tbuckley/cabot-search huggingface dataset:
Randomized phase 2b trial comparing first-line treatment with aldoxorubicin versus doxorubicin in patients with advanced soft tissue sarcomas.
Authors: Sant P. Chawla, Zsuzsanna Papai, Kamalesh Sankhala, Leonid Vasylyev, Guzel Mukhametsina, Mamed Aliev, Kenneth Khamly, Scott Wieland, Daniel J. Levitt
Journal: Journal of Clinical Oncology (2014)

10502 Background: Doxorubicin (D) is the only approved first line therapy for most advanced soft tissue sarcomas (STS). Aldoxorubicin (A) consists of doxorubicin attached to an acid-sensitive linker that binds covalently to serum albumin. We compared the efficacy and safety of A to D as first line treatment for patients with advanced STS. Methods: 31 site international trial; 123 patients ages 18-78 years with histologically confirmed metastatic, locally advanced or unresectable STS randomized 2:1 to receive either 350 mg/m2 A (260 mg/m2 D equivalents) or 75 mg/m2D, every 3 weeks for a maximum of 6 cycles. Tumor response by CT was monitored every 6 weeks until completion of treatment, 2 months post treatment, then every 3 months to progression or withdrawal from study. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall response rate (ORR), PFS at 6 months and overall survival (OS). Both a blinded, independent review and an investigator site review were performed for each scan. Results: 83 patients were randomized to A and 40 to D. Groups were well-balanced for age, sex, race, performance status, and sarcoma pathology. Median (range) # of completed cycles: A = 6 (1-6); D = 4 (1-6). 30% of patients were from the U.S., 47% from Europe and 23% from Asia Pacific. Efficacy results are shown in the Table. Grade 3 or 4 adverse events that were increased in patients treated with A were neutropenia (28% vs 15%), nausea/vomiting (10% vs 0%), mucositis (12% vs 2 %), fatigue (5% vs 0%) and anorexia (4% vs 0%). LVEF < 50%: A = 0, D = 9.5%. Grade 3/4 pain was increased in the D arm (2% vs 8%). Grade 3/4 febrile neutropenia (17% vs 18%), anemia (17% vs 20%) thrombocytopenia (7% vs 5%) were similar for patients receiving A or D. Conclusions: Aldoxorubin is more efficacious than doxorubicin in the treatment of advanced STS with an acceptable safety profile. Clinical trial information: NCT01514188. Investigator review A D p PFS (months, median) 8.4 4.7 0.0002 HR (CI) 0.370 (0.212-0.643) 0.0004 PFS, 6 months 67.1% 36.1% 0.008 ORR (%) 24.0 5.3 CR 2.7 0 PR 21.3 5.3 Blinded independent review PFS (months, median) 5.7 2.8 0.018 HR (CI) 0.586 (0.358-0.960) 0.034 PFS, 6 months 46.8% 23.7% 0.038 ORR (%) 23 0 CR 0 0 PR 23 0
Severe dystrophic cardiomyopathy caused by the enteroviral protease 2A–mediated C-terminal dystrophin cleavage fragment
Authors: Matthew S. Barnabei, Frances V. Sjaastad, DeWayne Townsend, Fikru B. Bedada, Joseph M. Metzger
Journal: Science Translational Medicine (2015)

Enterovirus-derived C-terminal dystrophin fragment is a dominant-negative peptide representing a new therapeutic target for viral cardiomyopathy remediation.
Abstract P4-09-21: Dual expression of aquaporin 3 and 5 in patients with early breast cancer
Authors: SJ Lee, YS Chae, TJ Kwon, JH Chung, J Lee, JH Jung, WW Kim, HY Park, JY Jeong, S-H Park, S Park
Journal: Cancer Research (2016)

