tbuckley/cabot-search huggingface dataset:
A phase II study to determine if sensory neuropathy of nab-paclitaxel can be reduced by prolonging infusion in patients with non-small cell lung cancer (NSCLC)
Authors: L. P. James, M. G. Kris, R. T. Heelan, K. K. Ng, G. H. Chia, J. E. Gomez, L. M. Krug, E. Moore, M. J. Hawkins, N. A. Rizvi
Journal: Journal of Clinical Oncology (2007)

18087 Background: We have previously reported that nab-paclitaxel (ABI-007; Abraxane) administered at 125 mg/m 2 over 30 minutes on days 1, 8, and 15 every 28 days has a response rate (RR) of 30% and median survival of 11 months [Rizvi, Proc. ASCO 2006]. We also observed 15/40 (38%) patients developed grade 2/3 sensory neuropathy with a 30 minute infusion. We hypothesize that a longer infusion with nab-paclitaxel may reduce peak plasma levels and accordingly reduce sensory neuropathy. Methods: After enrollment of 40 patients at 125 mg/m 2 over 30 minutes on days 1, 8, and 15 every 28 days, we amended the protocol to study an additional 25 patients with chemotherapy naïve stage IV NSCLC with a 2 hour infusion. The enrollment criteria and treatment schedule otherwise remained the same. Our goal was to detect 1 to 2 grade improvement of peripheral neuropathy with 80% power at the two sided p=0.10 significance level compared to the 40 patients treated with this dose given over 30 minutes. Results: To date, 22 of 25 planned patients have been treated with a 2 hour infusion. The mean number of doses administered was 11 for the initial 40 patients treated with a 30 minute infusion and 10 for the 22 patients treated with the 2 hour infusion. We observed 9/40 grade 2 and 6/40 grade 3 sensory neuropathy with the 30 minute infusion and 2/22 grade 2 and 1/22 grade 3 sensory neuropathy with the 2 hour infusion. The combined grade 2 and 3 toxicities were less with the 2 hour infusion (3/22, 14%) compared with the 30 minute infusion (15/40, 38%; p=0.078, Fisher’s exact test). Conclusions: Prolonging the infusion rate of nab-paclitaxel from 30 minutes to 2 hours is associated with a significant decrease in grade 2 and 3 sensory neuropathy. Efficacy data is presently being evaluated. [Table: see text]
<i>Clostridium welchii</i>Infection Complicating Biliary-Tract Surgery
Authors: Ludwig J. Pyrtek, Stanley H. Bartus
Journal: New England Journal of Medicine (1962)

CLOSTRIDIUM WELCHII infection is a serious, fulminating complication of biliary-tract surgery. Although rapid in onset, it has a definite symptom complex. In contrast to the usual complications of untreated and surgically treated disease of the biliary system, it does not permit a period of unhurried observation and investigation before therapy is started. The delay involved in awaiting a positive bile, wound or blood culture before antibiotic treatment is instituted will allow the organism to overwhelm its host. This infection may be aborted by prophylactic antibiotic therapy, or it may be cured if it is suspected early. The following cases illustrate . . .
The Cardiologist Looks at the Hand
Authors: Jacob J. Silverman, Donald S. Littman
Journal: New England Journal of Medicine (1953)

THE hand as a source of clinical information is so obvious that it may be neglected; yet there are no parts of the body more accessible for clinical study. Unique for its abundance of muscles, nerves and blood vessels, the hand is a powerful, dynamic organ capable of all kinds of reactions.A physician first introduces himself as an examiner not only through the visual sense but also, very early, through the sense of touch. Thus, the greeting of a patient with a formal, though cordial, handshake can be highly informative: this is the first direct contact between physician and . . .
Fatal Coronary-Artery Embolism after Pulmonary Resection
Authors: James D. Sprinkle, E. D. Peasley
Journal: New England Journal of Medicine (1963)

THROMBOSIS of the ligated stump of the pulmonary vein, with subsequent embolization to the coronary artery, is a most unusual complication of pulmonary resection. This mechanism of death after pulmonary resection has been neither recorded previously in the English literature nor encountered in our experience. In the following case the diagnosis of myocardial infarction was possible clinically, but the pathogenesis was established only at autopsy.Case ReportP.F.R., a 66-year-old man, was admitted to the hospital on May 21, 1962, for evaluation and treatment of an undiagnosed lesion of the left upper lobe.He appeared chronically ill, with evidence of . . .
Therapeutic-Class Wars -- Drug Promotion in a Competitive Marketplace
Authors: David A. Kessler, Janet L. Rose, Robert J. Temple, Renie Schapiro, Joseph P. Griffin
Journal: New England Journal of Medicine (1994)

