tbuckley/cabot-search huggingface dataset:
Dickkopf-3 (DKK-3) protein in cerebrospinal fluid (CSF): A biomarker for neoplastic meningitis?
Authors: M. Hutterer, M. Medinger, G. Untergasser, K. Steinlechner, I. Gstrein, F. Deisenhammer, G. Stockhammer, E. Gunsilius
Journal: Journal of Clinical Oncology (2010)

e12517 Background: New markers in CSF are needed to improve the diagnostic accuracy for neoplastic meningitis (NM). The DKK-3 glycoprotein has been proposed to function as a secreted tumor suppressor. Here, we determined the value of Dkk-3 in CSF and serum as a marker for NM. Methods: Dkk-3 concentrations were measured by ELISA in matched samples of CSF and serum from 156 patients (pts): solid tumors/meningeosis carcinomatosa (MC, n = 33), meningeosis leucaemica/lymphomatosa (ML, n = 13), pts with cancer with or without brain metastases but in the absence of concomitant NM (non-NM, n = 25), bacterial (BM, n = 25) and viral (VM, n = 20) meningitis, multiple sclerosis (MS, n = 10), and pts with with tension type headache (HA, n = 30). Results: There were significant differences of CSF Dkk-3 levels (mean ± SEM) between the following groups (p = 0.0001, Kruskal-Wallis): MC 883 ng/mL ± 406, ML 1,499 ng/mL ± 1,579, non-NM 650 ng/mL ± 278, BM 683 ng/mL ± 290, VM 901 ng/mL ± 370, MS 587 ng/mL ± 226 and HA 579 ng/mL ± 320. In all groups significantly higher amounts of Dkk-3 in CSF compared to serum were found (HA mean 40 ng/mL ± 22, 14.6 times higher). CSF Dkk-3 levels were higher in ML than in MC pts (p = 0.041, students-T). CSF DKK3 significantly distinguishes MC/ML from non-NM (p = 0.017/p = 0.012), BM (p = 0.041/p = 0.016), MS (p = 0.034/p = 0.036) and HA (p = 0.001/p = 0.003) pts. VM pts also showed high CSF Dkk-3 levels, not discriminative between NM or VM. Furthermore, in VM pts serum Dkk-3 levels were significantly higher compared to all other groups (VM mean 53 ng/mL ± 18 vs. HA mean 40 ng/mL ± 22, p = 0.001). During intrathecal treatment CSF Dkk-3 levels correlated to treatment response. Conclusions: In NM and VM pts significantly higher amounts of Dkk-3 are released into CSF. This study provides first evidence that CSF Dkk-3 may be a useful biologic marker for both the diagnosis and treatment response evaluation of NM. Its specificity, however, is limited by similarly high CSF Dkk-3 levels in pts with VM. No significant financial relationships to disclose.
Mechanism for Hyperoxaluria in Patients with Ileal Dysfunction
Authors: V. S. Chadwick, K. Modha, R. Hermon Dowling
Journal: New England Journal of Medicine (1973)

Hyperoxaluria was found in 66 per cent of 18 patients with disease or resection of the ileum. Previous theories to explain the mechanism for this secondary hyperoxaluria have implicated bacterial metabolism of bile-salt glycine in the colon or altered glyoxylate metabolism in the liver. The present studies show that, in this situation, bile-salt glycine is not a precursor of urinary oxalate and that glyoxylate metabolism is normal. However, patients with ileal resection and hyperoxaluria absorbed up to five times as much 14C oxalate as control subjects —mean ± S.E.M. of 31 ± 9.2 per cent, as compared with 6.6 ± 0.9 per cent — when the isotope was given with food, and treatment of these patients with low oxalate diets (<4 mg of oxalate per 24 hours) promptly abolished the hyperoxaluria. These results suggest that increased absorption of dietary oxalate is the cause of the hyperoxaluria seen in patients with ileal dysfunction. (N Engl J Med 289:172–176, 1973)
Changes in Cigarette Smoking
Authors: E. Cuyler Hammond, Sc.D., Lawrence Garfinkel, M.A.
Journal: JNCI Journal of the National Cancer Institute (1964)

