tbuckley/cabot-search huggingface dataset:
Influence of regular aspirin use on survival for patients with stage III colon cancer: Findings from Intergroup trial CALGB 89803
Authors: C. Fuchs, J. A. Meyerhardt, D. L. Heseltine, D. Niedzwiecki, D. Hollis, A. T. Chan, L. B. Saltz, R. L. Schilsky, R. J. Mayer
Journal: Journal of Clinical Oncology (2005)

3530 Background: Regular aspirin use reduces the risk of colorectal neoplasia. In animals, aspirin and COX-2 inhibitors appear to inhibit tumor growth. The effect of aspirin use on outcome in patients with established colon cancer is unknown. Methods: We prospectively studied aspirin use in 830 pts with stage III colon cancer enrolled in a randomized trial of post-operative adjuvant chemotherapy (5-fluorouracil/leucovorin +/− irinotecan). Patients completed a detailed survey of medication use and lifestyle midway through adjuvant therapy and then again 6 months after completion of therapy. We computed Cox proportional hazards for recurrence-free (RFS), disease-free (DFS) and overall survival (OS) according to aspirin use. Time intervals were measured from completion of the 2nd questionnaire to recurrence or death, excluding events within the 1st 60 days to avoid bias from analgesic use due to underlying disease. Median follow-up after the last questionnaire was 2.4 years. Results: Among 830 patients who completed both questionnaires, 72 (8.7%) pts reported aspirin use both midway and 6 months after adjuvant therapy (consistent users). Compared to those who did not report consistent use, consistent aspirin users experienced a hazard ratio (HR) for disease recurrence (RFS) of 0.45 (95% CI, 0.21–0.97), after adjustment for age, gender, baseline performance status, N stage, T stage, preoperative CEA, bowel obstruction, perforation, tumor differentiation, and treatment arm. After identical adjustment, consistent aspirin use was associated with a HR for disease recurrence and/or death (DFS) of 0.48 (95% CI, 0.24–0.99) and a HR for death (OS) of 0.52 (95% CI, 0.19–1.46). Regular users of either celecoxib or rofecoxib (n=35; 4.3%) experienced a HR for recurrence of 0.56 (95% CI, 0.21–1.54). To assess whether these associations reflected a non-specific analgesic effect, we assessed regular acetaminophen use and found no recurrence or survival benefit. Conclusions: Consistent aspirin use may be associated with improved outcome in patients with stage III colon cancer. Ongoing randomized trials are assessing the addition of COX-2 inhibitors to chemotherapy in patients with advanced disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Pfizer, Sanofi
Rapid cycling in unipolar and bipolar affective disorders
Authors: E A Wolpert, J F Goldberg, M Harrow
Journal: American Journal of Psychiatry (1990)

To characterize the nature of rapid cycling affective disorders, the authors analyzed mood fluctuation patterns in 570 patients with affective disorders hospitalized in 1960, 1975, or 1985. Patients' records were rated for the frequency, duration, and complexity of distinct affective states. Very rapid mood fluctuations were absent among bipolar patients in 1960 but were evident in 1975 and 1985. In each year, bipolar patients displayed more frequent, complex, and mixed episodes than did unipolar patients. The results suggest that more frequent episodes occur among bipolar than unipolar patients and that very rapid switch processes have become more widespread for some bipolar patients.
Among human macrophages polarised to different phenotypes, the M-CSF-oriented cells present the highest pro-inflammatory response to the rheumatoid arthritis-specific immune complexes containing ACPA
Authors: Cyril Clavel, Laurie Ceccato, Florence Anquetil, Guy Serre, Mireille Sebbag
Journal: Annals of the Rheumatic Diseases (2016)

