tbuckley/cabot-search huggingface dataset:
Associated Factors and Prognostic Implications of Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges
Authors: Sherri A. Braksick, David B. Burkholder, Spyridoula Tsetsou, Laurence Martineau, Jay Mandrekar, Andrea O. Rossetti, Martin Savard, Jeffrey W. Britton, Alejandro A. Rabinstein
Journal: JAMA Neurology (2016)

<h3>Importance</h3> The implications of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) sometimes found on prolonged electroencephalographic (EEG) recordings are uncertain. <h3>Objective</h3> To evaluate the incidence of SIRPIDs and their clinical implications in critically ill patients. <h3>Design, Setting, and Participants</h3> A multicenter, international retrospective study was performed from October 1, 2012, through September 30, 2014, of consecutive adult patients hospitalized in intensive care units with alteration of consciousness who underwent EEG recordings at 3 separate centers. Demographic data, including admission diagnosis, age, sex, history of epilepsy, and EEG findings, were noted. Characteristics of SIRPIDs were documented. Data were evaluated for predictors of SIRPIDs and in-hospital mortality. Data analysis was performed from January 16, 2015, to June 15, 2015. <h3>Main Outcomes and Measures</h3> Incidence of SIRPIDs, association of SIRPIDs with mortality and other EEG characteristics, and EEG and clinical predictors of mortality. <h3>Results</h3> A total of 416 patients were studied. The median age of patients was 60 years (interquartile range, 46-71 years), and 252 (60.6%) were male. A total of 104 patients (25.0%) did not survive to hospital discharge. SIRPIDs were identified in 43 patients (10.3%). The proportion of patients with SIRPIDs was not significantly different across the 3 sites (<i>P</i> = .34). Anoxic brain injury (odds ratio [OR], 3.80; 95% CI, 1.73-8.33;<i>P</i> &lt; .001), the use of antiepileptic medications (OR, 3.24; 95% CI, 1.31-8.00;<i>P</i> = .01), electrographic seizures (OR, 2.85; 95% CI, 1.13-7.19;<i>P</i> = .03), generalized periodic discharges with triphasic morphologic features (OR, 3.66; 95% CI, 1.67-8.02;<i>P</i> = .001), and sporadic sharp waves and periodic discharges (OR, 2.59; 95% CI, 1.13-5.92;<i>P</i> = .02) were independently associated with the presence of SIRPIDs. Older age (OR, 1.02; 95% CI, 1.01-1.04;<i>P</i> = .005), anoxic brain injury (OR, 3.49; 95% CI, 1.96-6.21;<i>P</i> ≤ .001), and absence of EEG reactivity (OR, 8.14; 95% CI, 4.20-15.79;<i>P</i> &lt; .001) but not SIRPIDs (OR, 1.73; 95% CI, 0.79-3.78;<i>P</i> = .17) were independently associated with in-hospital mortality. <h3>Conclusions and Relevance</h3> In critically ill patients undergoing EEG recordings, SIRPIDs occurred in 43 (10.3%) and were associated with other electrographic abnormalities previously reported to indicate poor prognosis. However, SIRPIDs were not independently associated with in-hospital mortality.
Pretreatment Plasma Cell Proteasome Levels Predict Responses To Treatment With Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Followed By Lenalidomide Extended Dosing (CRd-R) In Newly Diagnosed Multiple Myeloma Patients
Authors: Irina Maric, Olga Simakova, Neha Korde, Adriana Zingone, Rene Costello, Elisabet E. Manasanch, Manisha Bhutani, Nishant Tageja, George Carter, Marcia Mulquin, Diamond Zuchlinski, Mark Roschewski, Ola Landgren
Journal: Blood (2013)
The condom. (Letter to the editor)
Authors: Periman P, Greene M
Journal: New England Journal of Medicine (1972)

This letter was written in response to recent letters (New England J ournal of Medicine 285: 972 1971 and 286: 218 1972) maligning the condom and prompted an inquiry as to whether or not the condom is used by patients receiving treatment  for gonorrhea.  Only 3 out of 102 patients used condoms during the sexual exposure believed to be the source of infection.  5 frequently used the condom 44 occasionally used the condom and 51 never used the condom.  74 of the patients had a history of previous gonorrhea infection.  It is suggested that more vigorous preventive medicine be practiced at the time of treatment.
Trial of perioperative endocrine therapy: Individualizing care (POETIC).
Authors: I. E. Smith, L. Johnson, M. Dowsett, J. F. R. Robertson, L. E. Robison, J. S. Kokan, A. A. Evans, C. Holcombe, K. Horgan, A. Skene, R. Prasad, M. S. Absar, R. Vidya, N. J. Bundred, C. Harding-Mackean, D. A. Wheatley, M. W. Kissin, I. F. Pinhel, L. S. Kilburn, J. M. Bliss
Journal: Journal of Clinical Oncology (2011)

