tbuckley/cabot-search huggingface dataset:
Cardiovascular outcomes associated with use of clarithromycin: population based study
Authors: Angel Y S Wong, Adrian Root, Ian J Douglas, Celine S L Chui, Esther W Chan, Yonas Ghebremichael-Weldeselassie, Chung-Wah Siu, Liam Smeeth, Ian C K Wong
Journal: BMJ (2016)

<b>Study question</b>&nbsp;What is the association between clarithromycin use and cardiovascular outcomes? <b>Methods</b>&nbsp;In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received <i>Helicobacter pylori</i> eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke. <b>Study answer and limitations</b>&nbsp;The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of <i>H pylori</i> eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of <i>H pylori</i> eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients. <b>What this study adds</b>&nbsp;Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population. <b>Funding, competing interests, data sharing</b>&nbsp;ID was funded by grants from the Medical Research Council for this project. LS was funded by a grant from the Wellcome Trust. The authors have no competing interests. No additional data are available.
Women aged 50 to 74 should have mammogram every two years, say US guidelines
Authors: Jacqui Wise
Journal: BMJ (2016)

New guidelines from the United States Preventive Task Force confirm that women at average risk for breast cancer should have mammography screening every other year from age 50 to 74. The guidelines, together with 11 supporting studies and editorials, were published in the Annals of Internal Medicine .1

After reviewing all of the evidence the task force confirmed that mammography screening was effective at reducing deaths from breast cancer in women aged 40 to 74. Women aged 40 to 49 were found to benefit the least, and women aged 60 to 69 benefited the most, the guidelines said. The task …
Deregulated expression of cryptochrome genes in human colorectal cancer
Authors: Gianluigi Mazzoccoli, Tommaso Colangelo, Anna Panza, Rosa Rubino, Angelo De Cata, Cristiana Tiberio, Maria Rosa Valvano, Valerio Pazienza, Giuseppe Merla, Bartolomeo Augello, Domenico Trombetta, Clelia Tiziana Storlazzi, Gemma Macchia, Annamaria Gentile, Francesca Tavano, Manlio Vinciguerra, Giovanni Bisceglia, Valeria Rosato, Vittorio Colantuoni, Lina Sabatino, Ada Piepoli
Journal: Molecular Cancer (2016)

Circadian disruption and deranged molecular clockworks are involved in carcinogenesis. The cryptochrome genes (CRY1 and CRY2) encode circadian proteins important for the functioning of biological oscillators. Their expression in human colorectal cancer (CRC) and in colon cancer cell lines has not been evaluated so far. We investigated CRY1 and CRY2 expression in fifty CRCs and in the CaCo2, HCT116, HT29, SW480 cell lines. CRY1 (p = 0.01) and CRY2 (p < 0.0001) expression was significantly changed in tumour tissue, as confirmed in a large independent CRC dataset. In addition, lower CRY1 mRNA levels were observed in patients in the age range of 62-74 years (p = 0.018), in female patients (p = 0.003) and in cancers located at the transverse colon (p = 0.008). Lower CRY2 levels were also associated with cancer location at the transverse colon (p = 0.007). CRC patients displaying CRY1 (p = 0.042) and CRY2 (p = 0.043) expression levels over the median were hallmarked by a poorer survival rate. Survey of selected colon cancer cell lines evidenced variable levels of cryptochrome genes expression and time-dependent changes in their mRNA levels. Moreover, they showed reduced apoptosis, increased proliferation and different response to 5-fluorouracil and oxaliplatin upon CRY1 and CRY2 ectopic expression. The relationship with p53 status came out as an additional layer of regulation: higher CRY1 and CRY2 protein levels coincided with a wild type p53 as in HCT116 cells and this condition only marginally affected the apoptotic and cell proliferation characteristics of the cells upon CRY ectopic expression. Conversely, lower CRY and CRY2 levels as in HT29 and SW480 cells coincided with a mutated p53 and a more robust apoptosis and proliferation upon CRY transfection. Besides, an heterogeneous pattern of ARNTL, WEE and c-MYC expression hallmarked the chosen colon cancer cell lines and likely influenced their phenotypic changes. Cryptochrome gene expression is altered in CRC, particularly in elderly subjects, female patients and cancers located at the transverse colon, affecting overall survival. Altered CRY1 and CRY2 expression patterns and the interplay with the genetic landscape in colon cancer cells may underlie phenotypic divergence that could influence disease behavior as well as CRC patients survival and response to chemotherapy.
Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation
Authors: Rocío López-Posadas, Christoph Becker, Claudia Günther, Stefan Tenzer, Kerstin Amann, Ulrike Billmeier, Raja Atreya, Gionata Fiorino, Stefania Vetrano, Silvio Danese, Arif B. Ekici, Stefan Wirtz, Veronika Thonn, Alastair J.M. Watson, Cord Brakebusch, Martin Bergö, Markus F. Neurath, Imke Atreya
Journal: Journal of Clinical Investigation (2016)

Although defects in intestinal barrier function are a key pathogenic factor in patients with inflammatory bowel diseases (IBDs), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we addressed this issue by characterizing the transcriptome of IECs from IBD patients using a genome-wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBDs, and inflammation was associated with suppressed Rho-A activation due to reduced expression of the Rho-A prenylation enzyme geranylgeranyltransferase-I (GGTase-I). Functionally, we found that mice with conditional loss of Rhoa or the gene encoding GGTase-I, Pggt1b, in IECs exhibit spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4+ T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding, ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBDs. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-I–deficient IECs, our findings suggest new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients.
Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
Authors: Eli L. Diamond, Benjamin H. Durham, Julien Haroche, Zhan Yao, Jing Ma, Sameer A. Parikh, Zhaoming Wang, John Choi, Eunhee Kim, Fleur Cohen-Aubart, Stanley Chun-Wei Lee, Yijun Gao, Jean-Baptiste Micol, Patrick Campbell, Michael P. Walsh, Brooke Sylvester, Igor Dolgalev, Olga Aminova, Adriana Heguy, Paul Zappile, Joy Nakitandwe, Chezi Ganzel, James D. Dalton, David W. Ellison, Juvianee Estrada-Veras, Mario Lacouture, William A. Gahl, Philip J. Stephens, Vincent A. Miller, Jeffrey S. Ross, Siraj M. Ali, Samuel R. Briggs, Omotayo Fasan, Jared Block, Sebastien Héritier, Jean Donadieu, David B. Solit, David M. Hyman, José Baselga, Filip Janku, Barry S. Taylor, Christopher Y. Park, Zahir Amoura, Ahmet Dogan, Jean-Francois Emile, Neal Rosen, Tanja A. Gruber, Omar Abdel-Wahab
Journal: Cancer Discovery (2015)

Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH), respectively. The discovery of BRAF(V600E) mutations in approximately 50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of patients with BRAF(V600E)-wild-type non-LCH are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole-exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in patients with BRAF(V600E)-wild-type non-LCH. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of patients with MAP2K1- and ARAF-mutated non-LCH using MEK and RAF inhibitors, respectively, resulted in clinical efficacy, demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders.We provide the first description of kinase fusions in systemic histiocytic neoplasms and activating ARAF and MAP2K1 mutations in non-Langerhans histiocytic neoplasms. Refractory patients with MAP2K1- and ARAF-mutant histiocytoses had clinical responses to MEK inhibition and sorafenib, respectively, highlighting the importance of comprehensive genomic analysis of these disorders.
Abstract 17829: Optimal Treatment of Recurrent Restenosis Lesions After Sirolimus-Eluting Stent Implantation for In-Stent Restenosis Lesions
Authors: Shunsuke Kubo, Kazushige Kadota, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Naoki Oka, Harumi Katoh, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Circulation (2012)