In today's prescription-drug marketplace a host of similar products compete for essentially the same population of patients. Between 1989 and 1993, for example, the Center for Drug Evaluation and Research of the Food and Drug Administration (FDA) approved 127 new molecular entities (excluding generic drugs), but only a minority offered a clear clinical advantage over existing therapies1. Many of the others are considered “me too” drugs because they are so similar to brand-name drugs already on the market. The preponderance of “me too” drugs has created a highly competitive marketplace for prescription drugs. Pharmaceutical companies are waging aggressive campaigns . . .
Prolactin-Secreting Tumors and Hypogonadism in 22 Men
Authors: John N. Carter, John E. Tyson, George Tous, Stuart Van Vliet, Charles Faiman, Henry G. Friesen
Journal: New England Journal of Medicine (1978)

We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.
RTRB-14TREATMENT RECOMMENDATIONS FOR ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA LACK WORLDWIDE CONSENSUS
Authors: Joshua Palmer, Minesh Mehta, Noelle Williams, Adam Dicker, Maria Werner-Wasik, Wenyin Shi
Journal: Neuro-Oncology (2015)

This study explored the current worldwide management strategies for elderly patients with newly diagnosed glioblastoma. A web-based survey was distributed to 168 radiation oncologists (RO), neuro-oncologists (NO) and neurosurgeons (NS) from the United Council for Neurologic Subspecialties and CNS subcommittees of international cancer groups. Questions addressed the influence of molecular information, age, and comorbidities on treatment recommendations to determine whether management consensus exists. Respondents were allowed to choose more than one response. There were 58 (39%) respondents (50% NO, 3.5% NS and 50% RO) with 73% having > 10 years experience. 90% were academicians and 55% reportedly saw >50 patients with GBM annually. The most important factors influencing treatment decisions were KPS (92%), MGMT methylation status (72%), and comorbidity index (31%). Only 42% of respondents factor in age with 60% defining elderly as > 70 years-old. The most common recommendations for MGMT-methylated elderly patients with KPS > 70 were standard chemoRT (58%), temozolomide alone (28%), and short course RT (28%). The most common recommendations for MGMT-unmethylated patients with KPS > 70 were standard chemoRT (45%), short course RT (45%), and short course chemoRT (20%). Recommendations for patients with KPS < 50 were short course RT (52%), supportive care (50%), or TMZ alone (22%). Novo-TTF is or will soon be available at 74% of institutions. The majority (85%) of institutions do not have a clinical trial specifically for elderly patients with GBM, although 94% expressed interest in participating in such a trial. 98% of respondents are willing to randomize MGMT-unmethylated elderly patients to an arm without TMZ. Over 90% of respondents are willing to use short course RT as the standard RT for elderly patients, irrespective of MGMT methylation status. This study highlights that worldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely. Further randomized studies are warranted to elucidate the optimal treatment strategy.
CD38-Targeted Immunochemotherapy Of Multiple Myeloma: Preclinical Evidence For Its Combinatorial Use In Lenalidomide and Bortezomib Refractory/Intolerant MM Patients
Authors: Inger S. Nijhof, Willy A. Noort, Jeroen Lammerts van Bueren, Berris van Kessel, Joost M. Bakker, Paul W.H.I. Parren, Richard W.J. Groen, Niels W.C.J. van de Donk, Henk Lokhorst, Tuna Mutis, Anton Martens
Journal: Blood (2013)
Clinical Features of Acute Pulmonary Blastomycosis
Authors: George A. Sarosi, Kenneth J. Hammerman, Fred E. Tosh, Richard S. Kronenberg
Journal: New England Journal of Medicine (1974)