In the inflamed synovium of patients with rheumatoid arthritis (RA), autoantibodies to citrullinated proteins (ACPA) probably form immune complexes (IC) on deposits of citrullinated fibrin. We showed that in vitro such ACPA-IC activate a pro-inflammatory cytokine response in M-CSF-differentiated macrophages. Our objective was to evaluate how macrophage polarisation influences this response.CD14-positive monocytes from healthy donors were cultured in the presence of M-CSF, IFN-γ, interleukin (IL)-4 or IL-10. Expression of markers specific for polarised macrophages was analysed by flow cytometry. Their cytokine secretion was prompted by in vitro generated autoantibodies to citrullinated proteins immune complexes (ACPA-IC) and assayed in the culture supernatants.IFN-γ-polarised cells exhibited high levels of CD64 and CD80. Low expression of CD14 and high expression of CD206 characterised the IL-4-polarised cells. Exposure to IL-10 or M-CSF raised the expression of CD14, CD32 and CD163. The two cell types lacked CD80 and exhibited similar expression of CD64, CD200R and CD206. In response to ACPA-IC, the secretion of IL-1β, IL-6 and IL-8 was similar among cells exposed to IFN-γ, IL-4 or IL-10. However, the later cells were associated with the highest IL-1Ra:IL-1β ratio and the lowest tumour necrosis factor (TNF)-α:IL-10 ratio. Conversely, M-CSF-exposed cells secreted the highest levels of pro-inflammatory cytokines, exhibited a high TNF-α:IL-10 ratio and the lowest IL-1Ra:IL-1β ratio.Despite their phenotypic similarity, IL-10-polarised and M-CSF-polarised macrophages clearly differ in their cytokine response to ACPA-IC. M-CSF-polarised cells exhibit the highest pro-inflammatory potential. Since M-CSF is abundant in the RA synovium, therein it probably drives macrophages towards a strong pro-inflammatory cytokine response to the locally formed ACPA-IC.
Polycomb-dependent epigenetic landscape in adult T-cell leukemia
Authors: Dai Fujikawa, Shota Nakagawa, Makoto Hori, Naoya Kurokawa, Ai Soejima, Kazumi Nakano, Tadanori Yamochi, Makoto Nakashima, Seiichiro Kobayashi, Yuetsu Tanaka, Masako Iwanaga, Atae Utsunomiya, Kaoru Uchimaru, Makoto Yamagishi, Toshiki Watanabe
Journal: Blood (2016)
Multiple giant bullae of the lung mimicking massive pneumothorax in a patient with osteogenesis imperfecta
Authors: Marco Chiappetta, Dania Nachira, Venanzio Porziella, Maria Letizia Vita, Stefano Margaritora
Journal: Thorax (2016)

A 60-year-old Caucasian man was admitted to our emergency department with progressive dyspnoea, chronic cough and general asthenia. Physical examination revealed lack of left chest wall motion and absent breath sounds over the left hemithorax.

Vital signs were stable with a heart rate of 90 bpm, blood pressure of 120/70 mm Hg, respiratory rate of 20 breaths per minute and oxygen saturation by pulse oximetry of 95% while breathing room air.

The patient reported being an active smoker with …
Large-Bowel Carcinogenesis: Fecal Constituents of Populations With Diverse Incidence Rates of Colon Cancer2
Authors: Bandaru S. Reddy, Ernest L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1973)

We studied the quantitative and qualitative aspects of fecal neutral sterols and bile acids and fecal β-glucuronidase activity from populations with various dietary patterns to elucidate the etiologic role of these compounds on colon cancer. The fecal microflora of Americans consuming a mixed Western diet were more able to hydrolyze glucuronide conjugates than were those of American vegetarians and Seventh-Day Adventists, and Japanese and Chinese. The daily fecal excretion of coprostanol, coprostanone, and total neutral sterols was higher in Americans than in other groups. Americans who ate a Westerntype diet excreted high levels of bile acids and more microbially degraded bile acids than did others. Our data showed a strong association between the incidence of colon cancer and the fecal bile acid and neutral sterol excretion.
Abstract 17091: Rotor Prevalence and Stability Predict Longer Duration of Self-terminating Ventricular Fibrillation Episodes
Authors: Justin Hayase, Yonatan Faiwiszewski, Stephen Vampola, Luis Kazmirczak, Tina Baykaner, Gordon Ho, Gautam Lalani, Amir Schricker, Sanjiv Narayan, David Krummen
Journal: Circulation (2014)