Abstract Background: We reported separately that AQP5 or AQP3 expression in tumor tissue may predict survival after surgery for the specific types of early breast cancer (EBC). However, there is no definitive evidence for the role of dual expression of the two AQPs. Therefore, the current study focused the association and its prognostic impact of their tumoral expressions in the same patients. Patients and Methods: AQP3 and AQP5 expressions were investigated on the basis of the immunohistochemistry of tissue microarray specimens from 447 EBC patients who underwent surgery between 2003 and 2008 as described in previous studies. Patients were divided into 4 subgroups based on AQP3 and AQP5 expressions: group1 for (-/-), group2 for (-/+), group 3 for (+/-), and group 4 for (+/+), respectively. Results: Among 477 patients, the number of patients for each group was as follows: group 1 (n=193, 43.2%), group 2 (n=74, 16.6%), group3 (n=110, 24.6%) and group 4 (n=70, 15.7%), respectively. In the current study a positive correlation was identified between AQP3 and 5 expressions (P=0.017 by a χ2- test) in particular for HER2- overexpressing and ER-positive tumors (P=0.009 and 0.044, respectively). Multivariate survival analysis showed that dual expression of AQP3 and AQP5 was a negative prognostic factor for relapse-free or distant disease-free survival for patients with HER2-overexpressing EBC (HR=3.107 and 3.683; P=0.043 and 0.027, respectively), statistically more prominent compared in case with AQP3 expression alone (HR=3.137 and 2.784; P=0.036 and 0.070, respectively). Conclusion: Dual expression of AQP3 and AQP5 in tumor tissue may be considered as a potential prognostic marker in patients with HER2-overexpressing EBC after curative surgery. Citation Format: Lee SJ, Chae YS, Kwon TJ, Chung JH, Lee J, Jung JH, Kim WW, Park HY, Jeong JY, Park S-H, Park S. Dual expression of aquaporin 3 and 5 in patients with early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-21.
QOL-05IMPACT OF HEADACHES UPON THE POST-RADIOTHERAPEUTIC QUALITY OF LIFE OF GLIOBLASTOMA MULTIFORME PATIENTS: A QUALITATIVE STUDY
Authors: Samuel Bennett, Garth Cruickshank, Antje Lindenmeyer, Simon Morris
Journal: Neuro-Oncology (2015)

BACKGROUND: Headaches and facial pain have been accredited as accounting for the most prevalent form of pain amongst patients with glioblastoma mulitforme (GBM) - the most common malignant primary brain tumour. Despite this, minimal research has previously been undertaken investigating the direct and indirect impact that headaches have upon the quality of life (QoL) of GBM patients. METHODS: Exploratory qualitative study utilising face-to-face semi-structured interviews, with GBM patients registered as outpatients at the Queen Elizabeth Hospital Birmingham (UK), to gain an insight into the factors impacting upon their QoL, specifically focusing upon the impact of headaches post-radiotherapy. Interviews were audio-recorded, transcribed verbatim and underwent qualitative thematic analysis to identify key themes, viewpoints and dynamics. RESULTS: From the 8 participants (median = 47.5 (44 - 57.5) years; 3 male) interviewed, 3 core themes were identified and developed: Headache of social situations, Underlying determination and positivity and Psychological springboard of headaches. Important to note, is that 5-7 more participants are still to be interviewed, with the research scheduled to finish by the end of July. CONCLUSION: Whilst the QoL of patients with GBM is clearly multifactorial, headaches do indeed play a part for some. However, it is not the direct pain of the headache as perhaps expected that impacts upon the QoL of these patients, but the indirect repercussive effect of the limitations headaches place upon social life and that they may serve as a painful psychological reminder to these patients of their prognosis and threat to autonomy. The findings from the remaining participant interviews will be incorporated into the current findings.
Prevalence of Various Respiratory Viruses in the Middle Ear during Acute Otitis Media
Authors: Terho Heikkinen, Monica Thint, Tasnee Chonmaitree
Journal: New England Journal of Medicine (1999)

Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media. Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown.We determined the prevalence of various respiratory viruses in the middle-ear fluid in 456 children (age, two months to seven years) with acute otitis media. At enrollment and after two to five days of antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were obtained for viral and bacterial cultures and the detection of viral antigens. The viral cause of the infections was also assessed by serologic studies of serum samples obtained during the acute illness and convalescence.A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent). Respiratory syncytial virus was the most common virus identified in middle-ear fluid: it was detected in the middle-ear fluid of 48 of the 65 children (74 percent) infected by this virus (P< or =0.04 for the comparison with any other virus). Parainfluenza viruses (15 of 29 children [52 percent]) and influenzaviruses (10 of 24 children [42 percent]) were detected in the middle-ear fluid significantly more often than enteroviruses (3 of 27 children [11 percent]) or adenoviruses (1 of 23 children [4 percent]) (P< or =0.01 for all comparisons).Respiratory syncytial virus is the principal virus invading the middle ear during acute otitis media. An effective vaccine against upper respiratory tract infections caused by respiratory syncytial virus may reduce the incidence of acute otitis media in children.
Adverse events following school-based vaccination of girls with quadrivalent human papillomavirus vaccine in Slovenia, 2009 to 2013
Authors: Maja Šubelj, Veronika Učakar, Alenka Kraigher, Irena Klavs
Journal: Eurosurveillance (2016)