In a presumed common-source outbreak of blastomycosis 21 persons had extensive, repeated exposure. Eighteen of them gave evidence of infection by the fungus. Of the seven with symptoms three were severely ill, whereas the other four had clinically mild illness of short duration. An additional 11 asymptomatic persons were judged to have been infected on the basis of an abnormal chest roentgenogram or a positive blastomycin skin test or both. All patients recovered without specific antifungal therapy. Thus, it appears that the acute, epidemic form of blastomycosis can be a benign, self-limited illness. (N Engl J Med 290:540–543, 1974)
Production of Tetanus Antitoxin by Patients with Hepatic Cirrhosis
Authors: W. Paul Havens, Ralph M. Myerson, Jean Klatchko
Journal: New England Journal of Medicine (1957)

THE noteworthy effectiveness of active immunization against tetanus by means of tetanus toxoid has not obviated the use of equine antitoxin, since there is still a large segment of the population that has not been actively immunized. In addition, certain conditions in the presumably actively immunized person, such as uncertainty about immunization history, severe injuries about the head or neck, delay of twenty-four hours in treatment and the omission of a booster dose of toxoid for several years, are usually considered as indications for employing passive as well as active immunization when injury is sustained. Lastly, the rare occurrence of . . .
Case 21-2004
Authors: Donald S. Kaufman, W. Scott McDougal, Anthony L. Zietman, Mukesh G. Harisinghani, Robert H. Young
Journal: New England Journal of Medicine (2004)

This patient presented at the age of 55 years with prostate cancer, detected because of urinary symptoms and a rising prostate-specific antigen (PSA) level. He was well for seven years after local radiation therapy and androgen-deprivation treatment; then his PSA level began to rise, and metastatic lesions were detected. The care of this patient necessitated consideration of treatment options for patients with localized and advanced prostate cancer and hormone-refractory disease.
Inhibition of the JAK/STAT and Bcl-2 Pathways Enhances Anti-Tumor Effects in an in Vitro model of T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Authors: Tara Bree Gavcovich, Kirsti Lorraine Walker, Myriam N. Bouchlaka, Christian M Capitini
Journal: Blood (2015)
Sequential Intensified Conditioning Followed By Early Tapering Immunosuppressants and DLI In Allogeneic Hematopoietic Stem Cell Transplantation For Refractory/Recurrent T Lymphoblastic Lymphoma
Authors: Min Dai, Hongsheng Zhou, Fen Huang, Yu Zhang, Zhiping Fan, Xutao Guo, Na Xu, Jing Sun, Qifa Liu
Journal: Blood (2013)
Case 20-2010
Authors: Andrea L. Utz, Pamela W. Schaefer, Matija Snuderl
Journal: New England Journal of Medicine (2010)

A 32-year-old woman was evaluated because of oligomenorrhea and difficulty becoming pregnant. At 25 years of age, after 5 years of oral contraceptive use, irregular menstrual cycles developed, and she was unable to become pregnant. She reported acne and increased facial hair; results of laboratory tests were consistent with anovulation. She became pregnant after two cycles of clomiphene, gestational diabetes developed, she delivered a healthy infant, and she breast-fed normally. Glucose intolerance and amenorrhea persisted after delivery. A diagnostic test was performed.
ATPS-33EVIDENCE OF ABSENCE FOR CYTOMEGALOVIRUS IN PATIENTS WITH GLIOBLASTOMAS AND OTHER HIGH-GRADE GLIOMAS BY REAL-TIME PCR FOR DNA, IMMUNOHISTOCHEMISTRY FOR PROTEIN AND<i>IN-SITU</i>HYBRIDIZATION FOR mRNA
Authors: Matthias Holdhoff, Fausto Rodriguez, Jessica Hicks, Qizhi Zheng, Michael Forman, Xiaobu Ye, Stuart A. Grossman, Peter C. Burger, Charles Eberhart, Angelo M. De Marzo, Ravit Arav-Boger
Journal: Neuro-Oncology (2015)