Per capita sales of filter-tip cigarettes have increased rapidly since 1954 while sales of plain-tip brands have decreased. Annual consumption of nicotine from cigarettes per person showed a steady decline from 1952–59. An evaluation was made of the changes in cigarette smoking habits in a 2-year period (1959–60 to 1961–62) among 403,838 men and 527,287 women. There was a slight decrease in the number of persons reporting cigarette smoking in 1961–62 as compared with 1959–60, but more women reported heavy smoking in the later period. The tendency of ex-cigarette smokers to resume cigarette smoking was directly related to the former amount of smoking and inversely related to the length of time they had stopped smoking. Among persons who smoked less than 20 cigarettes a day in 1959–60, the proportion who increased their cigarette consumption in 1961–62 exceeded the proportion who stopped or decreased their consumption. Heavy smokers and persons over 70 tended to decrease their cigarette consumption during this period. The highest proportion of ex-cigarette smokers was found among men and women who were college graduates. Sixty-five percent of men who switched to low-nicotine and low-tar content cigarettes did not change the number smoked per day. Number of years of smoking, number of cigarettes smoked per day, and degree of inhalation of smoke are all related to the age at start of smoking.
Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study.
Authors: M J O'Connell, J P Colgan, M M Oken, R E Ritts, N E Kay, L M Itri
Journal: Journal of Clinical Oncology (1986)

Twenty patients with disseminated favorable histology non-Hodgkin's lymphomas (16 patients) or chronic lymphocytic leukemia (four patients) who had not received previous chemotherapy were treated with recombinant leukocyte A interferon (IFL-rA) (Hoffmann-La Roche, Nutley, NJ). Treatment was administered in a moderate dose (12 X 10(6) U/m2) by intramuscular (IM) injection three times weekly for 8 weeks, followed by weekly maintenance therapy for an additional 16 weeks in patients responding to therapy. Five patients with stable disease at 8 weeks received four additional weeks of three-times-weekly treatment at an escalated dose (25 X 10(6) U/m2). Interferon was tolerated without severe toxicity by most patients, although treatment was discontinued prematurely due to side effects in four patients. Objective tumor responses (one complete response [CR] and six partial responses [PRs]) were seen in seven of 16 patients with lymphoma (44%). One of four patients with chronic lymphocytic leukemia also experienced a PR. Median time-to-progression from initiation of therapy among responding patients was 26 + weeks (range, 7 + to 84 + weeks). This study has demonstrated single agent antitumor activity of IFL-rA given in a tolerable outpatient dosage regimen in patients with advanced favorable histology non-Hodgkin's lymphomas, and serves as a basis for further trials of IFL-rA combined with chemotherapy as initial therapy for such patients in the future.
EPID-14OUTCOMES IN ELDERLY PATIENTS WITH HIGH GRADE GLIOMAS
Authors: Lauren Gotterer, Nehaw Sarmey, Ming Chi, Zhijian Chen, Glen Stevens, David Peereboom, Paul Elson, Manmeet Ahluwalia
Journal: Neuro-Oncology (2015)

BACKGROUND: High Grade Gliomas (HGG, grade 3 or grade 4 gliomas) are common malignant primary brain tumors and a large number of cases occur in patients aged >65 years. However, there is limited data on specific prognostic factors and outcomes in this population. METHODS: After IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center's database was used to identify patients > 65 years of age with HGG diagnosed from 2007-2014 . Multivariate analysis was conducted using a Cox proportional hazards model and stepwise selection algorithm using p = .10 and p = .05 as criteria for entry and retention to identify independent predictors of survival from diagnosis. RESULTS: 193 patients were included in the analysis (61% male). Median age at diagnosis was 73 years (range 66-94). At presentation, 45% had Karnofsky performance status (KPS) > 80; 34% had KPS  75, p = .03), performance status (KPS >80 vs 70 vs 50-60 vs <50, p < .0001) and multifocal disease (no vs yes, p = .02) were independently associated with overall survival. CONCLUSIONS: Overall survival in elderly patients with HGG is dismal. Younger age, better performance status, and absence of multifocal disease were associated with improved survival.
Streptococcus pyogenes –induced cutaneous lymphocyte antigen–positive T cell–dependent epidermal cell activation triggers T H 17 responses in patients with guttate psoriasis
Authors: Ester Ruiz-Romeu, Marta Ferran, Marc Sagristà, Julià Gómez, Ana Giménez-Arnau, Krisztina Herszenyi, Péter Hóllo, Antonio Celada, Ramon Pujol, Luis F. Santamaria-Babí
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 3-2012
Authors: Elliot Melendez, Allan M. Goldstein, Pallavi Sagar, Kamran Badizadegan
Journal: New England Journal of Medicine (2012)

