tbuckley/cabot-search huggingface dataset:
Long term outcome in patients with cisplatin-refractory or multiply relapsed germ cell tumors following treatment with gemcitabine and oxaliplatin ± paclitaxel.
Authors: K. Oechsle, C. K. Kollmannsberger, F. Honecker, F. Mayer, C. F. Waller, I. Böhlke, C. Bokemeyer
Journal: Journal of Clinical Oncology (2010)

4585 Background: Patients (pts) with cisplatin-refractory or multiply relapsed germ cell tumors (GCT) have a poor prognosis and rarely achieve long term survival. Different combination chemotherapy regimens (CTX) including gemcitabine, oxaliplatin and paclitaxel have shown efficacy in these pts with resonse rates of 20-40 % and complete responses in 5-15%. However, long term survival appears to be rare and most studies have only been reported with short follow up. We here report long-term outcome from two previously reported trials. Methods: Two phase II trials have previously evaluated CTX with gemcitabine and oxaliplatin (GO) or GO plus paclitaxel (GOP) including a total of 76 pts (GO 35 pts / GOP 41 pts) (Kollmannsberger 2004; Bokemeyer 2008). A total of 26 patients were alive at the time of reporting of the studies, with 9 pts (12%) being in free of disease after CTX ± surgery and 17 alive with disease. Of the 9 pts free of disease 3 (3/35; 9%) and 6 (6/41; 15%) had received GO and GOP, respectively. Results: After a median follow up of 16 months (2 – 64+) for the 26 pts still alive, 8 (8/76; 11%) pts remain disease free with a median progression free and overall survival time of 32 months (11 – 64+) and 35 months [11-64+], respectively: 1/35 pts (3%) after GO and 7/41 pts (17%) after GOP. Another 3 pts, one after GO and 2 after GOP, who had relapsed after one, two and 6 months, achieved a complete remission after salvage treatment with CTX + surgery resulting in an overall long term survival rate of 13% (10/76 pts): 6% (2/35) after GO and 20% (8/41) after GOP. 2/10 pts had been absolutely refractory to previous cisplatin-based CTX. Eight pts have been now disease free for > 2 years after GO/GOP treatment, indicating potential long term cure in these heavily pretreated pts. Conclusions: Long term survival can be achieved with GO or GOP CTX in about 15% of pts with cisplatin-refractory or multiply relapsed GCT. Based on this retrospective analysis, the triple CTX combination GOP appears to achieve higher long term survival rates than two drug combinations. This finding requires confirmation in a randomized trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly, sanofi-aventis
Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility
Authors: Rosemary C. Bagot, Hannah M. Cates, Immanuel Purushothaman, Zachary S. Lorsch, Deena M. Walker, Junshi Wang, Xiaojie Huang, Oliver M. Schlüter, Ian Maze, Catherine J. Peña, Elizabeth A. Heller, Orna Issler, Minghui Wang, Won-min Song, Jason. L. Stein, Xiaochuan Liu, Marie A. Doyle, Kimberly N. Scobie, Hao Sheng Sun, Rachael L. Neve, Daniel Geschwind, Yan Dong, Li Shen, Bin Zhang, Eric J. Nestler
Journal: Neuron (2016)
The blind men and the AML elephant: can we feel the progress?
Authors: S Tauro
Journal: Blood Cancer Journal (2016)

Abstract The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline–cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems.
Abstract 143: Effects of Long-Term Administration of Dexmedetomidine on Inflammatory Responses in Patients with Severe Sepsis
Authors: Takumi Taniguchi, Akihide Kurita, Koji Sato, Takashi Fujita, Kenji Sakata, Masaki Okajima
Journal: Circulation (2011)

Background: Several studies showed that dexmedetomidine (DEX), a new sedative and alpha-2 adrenoceptor agonist, drastically inhibited the inflammatory responses in septic animals. Moreover, DEX was...
Impaired Renal Tubular Function in Chronic Alcoholics
Authors: M Labib, M Abdel-Kader, L Ranganath, S Martin, V Marks
Journal: Journal of the Royal Society of Medicine (1989)

