tbuckley/cabot-search huggingface dataset:
Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography Screening Participants
Authors: Ugo Pastorino, Roberto Boffi, Alfonso Marchianò, Stefano Sestini, Elena Munarini, Giuseppina Calareso, Mattia Boeri, Giuseppe Pelosi, Gabriella Sozzi, Mario Silva, Nicola Sverzellati, Carlotta Galeone, Carlo La Vecchia, Arianna Ghirardi, Giovanni Corrao
Journal: Journal of Thoracic Oncology (2016)

IntroductionThe National Lung Screening Trial has achieved a 7% reduction in total mortality with low-dose computed tomography (LDCT) screening as compared with in the chest radiography arm. Other randomized trials are under way, comparing LDCT screening with no intervention. None of these studies was designed to investigate the impact of smoking habits on screening outcome. In the present study, we tested the effect of stopping smoking on the overall mortality of participants undergoing repeated LDCT screening for many years.MethodsBetween 2000 and 2010, 3381 smokers aged 50 years or older were enrolled in two LDCT screening programs. On the basis of the last follow-up information, subjects were divided into two groups: current smokers throughout the screening period and former smokers.ResultsWith a median follow-up time of 9.7 years and a total of 32,857 person-years (PYs) of follow-up, a total of 151 deaths were observed in the group of 1797 current smokers (17,846 PYs) versus 109 among 1584 former smokers (15,011 PYs), corresponding to mortality rates of 8.46 and 7.26 for every 1000 PYs, respectively. Compared with current smokers, former smokers had an adjusted mortality hazard ratio of 0.61 (95% confidence interval: 0.44–0.83), with a 39% reduction in mortality. A similar reduction in mortality was observed in the subset of 712 late quitters, with a hazard ratio of 0.65 (95% confidence interval: 0.44–0.96).ConclusionsStopping smoking significantly reduces the overall mortality of smokers enrolled in LDCT screening programs. The beneficial effect of stopping smoking on total mortality appears to be threefold to fivefold greater than the one achieved by earlier detection in the National Lung Screening Trial.
Preliminary results of concurrent chemotherapy with intensity-modulated radiation therapy (IMRT) for advanced cancer of the larynx/hypopharynx
Authors: N. Lee, K. Chan, J. Zhung, S. Wolden, Y. B. Su, D. Kraus, B. Singh, A. Shaha, J. Shah, D. G. Pfister
Journal: Journal of Clinical Oncology (2006)

5544 Purpose: Retrospective review of an institution’s IMRT experience in treating advanced laryngeal/hypopharyngeal carcinoma with concurrent chemotherapy. Methods: Between 1/02–6/05, 31 patients with advanced laryngeal/hypopharyngeal carcinoma (74% T3/T4 disease;71% stage IV) underwent combined modality treatment. There were 20 laryngeal and 11 hypopharyngeal carcinomas. All patients received definitive IMRT with a median RT dose of 70 Gy. Concurrent chemotherapy was also given to all patients [cis-platinum (100mg/m 2 /cycle) or carboplatin/5-fluorouracil (J Clin Oncol 2004;22:69) every 3 weeks for 2–3 planned cycles; 3 patients received a weekly paclitaxel/carboplatin program]. Prophylactic feeding tubes (PEG) were placed in all patients. Acute toxicity and late xerostomia were scored using the RTOG radiation morbidity scale. The 2-year estimates for local progression-free rate (LPF), regional progression-free rate (RPF), distant metastases-free rate (DMF), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: With a median follow-up of 17 months (range: 7–48), 2-year estimates of LPF, RPF, DMF, and OS rates were 76%, 94%, 96%, 87%, respectively. All patients with local failure of laryngeal carcinoma had persistent disease at the end of treatment. Grade ≥2 mucositis was experienced by 68% of the patients during treatment. Xerostomia continued to decrease over time from the end of RT and only 4 still complained of Grade 2 xerostomia. A greater proportion of patients with hypopharynx than larynx cancer were still PEG-dependent (55% versus 25%) after combined modality treatment at the time of this analysis. One patient developed laryngeal necrosis. Conclusions: These preliminary results show that IMRT, in combination with chemotherapy, achieved encouraging local control rates in patients with advanced laryngeal/hypopharyngeal carcinoma. Xerostomia improved over time. Pharyngoesophageal stricture with PEG dependency remains a problem especially in patients with hypopharyngeal carcinoma. Strategies using the ability of IMRT to limit the dose delivered to the esophagus and inferior constrictor musculature may be useful to further minimize this late complication. No significant financial relationships to disclose.
Survey of the prevalence and severity of sexual dysfunction in breast cancer patients
Authors: J. L. Capodice, K. D. Crew, Y. Ortiz-Pride, J. Specht, L. Braffman, D. Fuentes, D. L. Hershman
Journal: Journal of Clinical Oncology (2008)