Adverse events following immunisation (AEFIs) with qHPV reported to the Slovenian AEFI Registry for the first four school years of the vaccination programme were analysed. We calculated annual reporting rates for 11–14 year-old vaccinees with AEFIs, using the number of qHPV doses distributed within the school-based vaccination programme as the denominator. Between September 2009 and August 2013, 211 AEFIs that occurred in 89 vaccinees were reported, a rate of 149.5 vaccinees with AEFI per 100,000 qHPV doses distributed. For five vaccinees, serious AEFIs (8.4 per 100,000 doses distributed) were reported. The highest reporting rates were for fatigue, headache, and fever (≥ 38.0⁰) (53.8, 40.3, and 35.3 per 100,000 qHPV doses distributed, respectively). As no AEFI resulted in permanent sequelae and they all were categorised as serious only due to the criterion of a minimum of one day of hospitalisation, this provides reassurance for the safety of our school-based HPV vaccination programme. Further AEFI surveillance is warranted to provide data for HPV vaccination programme monitoring and evaluation of its safety.
Wilsons Disease, Portal Hypertension and Intrahepatic Vascular Obstruction
Authors: W. Jape Taylor, F. C. Jackson, Wallace N. Jensen
Journal: New England Journal of Medicine (1959)

APPLICATION of the technics of hepatic-vein catheterization and percutaneous splenic puncture, with appropriate blood-flow and pressure measurements and radiologic visualization of the portal bed, has permitted the clear definition of portal hypertension as a factor in the causation of splenomegaly in Wilson's disease. Despite the universal pathologic involvement of the liver with an associated but variable degree of impairment of hepatic function, of splenomegaly in most cases and the occasional rupture of an esophageal varix (as in the patient described in Wilson's1 original report), with disastrous results, portal hypertension has not been previously quantified or properly emphasized as a major . . .
Identification of a Genetic Locus for Familial Atrial Fibrillation
Authors: Ramon Brugada, Terry Tapscott, Grazyna Z. Czernuszewicz, A.J. Marian, Anna Iglesias, Lluis Mont, Josep Brugada, Josep Girona, Anna Domingo, Linda L. Bachinski, Robert Roberts
Journal: New England Journal of Medicine (1997)

Atrial fibrillation, the most common sustained cardiac-rhythm disturbance, affects over 2 million Americans and accounts for one third of all strokes in patients over 65 years of age. The molecular basis for atrial fibrillation is unknown, and palliative therapy is used to control the ventricular rate and prevent systemic emboli. We identified a family of 26 members of whom 10 had atrial fibrillation that segregated as an autosomal dominant disease. We subsequently identified two additional families in which the disease was linked to the same locus.
Abortion, Breast Cancer, and Epidemiology
Authors: Patricia Hartge
Journal: New England Journal of Medicine (1997)

In this issue of the Journal, 1 Melbye et al. present substantial epidemiologic evidence that induced abortions do not affect a woman's risk of having breast cancer. In a linkage study, they compared the abortion histories of women with and without breast cancer in Denmark. The use of data on abortion obtained from population registries rather than from interviews, the large size of the study, the inclusion of one country's entire population of women, and the adjustment for other aspects of reproductive history all strengthen the credibility of the findings. The study thus provides important new evidence to resolve a controversy . . .
Vonoprazan <i>Helicobacter pylori</i> eradication therapy: ethical and interpretation issues
Authors: David Y Graham
Journal: Gut (2016)

