Marisa Nucci, Suzanne George, Nicoletta Colombo, Silvestro Carinelli, Martee Leigh Hensley, Chandrajit P. Raut
Journal: Journal of Clinical Oncology (2012)

5090 Background: A nomogram for predicting OS of women with ULMS was developed , given the poor prognostic performance of FIGO and AJCC staging systems. We aimed to determine the validity of the ULMS nomogram using independent, external cohorts. Methods: The ULMS nomogram incorporates 7 clinical characteristics: age at diagnosis, tumor size, grade, involvement of cervix, locoregional metastases (direct extrauterine spread, locoregional lymph node), distant metastases, and mitotic index (per 10 HPF) to predict OS following primary surgery. Two independent cohorts from sarcoma centers (1 US, 1 Europe) were included. Eligible women were treated at the institutions (1994-2010) and had undergone hysterectomy. Women with locally advanced or metastatic disease who underwent more extensive surgery were included if the primary tumor (uterus) was resected. Women who previously underwent resection of the primary tumor or recurrences at other institutions were included if they received followup care at 1 of the centers. Women who presented with unresectable disease who never underwent surgery and those with insufficient information on any of the nomogram variables were excluded. Results: 187 women with ULMS were identified who met the above criteria (median age 51 yrs, median tumor size 9 cm, median mitotic index 20). Tumors were generally high grade (88%), FIGO stage I-II (61%) without cervical involvement (93%) and without locoregional (77%) or distant metastases (83%). Median and 5-yr OS rates were 4.5 (95% CI 3.2-5.3) yrs and 46%, respectively; 65 women (35%) were alive at last follow up. The nomogram concordance index was 0.67(SE=0.02) which was as high as the concordance index from the initial cohort used for nomogram development. The concordance between actual OS and nomogram predictions suggests excellent calibration of the nomogram in the validation cohort. Predictions were within 1% of actual 5-yr OS rates, except for the patients with a 5-yr OS rate of greater than 0.68. Conclusions: The ULMS nomogram was externally validated and can be generalized to independent cohorts. The nomogram provides a more individualized and accurate estimation of OS of women diagnosed with ULMS following primary surgery.
A STUDY OF THE MECHANISM BY WHICH EXERCISE INCREASES THE PULMONARY DIFFUSING CAPACITY FOR CARBON MONOXIDE*†
Authors: Joseph C. Ross, Regina Frayser, John B. Hickam
Journal: Journal of Clinical Investigation (1959)

The pulmonary diffusing capacity (DL) increases with exercise. This was first shown by Krogh in 1915 (1) and has been confirmed by investigators who have studied the matter since that time, using both carbon monoxide and oxygen (2-5). The mechanism by which exercise increases the diffusing capacity is not altogether clear, however, and the apparent amount of increase with exercise is dependent on the technique used for determining the diffusing capacity, and on the severity of the exercise.  Two methods widely used for estimating the pulmonary diffusing capacity for carbon monoxide are the steady state method of Filley, MacIntosh and Wright (3) and the Krogh breath holding technique as modified by Ogilvie, Forster, Blakemore and Morton (5). In the steady state technique, the subject breathes continuously throughout the test period, which makes minute ventilation a variable factor. In the breath holding method, however, the breath is held and minute
Medical Aspects of Driver Limitation
Authors: O L SAPP
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
SMAD4 Loss Is Associated with Cetuximab Resistance and Induction of MAPK/JNK Activation in Head and Neck Cancer Cells
Authors: Hiroyuki Ozawa, Ruchira S. Ranaweera, Evgeny Izumchenko, Eugene Makarev, Alex Zhavoronkov, Elana J. Fertig, Jason D. Howard, Ana Markovic, Atul Bedi, Rajani Ravi, Jimena Perez, Quynh-Thu Le, Christina S. Kong, Richard C. Jordan, Hao Wang, Hyunseok Kang, Harry Quon, David Sidransky, Christine H. Chung
Journal: Clinical Cancer Research (2017)