BACKGROUND: Several groups have suggested a potential causative role of cytomegalovirus (CMV) in the development of high-grade gliomas (HGG), while others have not found any evidence of CMV in these cancers. We used 3 different molecular technologies to assay for the presence of CMV DNA, mRNA and protein in tumor tissue and blood samples of patients with HGG. METHODS: Part A: Fresh-frozen tissues from 27 glioblastomas (GBM) were analyzed for CMV by real-time PCR of US17. Part B: Prospective study of patients with newly-diagnosed HGG (grades III or IV) who underwent standard chemoradiation. Plasma and serum were collected at baseline, and plasma at follow-up visits. FFPE tumor tissue was analyzed for CMV proteins by genetically validated immunohistochemistry (IHC), in-situ hybridization assays targeting 1E1/2 and pp65, and by real-time PCR for US17 (tissue and plasma). RESULTS: Part A: CMV was detected in 0/27 fresh-frozen GBM tissue samples using real-time PCR. Part B: Eighteen patients with HGG (12 grade IV, 6 grade III) were enrolled. CMV tissue testing was negative in all samples by both probes for in-situ hybridization, both antibodies for IHC (n = 11 available samples), and CMV US17 real-time PCR (PCR successful in 8/14 samples). Serum CMV IgG avidity index was positive (0.55-0.82) in 8/15 cases, consistent with rates in the general population. CMV was detected in baseline plasma samples of 3/16 patients and in 1 single follow-up sample. All other plasma samples were negative for CMV (n = 34). CONCLUSION: CMV was not detected in any HGG tissue. Half of the patients with HGG did not have an exposure to CMV prior to their diagnosis, and viremia was rare at presentation and follow-up. An independent, unbiased investigation of CMV positivity rates using a central reference laboratory with standardized tissue samples and controls is warranted before further consideration of CMV-targeted therapy in HGG.
Retrospective evaluation of ADCC activity and cetuximab response in KRAS wild-type metastatic colorectal cancer patients (mCRC)
Authors: E. Miraglio, V. Ricci, D. Vivenza, M. Monteverde, G. Strola, C. Granetto, C. Lo Nigro, M.C. Merlano
Journal: Annals of Oncology (2015)
Follow-up after colorectal cancer surgery: Preliminary observational findings from the UK FACS trial.
Authors: J. N. Primrose, A. Fuller, P. Rose, R. Perera-Salazar, J. Mellor, A. Corkhill, S. George, D. Mant
Journal: Journal of Clinical Oncology (2011)

3521 Background: The optimal follow up after potentially curative resection of primary colorectal cancer is not known. Methods: In this National Institute of Health Research funded trial 1,211 patients with curatively treated primary colorectal cancer were randomised in a 2x2 trial design: Arm 1; Single CT chest/abdomen/pelvis (CT-CAP) at 12-18 months post treatment: Arm 2; Regular CEA measurement in family practice plus a single CT-CAP at 12-18 months: Arm 3; Intensive hospital based imaging (6 monthly CT-CAP for 2 years, annually for an additional 3 years, combined with colonoscopy at 2 years: Arm 4; Combination of Arms 2 and 3. All patients had full evaluation by CT-CAP after surgery or adjuvant chemotherapy if given and had a normal CEA prior to trial entry. All patients have a colonoscopy scheduled at 5 years. Recurrence is managed by a multi-discipline team which includes liver and lung surgeons. The primary end point is complete resection of recurrent disease with curative intent (89% power to detect a 6% difference between arms 1 and 4). Secondary end points are overall survival, recurrence free survival, quality of life and cost effectiveness of follow up. Results: This observational analysis includes all randomisation arms at a median follow up of 54 months. The mean age of the participants was 68.6 years, 61% were male and 97% ethnically white. 22% were in stage I, 48% in stage II and 30% in stage III. At follow up 85.6% of patients were alive without recurrence (stage I: 90.9%, stage II: 86.7%, stage III: 80.4%). Of the 174 recurrences 42 (24.1%) were liver only and 29 (16.1%) lung only. The remainder were loco-regional or at multiple sites. 72 (41.4%) of the 174 patients with recurrence had further surgery. In 38 (23%) this was potentially curative. Conclusions: If patients are fully staged by CT after treatment of the primary tumour and have a normal CEA the relapse rate is low. Only 38 (3.1%) of the 1,211 patients were suitable for potentially curative treatment and most patients with recurrence had incurable disease. These preliminary data militate against the cost effectiveness of very intensive follow up schedules. The final analysis is planned in 2013 to minimise the risk of lead-time bias.
Mutations in the EGFR gene demonstrating a close association with gefitinib-sensitivity specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking
Authors: K. Sugio, H. Uramoto, M. Morita, T. Oyama, T. Hanagiri, T. Yoshimatsu, M. Sugaya, K. Ono, K. Yasumoto
Journal: Journal of Clinical Oncology (2005)