TPS117 Background: The neoadjuvant IMPACT trial suggested Ki67 levels after 2 weeks endocrine therapy predicts long-term outcome. Major changes in gene expression have also been seen in ER+ breast cancer after aromatase inhibitor (AI) treatment. POETIC evaluates whether changes in Ki67 level after 2 weeks treatment predicts for relapse-free survival (RFS) more effectively than the baseline value. It also tests whether gene expression profile at this timepoint provides more accurate prognostic and predictive information than the pre-treatment profile. Experimental evidence suggests peri-operative endocrine therapy may improve disease outcome. This hypothesis is also addressed in POETIC. (ISRCTN63882543) With a sample size of 4000, an improvement in 5 year relapse from 10% to 7% could be detected with 91% power (two sided alpha of 5%), as would a 1.3 fold difference in the ability of Ki67 to predict RFS (90% power, two sided 5% significance level). Target recruitment is 4000 patients from 100 UK hospitals over 3-4 years. Methods: Patients are randomised in the ratio of 2:1 to perioperative AI (letrozole 2.5mg or anastrozole 1mg daily) starting 2 weeks before planned surgery until 2 weeks after surgery. FFPE and RNA-later samples are taken prior to trial entry (baseline) and at surgery. Eligible patients are postmenopausal with ER+ invasive breast cancer. Consent to take additional research tissue is sought from patients undergoing diagnostic biopsy. Consenting patients donate tumour tissue in RNA-later and/or a FFPE research sample and enter POETIC following diagnosis of ER+ breast cancer. Matching tumour tissue is taken at surgery. Where an RNA-later sample at baseline is unavailable, consenting patients may undergo a further biopsy for research tissue immediately before study entry. Where consent procedures at diagnosis present logistical challenges, sites may provide FFPE tissue left over from diagnosis only. The 1st patient was entered in September 2008, and by January 2011 102 UK hospitals open and 1200 patients were entered. 182 optional RNA-later samples at both timepoints are available. Current success is due to a flexible approach to tissue sample collection and overcoming local and national logistical challenges.
Abstract 16161: GSK-3β Activates Autophagy and Protects Against Cardiac Aging Through Ulk1
Authors: Peiyong Zhai, Akihiro Shirakabe, Takanobu Yamamoto, Yoshiyuki Ikeda, Bonaventure Magrys, Yasuhiro Maejima, Junichi Sadoshima
Journal: Circulation (2015)

Accumulating lines of evidence suggest that glycogen synthase kinase-3β (GSK-3β) is involved in aging. However, the effects of GSK-3β on cardiac aging and the underlying mechanisms remain to be elucidated. Autophagy, a protective mechanism in aging, decreases with age. We hypothesized that GSK-3β attenuates cardiac aging via Ulk1, a regulator of autophagy, and studied constitutively active GSK-3βS9A knock-in mice (βKI), GSK-3βS9A/Ulk1+/- bigenic mice (Bigenic), and GSK-3β+/- mice (βKO) up to 24 months (M) of age. Left ventricular (LV) weight/body weight (LVW/BW, mg/g) was not significantly different among wild-type mice (WT), βKI and βKO at 6M. It was lower in βKI (2.4±0.1, p&lt;0.005) and higher in βKO (4.8±0.8, p&lt;0.05) than in WT (3.8±0.2) at 24M. Cardiomyocyte cross-sectional area (CSA, μm2) was smaller in βKI (360±9, p&lt;0.001) but bigger in βKO (540±11, p&lt;0.01) than in WT (502±5) at 24M. The LVW/BW was greater (3.5±0.2, p&lt;0.001) and the CSA was bigger (527±4, p&lt;0.001) in Bigenic than in βKI at 24M. These data demonstrate that GSK-3β inhibits age-dependent cardiac hypertrophy via Ulk1. Cardiac fibrosis (%) was more in βKO (5.4±0.1, p&lt;0.001) and less in βKI (2.4±0.1, p&lt;0.001) than in WT (4.0±0.3) at 24M. There was much more fibrosis in Bigenic (5.5±0.6, p&lt;0.001) than in βKI at 24M. These data show that GSK-3β reduces age-related cardiac fibrosis via Ulk1. LV end-systolic elastance (Ees, mmHg/μl) and chamber stiffness constant (CSC, μl-1) were not significantly different among WT, βKI, and βKO at 6M. At 24M, the Ees was lower in βKO (4±1, p&lt;0.05) and higher in βKI (12±3, p&lt;0.05) than in WT (7±0), and the CSC was higher in βKO (0.19±0.01, p&lt;0.001) and lower in βKI (0.06±0.01, p&lt;0.001) than in WT (0.14±0.01). The beneficial effects of GSK-3β on cardiac function were abolished in the Bigenic, indicating that GSK-3β prevents age-specific cardiac dysfunction via Ulk1. The level of p62, a protein degraded by autophagy, was lower in βKI and higher in βKO than in WT. The numbers of autophagosomes and autolysosomes were significantly greater in βKI/tfLC3 (tandem fluorescent mRFP-GFP-LC3) mice than in tfLC3 or βKI/tfLC3/Ulk1+/- mice. These data suggest that GSK-3β activates autophagy via Ulk1. In conclusion, GSK-3β attenuates cardiac aging by activating Ulk1-dependent autophagy.
Cancer, Vitamins, and Plasma Lipids: Prospective Basel Study&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hannes B. Stähelin, Fritz Rösel, Eduard Buess, Georges Brubacher
Journal: JNCI Journal of the National Cancer Institute (1984)

In the Basel study (BS) (1960-73) on cardiovascular and peripheral arterial diseases, a mortality follow-up was completed for the period 1965-80. Of the 4,224 men at risk for these diseases, 531 died. The causes of death were established from the death certificates and classified into 8 groups. For each case 2 age- and sex-matched controls were selected and compared with the corresponding cases with regard to the various variables obtained at the three examinations (1960, 1965, 1971). This report dealth with cancer mortality, plasma lipids, plasma vitamins, alcohol and cigarette consumption, and intake of milk and citrus fruits. The results were all obtained at the second follow-up examination (BS III, 1971-73). Cancer of the lung, stomach, large bowel, and all other sites were treated separately. The average follow-up from BS III until death varied from 3.7 years (other sites) to 4.9 years (cancer of the lung). Of 129 cancer deaths, the highest incidence was found for cancer of the lung (38) followed by stomach (19) and large bowel, (15) and the remainder (57) was for other sites. Plasma lipids did not differ significantly among cases and controls. However, the lowest values were observed in colorectal cancer and gastric carcinoma (mean cholesterol, 213 mg/dl). beta-Carotene was significantly lower in cancer cases of the lung than in controls (14.8 micrograms/dl vs. 23.7; P less than .05). It was also low in gastric cancer cases (13.0 micrograms/dl). Vitamin A was below average only in cases with gastric cancer (difference due to the small number not significant). Vitamin C was consistently lower in cancer cases than in controls. The lowest value was found for cancer of the stomach and corresponded to a below-average consumption of citrus fruits. Vitamin E was low in cancer of the colon. Plasma lipids correlated strongly with vitamin E (tau = 0.5) and to a lesser extent with vitamin A (tau = 0.25). beta-Carotene correlated poorly with beta-lipoproteins (low-density and very low-density lipoproteins) but significantly with total cholesterol. Smoking was inversely related, as was alcohol consumption, to the beta-carotene level. From these results, the conclusion was that vitamins influence carcinogenesis in humans.
Abstract 17434: Simple Renal Cysts as Predictors of Thoracic Aortic Disease
Authors: Bulat A Ziganshin, Panagiotis Theodoropoulos, Mohammad N Salloum, Khaled J Zaza, Maryann Tranquilli, John A Elefteriades
Journal: Circulation (2013)

Thoracic aortic diseases (TAD), namely aneurysm and dissection, are usually clinically silent, so that the first symptom is often either death or a life-threatening complication. Several medical conditions such as bicuspid aortic valve, intracranial aortic aneurysm, and family history of TAD have all been associated with an increased risk of developing a TAD in the patient. The aim of our study was to evaluate the prevalence of simple renal cysts (SRC) in patients with TAD in order to assess the hypothesis that the presence of SRC can be used as a predictor for development of TAD. We evaluated the prevalence of SRC in patients with TAD (n=842, 539 males, 303 females, mean age 63.5 ± 14.2) undergoing treatment at our institution during the period 2004-2013. The patients were divided into four groups: ascending aortic aneurysm (456, 54.2%), descending aortic aneurysm (86, 10.2%), Type A aortic dissection (118, 14.0%), and Type B aortic dissection (182, 21.6%). The prevalence of SRC was determined by analyzing the reports of computed tomography imaging of the chest and abdomen of these patients. The results of our study are presented in the Table. We found that the prevalence of SRC is 37.1%, 57.0%, 44.1%, and 46.7% for patients with ascending, descending aortic aneurysm, Type A, and Type B aortic dissection, respectively. These numbers are considerably greater than expectations for the overall prevalence of SRC for the general public (range 10% to 14% in recent reports). In addition, the prevalence of SRC was not significantly different between males and females (p>0.05), despite the reported male predominance for the general population (2:1 male:female ratio). In conclusion, in this study we established an increased prevalence of SRC in patients with TAD. These results are suggestive that SRC can potentially be used as a marker for timely detection of patients at risk of developing TAD.
Does the co-existence of acute anterior uveitis and chronic back pain prompt primary care physicians to consider a diagnosis of axial spondyloarthritis?
Authors: Alexander Maxwell, Max Yates, Paul Everden, Karl Gaffney
Journal: Annals of the Rheumatic Diseases (2016)

We read with interest the article by Haroon et al 1 indicating that approximately 40% of patients with acute anterior uveitis (AAU) have undiagnosed spondyloarthritis. Unfortunately, delay to diagnosis remains a huge challenge in axial spondyloarthritis (axSpA) despite the publication of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria, which formally recognises the role of MRI in diagnosis.2 We recently reported that the mean delay in diagnosis among 1193 patients attending two large secondary care centres in the UK was 8.5 years.3 Despite a 51% increase in new diagnoses since 2009, the delay in diagnosis has not improved and the presence of AAU was associated …
Basic : Cytochrome P450 epoxygenase 2C9 inhibitor sensitizes cancer stem cell apoptosis under hypoxia (초)
Authors: Sun Jung Myung, Jung Hwan Yoon, Joeng Hoon Lee, Su Jong Yu, Yoon Jun Kim, Hyo Suk Lee
Journal: Clinical and Molecular Hepatology (2011)

-S117 mouse albumin promoter and mouse alpha-feptoprotein enhancer are integrated. Methods: The pLive vector was cloned with SV40 T antigen gene, and then the plasmid was microinjected into pronuclearstage zygotes from C57/B6 mice. The incorporation of the transgene among progenies was evaluated using PCR, and the SV40T gene positive animals were continuously crossed with normal mice. Histological confirmation of HCC was carried out in 24 weeks old transgenic mice. Results: Multiple large tumor nodules were shown on the liver surface of the transgenic mice. In timorous tissues, poorly differentiated HCC were observed in H&E stains, AFP and Ki-67 were overexpressed in immunohistochemistry, suggesting HCC was successfully induced by SV40T antigen under organ specific promoter. Conclusion: Our study demonstrated the establishment of transgenic mouse model of HCC using SV40T gene and pLive vector system and this model could be applied to evaluate the anti-tumor efficacy of several anti-cancer drugs or target therapy in HCC.
Treatment and outcome of metastatic HER2-positive breast cancer relapsing post adjuvant trastuzumab exposure.
Authors: J. Krell, C. R. James, D. Shah, P. Riddle, R. Ahmad, K. Hogben, R. C. Coombes, P. Madden, S. Cleator, C. Palmieri
Journal: Journal of Clinical Oncology (2010)

1080 Background: Since 2006 adjuvant trastuzumab (AT) has been standard care for HER2 +ve early breast cancer (BC) treated with chemotherapy (CT). No data exists on the response and benefit of subsequent treatment, including trastuzumab (T) re-exposure, in cases developing recurrent disease following AT. Methods: All cases of early HER2 +ve BC exposed to AT at our institutions were reviewed and cases of recurrent/metastatic disease identified. Clinicopathological and adjuvant treatment details in recurrent cases were recorded. Sites of relapse, treatment, and details of further T based therapy were recorded. Response to treatment and outcome were analyzed. Results: 284 cases were identified who had received ≥1 dose of AT and 29relapses recorded (Local recurrence: 13.8%; distant recurrence: 86.2%). 34.5% received adjuvant CT and 65.5% neoadjuvant (NA) CT, 2 received NA T. Median time to relapse from diagnosis was 18.3 months (m) (range 9.2-48.2) and 8.5m (range 1.4-40.0) from AT initiation. 55% of relapses occurred on AT. 2 cases received no active treatment (poor performance status) and 1 case records were unavailable. At a median time of observation of 9.9m (range 0.8-39), 69.2% had progressed on first-line therapy with a median time to progression (TTP) of 6.5m (range 2.0-21.8). 57.7% of patients received further T as first-line treatment, no difference in TTP was seen between this group and the group who were not re-exposed to T (p=0.36). TTP (first-line) was not statistically different between the group relapsing on AT versus those completing 1 year AT (p=0.51). 15/28 deaths have been recorded, median overall survival (OS) from relapse to death was 8.8m (range 0.8-38.3), for those alive/censor (n=13) median OS 10.9m (range 2.5-39.0). There was no statistical difference in OS for patients receiving T versus no T in the metastatic setting (p=0.65), or those relapsing during AT or after AT (p=0.69). CT used in the metastatic setting (1, 2, and 3 line) and the response rates will be presented. Conclusions: This studyshows no difference in TTP or OS in patients receiving first-line metastatic treatment with T versus no T following AT. The benefits of first-line therapy did not differ based on the relationship of relapse to AT. A larger study is ongoing. No significant financial relationships to disclose.
Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets
Authors: Denis David, Lynda Bani, Jean-Louis Moreau, Christophe Demaison, Karine Sun, Ombretta Salvucci, Takayuki Nakarai, Marianne de Montalembert, Salem Chouaı̈b, Marcel Joussemet, Jerome Ritz, Jacques Thèze
Journal: Blood (1998)
Cancer in women who have taken contraceptive steroids.
Authors: Matthews Pn, Millis Rr, Hayward Jl
Journal: BMJ (1981)

The prognosis and clinical/pathological findings in 93 patients with breast cancer who had taken contraceptive steroids before diagnosis (study group) were compared with those in 93 control patients with breast cancer matched for age and parity.  The tumors in the study group women were found to have more favorable clinical and histological features than those in the control group.  When only patients who had been treated by radical mastectomy were considered those who had taken contraceptive steroids survived significantly longer even when differences in nodal state were taken into account.  Significantly more patients in the study group had a family history of breast cancer.  No evidence was found that taking oral contraceptives had any harmful effects on tumor growth and spread except possibly in patients with a close family history of breast cancer.  (Authors modified)
PTU-049 Rate of disease progression and the influence of co-factors in hepatitis C virus as determined by interval liver biopsy
Authors: A Abbara, P Kennedy, F Gordon, A Brown, R Goldin, J Main, H Thomas, M Thursz
Journal: Gut (2010)

<h3>Introduction</h3> Treatment candidates for emerging small molecule therapy in hepatitis C virus (HCV) have yet to be defined. Treatment naive patients who have opted to delay standard of care therapy will compete with treatment failures for these novel agents. For this reason, disease progression needs to be clearly defined. While the role of liver biopsy in the management of HCV remains contentious, data on the progression of fibrosis can only be ascertained from sequential liver biopsy. Thus, patients in our unit who underwent interval biopsies were studied to identify the factors which determine disease progression. <h3>Methods</h3> A total of 242 mono-infected HCV patients underwent a repeat liver biopsy. Patients who declined treatment and opted for a strategy of watchful waiting and those who failed combination antiviral therapy were offered an interval biopsy. Demographic data, viral parameters, ALT level, necro-inflammatory (NI) score and the presence of co-factors were collated to investigate their impact on progression of disease. Statistical analysis was performed using a Linear Mixed Model with SPSS 16 and the level of significance used was 5%. <h3>Results</h3> 121/242 patients had evidence of disease progression on interval biopsy. The median interval between biopsies was 50 months (range 11–133). Age, ALT level and necro-inflammatory score were all predictors of progressive fibrosis, p&lt;0.002, p&lt;0.001, p&lt;0.0001, respectively. The presence of a co-factor, defined as features of concurrent alcohol ingestion, steatosis or iron on liver biopsy lead to a doubling of the rate of fibrosis when compared with no co-factor. Neither genotype nor gender had a significant impact on fibrosis progression. <h3>Conclusion</h3> Liver biopsy benchmarks the extent of fibrosis in chronic HCV infection. This is critical in determining treatment response; moreover it provides an insight into future disease progression in those who decline treatment. This study demonstrates age. ALT and NI score as factors associated with accelerated disease, while the presence of a co-factor can have a synergistic effect, doubling the rate of fibrosis progression in HCV infection.