Abstract Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. Experimental Design: SMAD4 expression was assessed by IHC in 130 newly diagnosed and 43 patients with recurrent HNSCC. Correlative statistical analysis with clinicopathologic data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels. The role of SMAD4 was investigated by shRNA knockdown and gene reconstitution of HPV-negative HNSCC cell lines in vitro and in vivo. Results: Our analysis revealed that SMAD4 loss was associated with an aggressive, HPV-negative, cetuximab-resistant phenotype. We found a signature of prosurvival and antiapoptotic pathways that were commonly dysregulated in SMAD4-low cases derived from TCGA-HNSCC dataset and an independent oral cavity squamous cell carcinoma (OSCC) cohort obtained from GEO. We show that SMAD4 depletion in an HNSCC cell line induces cetuximab resistance and results in worse survival in an orthotopic mouse model in vivo. We implicate JNK and MAPK activation as mediators of cetuximab resistance and provide the foundation for the concomitant EGFR and JNK/MAPK inhibition as a potential strategy for overcoming cetuximab resistance in HNSCCs with SMAD4 loss. Conclusions: Our study demonstrates that loss of SMAD4 expression is a signature characterizing the cetuximab-resistant phenotype and suggests that SMAD4 expression may be a determinant of sensitivity/resistance to EGFR/MAPK or EGFR/JNK inhibition in HPV-negative HNSCC tumors. Clin Cancer Res; 23(17); 5162–75. ©2017 AACR.
Stensen Duct Relapse of Diffuse Large B-Cell Lymphoma
Authors: Punit Sharma, Shilpa Bhartia
Journal: Clinical Nuclear Medicine (2017)

18F-FDG PET/CT is now an established modality for staging and restaging high-grade lymphomas, including diffuse large B-cell lymphoma. We here present the case of a 51-year-old woman successfully treated for diffuse large B-cell lymphoma. Follow-up 18F-FDG PET/CT demonstrated an unusual site of relapse involving left Stensen (parotid) duct, which was confirmed with cytology. By identifying such unusual sites of lymphomatous involvement, 18F-FDG PET/CT can have significant bearing on patient management.
AZD3759, an EGFR inhibitor with blood brain barrier (BBB) penetration for the treatment of non-small cell lung cancer (NSCLC) with brain metastasis (BM): Preclinical evidence and clinical cases.
Authors: Dong-Wan Kim, James Chih-Hsin Yang, Kan Chen, Ziqiang Cheng, Lucy Yin, Paul David Martin, Zhenfan Yang, Haiyi Jiang, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2015)

8016 Background: Increasing numbers of EGFRm+ NSCLC patients with BM have been reported, while effective treatment is lacking due to limited BBB penetration of currently available EGFR TKIs. Here we report preliminary data on AZD3759, an EGFR TKI with BBB penetration, for the treatment of BM. Methods: Preclinically, AZD3759 was assessed in both in vitro and in vivo assays, including MDCKII/Pgp and BCRP assays and CNS penetration in rats, mice and monkeys. PC-9 cells (Exon19Del) were transfected with luciferase and implanted through intra-carotid artery injection to establish a BM model in mice. Tumor growth was monitored weekly by a Xenogen Imaging System and the animal survival time was recorded. Blood and brain tissues were collected for pharmacokinetics, histopathology and pEGFR expression analyses. An ongoing, open label, dose escalation phase I study (NCT02228369; sponsor AstraZeneca) is investigating safety and tolerability of AZD3759 in patients with EGFRm+ advanced NSCLC. Results: AZD3759 has high passive permeability (29.5x10-6 cm/sec) and is not a substrate of the efflux transporters Pgp or BCRP at the BBB. In vivo, AZD3759 reached distribution equilibrium in rats, mice and monkey (Kpuu,brain and Kpuu,CSF > 0.5), suggesting BBB penetration. In the BM model, AZD3759 induced profound tumor regression and significantly improved animal survival. A correlation between free brain exposure and pEGFR modulation was also detected in tumor tissues on AZD3759 treatment. To date, 4 patients with measurable BM have been enrolled into 50mg bid and 100mg bid cohorts (3 patients and 1 patient, respectively). In the 2 evaluable patients with BM, one unconfirmed PR and one SD in the brain have been observed. Ctrough CSF concentrations of these patients were 7.7 and 6nM, respectively, close to the pEGFR IC50 of AZD3759. No DLTs were reported to date and two cases of grade I skin rash were observed. Conclusions: Preclinical and initial clinical evidence indicate that AZD3759 is an EGFR TKI with BBB penetration with potential to treat EGFRm+ NSCLC patients with BM. Updated clinical data will be shared at the meeting. Clinical trial information: NCT02228369.
Novel reassortment of avian influenza A(H7N9) virus with subtype H6N6 and H5N6 viruses circulating in Guangdong Province, China
Authors: Yuan Jin, Hongguang Ren, Yue Teng, Mingda Hu, Xiaochuan Peng, Junjie Yue, Long Liang
Journal: Journal of Infection (2017)
Multiplexed immunobead-based assay application of a biomarker CA125 in ovarian cancer
Authors: Jeong Eun Park, Su-Mi Bae, Eun Kyeong Oh, Lanying Wen, Woong Shick Ahn
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3643 