Despite the well known effects of chronic alcohol abuse on the gastrointestinal, cardiovascular, nervous and endocrine systems, little information is available on its effect on renal function. To assess renal function we measured urinary excretion of albumin, α 1 microglobulin and retinol binding protein in 30 chronic alcoholic patients. Our data shows that 40% of chronic alcoholic patients have impaired renal tubular function.
Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP
Authors: Vikram G. Pillai, Jialing Bao, Catherine B. Zander, Jenny K. McDaniel, Palaniappan S. Chetty, Steven H. Seeholzer, Khalil Bdeir, Douglas B. Cines, X. Long Zheng
Journal: Blood (2016)
P0598 : Natural history of chronic hepatitis B infection in The Gambia, West Africa: A longitudinal population-based study
Authors: Y. Shimakawa, M. Lemoine, C. Bottomley, H. Freeya Njai, G. Ndow, R. Wegmuller, S.E. Moore, U. D'Alessandro, H. Whittle, M. Mendy, M. Thursz, R. Njie
Journal: Journal of Hepatology (2015)
Do microbiotas warm their hosts?
Authors: Eugene Rosenberg, Ilana Zilber-Rosenberg
Journal: Gut Microbes (2016)

All natural animals and plants are holobionts, consisting of a host and abundant and diverse microbiota. During the last 20 years, numerous studies have shown that microbiotas participate in the ability of their hosts to survive and reproduce in a particular environment in many ways, including contributing to their morphology, development, behavior, physiology, resistance to disease and to their evolution. Here we posit another possible contribution of microbiotas to their hosts, which has been underexplored - the generation of heat. We estimate that microbial metabolism in the human gut, for example, produces 61 kcal/h, which corresponds to approximately 70% of the total heat production of an average person at rest.
Case 27-1974
Authors: Richard C. Cabot, Robert E. Scully, Betty U. McNeely, Gerald S. Foster, James J. Galdabini
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 67-year-old man was admitted to the hospital because of abdominal pain and fever.Eighteen years previously he began to have bouts of pain in the right upper abdominal quadrant accompanied by fever, and one year later a cholecystectomy was performed for gallstones. He was then well until 10 years before entry, when pain recurred in the right upper abdominal quadrant after a heavy meal, with fever and chills. He entered another hospital, where tetracycline was given, with subsidence of the fever in 10 days. A hepatic scan was normal (Fig. 1A). Later in the year . . .
Smoking, Not COPD, as the Disease
Authors: Leonardo M. Fabbri
Journal: New England Journal of Medicine (2016)

Smoking causes not only cancer but also cardiovascular diseases such as stroke, coronary heart disease, hypertension, thromboembolism, and peripheral artery disease, lung disease such as chronic obstructive pulmonary disease (COPD), and many other diseases, including (but not limited to) type 2 diabetes, rheumatoid arthritis, cataracts, and macular degeneration.1 These diseases develop with age and contribute in different measure to the current epidemic of chronic noncommunicable diseases that are associated with smoking and aging.1,2 Even though the effects of smoking are broad and devastating, much smoking-related research traditionally focuses on the lung because the lung is considered to be the . . .
Proteinase inhibition regulates the anti-tumor activity of PAI-1 towards lung and prostate cancer cells
Authors: Adriana Rozy, Marta Kedzior, Joanna Chorostowska-Wynimko, Paulina Jagus, Adam Szpechcinski, Ewa Skrzypczak-Jankun, Jerzy Jankun
Journal: European Respiratory Journal (2011)

Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in tumor growth and metastasis formation, directly via specific urokinase complexing or indirectly due to its affinity to vitronectin. The aim of this study was to analyze the impact of the mutant forms of PAI-1: very long half-life (VLHL PAI-1) or devoid of affinity towards vitronectin (Vn neg PAI-1) and wild form (wPAI -1) on proliferation of lung cancer (A549 and H1299) and prostate cancer (LNCaP and DU145) cells characterized by different proteinase (urokinase) production.