9557 Background: Advances in early detection and treatment have improved life expectancy in women with breast cancer (CaBr). However, long-term side effects from primary and adjuvant treatments impact quality of life including sexual function in women with breast cancer. Methods: We conducted a cross-sectional study of women with early stage CaBr. Of 206 consecutive women screened, all were asked to complete the Female Sexual Function Index (FSFI), a 19-item validated questionnaire that asks about 6 domains: arousal, lubrication, desire, pain, orgasm, and satisfaction. Women were also asked if they were using any medications and/or non-pharmacologic interventions for symptoms. Scores were compared to published normal female controls. Abnormal was defined as >2 standard deviations below the mean of female controls. Baseline demographic and clinical characteristics were also obtained. Results: Of the 206 women approached, 167 (81%) responded. 29 were excluded who did not have stage I-III CaBr and analysis consisted of 117 patients. Main reasons for participant refusal were personal nature of the questions, no partner or not sexually active. Median age was 52 (range 29–82); White/Black/Hispanic/Other (%): 38/13/44/6; pre-/postmenopausal (%): 18/82; median BMI (kg/m2): 27 (17–61). Percentage of CaBr patients with abnormal FSFI scores were: Desire (43%), Arousal (54%), Lubrication (62%), Orgasm (46%), Satisfaction (50%), Pain (63%) and Total (57%). No significant differences found by race or ethnicity. Of 117 responders, only 6 (4.4%) reported use of lubricants as a non-pharmacologic intervention and 1 (0.74%) reported use of a synthetic estrogen gel. In a multivariate linear regression model, sexual dysfunction based on low total FSFI scores was significantly associated with being unmarried (p=0.02), postmenopausal status (p=0.05, regardless of early or late onset), and receipt of adriamycin-based chemotherapy (p=0.03). No association was seen with age, BMI or type of hormonal therapy. Conclusions: Our study suggests that sexual function in breast cancer patients is more prevalent and severe than what has been previously reported. More research is necessary to evaluate therapeutic interventions for sexual dysfunction in breast cancer patients. No significant financial relationships to disclose.
Abstract 13310: Selective Inhibition of the Late Sodium Current to Prevent Ventricular Fibrillation
Authors: Arash Pezhouman, Sepideh Madahian, Hayk Stepanyan, Luiz Belardinelli, Zhilin Qu, James N Weiss, Hrayr S Karagueuzian
Journal: Circulation (2013)

Background: An emerging new strategy to suppress early afterdepolarization (EAD)- and delayed afterdepolarizations (DADs)-mediated triggered activity and VT/VF is to eliminate the increased late inward Na current (INa-L). The new triazolopyridine derivative, GS-967 (Gilead Science Inc.) is shown to selectively and potently (IC50=0.45 μM) inhibit INa-L. Hypothesis: GS-967 suppresses and prevents VT/VF in fibrotic aged hearts exposed to hydrogen peroxide (H2O2) and local LV injection of aconitine by inhibiting EADs and DADs that trigger the VT/VF. Methods: VT/VF were induced by arterial perfusion of 0.1 mM H2O2 in aged rats (24-26 months, N=18), or local aconitine injection (50 μg) in the LV muscle of adult (3-4 months) rats (N=14). All isolated hearts were perfused in Langendorff setting; the activation of the LV epicardium was optically mapped along with simultaneous ECG and single cell action potential (AP) recordings with microelectrode near the aconitine site. Results: Optical mapping showed the sudden...
Sentinel lymph node identification using near-infrared fluorescence imaging and ultrasound in patients with breast cancer
Authors: N. Tagaya, A. Nakagawa, T. Kosuge, K. Hamada, K. Kubota, Y. Ishikawa, T. Oyama
Journal: Journal of Clinical Oncology (2008)