Introduction:  Ventricular fibrillation (VF) is an important mediator of sudden cardiac death, yet the perpetuating mechanisms for VF remain unclear.   Methods:  In 26 consecutive patients (age 64 ± 10 years) presenting for ventricular arrhythmia ablation, 64-electrode basket catheters were inserted into the left and right ventricles, and VF was induced according to an IRB-approved research study. Using proprietary software (RhythmView, Topera, Palo Alto, California), computational VF phase movies were made and analyzed. Each VF cycle in non-sustained episodes was characterized as either a rotor, focal, or disorganized activation pattern. The proportion of rotor activation was then correlated to the duration of the VF episode using linear regression analysis.   Results:  There were 35 total episodes of VF, with 20 episodes requiring defibrillation for termination and 15 episodes that were self-terminating. Mean duration of self-terminating VF episodes was 3.5 ± 1.3 seconds. There was a significant correlation between both rotor prevalence (R2 = 0.29, p = 0.039) (Figure 1A) and rotor stability (R = 0.50, p = 0.0031) (Figure 1B) with the duration of the self-terminating VF episode.   Conclusions:  These data show that rotor activity is increasingly prevalent in longer episodes of VF and suggest that rotors are mechanistically important in VF perpetuation. Future studies should investigate whether rotor modulation decreases VF susceptibility.
Adjuvant Therapy for Soft Tissue Sarcoma
Authors: Scott M. Schuetze, Michael E. Ray
Journal: Journal of the National Comprehensive Cancer Network (2005)

Wide surgical excision is the backbone of therapy for localized soft tissue sarcoma and often produces excellent results. Patients with a marginal resection of disease and high-grade or large tumors are at an increased risk of recurrence. Radiation therapy (external beam or brachytherapy) has been shown to reduce the risk of local recurrence of disease and should be offered to patients with large (&gt;5 cm) or high-grade sarcomas, especially if a wide resection cannot be performed. Use of preoperative versus postoperative radiation therapy should be planned, in consultation with a radiation oncologist and a surgical oncologist, before resection of the sarcoma if possible. Chemotherapy using an anthracycline- and ifosfamide-based regimen may improve disease-free and overall survival rates. Chemotherapy appears to be most beneficial for patients with very large (≥10 cm), high-grade sarcomas of the extremity who are at a high risk of experiencing distant recurrence of disease. The effect of adjuvant chemotherapy on overall survival remains controversial. Research is greatly needed to identify the patients who are most likely to benefit from conventional chemotherapy, improve the treatment of retroperitoneal sarcomas, and identify novel agents that may impact the natural history of high-risk soft tissue sarcoma.
OP11 Final results from telaprevir phase II studies in genotype 1 treatment-naive or experienced subjects with chronic hepatitis C
Authors: G F Foster, G Dusheiko, C Hezode, P Marcellin, J McHutchison, M Beumont, B Kauffman
Journal: Gut (2010)

Introduction  Current standard of care (SOC) for treatment of HCV Genotype 1 (G1) naive patients comprises of pegylated interferon (P) plus ribavirin (R) for 48 weeks resulting in a sustained viral response (SVR) of 42 to 46% in treated patients. Telaprevir (TVR) is a novel selective inhibitor of the HCV NS3-4A protease. We report here results from phase II program.  Method  PROVE 1 (n=263) and PROVE 2 (n=334) were randomised controlled phase IIb comparisons of 12 weeks TVR plus PR up to 48 weeks vs PR alone in G1 treatment-naive patients. In the same population, the C208 study (n=161) compared TVR dosed every 8 h or every 12 h in combination with P2a or P2b with a response guided therapy design. In treatment experienced patients, the PROVE 3 trial (n=453) compared different TVR-based regimens to PR.  Results  Higher SVRs compared to SOC in treatment-naive subjects were observed in the TVR groups (61–69%) in the PROVE 1 and 2 studies as well as the C208 study (81–85%). In PROVE 3, 51% (vs. 14% in control) of previous non-responders achieved SVR. The most common AEs through week 48 included; pruritus, rash, anemia, fatigue, weakness and headaches. Overall discontinuation of all drugs due to rash was observed in 4–7% of the subjects.  Conclusion  TVR-based triple therapy significantly improves SVR rates in comparison to SOC in G1 HCV infected patients. It offers the potential to reduce treatment duration by half in the majority of treatment-naive patients. Phase III studies of TVR-based regimen are currently underway.
Identification of Polynuclear Aromatic Hydrocarbons in Cigarette Smoke and Their Importance as Tumorigens 2
Authors: F. J. Akin, M. E. Snook, R. E. Severson, W. J. Chamberlain, D. B. Walters
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Identification of Polynuclear Aromatic Hydrocarbons in Cigarette Smoke and Their Importance as Tumorigens Get access F. J. Akin, F. J. Akin Search for other works by this author on: Oxford Academic PubMed Google Scholar M. E. Snook, M. E. Snook Search for other works by this author on: Oxford Academic PubMed Google Scholar R. E. Severson, R. E. Severson Search for other works by this author on: Oxford Academic PubMed Google Scholar W. J. Chamberlain, W. J. Chamberlain Search for other works by this author on: Oxford Academic PubMed Google Scholar D. B. Walters D. B. Walters Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 1, July 1976, Pages 191–195, https://doi.org/10.1093/jnci/57.1.191 Published: 01 July 1976 Article history Received: 15 November 1975 Accepted: 15 January 1976 Published: 01 July 1976
Increased Synthesis of Liver Erythropoietin with CKD
Authors: Sophie de Seigneux, Anne-Kristine Meinild Lundby, Lena Berchtold, Anders H. Berg, Patrick Saudan, Carsten Lundby
Journal: Journal of the American Society of Nephrology (2016)

Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0–20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6–9.0 IU/L; P &lt;0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P &lt;0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P &gt;0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.
P11.08 * CENTRAL NERVOUS SYSTEM LYMPHOMA IN A PATIENT WITH MYCOSIS FUNGOIDES
Authors: S. Koeppen, S. Goricke, N. Rompoti, M. Sakarou, K. Keyvani
Journal: Neuro-Oncology (2014)

Mycosis fungoides (MF), the most common malignant T-cell lymphoma of the skin with an annual incidence of 4.2 cases per million in the United States, usually evolves slowly over many years. Extracutaneous manifestations of MF are observed in 50-75% of cases, typically occurring in patients with advanced infiltration of other organs. The incidence of central nervous system (CNS) involvement in MF was reported to be 14% in autopsy series and less than 1.6% in clinical cohorts particularly in patients with large-cell transformation of MF. A 67-year-old woman was diagnosed with plaque stage MF in 1990 after having developed disseminated, well demarcated, erythematous macules and plaques on the trunk. The patient reported that psoriasiform skin lesions had been present over the past 35 years. Treatment consisted of topical corticosteroids, systemic psoralen plus ultraviolet A, acitretin and interferon, resulting in a complete remission since 2007, without further treatment. In April 2013, the patient presented with a 2-month history of cognitive deficits and bifrontal headache, followed by rapidly decreasing visual acuity with central and peripheral visual field defects. Magnetic resonance imaging (MRI) showed thickening of the optic chiasm and both optic nerves with homogeneous contrast medium enhancement and space-occupying effect on the hypothalamus. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis of 107 cells/µl, no lymphoma cells were detected, CSF protein was elevated (116 mg/dl), glucose and lactate were normal. A subsequent brain biopsy confirmed the diagnosis of a diffuse large-cell lymphoma of the B-cell type. Despite preoperatively started dexamethasone treatment the patient experienced severe visual loss. Following 4 cycles of chemotherapy containing high-dose methotrexate and cytarabine according to the IELSG protocol and 2 cycles of methotrexate monotherapy from May until October 2013, clinical examination showed marked visual improvement, consistent with almost complete resolution of the MRI abnormalities. Due to pituitary gland insufficiency the patient needs further hormone replacement therapy. This case illustrates the importance of considering CNS lymphoma in the context of MF, even after long-term remission of the disease limited to the skin. To the best of our knowledge, this is the first description of a primary CNS B-cell lymphoma secondary to MF.
Antibiotic Exposure During the First 6 Months of Life and Weight Gain During Childhood
Authors: Jeffrey S. Gerber, Matthew Bryan, Rachael K. Ross, Carrie Daymont, Elizabeth P. Parks, A. Russell Localio, Robert W. Grundmeier, Virginia A. Stallings, Theoklis E. Zaoutis
Journal: JAMA (2016)