A 6-day-old boy was admitted to the hospital because of vomiting, diarrhea, and abdominal distention, which had begun earlier that day and worsened. On admission, he showed signs of sepsis. Imaging showed narrowing of the rectosigmoid colon.
Neoexpression of ABH and Lewis Blood Group Antigens in Human Hepatocellular Carcinomas2
Authors: Yoshio Okada, Terukatsu Arima, Kazumi Togawa, Hideo Nagashima, Kenji Jinno, Shousuke Moriwaki, Tadayoshi Kunitomo, Jan Thurin, Hilary Koprowski
Journal: JNCI Journal of the National Cancer Institute (1987)

Expression of blood group ABH, Lewis, and sialylated-Lea antigens in human hepatocellular carcinomas and the adjacent nontumorous liver tissues was investigated with the use of seven monoclonal antibodies against these carbohydrate determinants. Chromatogram antibody-binding assay and solid-phase enzyme immunoassay of the upper-phase neutral glycolipids revealed the tumor-associated expression of a) blood group A-active glycolipids incompatible with blood-type status of the patients, b) a blood group A-active glycolipid with mobility on thin-layer chromatography between the known 6- and 8-sugar blood group A-active glycolipids in human erythrocytes, c) blood group H-active glycolipids, and d) blocked synthesis of Lea-active glycolipids with or without concomitant accumulation of Leb-active glycolipids. Immunohistochemical analysis of the fixed tissues with the use of an avidin-biotin-peroxidase complex method revealed blood group antigens in biliary epithelial cells but not in parenchymal liver cells. However, hepatocellular carcinoma cells in some cases expressed H and Leb antigens. Although only type 1 chain H antigen was detected in biliary epithelial cells, both type 1 and type 2 chain H antigens were found in hepatocellular carcinoma cells.
The patterns of tumor locoregional recurrence in thoracic esophageal squamous cell carcinoma after curative surgery.
Authors: W. Mao, Y. Xu, Y. JI, X. Sun, H. Jiang, P. Zhao, J. Cheng, X. Du
Journal: Journal of Clinical Oncology (2010)

e14613 Background: Esophageal squamous cell carcinoma (SCC) is a most common type of thoracic esophageal cancer in China. The evaluation of its pattern of locoregional recurrence after curative resection would be of clinical value for surgical and radiation oncologists to treat this disease. Herein we investigated retrospectively the patterns of tumor locoregional recurrence in this patient group. Methods: Between January 2004 and December 2009, 102 patients with locoregional recurrence as the first site of failure after R0 resection for thoracic esophageal squamous cell carcinoma were analyzed. Results: Among these patients, male/female was 89/13. Upper esophagus/mid esophagus/lower esophagus was 9/62/31. There are 30 (29.4%) patients received adjuvant chemotherapy, and no patients received adjuvant radiotherapy. For the upper oesophageal SCC, the most common recurrence location was in the upper mediastinal (55.5%) lymph nodes and followed by the local recurrence (the site of anastomosis and the site of esophageal resection) (44.4%), similar rates (11.1%) in the mid-lower mediastinal and supraclavicular lymph nodes. For the middle oesophageal SCC, more recurrence occurred in the local recurrence (41.9%), followed by the supraclavicular (35.5%), the upper mediastinal (33.9%), the mid-lower mediastinal (17.7%), and the abdominal (6.4%) lymph nodes. For the lower oesophageal SCC, the highest incidence of recurrence was also in the local recurrence (51.6%), followed by the supraclavicular (35.5%), the upper mediastinal (29.0%), the mid-lower mediastinal (12.9%) lymph nodes, but the least in the abdominal (9.6%) lymph nodes. Conclusions: The local recurrence, metastasis to supraclavicular and upper mediastinal lymph nodes are more often than metastasis to mid-low mediastinal and abdominal lymph node. These fndings suggest that the target of postoperative radiotherapy of thoracic esophageal squamous cell carcinoma should include the anastomosis, supraclavicular and upper mediastinal lymph nodes. No significant financial relationships to disclose.
Case 4-1999
Authors: Michael J. Landzberg, Drucilla J. Roberts, Eugene J. Mark
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 38-year-old woman (gravida 3, para 2) was admitted to the hospital because of left-sided chest pain.The patient, who worked as a day-care provider, had been well until seven months earlier, when headaches and pain in the neck and shoulder began. One month later she was discovered to be pregnant. A test for antinuclear antibodies was positive, at a titer of 1:5120, with a nucleolar pattern of staining. Systemic lupus erythematosus was diagnosed, and prednisone was administered. Three months before admission, severe myalgias and progressive dysphagia developed, with a weight loss of about 7 kg.Four . . .
Pleural-Fluid Eosinophilia
Authors: F. G. MacMurray, Sol Katz, H. J. Zimmerman
Journal: New England Journal of Medicine (1950)