The dose- and time-dependent inhibition of cell proliferation in the presence of VLHL PAI-1 was evident in A549 and LNCaP cultures. In H1299 cells inhibitory effect was only dose-depended (p<0.001), while in DU145 only 100 μg/ml of VLHL PAI-1 in 72 hrs cultures suppresed prostate cancer cells proliferative activity (p <0.001). No significant effect of Vn neg PAI-1 on the proliferation of A549 and H1299 was observed while in prostate cancer lines (DU145, LNCaP) only the inhibitory effect of the highest Vn neg PAI-1 concentration (100μg/ml) was evident (p <0.001) but not time-dependent. wPAI-1 did't affect A549 and LNCaP proliferation while in highest concentration it had the stimulating effect on H1299 and Du145 (24,48 hrs cultures).

PAI-1 is a negative regulator of cancer cells proliferation due to its anti-proteinase activity. Its biological effect on lung cancer cells is time and dosage-dependent.
A Robust Ex-Vivo Erythropoiesis System For Studying Transcriptional Regulation Of Globin Genes In Thalassaemia
Authors: Janakiram Rayabaram, Thiyagaraj Mayuranathan, Divya Jayasree, Neeraj Arora, Eunice Sindhuvi Edison, Alok Srivastava, Shaji Velayudhan
Journal: Blood (2013)
Endoscopic Therapy With Lumen-apposing Metal Stents Is Safe and Effective for Patients With Pancreatic Walled-off Necrosis
Authors: Reem Z. Sharaiha, Amy Tyberg, Mouen A. Khashab, Nikhil A. Kumta, Kunal Karia, Jose Nieto, Uzma D. Siddiqui, Irving Waxman, Virendra Joshi, Petros C. Benias, Peter Darwin, Christopher J. DiMaio, Christopher J. Mulder, Shai Friedland, David G. Forcione, Divyesh V. Sejpal, Tamas A. Gonda, Frank G. Gress, Monica Gaidhane, Ann Koons, Ersilia M. DeFilippis, Sanjay Salgado, Kristen R. Weaver, John M. Poneros, Amrita Sethi, Sammy Ho, Vivek Kumbhari, Vikesh K. Singh, Alan H. Tieu, Viviana Parra, Alisa Likhitsup, Craig Womeldorph, Brenna Casey, Sreeni S. Jonnalagadda, Amit P. Desai, David L. Carr-Locke, Michel Kahaleh, Ali A. Siddiqui
Journal: Clinical Gastroenterology and Hepatology (2016)
Gout
Authors: Robert A. Terkeltaub
Journal: New England Journal of Medicine (2003)

A 59-year-old man with bilateral olecranon-bursa tophi has frequent bouts of acute gouty arthritis, including three in the past year. Serum uric acid levels are consistently above 9 mg per deciliter. He is moderately obese and has mild, untreated hypertension. Allopurinol was discontinued after a maculopapular rash developed. How should this patient be treated?
James Hutton, M.D. (1726–1797)— Founder of Modern Geology
Authors: Henry N. Claman
Journal: New England Journal of Medicine (1962)

WHAT is it that has lured so many trained physicians "afield"? Each man's motive is unique for himself, and yet one general aspect should be remembered: until the nineteenth century, the young man who was curious about the natural world in general had little formal training available to him. However "unscientific" the nineteenth-century medical curriculum may seem today, it was the best available introduction to natural science, and medicine therefore drew many men who were not primarily interested in the healing of the sick.Young James Hutton, attracted at first by chemistry, spent three years in the medical school of . . .
Safety and Efficacy of Preoperative Chemoradiotherapy (Crt) in Locally Advanced Rectal Cancers (Larc): a Retrospective Italian Survey of 389 Elderly Patients
Authors: C. Martines, S. Cordio, G. Aprile, A. Galiano, S. Lonardi, G. Rosati, A. Avallone, S. Pini, S. Leo, S. Lutrino, M. Uccello, P. Delrio, S. Franco, R. Bordonaro
Journal: Annals of Oncology (2014)
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Authors: Matthew R. Brier, Brian Gordon, Karl Friedrichsen, John McCarthy, Ari Stern, Jon Christensen, Christopher Owen, Patricia Aldea, Yi Su, Jason Hassenstab, Nigel J. Cairns, David M. Holtzman, Anne M. Fagan, John C. Morris, Tammie L. S. Benzinger, Beau M. Ances
Journal: Science Translational Medicine (2016)

PET imaging of pathological tau correlates more closely with Alzheimer’s disease–related cognitive impairment than does imaging of β-amyloid.
Combined Chemotherapy and Radiation Therapy for Cervical Cancer
Authors: David H. Moore
Journal: Journal of the National Comprehensive Cancer Network (2004)

More than 50% of patients with newly diagnosed cervical cancer will undergo radiation therapy as a primary treatment modality. Results from five phase III trials conducted by National Cancer Institute (NCI)-sponsored cooperative groups showed significant survival advantages from the addition of cisplatin-based chemotherapy to primary radiation therapy, changing the standard of care for patients with bulky or locally advanced cervical carcinoma. The majority of patients for whom treatment fails, however, have persistent pelvic disease. Other agents (alone or in combination with cisplatin) with potential synergy with radiation therapy should be studied. Future trials should investigate potential interrelationships between anemia, tumor hypoxia, angiogenesis, and the effectiveness of radiation therapy. Therapies specific to tumor hypoxia (tirapazamine) or strategies to maintain higher nadir hemoglobin levels during treatment (aggressive transfusion policies; erythropoietin) should also be studied.
Case 49-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Harold C. Urschel, Eugene J. Mark
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 40-year-old man was admitted to the hospital because of a persistent nodular density in the lower lobe of the left lung.The patient was well until seven months earlier, when he inhaled a large amount of dust while sawing material containing laminated melamine and phenolic plastic and fiber during the construction of a new house. Two days later dyspnea and cough developed, and he occasionally coughed up whitish sputum; he began to have left-sided chest pain. An x-ray film of the chest was reported to show pneumonia, and an oral antibiotic was prescribed, without improvement. Several . . .
HRPAP20 : a novel tumor progression regulator in human breast cancer.
Authors: Cristina M. Karp
Journal: Cancer Research (2005)

3408   The majority of human breast cancers develop as hormone-dependent tumors; however, with malignant progression, these tumors frequently progress to a more virulent phenotype characterized by hormone-independent growth, resistance to chemotherapy, and increased invasiveness. We recently cloned a novel gene in breast cancer cells that was designated Hormone-Regulated Proliferation-Associated Protein 20 (HRPAP20) based upon its pattern of expression. Initial studies indicated that HRPAP20 was induced by prolactin in hormone-responsive human breast adenocarcinoma (MCF-7) cells and reduced by serum starvation and differentiating agents. Stable transfection of HRPAP20 significantly increased proliferation and suppressed apoptosis, characteristics frequently observed in breast tumors as they progress toward greater malignancy. Since tumor progression is also associated with acquisition of an invasive phenotype, we investigated whether MCF-7 cells, stably expressing HRPAP20, exhibited an altered invasive capacity. Results from experiments performed in collagen/fibronectin/Matrigel®-coated transwell chambers indicated that constitutive HRPAP20 expression significantly (p  25-fold higher in the ADC-2 (63 year old, postmenopausal) compared to normal breast epithelium. MMP-1 was only detectable in ADC-2, while MMP-2 was increased > 5-fold and nearly 35-fold in ADC-1 and ADC-2, respectively. These observations suggest that in addition to enhancing growth, HRPAP20 facilitates breast tumor cell invasion by augmenting expression of MMPs. We conclude that alterations in HRPAP20 expression may underlie changes in growth and invasion associated with malignant progression in breast cancer.
Primary prophylaxis of neutropenia in women affected by breast cancer undergoing adjuvant chemotherapy with fec 100 +/- docetaxel: comparison of efficacy and tolerability between lenograstim and pegfilgrastim
Authors: L. Rossi, A. Papa, F. Tomao, D. Caruso, F. Ricci, M. Verrico, E. Giordani, F. Perrone Congedi, D. Giannarelli, E. Zaccarelli, M. Minozzi, G.P. Spinelli, V. Stati, S. Tomao
Journal: Annals of Oncology (2015)
Doctors in the Kitchen
Authors: Giuseppe Giusti, Giovanni B. Gaeta
Journal: New England Journal of Medicine (1981)