9520 Background: Somatically acquired mutations in the epidermal growth factor receptor gene (EGFR) in lung cancer are associated with significant clinical responses to gefitinib (Iressa), a tyrosine kinase inhibitor (TKI) that targets EGFR. An in-flame deletion in exon 19 or a point mutation in codon 858 of exon 21 was found in about 90% of all cases with EGFR mutations. We therefore examined exons 19 and 21 of EGFR using a simple screening method. Methods: We screened the EGFR in 366 resected tumors of patients with lung cancer, which included 233 adenocarcinomas, 91 squamous cell carcinomas, 21 large cell carcinomas, 13 small cell carcinomas, and 8 other cell types. PCR with a specific condition was performed to identify any deletion in exon 19, while mutant-allele specific amplification (MASA) was performed to identify a mutation in codon 858 of exon 21. Results: EGFR mutations were found in 106 cases (45.5%) with adenocarcinoma, in one case with large cell carcinoma, and in one case with pleomorphic carcinoma. An in-flame deletion in exon 19 was found in 54 cases while an L858R mutation was found in 52 cases. In the 233 cases with adenocarcinoma, these mutations were more frequently found in women than in men (55.9% vs 37.4%, p<0.0001), in well differentiated tumors than in poorly differentiated tumors (58.8% vs 26.5%, p<0.0001), and in patients who were never/former smokers than in patients who were current smokers (56.1% vs 27.0%, p<0.0001). The mutation rate was more frequently observed in patients who smoked <30 pack-year, and in patients who quit at least 10 years before surgery. We found that 6 of the 6 gefitinib-sensitive tumors had these types of mutations, while only 3 of the 14 gefitinib-refractory tumors demonstrated such mutations. Conclusions: The mutations within the tyrosine kinase domain of EGFR which are associated with gefitinib sensitivity, were thus found to specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking. No significant financial relationships to disclose.
Effect Of Cumulative Adverse Clinical Risk Factors On Patients With Multiple Myeloma Undergoing First GCSF Apheresis
Authors: Ilicia L. Shugarman, Randy A Brown, Christopher R Cogle, John W Hiemenz, W. Stratford May, Maxim Norkin, Helen Leather, Xiaomin Lu, Michele W. Sugrue, John R. Wingard, Jan Moreb, Jack W Hsu
Journal: Blood (2013)
Omentin-1, Adiponectin, and the Risk of Developing Type 2 Diabetes
Authors: Clemens Wittenbecher, Juliane Menzel, Maren Carstensen-Kirberg, Ronald Biemann, Romina di Giuseppe, Andreas Fritsche, Berend Isermann, Christian Herder, Krasimira Aleksandrova, Heiner Boeing, Cornelia Weikert, Matthias B. Schulze
Journal: Diabetes Care (2016)

Omentin-1 is a novel adipokine (1), and its potential role in diabetes pathogenesis is still under debate (2). We aimed to evaluate the longitudinal association of omentin-1 concentrations with the risk of type 2 diabetes.

This observational study was based on 2,500 randomly selected participants of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort ( n = 27,548) (3,4). Exclusion criteria were prevalent diabetes at baseline ( n = 112), unclear diabetes status ( n = 19), and incomplete follow-up information ( n = 50). Missing biomarker information (HbA1c 14%, all others below 10%) was handled by multiple imputation. The final sample comprised 2,319 participants, including 123 incident type 2 diabetes cases. Omentin-1 plasma concentrations were quantified by a commercial sandwich ELISA (BioVendor, Brno, Czech Republic). We previously demonstrated excellent reliability of single omentin-1 measurements (5). Applied statistical methods were multivariable-adjusted linear regression (cross-sectional associations) and Cox proportional hazards regression (longitudinal association of baseline omentin-1 with …
Treatment of Subacute Thyroiditis with Cortisone
Authors: Robert C. Hunter, Daniel J. Sheehan
Journal: New England Journal of Medicine (1954)

ONE of the fields of usefulness for ACTH and cortisone is in the treatment of certain acute, self-limited inflammatory or allergic disorders, in which discomfort or even disability may be relieved by suppressive doses.1 There are indications that subacute thyroiditis may be one of these diseases. Data to prove this point are difficult to assemble since the disease is uncommon and its course variable. We have found reports of 15 cases of subacute thyroiditis,2 3 4 5 6 7 8 9 to which we have added 3 of our own, all with favorable response to ACTH and cortisone (Table 1). We did not find any reports of . . .