605 Background: Recently, we reported a novel technique of sentinel lymph node (SLN) identification using near-infrared fluorescence imaging that provides high detection and low false-negative rates. Furthermore, we present the combination of near-infrared fluorescence imaging and ultrasound to obtain better outcomes. Methods: This study enrolled 91 patients with a breast tumor less than 3 cm in diameter. Their mean age was 52 years. Preoperative TNM stage was I in 61 cases, IIa in 21, and IIb in 9, respectively. Initially axillary lymph nodes were identified by ultrasound and their locations were marked on the axillary skin. And then the dye of indocyanine green was injected subdermally in the areola. Subcutaneous lymphatic channels draining from the areola to the axilla became visible by fluorescence imagings (Photodynamic eye: PDE, Hamamatsu Photonics Co.) immediately. After incising the axillary skin 1 cm cranial side from the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence with adequate adjustment of sensitivity. Results: Lymphatic channels and SLN were successfully identified by PDE in 89 patients (identification rate: 97.8%). The SLN of remaining two patients were compensated by ultrasound. The number of fluorescence SLN ranged from 0 to 11 (mean: 3.9). An adequate adjustment of sensitivity of PDE provided with less time-consuming to identify SLN. The identification rate of near-infrared fluorescence imaging and ultrasound was 93.4% (85/91). Twenty-two patients (24.2%) had lymph node metastases pathologically. One of them was not recognized by fluorescence imaging due to the whole massive metastasis of LN. There were no intra- or postoperative complications associated with SLN identification. Conclusions: This combination method was considered more effective to detect SLN intraoperatively than near-infrared fluorescence imaging alone. An adequate adjustment of sensitivity of PDE enabled a pin-point identification of SLN. No significant financial relationships to disclose.
Recurrent epithelial ovarian cancer (EOC): What determines the outcome?
Authors: P. Kumanthem, L. Kumar, D. Janga, R. Hariprasad, R. Patnaik, A. Gupta, S. Kumar, R. Singh
Journal: Journal of Clinical Oncology (2006)

15003 Background: Recurrent EOC is a common clinical problem and treatment is not curative. We retrospectively analyzed the data on 354 patients with recurrent EOC to determine the impact of various prognostic factors on outcome. Methods: Between August, 1989 and June, 2005, 354 patients (median age 49 years, range, 28 to 80 years) were diagnosed as recurrent EOC. 259 patients received chemotherapy alone, 44 were treated with combination of secondary debulking surgery and chemotherapy or radiotherapy. Remaining 51 (14.4%) patients had no treatment. Main types of salvage chemotherapy included- cisplatin + cyclophosphamide (CP, n = 53), CP + adriamycin (CAP, n = 68), paclitaxel + carboplatin/cisplatin (TP, n = 78). 10 factors were analyzed for survival. Results: 56.5% of patients responded to chemotherapy; complete (CR)-34.2% and partial response (PR) in 22.3% of patients. 124 (35%) patients had no response or progressive disease. 10 (2.8%) died of chemo-toxicity and in remaining 20 status was not known. Median overall survival for patients who received treatment is 19 months vs 3 months for 51 patients who did not receive treatment, p &lt; .001. Predictors of survival were - response to salvage chemotherapy (20 vs 8 months, p &lt; .001), treatment-free interval (&gt;6 months vs ≤ 6 months, 23 vs 9 months p &lt; .001), site of relapse (single vs multiple, 22 vs 16 months, p &lt; .001), Chemotherapy regimen (CP vs CAP vs Paclitaxel + carboplatin) p &lt; .003 on univariate analysis. Age (≤50 years vs &gt;50 years, p = 0.02), initial stage (I vs II vs III vs IV, p = 0.079), histology (serous vs others, p = 0.849), site of relapse (vault vs others, p = 0.156) were not significant predictors. On multivariate logistic regression analysis- response to salvage chemotherapy (HR 0.21, 95% CI 0.15–0.30), treatment-free interval (HR 0.36, 95% CI, 0.20–0.64), and site of relapse (vault vs others, HR 1.22, 95% CI 0.78–1.94) attained significance among 10 factors analyzed. Conclusions: Present study confirms that all patients with recurrent EOC should receive treatment. Response to salvage chemotherapy, a longer treatment-free interval (&gt;6 months) and single site of metastasis are predictors of significantly superior outcome. No significant financial relationships to disclose.
Phase I clinical trial of quarfloxin administered weekly×3 of a four week cycle
Authors: T. R. Fitch, D. W. Northfelt, P. P. Griffin, M. Goldston, J. K. Lim, C. S. Padgett, D. D. Von Hoff, K. P. Papadopoulos
Journal: Journal of Clinical Oncology (2008)

14667 Background: Quarfloxin (Q) is a novel small molecule specifically designed to induce apoptosis in cancer cells by disrupting an essential protein:rDNA quadruplex complex. Pharmacokinetic parameters derived from a phase I study of Q (administered intravenously (IV) daily x5 every three weeks) suggested that blood levels could be sustained with less frequent dosing. Therefore, a phase I trial of Q administered IV weekly for three weeks of a four week cycle was initiated. The objectives of this phase I study are: to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs), to establish the pharmacokinetics (PKs), to determine the recommended dose for further clinical development of Q with this weekly dosing schedule, and to document evidence of antitumor activity. Methods: Eligible patients with advanced solid tumors or lymphomas whose tumors had progressed on, or for whom there are no standard therapies receive Q in successive dose cohorts at: 360, 540, 810, 1053 and 1370 mg/m2 in an accelerated cohort design. Dosing is by 24 hour infusion once weekly for the first three consecutive weeks of a four week cycle. Therapy is continued until the patient shows signs of intolerance to Q, or evidence of disease progression. Response by RECIST is determined after every 2 cycles. Results: Eight patients (Male/Female: 4/4; median age 57 (range 47–78)) have received Q on this schedule (2–3 per cohort). Doses up to 810 mg/m2 have been well tolerated, with only one reported grade 3 fatigue deemed possibly drug related. Q PK parameters have generally been in proportion to dose, and blood level data confirm that weekly infusions resulted in an extended Q half life, thus supporting the basis for less frequent doses. No objective responses have yet been observed. Conclusions: Q administered weekly has no significant drug related toxicity. No DLTs have yet been observed. PK results show sustained blood levels, supporting less frequent dosing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cylene Pharmaceuticals, Inc. Cylene Pharmaceuticals, Inc. Cylene Pharmaceuticals, Inc. Cylene Pharmaceuticals, Inc.
Pregnancy in the Time of Zika
Authors: Saad B. Omer, Richard H. Beigi
Journal: JAMA (2016)

Three recent infectious disease outbreaks of global importance—H1N1 influenza, Ebola, and now Zika—have had specific implications for pregnant women. For the H1N1 pandemic, pregnant women and their infants were high-risk groups for severe complications and death. During the Ebola outbreak, there were concerns about worse outcomes among pregnant women and specific concerns regarding vertical transmission of infection to newborns. The current Zika outbreak, with its ostensible association with microcephaly, has direct and highly concerning implications for pregnant women and women of reproductive age.
Enhanced Transformation of Human Immunocompetent Cells by Dibutyryl Adenosine Cyclic 3′,5′-Monophosphate
Authors: Robert C. Gallo, Jacqueline Whang-Peng
Journal: JNCI Journal of the National Cancer Institute (1971)

Dibutyryl adenosine cyclic 3′,5′-monophosphate(10−7−10−6 M) augmented the response (transformation, DNA synthesis, and mitosis) of normal human lymphocytes to antigenic or mitogenic stimulation. In contrast, the response of lymphocytes from patients with lymphocytic leukemia was not enhanced. Higher concentrations (10−6−10−5 M) were inhibitory with both normal and leukemic lymphocytes.
Neonatal and adult ICU ventilators to provide ventilation in neonates, infants, and children: a bench model study
Authors: Laurence Vignaux, Lise Piquilloud, Pierre Tourneux, Philippe Jolliet, Peter Rimensberger
Journal: JAMA Pediatrics (2014)

Using a bench test model, we investigated the hypothesis that neonatal and/or adult ventilators equipped with neonatal/pediatric modes currently do not reliably administer pressure support (PS) in neonatal or pediatric patient groups in either the absence or presence of air leaks.
The History of Psychiatry from the Patient's Viewpoint
Authors: PETER BUCKLEY, FRED SANDER
Journal: American Journal of Psychiatry (1974)

The authors describe a course in the history of psychiatry in which patients' autobiographies are used to illustrate different eras and approaches to the treatment of the mentaly ill. They feel that this approach highlights recurrent historical themes and provides a perspective on the present transitional state of psychiatry.
Horizontal transfer of hobo transposable elements within the Drosophila melanogaster species complex: evidence from DNA sequencing.
Authors: G M Simmons
Journal: Molecular Biology and Evolution (1992)

The hobo family of transposable elements, one of three transposable-element families that cause hybrid dysgenesis in Drosophila melanogaster, appears to be present in all members of the D. melanogaster species complex: D. melanogaster, D. simulans, D. mauritiana, and D. sechellia. Some hobo-hybridizing sequences are also found in the other members of the melanogaster subgroup and in many members of the related montium subgroup. Surveys of older isofemale lines of D. melanogaster suggest that complete hobo elements were absent prior to 50 years ago and that hobo has recently been introduced into the species by horizontal transfer. To test the horizontal transfer hypothesis, the 2.6-kb XhoI fragments of hobo elements from D. melanogaster, D. simulans, and D. mauritiana were cloned and sequenced. The DNA sequences reveal an extremely low level of divergence and support the conclusion that the active hobo element has been horizontally transferred into or among these species in the recent past.
Changes in RBC supportive medications and transfusions in cancer patients undergoing chemotherapy before and after FDA and Medicare actions in 2007
Authors: A. Naeim, J. Glaspy
Journal: Journal of Clinical Oncology (2008)

20595 Background: In 2007, changes occurred to restrict the use and reimbursement of RBC supportive medications in cancer patients through the FDA and Medicare National Coverage (NCD) Decision. This study was designed to evaluate the use of RBC supportive medications and transfusions over a 12 month period when these changes were occurring and to compare Medicare-insured patients against non-Medicare patients undergoing chemotherapy. Methods: Demographics, outpatient nursing chemotherapy and support administration records, and labs were abstracted from the UCLA oncology electronic medical record system from November 1, 2006 to October 31, 2007. For at-risk patients (undergoing chemotherapy with a hemoglobin <12 g/dL), monthly total use of RBC transfusions and the administration of either darbepoetin or epoetin alpha was tabulated. Utilization was standardized over the monthly number of patients at risk and compared month by month. In addition, utilization was aggregated into 3 time periods (P1–3): Nov06 to Feb07 (P1, Baseline), Mar07 to July07 (P2, Post FDA label changes), and Aug07-Oct07 (P3, Post NCD decision). Subgroup analysis was performed based on insurance type. Results: A total of 56,651 patient-visits were evaluated across the university oncology clinic and 3 academically affiliated community clinics. The data represented 10,167 total patients, of which 1,444 were on active chemotherapy. Utilization of RBC transfusions per at risk patient was 0.244 in P1, 0.237 in P2, and 0.277 in P3. Utilization of RBC support medication per patient at risk was 0.418 in P1, 0.203 in P2 (P<0.01), 0.155 in P3 (P<0.05). In Medicare patients, there was an increase in the utilization of transfusions per at risk patient in P2, 0.311, as compared to P3, 0.392 (P=0.05). Utilization of both RBC transfusions and medications was significantly greater in Medicare patients compared to non-Medicare patients across all periods (p=0.02). Conclusions: There has been a overall decrease in the use of RBC support medication in cancer patients undergoing chemotherapy since the FDA label change. In Medicare patients, the use of transfusions increased during the period following the NCD decision. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen
A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program
Authors: Vijayendran Chandran, Giovanni Coppola, Homaira Nawabi, Takao Omura, Revital Versano, Eric A. Huebner, Alice Zhang, Michael Costigan, Ajay Yekkirala, Lee Barrett, Armin Blesch, Izhak Michaelevski, Jeremy Davis-Turak, Fuying Gao, Peter Langfelder, Steve Horvath, Zhigang He, Larry Benowitz, Mike Fainzilber, Mark Tuszynski, Clifford J. Woolf, Daniel H. Geschwind
Journal: Neuron (2016)
Urographic Appearances in Renal Failure Due to Intraluminal Ureteric Obstruction
Authors: Peter Davies
Journal: Journal of the Royal Society of Medicine (1982)

With reference to a series of 13 patients, the urographic signs seen in the conditions of acute, post-acute, chronic and acute-on-chronic obstruction are described. These are seen in a relatively pure form in patients with renal failure due to ureteric calculi. Patients in renal failure with acute, post-acute or acute-on-chronic obstruction are anuric or oliguric; patients with chronic obstruction due to bilateral ureteric stones are polyuric. After removal of the stones the urine output returns to normal in cases of acute obstruction, is reduced in chronic obstruction but is increased in post-acute obstruction. A further case is described which illustrates the importance of recognizing post-acute obstruction unaccompanied by pain: the kidney may be completely obstructed and so be destroyed. The different types of obstruction are recognized by considering the nephrographic and pyelographic signs together with the presence of pain.