PLEURAL-fluid eosinophilia has occurred rarely enough to be an unfamiliar phenomenon but frequently enough to have been the subject of considerable speculation about its diagnostic and prognostic significance. Since eosinophils are uncommon in the usual cytology of pleural fluid, the presence of any might be considered as representing a significant eosinophilia. For the purposes of this discussion, however, pleural-fluid eosinophilia is considered to be present when over 5 per cent of the cells in an effusion are eosinophils. Ever since Widal and Ravaut1 first called attention in 1900 to the value of the cytologic study of thoracic fluid, pleural-fluid eosinophilia . . .
S38 Predictive accuracy and clinical impact of Xpert MTB/RIF for the diagnosis of sputum smear-negative pulmonary tuberculosis using bronchoalveolar lavage fluid
Authors: W Ho, DW Connell, A Singanayagam, A Singanayagam, H Donaldson, OM Kon
Journal: Thorax (2015)

<h3>Introduction</h3> Sputum smear-negative pulmonary tuberculosis (TB) is increasingly prevalent with bronchoalveolar lavage (BAL) frequently used for diagnostic sampling. Direct molecular testing has reported higher sensitivities compared to smear microscopy. This study aims to assess the predictive accuracy and clinical impact of Xpert MTB/RIF; a PCR-based cartridge assay used to identify M.tb in BAL fluid samples. <h3>Methods</h3> A retrospective evaluation of adult patients (n = 293) with suspected pulmonary TB who underwent BAL in a tertiary centre in London between January 2011 and December 2014 were collected. MTB/RIF, smear microscopy, and liquid culture were performed on all sets of BAL fluid. The impact of MTB/RIF on time to TB diagnosis and anti-TB treatment initiation were recorded as markers of clinical impact. <h3>Results</h3> 57/293 (19.5%) patients had BAL culture-positive TB for which a significantly higher proportion had positive MTB/RIF results compared to smear microscopy (77.2%, 95% CI 63.8%–86.8% vs. 38.6%, 95% CI 26.3%–52.4%; p &lt; 0.001). The specificity of MTB/RIF was 95.7% (92.1%–97.8%) with a negative predictive value (NPV) of 94.6% (90.7%–97.0%). 22/57 (38.6%) culture-positive patients had negative smear microscopy results but positive MTB/RIF results. 90/293 (30.7%) patients were clinically-diagnosed and treated for pulmonary TB. In this subgroup, MTB/RIF again outperformed smear microscopy in terms of sensitivity (54.2%; 95% CI 43.7%–64.3% vs. 27.1%, 95% CI 18.8%–37.3%; p &lt; 0.001). The specificity of MTB/RIF was 81.6% (80.0%–86.2%). The use of MTB/RIF provided a significant advantage in time to TB diagnosis in culture-positive patients as compared to smear microscopy (1 days; IQR 0–2 days versus 10 days; IQR 0–15 days; p &lt; 0.05). In a specific cohort of smear-negative culture-confirmed TB patients, MTB/RIF reduced the time to TB diagnosis from an average of 14 days (95% CI 12–16 days) to 1 day (95% CI 0–2 days; p &lt; 0.05). There was no statistical difference in time to anti-TB treatment initiation between those who were either smear microscopy positive and/or MTB/RIF positive in culture-positive patients (1 day; IQR 0–3 days versus 1 day; IQR 0–2 days; p = 0.164). <h3>Conclusion</h3> MTB/RIF used in BAL samples had a higher and more rapid diagnostic accuracy compared to smear microscopy and could replace routine smear microscopy in pulmonary TB diagnosis.
Autologous Bone Marrow Transplantation in Patients with Acute Nonlymphocytic Leukemia, Using ex Vivo Marrow Treatment with 4-Hydroperoxycyclophosphamide
Authors: Andrew M. Yeager, Herbert Kaizer, George W. Santos, Rein Saral, O. Michael Colvin, Robert K. Stuart, Hayden G. Braine, Philip J. Burke, Richard F. Ambinder, William H. Burns, Donald J. Fuller, Janice M. Davis, Judith E. Karp, W. Stratford May, Scott D. Rowley, Lyle L. Sensenbrenner, Georgia B. Vogelsang, John R. Wingard
Journal: New England Journal of Medicine (1986)