We read with interest the important study on vonoprazan in Helicobacter pylori eradication therapy.1 Vonoprazan likely represents a significant advance in antisecretory and H. pylori eradication therapy. Despite being technically well done, several issues related to study conduct and interpretation remain. Their sample size was based on 90% success with lansoprazole, which has not been achieved in Japan for several decades. When the cure rates proved to be lower, the sample size was increased to ‘maintain the statistical power of the study’. We question whether this was ethical. It is generally considered unethical to randomise against a regimen that provides unacceptably low cure rates; many journals reject papers that do this.2 , …
Multiple Sclerosis and Antibodies against KIR4.1
Authors: Anne-Katrin Pröbstel, Jens Kuhle, Anne-Catherine Lecourt, Isabelle Vock, Nicholas S R Sanderson, Ludwig Kappos, Tobias Derfuss
Journal: New England Journal of Medicine (2016)

at our center.None of the samples from either the multiple sclerosis group or the control group showed KIR4.1 reactivity, and no significant between-group difference (P>0.05) was established (Fig. 1A).The enrichment of low-glycosylated KIR4.1 tetramer isoforms was confirmed with the 20F9 monoclonal antibody (P = 0.002) (Fig. 1B).Taken together, these results indicate that autoantibodies against KIR4.1 may not be specific for multiple sclerosis.Further support for this point of view is provided in this issue of the Journal by Pröbstel et al., who used approaches that were similar to ours and that produced similar results. 6However, our experience with the ELISA revealed considerable methodologic challenges and demands that are inherent to the assay -particularly, those associated with posttranslational modifications and higher-order structure formation of the KIR4.1 protein.Additional study is required to better identify these technical issues and address discrepancies between investigations through cooperative sharing of specimens.We conclude that although there are technical challenges with measuring anti-KIR4.1 autoantibodies, future investigations are required to clarify their possible role in multiple sclerosis.
Timeliness of breast cancer diagnosis and initiation of treatment in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP)
Authors: L. C. Richardson, J. Royalty, W. Howe, W. Helsel, W. Kammerer, V. B. Benard
Journal: Journal of Clinical Oncology (2007)

6571 Background: To examine intervals between breast cancer screening, diagnosis, and treatment initiation among low income and uninsured women in the National Breast and Cervical Cancer Early Detection Program during two time periods. Methods: We examined diagnostic and treatment intervals for the time periods of 1996–2000 and 2001–2005 to evaluate program progress. The intervals were defined as: (1) time between mammography and final diagnosis for all women receiving an abnormal mammogram result (including suspicious abnormality (SA), highly suspicious for malignancy (HSM) and assessment is incomplete (AI)) or abnormal clinical breast exam and; (2) time between diagnosis and treatment initiation among those diagnosed with cancer. Covariates including mammography result, age at screening, race/ethnicity, and metropolitan/urban/rural classification of residence were included in the analysis. Results: For the entire study period, 369,557 women screened for breast cancer through the NBCCEDP had abnormal screen results. For 1996–2000 and 2001–2005 time periods, the median interval to diagnosis after screening was 25 days and 23 days respectively. For those 22,302 women found to have cancer, the median interval from diagnosis to treatment increased from 12 days in the first time period to 14 days in the later time period. Overall, time to diagnosis improved from 1996–2000 compared to 2001–2005. However, time to treatment initiation was slightly longer (median increased by 2–3 days). Using data from the most recent period of 2001–2005, 93% of women with cancer initiated treatment within 120 days of screening. Conclusions: The goal of the NBCCEDP is to assure that women receive timely, quality breast cancer screening and diagnostic services and initiate treatment. Our data show that the program is meeting these goals. Disparities in breast cancer incidence, mortality and survival should diminish once all women have access to breast cancer early detection and treatment services. No significant financial relationships to disclose.
Frederick Schwatka — Cavalry Officer, Explorer, Physician
Authors: Robert E. Johnson, Harriet S. Jeanes
Journal: New England Journal of Medicine (1968)

FREDERICK Schwatka, M.D. (1849–1892), was successful in three professional careers; none was the practice of medicine.1 The first was as a fighting cavalry officer in the Indian Wars in the desert and plains, the second as a military explorer in the Canadian Arctic and Alaska, and the last as a free-lance explorer in Alaska and the Sierra Madre Occidental of Chihuahua.Schwatka graduated from the United States Military Academy in 1871, ranking twentieth in a class of 41 cadets.2 The best known member of the class was another native of Galena, Illinois, F. D. Grant, the son of the President . . .
Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma
Authors: A. Santin, S. Bellone, K. El-Sahwi, N. Buza, F. A. Tavassoli, D. Silasi, M. Azodi, P. E. Schwartz, T. J. Rutherford, S. Pecorelli
Journal: Journal of Clinical Oncology (2009)

e16502 Background: Uterine serous papillary carcinoma (USPC) represents a variant of endometrial cancer characterized by a highly aggressive biologic behavior and inborn resistance to chemotherapy. MT201 is a fully human monoclonal antibody recently developed against epithelial cell adhesion molecule (EpCAM). In this study we have evaluated the potential of MT201 as a novel therapeutic strategy against USPC. Methods: EpCAM expression was evaluated by real time-PCR and immunohistochemistry (IHC) in a total of 54 USPC fresh-frozen biopsies and paraffin embedded tissues. EpCAM surface expression was evaluated by flow cytometry in 6 freshly established USPC cell lines derived from advanced stage USPC patients. Sensitivity to MT201 antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) was tested in standard 4-hour chromium ( 51 Cr) release cytotoxicity assays. Results: EpCAM transcript was significantly overexpressed in fresh frozen USPC when compared to fresh-frozen normal endometrial cells (NEC) [i.e., mean (minimum-maximum) copy number of 515.4 (31.5–1568.3) in tumor samples versus 8.1 (1.0–25.5) in flash-frozen NEC (p &lt; 0.001)]. By IHC, EpCAM protein expression was found in 96% (26 out of 27) USPC samples and this expression was significantly higher when compared to normal endometrial cells (p &lt; 0.01). High surface expression of EpCAM by flow cytometry was found in 83% (5 out of 6) of the primary USPC cell lines available to this study. Importantly, while primary USPC cell lines were highly resistant to natural killer dependent cytotoxicity in vitro, EpCAM positive cell lines were found highly sensitive to MT201-mediated ADCC. Human serum IgG did inhibit MT201-mediated cytotoxicity against USPC in vitro. Conclusions: These results demonstrate for the first time high EpCAM expression in uterine serous carcinoma at mRNA and protein levels and high sensitivity to MT201-mediated cytotoxicity in vitro by primary USPC cell lines. MT201 might be a novel and attractive therapeutic strategy in patients harboring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. No significant financial relationships to disclose.
Continuing Occurrence of Thyroid Carcinoma after Irradiation to the Neck in Infancy and Childhood
Authors: Samuel Refetoff, John Harrison, Borislav T. Karanfilski, Edwin L. Kaplan, Leslie J. De Groot, Carlos Bekerman
Journal: New England Journal of Medicine (1975)

To determine wether the occurrence of x-ray-induced thyroid carcinoma has not declined, we examined 100 patients with a history of irradiation to the neck area. Irradiation had been given to tonsils (42 per cent), adenoids (10 per cent), tonsils and adenoids (7 per cent) and thymus (30 per cent), for acne (7 per cent), and for various other reasons (7 per cent). Operation was recommended to 18 of 26 patients with palpable abnormalities and 15 were operated upon; we found seven carcinomas, and eight benign lesions. Five of six carcinomas had invasive characteristics, with or without metastases, five of seven were multifocal, and six of seven had a follicular component. Of seven patients irradiated to both tonsils and adenoids and thus receiving higher radiation exposure, two had carcinoma, suggesting a dose relation. The overall 7 per cent prevalence of carcinoma in unselected patients with a history of irradiation to the neck area is higher than expected and implies a continuing important public-health problem, at least in the Chicago area. (N Engl J Med 292:171–175, 1975)
Perioperative Nutritional Support in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma
Authors: Sheung-Tat Fan, Chung-Mau Lo, Edward Lai, Kent-Man Chu, Chi-Leung Liu, John Wong
Journal: New England Journal of Medicine (1994)

Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality. Since intensive nutritional support can reduce the catabolic response and improve protein synthesis and liver regeneration, we performed a prospective study to investigate whether perioperative nutritional support could improve outcome in patients undergoing hepatectomy for hepatocellular carcinoma.