Backgrounds: Several studies have reported the outcomes of various treatment modalities for in-stent restenosis (ISR) after sirolimus-eluting stent (SES) implantation. However, there is no data ava...
Thymoquinone, a component of the herb <i>Nigella sativa</i>, suppresses proliferation and viability of prostate cancer cells by down-regulating androgen receptor and E2F-1
Authors: A. O. Kaseb, S. Tejwani, K. Chinnakannu, E. Barrack, P. Reddy
Journal: Journal of Clinical Oncology (2006)

20038 Background: Prostate cancer (CaP) that relapses following androgen-ablation therapy is hormone refractory, yet its growth continues to depend on androgen receptor (AR). Therefore, a curative strategy must include structural elimination of AR. Thymoquinone (TQ) is a component of Nigella sativa, an herb that has been used for thousands of years for a variety of diseases including cancer. We examined TQ effect on AR and cell cycle regulatory proteins required for proliferation and viability of CaP cells. Methods: Inhibitory effect of TQ on DNA synthesis and proliferation of exponentially growing LNCaP cells was assessed by 3 H-thymidine incorporation into DNA and MTS assay respectively. We examined TQ effect on AR and cell cycle regulatory proteins by Western blot analysis. The effect of TQ on cell cycle progression was determined using synchronized LNCaP cells. Western blots were then used to analyze equal amounts of protein isolated from cells at regular intervals during their progression through the cell cycle in the presence or absence of TQ. Results: We observed a dose-dependent increase in the inhibitory effect of TQ on DNA synthesis and proliferation of LNCaP cells. We also observed a significant decrease in AR and E2F-1, and a dramatic increase in p21, p27, and pRB, and Bax. Synchronized LNCaP cells treated with TQ failed to enter S phase. Western blot analysis revealed that TQ treatment of synchronized cells resulted in: (i) a significant decrease in AR, that normally increases in early- to late-G 1 phase, and E2F-1, that normally increases in late-G 1 phase (ii) down-regulation of cyclins A and E, Cdks-2 and 4, and Cdc-6 (iii) induction of p53 and p27. Conclusion: These observations demonstrate that TQ inhibits proliferation and viability of prostate cancer cells by decreasing AR and E2F-1 levels and inducing the proteins that cause cell cycle arrest and promote apoptotic events. Thus TQ may prove to be an effective treatment of hormone refractory CaP and a promising chemo- and/or radiation- sensitizing agent in adjuvant therapy as well. This could represent a novel approach for treatment of prostate cancer by an herbal agent that was shown to spare normal cells in previous studies. No significant financial relationships to disclose.
Clinical and cost benefits of liaison psychiatry
Authors: S J Levitan, D S Kornfeld
Journal: American Journal of Psychiatry (1981)

A liaison psychiatrist participated in the postoperative care of a group of elderly patients who underwent surgery for fractured femurs. Clinical outcomes for this group were compared with a control group of patients who were not treated by a liaison psychiatrist. Length of stay for the treatment group was 12 days shorter than for the control group, and twice as many patients in the treatment group returned home rather than being discharged to a nursing home or other health-related institution; therefore, a substantial reduction in the cost of their medical care was effected. The authors suggest that psychiatric liaison services should be viewed as a potential cost containment mechanism for general medical care.
Abstract 16454: Microrna-7- Erbb2 Axis: A Critical Regulator of Cardiac Remodeling
Authors: Manveen Gupta, Sathyamangla V Naga Prasad
Journal: Circulation (2012)

miRNAs are short, non-coding RNAs that negatively regulate gene expression. In heart, miRNAs play an important role in altering pathological signaling resulting in cardiac remodeling transitioning ...
Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection
Authors: M Brautigam, S Nolting, R E Schopf, G Weidinger
Journal: BMJ (1995)

To compare the efficacy and tolerability of terbinafine and itraconazole in the treatment of toenail tinea unguium.Multicentre, double blind, parallel group study.17 university hospitals, one army hospital, and five dermatology practices.195 patients with clinically suspected toenail tinea and growth of dermatophytes in baseline culture; data on 86 patients in the terbinafine group and 84 patients in the itraconazole group were fully evaluated for efficacy.Daily dose of 250 mg terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40 weeks.Mycological cure (negative results on microscopy and culture) and clinical improvement (length and area of unaffected nail) at week 52 or at discontinuation of treatment.At the end of the study mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of 84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of 86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (2P < 0.05).Terbinafine is more effective than itraconazole in the treatment of toenail tinea infection.
Abstract 56: The Association Between Early Hyperoxemia and Oxygen Exposure with Development of Pulmonary Dysfunction, Survival and Neurological Outcomes After Cardiac Arrest
Authors: Jonathan Elmer, Raghevesh Pullalarevu, Bo Wang, Samer Melhem, Nishit Vaghasia, Jaya Buddineni, Jon C Rittenberger, Clifton W Callaway
Journal: Circulation (2014)

Introduction: Prior studies inconsistently report an association between hyperoxemia and worse outcomes after cardiac arrest (CA), but are methodologically limited. We used a high-resolution CA-specific database to control for cumulative early oxygen exposure, disease-specific covariates and care processes to test if rigorous adjustment would eliminate any association between hyperoxemia and outcomes. We also tested if exposure to higher inspired oxygen (FiO2) was associated with development of lung dysfunction. Methods: We included patients surviving and ventilated for &gt;24 hours after ROSC. To test the association between hyperoxemia and outcomes, we categorized PaO2 hourly for 24h as severe hyperoxemia (&gt;300mmHg), moderate hyperoxemia (101-299mmHg), normoxia (60-100mmHg) or hypoxia (&lt;60mmHg). We controlled for CA-specific covariates and markers of potentially less attentive care (time to first FiO2 wean, number of weans, etc). We used multiple logistic regression to test the association between PaO2 and survival and discharge CPC. To test for development of lung dysfunction, we calculated oxygen exposure as the area under the curve of the FiO2 x hour (FiO2AUC) for each patient over 24h. Our main outcomes in this analysis were change in the respiratory SOFA score (SOFA-R) and change in dynamic lung compliance from baseline to 48h. Results: Of 184 patients overall mortality was 54% and 36% had severe hyperoxemia. The first PaO2:FiO2 ratio was 241±137, and at baseline 85% had pulmonary failure and 55% had cardiovascular failure as assessed by SOFA. Only severe hyperoxemia was independently associated with decreased survival to hospital discharge (adjusted OR 0.83 per hour, P=0.04) and worse discharge CPC. Higher FiO2AUC was not associated with worsened SOFA-R or lung compliance over 48h but was associated with decreased survival to discharge and worse discharge CPC. This was driven by 50% decreased survival in the highest quartile of FiO2AUC (FIO2&gt;80%/24h) compared to other quartiles. Conclusion: Despite rigorous adjustment, severe hyperoxemia was independently associated with decreased survival to hospital discharge and discharge CPC. We did not observe toxicity at lower levels. High FiO2 was not associated with pulmonary toxicity.
Tardive dyskinesia: review and update
Authors: H L Klawans, C G Goetz, S Perlik
Journal: American Journal of Psychiatry (1980)

Tardive dyskinesia is an extrapyramidal syndrome associated with the chronic administration of major neuroleptic agents. The pathogenesis of the disorder appears to relate to chronic striatal dopaminergic receptor site blockade; the pathophysiology of tardive dyskinesia appears to relate to the resultant denervation hypersensitivity. Agents that deplete the brain of dopamine are the mainstay of therapy for tardive dyskinesia. Cholinergic agents that potentially modulate the balance between dopamine and acetycholine in the striatum offer possible additional therapeutic options. Clearly, resumption of neuroleptic therapy is treatment with the presumed pathogenic agent and is to be avoided whenever possible.
A phase I evaluation of the safety of escalating doses of atrasentan in adults with recurrent malignant glioma (MG)
Authors: S. Phuphanich, K. Carson, S. Grossman, G. Lesser, J. Olson, T. Mikkelsen, S. Desideri, J. D. Fisher
Journal: Journal of Clinical Oncology (2005)