We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 x109 per liter and platelet counts over 50x109 per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, >230 to >1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients. (N Engl J Med 1986; 315:141–7.)
Variation in National Use of Long-Term ADT by Disease Aggressiveness Among Men With Unfavorable-Risk Prostate Cancer
Authors: Vinayak Muralidhar, Paul J. Catalano, Gally Reznor, Brandon A. Mahal, Toni K. Choueiri, Christopher J. Sweeney, Neil E. Martin, Clair J. Beard, Yu-Wei Chen, Michelle D. Nezolosky, Karen E. Hoffman, Felix Y. Feng, Quoc-Dien Trinh, Paul L. Nguyen
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: The current NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer recommend long-term androgen deprivation therapy (ADT) for all men with high-risk prostate cancer treated with external-beam radiation therapy (EBRT). We determined whether the use of long-term ADT varied by the recently defined subcategories of high-risk disease (favorable, other, and very high) versus unfavorable intermediate-risk disease. Methods: We identified 5,524 patients with unfavorable-risk prostate cancer diagnosed from 2004 to 2007 and managed with EBRT using the SEER-Medicare linked database. Patients were stratified by risk group: unfavorable intermediate-risk, favorable high-risk (previously defined and validated as clinical stage T1c, Gleason score of 4 + 4 = 8, and prostate-specific antigen [PSA] level <10 ng/mL, or clinical stage T1c, Gleason score of 6, and PSA level >20 ng/mL), very-high-risk (clinical stage T3b–T4 or primary Gleason pattern 5), or other high risk (ie, neither favorable nor very high). We used multivariable competing risks regression to estimate the rates of long-term (≥2 years) ADT by group. Results: Men with favorable high-risk prostate cancer were significantly less likely to receive long-term ADT than those with other high-risk disease (15.4% vs 24.6%, adjusted hazard ratio [AHR], 0.68; 95% CI, 0.60–0.76; P<.001), and similarly likely as those with unfavorable intermediate-risk disease (AHR, 1.10; 95% CI, 0.99–1.23; P=.087). Other high-risk disease was less likely to receive long-term ADT than very high-risk cancer (24.6% vs 30.8%; AHR, 0.83; 95% CI, 0.74–0.93; P=.002). Conclusions: Despite current guidelines, patients with EBRT-managed high-risk prostate cancer received significantly different rates of long-course ADT based on subclassification. Our results suggest that oncologists view these patients as a heterogeneous group with favorable high-risk cancer warranting less aggressive therapy than other high-risk or very high-risk disease.
Large open-label, non-comparative, clinical experience trial of the multi-targeted kinase inhibitor sorafenib in European patients with advanced RCC
Authors: J. Beck, G. Procopio, E. Verzoni, S. Négrier, U. Keilholz, C. Szczylik, S. Mersmann, K. Burock, C. Huber, B. J. Escudier
Journal: Journal of Clinical Oncology (2008)

16021 Background: A randomized, controlled phase III trial showed sorafenib 400 mg BID doubled PFS and produced a 39% improvement trend in OS vs PBO in previously treated pts with RCC. Objectives of this trial were to collect safety and efficacy data from a large and broad study population reflecting clinical practice Methods: This nonrandomized, open-label study included pts with ECOG PS 0–2 and life expectancy >2 mo. Pts had to be unsuitable for or have failed prior cytokine therapy. Controlled, asymptomatic brain metastases were allowed. Pts received sorafenib 400 mg BID until progression, intolerable toxicity, or withdrawal. Study assessments were conducted at baseline and q mo. Tumor assessment and radiologic evaluation were conducted ≤28d prior to start of sorafenib therapy, then per local standard of care, but at least q3 mo Results: 1,155 pts were recruited in 11 European countries. 75% of pts were male with median age 62 yrs. Baseline ECOG PS was 0/1/2 in 40/45/15% of pts. 73% of pts had lesions in the lungs, 41% in lymph nodes, 36% in bone, 28% in the liver and 23% in the kidneys. Primary tumors were not resected in 11% of pts. 28% of pts enrolled had no prior systemic therapy, as they were unsuitable for cytokine treatment. Most frequent Grade ≥3 drug-related AEs were hand-foot-skin reaction 12%, fatigue 8%, diarrhea 5%, rash/desquamation 5% and hypertension 4%. Rates of Grade ≥3 drug-related AEs were similar across evaluated subpopulations. Median PFS was 6.8 mo (95% CI, 6.2–7.5 mo), and the median duration of treatment 6.9 mo (95% CI, 6.2–7.5 mo). Presentation will include analyses of the complete population and long-term follow up Conclusions: EU-ARCCS confirmed safety findings of the TARGET study in a clinical practice setting and in clinically relevant pt subsets. The efficacy of sorafenib in this clinical study appears similar to that reported in randomized controlled clinical trials Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer