tbuckley/cabot-search huggingface dataset:
Hepatitis C virus infection in intravenous drug users
Authors: J. Harder, E. Walter, B. Riecken, C. Ihling, T.M. Bauer
Journal: Clinical Microbiology and Infection (2004)

Intravenous drug use (IVDU) remains a major means of hepatitis C virus (HCV) transmission. In this study, 101 drug users were studied prospectively after cessation of IVDU. Of these, 75.8% were anti-HCV positive, and 71.4% had elevated levels of alanine aminotransferase. These levels decreased significantly within 1 month of IVDU cessation (p 0.02). Liver biopsies showed minimal or mild fibrosis in 32 (71%) of 45 subjects, and severe fibrosis in two (4.4%) subjects. Anti-HCV-positive intravenous drug users in this study presented with mild liver disease and variable stages of disease progression. Biochemical disease activity might be affected by IVDU.
Chromatin states and nuclear organization in development — a view from the nuclear lamina
Authors: Anna Mattout, Daphne S. Cabianca, Susan M. Gasser
Journal: Genome biology (2015)

The spatial distribution of chromatin domains in interphase nuclei changes dramatically during development in multicellular organisms. A crucial question is whether nuclear organization is a cause or a result of differentiation. Genetic perturbation of lamina–heterochromatin interactions is helping to reveal the cross-talk between chromatin states and nuclear organization.
Enhancement of radiation effects by pXLG-mEndo in a lung carcinoma model
Authors: Xian Luo, Melba L. Andres, Michael J. Pecaut, James M. Slater, Daila S. Gridley
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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The efficacy of radiotherapy for lung cancer is limited by normal tissue damage, including pulmonary, cardiac, esophageal, and spinal cord, that can lead to acute and late effects. Recent evidence indicates that the tumoricidal effects of radiation may be increased through the use of anti-angiogenic factors. The major goal of this study was to determine whether endostatin gene therapy has potential to augment radiation-mediated control of lung tumors. Plasmid pXLG-mEndo, constructed in our laboratories, consists of the mouse endostatin gene cloned into the pWS4 vector. Functionality of the expressed endostatin was tested using human umbilical vein endothelial cells (HUVEC) and Lewis Lung Carcinoma (LLC) cells in culture. The kinetics and dose-dependence of endostatin expression, as well as anti-tumor efficacy of combining pXLG-mEndo with 60Co irradiation were evaluated in the C57BL/6 mouse - LLC model. LLC cells were implanted subcutaneously and different doses of pXLG-mEndo were injected intratumorally 14 days later; a dose of 10 gray (Gy) radiation was applied 16 hr thereafter. Some of the groups received the treatments a second time one week later. Immunohistochemistry with anti-CD31 antibody was used to evaluate the effects of therapy on tumor vasculature. Based on 3H-thymidine incorporation into DNA, the endostatin gene alone resulted in highly significant depression in HUVEC and LLC cell growth compared to pWS4 vector and control with no plasmids (p< 0.005). In addition, radiation increased the inhibitory effects of endostatin on both HUVEC and LLC cells over a 3-day period after irradiation (p<0.05 or less). The time course study of endostatin expression within LLC tumor revealed that the expression peak was on day 7 after pXLG-mEndo injection. In the dose-dependence study we found that intratumoral injection of 100 μg pXLG-mEndo significantly increased expression of both endostatin and vascular endothelial growth factor (VEGF) locally. Tumor growth was significantly inhibited in mice receiving pXLG-mEndo plus radiation compared with no treatment (p<0.005), radiation only (p<0.05) and plasmid only (p<0.05). The number of LLC tumor vessels per high-power field was reduced following exposure to combined treatment compared with exposure to all other treatments (P<0.05). These data demonstrate that delivery of endostatin via pXLG-mEndo as an adjuvant to radiation can significantly enhance the anti-tumor efficacy of radiation therapy in the LLC mouse tumor model. Further investigation of this unique combination therapy appears warranted. [The view, opinion, and/or findings contained in this report are those of the author(s) and should not be construed as a position, policy, decision or endorsement of the federal government or the National Medical Technology Testbed, Inc. Supported in part by an award from the U.S. Army and NMTB.]
Serum total bilirubin as a predictive factor for severe neutropenia in lung cancer patients treated with cisplatin and irinotecan
Authors: Y. Fujiwara, I. Sekine, Y. Ohe, H. Kunitoh, N. Yamamoto, H. Nokihara, Y. Fujisaka, T. Kato, M. Kawaishi, N. Saijo, T. Tamura
Journal: Journal of Clinical Oncology (2005)

7206 Background: Irinotecan-based chemotherapy unexpectedly causes severe neutropenia and diarrhea. SN-38 is converted to SN-38G via glucronidation by UGT1A1, the enzyme responsible for bilirubin glucronidation with multi-genetic variants. Pre-treatment serum total bilirubin level [PTB] is related to severe neutropenia in patients receiving 350 mg/m2 of irinotecan. (JCO 2004; 22:1382–1388). We extended this observation in patients receiving cisplatin and irinotecan. Methods: We reviewed the clinical records retrospectively to analyse relationship between grade 4 neutropenia and age, performance status, prior chemotherapy, cisplatin dose, PTB at fasting and pre-treatment neutrophil counts [PNC] using a logistic regression model. Results: 127 patients (93 male, 34 female; median age: 61 years; range: 24–74 years), received cisplatin (60 or 80mg/m2) on day 1 and irinotecan (60 mg/m2) on days 1 and 8 every 3 weeks or days 1, 8 and 15 every 4 weeks. Grade 4 neutropenia occurred in 29 patients (23%), febrile neutropenia in 12 patients (9%) and grade 3 or 4 diarrhea in 13 patients (10%). PTB was higher in patients who developed grade 4 neutropenia than those who did not (p=0.033, Mann-Whitney U test). In an univariate analysis, PTB (≤0.7mg/dl vs. 0.7<) was associated with grade 4 neutropenia [OR]: 3.56; 95% CI: 1.30–9.73; p=0.01). In a multivariate analysis adjusted for the factors mentioned above, PTB (OR: 5.77; 95% CI: 1.76–18.98; p=0.004) and PNC (OR: 0.65; 95% CI: 0.44–0.96; p=0.03) were associated with grade 4 neutropenia. In this study, PTB was not associated with severe diarrhea. Conclusions: PTB was a predictive factor for severe neutropenia, suggesting that PTB would reflect UGT1A1 functional properties. No significant financial relationships to disclose.
A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C
Authors: Elisabeth Verpy, Michel Leibovici, Ingrid Zwaenepoel, Xue-Zhong Liu, Andreas Gal, Nabiha Salem, Ahmad Mansour, Stéphane Blanchard, Ichiro Kobayashi, Bronya J.B. Keats, Rima Slim, Christine Petit
Journal: Nature Genetics (2000)
Trauma Patients
Authors: Jarone Lee
Journal: JAMA Surgery (2015)

With the passing of the Affordable Care Act and the need for policymakers to focus on implementing the individual mandate, the article by Osler et al1 comes at a most needed time. This article adds to the nationaldebateby findinga surprising and interesting result: excessive deaths associated with increased insurance coverage among nonelderly adult trauma patients. The implications of the study are immediately evident; however,wemust interpret the resultswithin the correct context. The study reports an interesting association that is not causation. As a high-level study, with little sensitivity analysis to test for robustness of the findings, there are many epiphenomena that could confound the results. First, in 2008, an amendment to the original law passed2 thatdevelopedstandards foruniformbillingandcodingacross Massachusetts.Asdocumentedpreviously, injury coding is an imperfect process.3-5 In a review of Veteran Affairs discharge records, only 74%of patientswith injuries had an injury code documented.3 As a result, establishing uniform coding practices would only lead to improved injury coding and subsequent increases in injury-related mortality rates. Interestingly, the implementation of uniform coding across the state coincides with the increase in mortality rates in the study. Second, during the period of increased mortality, more nonelderly adults with injuries had insurance when visiting the hospital. Newly insured patients who would have previously been admitted for lack of access to services could now be safely discharged to outpatient specialty services. This increase in discharges of insured patients would result in a disproportionate increase in the number of sicker trauma patients being admitted to the hospital. Overall, the results of the study add to the national debate and require further study. If the findings prove true, the study adds to the growing discussion that health insurance is onlyone—albeit an important—aspectof the solution toournation’s health care crisis.
Fatigue is the Most Important Symptom for Advanced Cancer Patients Who Have Had Chemotherapy
Authors: Zeeshan Butt, Sarah K. Rosenbloom, Amy P. Abernethy, Jennifer L. Beaumont, Diane Paul, Debra Hampton, Paul B. Jacobsen, Karen L. Syrjala, Jamie H. Von Roenn, David Cella
Journal: Journal of the National Comprehensive Cancer Network (2008)

Cancer fatigue has been defined and described as an important problem. However, few studies have assessed the relative importance of fatigue compared with other patient symptoms and concerns. To explore this issue, the authors surveyed 534 patients and 91 physician experts from 5 NCCN member institutions and community support agencies. Specifically, they asked patients with advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreatic, kidney, lung, ovarian, or prostate cancer or lymphoma about their "most important symptoms or concerns to monitor." Across the entire sample, and individually for patients with 9 cancer types, fatigue emerged as the top-ranked symptom. Fatigue was also ranked most important among patients with 10 of 11 cancer types when asked to rank lists of common concerns. Patient fatigue ratings were most strongly associated with malaise (r = 0.50) and difficulties with activities of daily living, pain, and quality of life. Expert ratings of how much fatigue is attributable to disease versus treatment mostly suggested that both play an important role, with disease-related factors predominant in hepatobiliary and lung cancer, and treatment-related factors playing a stronger role in head and neck cancer.
Comparison in the efficacy of mobilization and active cycle of breathing technique in coronary artery bypass greft surgery
Authors: Hulya Arikan, Hatice Nur Turan, Betul Degirmenci, Sema Savci, Melda Saglam, Deniz Inal-Ince, Naciye Vardar-Yagli, Ebru Calik, Meral Bosnak-Guclu, Metin Demircin
Journal: European Respiratory Journal (2011)

Aim: The purpose of this study was to evaluate the efficacy of mobilization and active cycle of breathing techniques (ACBT) following coronary artery bypass graft (CABG) surgery.

Material and methods: Fifty patients (35-75 years) with CABG were included in this randomized study. Twenty-five patients (18 males, 7 females) underwent mobilization and 25 patients (21 males, 4 females) were applied ACBT combined with mobilization. Demographic variables were recorded. Patients were evaluated using pulmonary function testing, 6-minute walk test (6MWT), and respiratory muscle strength.

Results: Five days after surgery, pulmonary function variables were similarly but significantly decreased in both groups as compared to preoperative values (p 0.05). Inspiratory and expiratory muscle strength values were statistically higher in ACBT group (-6.4±18.2 vs. -30.1±22.7 cmH2O, and -8.2±15.7 vs. -28.9±24.1 cmH2O, respectively p<0.05) than the mobilization group. Intensive care unit stay was significantly shorter in ACTB group than the control group (30.9±11.9 vs. 40.7±11.8 hours, p<0.05).

Conclusion: Functional capacity preserved after short-term ACBT or mobilization intervention after CABG surgery. Improvement in respiratory muscle strength was faster in ACBT group.
Phase II study of single agent perifosine in patients with hepatocellular carcinoma (HCC)
Authors: L. T. Campos, J. Nemunaitis, J. Stephenson, D. Richards, M. Barve, L. Gardner, R. Niecestro, P. Sportelli
Journal: Journal of Clinical Oncology (2009)

e15505 Background: Perifosine (Peri) is a novel oral alkylphospholipid with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC continues to have dismal prognosis. In a phase III randomized study, sorafenib demonstrated a 2% partial response (PR) rate with a median time to symptomatic progression of 4.1 months (mos) and radiologic progression of 5.5 mos, however patients (pts) had not received prior systemic treatment. Hence, additional therapies are needed. Peri was evaluated in a phase II multi-disease trial where 558 pts were randomized to daily vs. weekly schedules of Peri (50/100 mg daily or 900/1,200 mg weekly) with 42 of the pts having HCC. The following are the efficacy and safety results of this sub-group. Methods: Pts with advanced measurable HCC, up to 3 prior systemic treatments allowed. Normal organ / marrow function required. Primary outcome analyses included median time to progression (TTP) and disease control rate (DCR; CR+PR+SD &gt; 12 weeks). Results: Of the 42 HCC pts treated, the median age was 71 (range 26–83), 22 were male and 48% had received &gt; 1 prior systemic therapy. Child-Pugh status not available. As of 12/08, 32/42 pts were evaluable for efficacy (5 withdrew consent &lt; 30 days, 4 toxicity &lt; 30 days, 1 lost to follow up). One patient achieved a PR (3%) and 15 (47%) had stable disease &gt; 12 weeks; overall DCR of 50%. Median TTP was 14 wks (range 2–86). As of 12/08, one patient remains active at 12 mos. The daily dose was well tolerated. The weekly dose was significantly more toxic (3 of the 4 who came off treatment &lt; 30 days due to toxicity were on weekly). Most common grade 1/2 toxicities were GI related and fatigue. Grade 3/4 drug-related toxicities &gt; 10% included: abdominal pain (12%), elevated liver enzymes (10%) and fatigue (10%). Conclusions: Perifosine was well tolerated at the daily dose and overall demonstrates clinical benefit in patients with advanced HCC as reflected by an encouraging TTP. A combination study with sorafenib is ongoing and future randomized studies are under consideration. [Table: see text]
A retrospective study of lung cancer in young patients
Authors: Pradeep Rajagopalan, Douglas George Price, Sivanantham Sasikumar, Ramin Baghai Ravary, Neil Robert Goldsack, Brett Pereira
Journal: European Respiratory Journal (2011)

Introduction:  Over-representation of women, more advanced disease staging at presentation, better performance status and similar survival figures have been noticed in younger (≤50 years) lung cancer patients as compared to the general patient population with the disease.   Objective:  A retrospective study (February 2010) was done to derive clinicopathological data from young lung cancer patients treated in our hospital in the last 5 years. We also compared our findings with National Lung Cancer Audit (NLCA), 2007 in the UK. The NLCA data were considered as a reflector of the patients from all age groups.   Findings:  36 patients were identified for the study. Median age was 47 (37-50). 19 (54%) were female. 76% had WHO performance status (PS)1 in patients with documented PS. 43% had family history of lung cancer. 89% were current smoker. Histology was achieved in 87%. 68% had non small cell carcinoma (NSCLC) including 40% adeno carcinoma, 24% had small cell carcinoma; 3 had carcinoid. 55% of histology proven NSCLC had stage 4 disease at presentation. 86% had some form of treatment (surgery, chemotherapy or radiotherapy). 6 (18%) had resection.   Conclusion:  Majority of these patients presented with advanced stage disease as in previously reported larger cohorts. Women were a majority but they had a better survival than men. 41% had positive family history suggesting a possible genetic factor. Favourable performance status resulted in higher resection rate and active treatment compared to overall patient population. But did not lead to better survival.
Conjugated bile acid–activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression
Authors: Masayuki Nagahashi, Kazuaki Takabe, Runping Liu, Kesong Peng, Xiang Wang, Yun Wang, Nitai C. Hait, Xuan Wang, Jeremy C. Allegood, Akimitsu Yamada, Tomoyoshi Aoyagi, Jie Liang, William M. Pandak, Sarah Spiegel, Phillip B. Hylemon, Huiping Zhou
Journal: Hepatology (2014)

Bile acids are important hormones during the feed/fast cycle, allowing the liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile acids activate both the ERK1/2 and AKT signaling pathways via sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes and in vivo. Here, we report that feeding mice a high-fat diet, infusion of taurocholate into the chronic bile fistula rat, or overexpression of the gene encoding S1PR2 in mouse hepatocytes significantly upregulated hepatic sphingosine kinase 2 (SphK2) but not SphK1. Key genes encoding nuclear receptors/enzymes involved in nutrient metabolism were significantly downregulated in livers of S1PR2(-/-) and SphK2(-/-) mice. In contrast, overexpression of the gene encoding S1PR2 in primary mouse hepatocytes differentially increased SphK2, but not SphK1, and mRNA levels of key genes involved in nutrient metabolism. Nuclear levels of sphingosine-1-phosphate, an endogenous inhibitor of histone deacetylases 1 and 2, as well as the acetylation of histones H3K9, H4K5, and H2BK12 were significantly decreased in hepatocytes prepared from S1PR2(-/-) and SphK2(-/-) mice.Both S1PR2(-/-) and SphK2(-/-) mice rapidly developed fatty livers on a high-fat diet, suggesting the importance of conjugated bile acids, S1PR2, and SphK2 in regulating hepatic lipid metabolism.
Gender differences in long-term outcomes of COPD: A population based study in Italy
Authors: Valeria Belleudi, Nera Agabiti, Ursula Kirchmayer, Mirko Di Martino, Silvia Cascini, Riccardo Pistelli, Giulio Formoso, Claudio Voci, Danilo Fusco, Marina Davoli
Journal: European Respiratory Journal (2014)

Background. Gender medicine is a neglected dimension of medicine.  Objectives. We tested the hypothesis that long-term outcomes vary between genders in patients discharged after a COPD exacerbation.  Methods. A cohort of patients aged 45+ with first hospitalization for COPD in 2006-2009 and resident in Lazio and Emilia-Romagna regions was enrolled from administrative databases. Patients were followed from discharge until death or end of 2010 and were characterized on the basis of information at cohort entry. A Cox proportional hazard model was used to determine the effect of female gender on natural, cardiovascular and respiratory mortality adjusting for age, region of residence, calendar time, comorbidities and prior drug use.  Results. The cohort consisted of 33846 patients with 47.4% women and median age of 78 years. During the 5-year follow-up, natural mortality crude rate was 14.8 per 100 person-years with 15.6 for men and 13.9 for women. Cardiovascular mortality rate was 6.6 (6.4 men, 6.8 women) and respiratory mortality rate 3.9 (4.4 men, 3.3 women). Mortality risk factors were: increasing age, psychiatric disorders, cardiovascular and respiratory comorbidities, while hypertension and statin use were protective. Natural mortality risk was significantly lower in women than in men, also after adjusting (HR=0.81; IC95%=0.78-0.84), and Kaplan-Meier curves showed a major reduction of female mortality for respiratory causes.  Conclusions. Our study confirms better long-term prognosis of women with COPD. These results suggest that different pathophysiology and risk factors may contribute to gender differences, which might be of potential relevance for prevention, diagnostics, and therapy.
Abstract 19214: Critical Preoperative State and Left Main Disease and not Timing of Coronary Artery Bypass Surgery after non-ST-Elevation Myocardial Infarction Impact Early and Long-term Survival
Authors: Piroze Davierwala, Alexander Verevkin, Sergey Leontyev, Martin Misfeld, Michael A Borger, Friedrich W Mohr
Journal: Circulation (2014)

Objective:  According to the most recent guidelines, revascularization of patients with non-ST-elevation myocardial infarction (NSTEMI) by coronary artery bypass graft surgery (CABG) should generally be based on the same considerations as for those without NSTEMI. Our study aimed to determine the impact of timing of CABG on early and late outcomes in patients with NSTEMI and define the predictors of in-hospital (HM) and long-term mortality.   Patients and Methods:  Demographic characteristics, preoperative risk factors, operative variables, and hospital outcomes were collected prospectively for 758 patients who underwent CABG within 21 days after NSTEMI between January 2008 and December 2012 at our institution. The patients were divided into three groups according to the time-interval between onset of NSTEMI and CABG: Group A:  72 hours-21 days (371 patients). Predictors of HM and long-term mortality were identified by logistic and Cox regression analyses, respectively.   Results:  The overall HM was 5.1%, being 5.4%, 4.6% and 5.1% in groups A, B, and C (p=0.1), respectively. Stepwise logistic regression analysis revealed critical preoperative state (odds ratio [OR]:3.1; 95% confidence interval [CI]:1.4-6.6; p=0.005), left main disease (OR:2.7; 95%CI:1.4-5.5; p=0.005), and peripheral vascular disease (OR:2.3; 95%CI:1.1-4.6; p=0.02) as independent predictors of HM.  Overall 5-year survival was 83±2%. The group-wise 5-year survival was 80±4%, 82±4%, and 84±2% for Groups A, B and C patients, respectively [log rank p=0.5]. Critical preoperative state (OR:2.2; 95%CI:1.4-3.6; p=0.001), left main disease (OR:1.5; 95%CI:1.0-2.2; p=0.05), peripheral vascular disease (OR:2.6; 95%CI:1.8-3.9; p=0.0001), and age (OR:1.1; 95%CI:1.0-1.1; p=0.0001) predicted long-term mortality.   Conclusions:  CABG can be performed with an acceptable HM and excellent long-term survival in patients presenting with NSTEMI irrespective of the time interval between symptom-onset and revascularization. However, presence of a critical preoperative state, left main disease, and/or peripheral vascular disease negatively impacts both early and long-term outcomes.
Effectiveness of once daily meropenem for the treatment of aspiration pneumonia of elderly patients in long-term care facilities
Authors: Arash Etemadi, Parviz Salehi, Khashayar Etemadi
Journal: European Respiratory Journal (2011)

Objective and background: Aspiration pneumonia is a major health problem in residents of long-term care facilities. Antibiotics with broad coverage aginst gram negative and anaerobic bacteria, such as carbapenems, are cornerstone of treatment. However, once daily administration of meropenem for ambulatory patients is not routine yet.

Methods: A retrospective study of 31 elderly patients with aspiration pneumonia (17 males, 14 females; mean age 85 years) was conducted. In addition, the efficacy and safety of once daily intravenous meropenem (3g) for the treatment of this condition were evaluated.

Results: The overall detection rate of bacteria was 87% (32% monomicrobial, 55% polymicrobial). gram-negative enteric bacilli and anaerobic bacteria were isolated with the same frequency (20%) The overall clinical efficacy rate of meropenem therapy was 61%. The mortality rate was 10%.

Conclusion: The use of antibiotics effective against anaerobic bacteria may be necessary for patients with potentially fatal aspiration pneumonia. Once daily therapy with Meropenem (3g) for aspiration pneumonia is clinically effective and tolerable in elderly patients.