1526 Background: Atrasentan is a highly potent and selective endothelin (ET) receptor antagonist that may inhibit cell proliferation by blocking the ET receptor that regulates angiogenesis of glioma growth. This dose-finding study evaluates the safety and toxicity, and seeks preliminary evidence of efficacy, of Atrasentan in the treatment of MG. Methods: Patients (pts) with MG with prior radiation and < 1 chemotherapy were eligible. Planned dose levels were: 10 and 20 mg/day (cohorts of size 2), then 30 and incrementing by 20 mg/day up to a dose of 150 (cohorts of size 3), until a dose-limiting toxicity (DLT) is observed. The maximum tolerated dose (MTD) is defined as the maximum dose that causes no DLT in an expanded cohort of 10 pts. The cycle length was 28 days and intra-pt dose escalation was not allowed. Patients remained on study until progression. Results: Twenty-five pts, 16 (64%) males, median age = 53 years (range: 25–70); median KPS = 90% (range: 60–100) were enrolled. 22 (88%) had GBM and only 1 patient had no prior chemotherapy. Thirteen pts were on enzyme-inducing anti-epileptic drugs, and 12 were not. Only 23 pts were evaluable for toxicity because two pts developed early progression (1 each in the 30 and 70 mg/day cohorts). One pt had a DLT of grade 3 hypoxia and peripheral edema after 18 days of dosing with Atrasentan at 90 mg/day. The 70 mg/day cohort was expanded to 10 patients with no observed DLT and was declared the MTD. The most common adverse events were rhinitis, headache, and peripheral edema. These events were reported as grade 1/2 and were probably related to Atrasentan. There were no events of myelosuppression. One GBM pt (90 mg/day) had a partial response (4% response rate) and 4 GBM pts had stable disease before progressing. To date, 18/25 (72%) pts have died. Kaplan-Meier median survival was 6.0 m (95% confidence interval, 4.2–9.5 m) and 6-month progression free survival was 13% (95% confidence interval, 3–32%). Conclusions: Chronic oral dosing of Atrasentan is safe in pts with recurrent malignant gliomas, and the MTD is 70 mg/day. Pharmacokinetic data are currently being analyzed. Further study of Atrasentan with radiation therapy in newly diagnosed malignant gliomas is planned. No significant financial relationships to disclose.
Inappropriate Admissions: Thoughts of Patients and Referring Doctors
Authors: John Campbell
Journal: Journal of the Royal Society of Medicine (2001)

Research on inappropriate hospital admissions has tended to neglect the views of the referring doctors and the patients. In this study, the Appropriateness Evaluation Protocol was applied to a random sample of 102 emergency medical admissions. The patients and doctors were then presented with a list of possible alternatives to admission that might have been used at the point of referral. Case notes were available for 88 patients. As judged by these, 28% of admissions were inappropriate, the commonest reason being the potential for treatment or tests to have been performed as outpatient procedures; next commonest was the possibility of lower level care. The response rate to the questionnaires was about two-thirds, for both doctors and patients. Of the general practitioners and casualty doctors who responded, 60% specified alternatives to admission that they would have considered, and the equivalent figure for patients was 70%. For both groups the major preferences were same-day outpatient assessment and admission to a community hospital. Referring doctors and patients, in this survey, favoured alternatives to acute medical care in proportions much higher than that of supposedly inappropriate admission.
Pomalidomide (POM) Plus Low-Dose Dexamethasone (LoDEX) Improves Health-Related Quality Of Life (HRQoL) Vs High-Dose Dexamethasone (HiDEX) In Relapsed Refractory Multiple Myeloma (RRMM) Patients Enrolled In MM-003 Phase 3 Randomized Trial
Authors: Kevin W. Song, Meletios A. Dimopoulos, Katja Weisel, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Andrew Spencer, Stefan Knop, Christoph Renner, Nizar J Bahlis, Ramesh Amatya, Xin Yu, Mara Silvia Monzini, Lars Sternas, Mohamed H. Zaki, Christian J. Jacques, Jesús F. San Miguel
Journal: Blood (2013)