The use of raw or hurriedly steamed shellfish is recognized as a vehicle for the transmission of typhoid fever and Type A viral hepatitis.1 Steaming contaminated clams for five minutes or less is not sufficient for them to reach an internal temperature suitable for sterilization.2 Steaming for 15 minutes does suffice for sterilization, but this method of cooking does not ensure a palatable result.In southern Italy, there is heavy bacterial pollution of sea water in most populated areas, and many lots of mollusks sold on the market lack official certification since they come from clandestine beds. Nevertheless, the use . . .
Quality of life (QoL) improvements in patients (pts) with metastatic breast cancer (MBC) receiving capecitabine (X)
Authors: C. Oliveira, C. Beato, R. Ribeiro, S. Cabral, S. Tessaro, S. Lago, E. Abdo, G. Moura, M. Perdicaris, B. Garicochea
Journal: Journal of Clinical Oncology (2005)

8036 Background: The oral fluoropyrimidine X is highly active and well tolerated as single-agent therapy and extends survival when added to docetaxel in MBC. In addition to response rates and survival times, pt preference for oral therapy and QoL are increasingly important considerations in MBC. QoL data would add to understanding the pt benefits of X. Methods: QoL was evaluated in women with anthracycline +/- taxane-pretreated MBC while receiving X (baseline, before cycle 1, at weeks 7 and 13, and at treatment end) using EORTC QLQ C-30 (v3.0) and BR-23 questionnaires. We used linear models with repeated measures (generalized estimating questions technique) and SAS (v8.2) to determine improvement, stabilization or worsening of QoL scores from week 7 on onwards. Results: Baseline characteristics of the 907 evaluable pts were: median age 53 years (range 22–90), median ECOG PS 1 (range 0–4), and most pts (82%) were Caucasian. Of these, at least 70% had stable or improved QoL for most scales during X treatment, including functional QoL (QLQ C-30 and QLQ BR-38) and symptomatic QoL (QLQ C-30). Pts receiving X also had a significant, sustained improvement (p<0.0001 unless stated) in the following: global health status; role and emotional functioning; social functioning (p=0.0054); fatigue (p=0.0002); nausea/vomiting; pain; insomnia; appetite loss; constipation; diarrhea (p=0.0005); financial problems; body image; future perspective; systemic therapy side effects; breast symptoms; arm symptoms (p=0.0006); and hair loss. Conclusions: Pts receiving X had a significant and sustained improvement in global health status, with substantial improvements in almost all functional and symptomatic QoL domains. These findings highlight the importance of considering QoL and other measurable benefits of oral treatments alongside well-established measures of clinical evaluation in pts with metastatic disease. The QoL benefits, together with other proven clinical outcomes, suggest that earlier use of X in MBC would be of benefit to pts. No significant financial relationships to disclose.
Complications, Costs, and Financial Incentives for Quality
Authors: Jonah J. Stulberg, Karl Y. Bilimoria
Journal: JAMA Surgery (2016)

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