<h3>Importance</h3> Early-life antibiotic exposure has been associated with increased adiposity in animal models, mediated through the gut microbiome. Infant antibiotic exposure is common and often inappropriate. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results. <h3>Objective</h3> To assess the association between early-life antibiotic exposure and childhood weight gain. <h3>Design and Setting</h3> Retrospective, longitudinal study of singleton births and matched longitudinal study of twin pairs conducted in a network of 30 pediatric primary care practices serving more than 200 000 children of diverse racial and socioeconomic backgrounds across Pennsylvania, New Jersey, and Delaware. <h3>Participants</h3> Children born between November 1, 2001, and December 31, 2011, at 35 weeks' gestational age or older, with birth weight of 2000 g or more and in the fifth percentile or higher for gestational age, and who had a preventive health visit within 14 days of life and at least 2 additional visits in the first year of life. Children with complex chronic conditions and those who received long-term antibiotics or multiple systemic corticosteroid prescriptions were excluded. We included 38 522 singleton children and 92 twins (46 matched pairs) discordant in antibiotic exposure. Final date of follow-up was December 31, 2012. <h3>Exposure</h3> Systemic antibiotic use in the first 6 months of life. <h3>Main Outcomes and Measures</h3> Weight, measured at preventive health visits from age 6 months through 7 years. <h3>Results</h3> Of 38 522 singleton children (50% female; mean birth weight, 3.4 kg), 5287 (14%) were exposed to antibiotics during the first 6 months of life (at a mean age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7%; 95% CI, −0.1% to 1.5%;<i>P</i> = .07, equivalent to approximately 0.05 kg; 95% CI, −0.004 to 0.11 kg of added weight gain between age 2 years and 5 years). Among 92 twins (38% female; mean birth weight, 2.8 kg), the 46 twins who were exposed to antibiotics during the first 6 months of life received them at a mean age of 4.5 months. Antibiotic exposure was not significantly associated with a weight difference (−0.09 kg; 95% CI, −0.26 to 0.08 kg;<i>P</i> = .30). <h3>Conclusions and Relevance</h3> Exposure to antibiotics within the first 6 months of life compared with no exposure was not associated with a statistically significant difference in weight gain through age 7 years. There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them.
Lorcaserin Use in the Management of Morbid Obesity in a Pre‐Liver Transplant Patient
Authors: Julio A. Gutierrez, Carmen Landaverde, Jennifer T. Wells, Fred Poordad
Journal: Hepatology (2016)

Management of obesity and decompensated cirrhosis in those requiring liver transplantation (LT) is a challenging dilemma. Because of concerns for perioperative complications, many centers avoid transplant in those with a body mass index (BMI) greater than 40 kg/m 2 . Bariatric surgery is associated with increased risk attributable to complications of portal hypertension, including variceal rupture. Therefore, weight loss and LT options are limited. Several new classes of weight loss drugs are commercially available, including the anoretic, lorcaserin. This case illustrates the successful use of lorcaserin in a morbidly obese individual with decompensated cirrhosis evaluated for LT listing. (H epatology 2016;64:301–302)
Abstract 15057: Omega-3-Acid Ethyl Esters to Treat Dyslipidemia in Patients with Hiv: A Multi-Center Randomized Placebo-Controlled Trial
Authors: Thomas Metkus, Joseph Timpone, David Leaf, Matthew Goetz, William Harris, Todd Brown
Journal: Circulation (2012)

Background The advent of antiretroviral therapy has resulted in increased life expectancy of patients with HIV, however cardiovascular disease is an increasing cause of death in these patients. Val...
<i>New England Journal of Medicine</i>essay on morcellation prompts a call for retraction
Authors: Michael McCarthy
Journal: BMJ (2016)

An essay by a New England Journal of Medicine correspondent that questioned the US Food and Drug Administration’s (FDA) ruling that power morcellation was contraindicated in most women for the removal of benign uterine fibroids has prompted a call for a retraction and an apology by two doctors leading the fight against the device’s use.

Power morcellators use rapidly spinning blades to cut uterine tissue into fragments that can be easily removed through a small incision, reducing complications and recovery time. However, if the fibroid tissue harbors undetected uterine sarcoma there is a risk that the morcellator’s spinning blades will seed the abdomen with tumour tissue, resulting in difficult to treat metastatic disease. Concerns about this complication prompted the FDA to issue its warning about the device in 2014. Opponents of the FDA’S decision have said that the complication is rare and the benefits of the procedure outweigh the risks.

In an essay published on 10 March, Lisa …