The aim of the study was to investigate the utilization comparison of three immunoassay methods for quantitation of CA125 as a ovarian cancer biomarker. CA125 was measured in sera of 42 pateints with ovarian cancer and 39 normal healthy women. Assay for CA125 was analytically validated and quantitatively developed in three technical methods: immunoradiometric assay (RIA), enzyme-linked immunosorbent assay (ELISA), and Luminex. The Luminex resulted in 81.0% sensitivity and 88.9% accuracy at 100% (False Positive = 0; False Negative = 9) specificity in terms of the positivity rate ( P <0.0001, 95% CI). The sensitivity and specificity of RIA was 83.3% and 97.4% and 81.0% with 88.89% accuracy (False Positive =1; Flase Negative =8), respectively. Bead-based ELISA obtained 81.0% sensitivity and 100% specificity with 87.7% accuracy (False Positive = 0; False Negative =10). The area under the curve (AUC) for the Luminex assay (0.954) was higher than AUCs for other methods tested (0.932 of RIA and 0.877 of ELISA). The correlation coefficient ( r ) between ELISA and Luminex was r = 0.82, P <0.0001, and between Luminex and RIA was r = 0.53, P <0.0001. We report in detail the analytical performance of a bead-based Luminex assay validated using human serum in ovarian cancer samples. We conclude that the Luminex is the preferable method for CA125 determinations and the screening of ovarian cancer.
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Is Highly BCL-2 Dependent and Sensitive to Venetoclax
Authors: Joan Montero, Jason Stephansky, Tianyu Cai, Gabriel K. Griffin, Katsuhiro Togami, Lucia Cabal-Hierro, Nicole R. LeBoeuf, Leah Hogdal, Ilene Galinsky, Jon C. Aster, Matthew S. Davids, Naveen Pemmaraju, Richard M. Stone, Marina Konopleva, Anthony Letai, Andrew A. Lane
Journal: Blood (2016)
Farmer's Lung
Authors: William P. Baldus, James B. Peter
Journal: New England Journal of Medicine (1960)

FARMER'S lung is recognized as a clinical entity in which the development of respiratory symptomatology follows the inhalation of dust from moldy hay, silage or grain. The condition was first described by Campbell1 in 1932; subsequently, additional reports appeared in the British and Scandinavian literature. In the past few years, cases of this disease occurring in the United States have been documented.2 3 4 The purpose of this report is to present 2 cases exhibiting the clinical, roentgenologic and pathological features of farmer's lung. The cases are of special interest because lung biopsies were obtained, symptoms were reproduced in 1 patient by . . .
Major global cyber-attack hits NHS and delays treatment
Authors: Adrian O’Dowd
Journal: BMJ (2017)

An unprecedented level of disruption hit the NHS in England and Scotland at the weekend after a “ransomware” cyber-attack that paralysed NHS information technology systems across dozens of organisations.

Operations were postponed, appointments were cancelled, and staff were asked to work over the weekend, as trusts put emergency plans into action to deal with the problem, which also affected many different organisations, including FedEx, Renault, and Germany’s railways, in around 150 countries, attacking around 200 000 computers.

On 12 May the virus started to cripple NHS computers. This particular virus, called WannaCry, is a type of computer malware that encrypts data, locks out the user, and demands a ransom from the user before releasing the data.

In England 48 trusts have experienced problems at hospitals, with GP surgeries and pharmacies also affected, and 13 NHS organisations in Scotland. Wales and Northern Ireland seem to have been unaffected so far.

In a statement NHS Digital, the body responsible for ensuring that organisations meet information and security standards, said that there was no evidence that patients’ data had been accessed.

Most NHS organisations were running up to date IT systems, but a small proportion, around 5%, were still in the process of upgrading their devices from older operating systems such as Windows XP, said NHS Digital.

It is thought that the continued use of the Windows XP platform had made the NHS vulnerable to ransomware attack. On Sunday 14 May Microsoft announced that it would be taking the “highly unusual” step of providing a security update for customers using older Windows platforms, including XP. Also on Sunday the UK National Cyber Security Centre said that it knew of no sustained new attacks of …