tbuckley/cabot-search huggingface dataset:
Randomized clinical trial eligibility rates for chemotherapy (CT) and antiangiogenic therapy (AAT) in a population-based cohort of newly diagnosed non-small cell lung cancer (NSCLC) patients
Authors: L. Fehrenbacher, L. Ackerson, C. Somkin
Journal: Journal of Clinical Oncology (2009)

6538 Background: NSCLC leads the US in cancer deaths, but randomized clinical trials (RCT) of CT with/without antiangiogenic therapy (AAT) are relatively slow to accrue. Treatment guidelines for NSCLC are based on RCTs that enroll patients with a mean age of 62–64 without serious comorbidities. SEER mean age of NSCLC diagnosis in the US is 70. Methods: 326 consecutively diagnosed (from January 1, 2006) NSCLC patients from a large prepaid health care delivery system (Kaiser Permanente Northern California-KPNC), were retrospectively evaluated by manual chart and electronic medical record review for eligibility criteria (EC) to enter treatment defining RCTs, i.e. E4599, S0023. The KPNC members are representative of the regional population. Ineligibility, the main endpoint, was determined on imaging and laboratory tests and history in the medical record. This may overestimate eligibility. Results: Age at diagnosis:&lt;60years-18%, &lt;65–28%, &lt;70–50%, &gt;75–34%, &gt;80–18%; mean (SD)age- 69.3 (10.6). Male:Female 51:49%. Adeno-49%; Squamous-22%; LargeCell-2.5%; NSC NOS-27%. Current/former smokers-90%. Staging: IA-14%; IB-13%; IIA+B-4%; IIIA-17%; IIIB+IV-52%. Surgical resection-26%. When standard RCT eligibility criteria were applied to the entire cohort, 34% (CI 29%-39%) were eligible. Only 23% (CI 19%-28%) were both eligible and &lt;75yo. stage IIIB+IV patients were 29% (CI 24%-36%) eligible at all ages, 20% (15%-26%) were both eligible and &lt;75yo. When AAT EC were added, 21% (17%-26%) were eligible for all ages, 14% (CI 10%-18%) eligible and &lt;75yo., and 9%(CI 6%-13%) eligible and &lt;70yo. Conclusions: Treatment guidelines for NSCLC are based on RCTs enrolling the healthiest quartile of the youngest half of patients. The majority of NSCLC patients are excluded by trial eligibility criteria or subjective age criteria from entering CT and/or AAT RCTs. Toxicities in these older and more comorbid NSCLC patients likely alter the risk:benefit ratio. RCTs specific for the 70+yo and comorbid NSCLC patients are needed to help define the best therapy for this understudied majority of lung cancer patients. No significant financial relationships to disclose.
Microalbuminuria in obstrucive sleep apnea syndrome
Authors: Emel Bulcun, Aydanur Ekici, Mehmet Ekici, Dilay Cimen, Ucler Kisa
Journal: European Respiratory Journal (2014)

Objectives: Microalbuminuria is an important risk factor for cardiovascular diseases. Microalbuminuria may be seen due to intermittent hypoxemia in patients with obstructive sleep apnea syndrome (OSAS). In this study, we investigated prevalence and relationship of microalbuminuria with clinical and physiological parameters in patients with OSAS  Method: Seventy seven patients with OSAS and twenty-one nonapneic snoring subjects upon polysomnography were included in this study. The urinary albumin creatinin ratio (UACR) was calculated according to previously described formula. The severity index of chronic diseases was evaluated by using The Modified Cumulative Illness Rating Scale (MCIRS). Subjective sleepiness was assessed using the epword sleepiness scale (ESS).  Results: BMI, MCIRS, UACR, ESS were higher in patients with OSAS than nonapneic snoring subjects. In linear regression model, there was a negative relationship between UARC and minimal O2 and there was a significantly positive relationship between UARC and desaturation index  .  Conclusion:Microalbuminuria may be seen in patients with OSAS, depending on the severity of disease and hypoxemia. Microalbuminuria in patients with COPD should be examined in regular periods for risk of cardiovascular morbidity or mortality.
Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States
Authors: Caroline Minassian, Sara L. Thomas, Liam Smeeth, Ian Douglas, Ruth Brauer, Sinéad M. Langan
Journal: PLoS Medicine (2015)

Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association.The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥ 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination.Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events.
Immunoactive prebiotics transiently prevent occurrence of early atopic dermatitis among low-atopy-risk infants
Authors: Christoph Grüber, Margriet van Stuivenberg, Fabio Mosca, Guido Moro, Gaetano Chirico, Christian P. Braegger, Josef Riedler, Yalcin Yavuz, Günther Boehm, Ulrich Wahn
Journal: Journal of Allergy and Clinical Immunology (2015)
Further Evolution of the ACC/AHA Clinical Practice Guideline Recommendation Classification System
Authors: Jonathan L. Halperin, Glenn N. Levine, Sana M. Al-Khatib, Kim K. Birtcher, Biykem Bozkurt, Ralph G. Brindis, Joaquin E. Cigarroa, Lesley H. Curtis, Lee A. Fleisher, Federico Gentile, Samuel Gidding, Mark A. Hlatky, John Ikonomidis, José Joglar, Susan J. Pressler, Duminda N. Wijeysundera
Journal: Circulation (2015)
Complications of sequential immunotherapy in metastatic melanoma
Authors: Shams Bufalino, Shruti Singh, Ewa Borys, Kelli Hutchens, I Caroline Le Poole, Joseph I Clark
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Advanced melanoma is associated with a poor prognosis. Targeted therapy and immunotherapy are mainstays of treatment. High-dose interleukin-2 (HD IL-2), interferon alfa-2b, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, and programmed cell death protein 1 (PD-1)
Prevention of Central Venous Catheter–Related Infections and Thrombotic Events in Immunocompromised Children by the Use of Vancomycin/Ciprofloxacin/Heparin Flush Solution: A Randomized, Multicenter, Double-Blind Trial
Authors: Kelly J. Henrickson, Richard A. Axtell, Susan M. Hoover, Suzanne M. Kuhn, Jodi Pritchett, Sue C. Kehl, John P. Klein
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine whether an antibiotic flush solution containing vancomycin, heparin, and ciprofloxacin (VHC) can prevent the majority of line infections. PATIENTS AND METHODS: A prospective double-blind study was performed comparing VHC to vancomycin and heparin (VH) to heparin alone in 126 pediatric oncology patients. RESULTS: The 153 assessable lines resulted in 36,944 line days studied. There were 58 blood stream infections (43 Gram-positive, 14 Gram-negative, and one fungal). Forty were defined as line infections (31 heparin, three VH, six VHC). The time to develop a line infection was significantly increased using either antibiotic flush (VH, P = .011; VHC, P = .036). The rate of total line infections (VH, P = .004; VHC, P = .005), Gram-positive line infections (VH, P = .028; VHC, P = .022), and Gram-negative line infections (VH, P = .006; VHC, P = .003) was significantly reduced by either VH or VHC. Sixty-two (41%) of the lines developed 119 occlusion episodes (heparin, 3.99 per 1,000 line days; VHC, 1.75 per 1,000 line days; P = .0005). Neither antibiotic could be detected after flushing, and no adverse events were detected, including increased incidence of vancomycin-resistant Enterococcus colonization or disease. CONCLUSION: The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care resources.
Abstract 12301: TUG Mediates GLUT4 Translocation by AMP-Activated Protein Kinase in the Heart
Authors: Yina Ma, Wanqing Sun, Emmanuel Yawson, George Techiryan, Jinli Wang, Zhenling Liu, Hui Yang, Xingchi Chen, Yanqing Wang, Jonathan Bogan, Ji Li
Journal: Circulation (2014)

Introduction:  Ischemic heart disease, which is the leading cause of death, is caused by reduced blood flow to the ischemic area. Therefore, increasing nutrient uptake is a key approach to increase cardiomyocyte survival rate during the ischemia and reperfusion (I/R) period. TUG (tether containing a UBX domain, for GLUT4, 60 KDa) is a regulator of GLUT4 trafficking, which is cleaved to mobilize GLUT4 from intracellular membranes to the cell surface after insulin stimulation in skeletal muscle and adipose. The energy sensor AMP-activated protein kinase (AMPK) is known to play an important cardioprotective role during myocardial I/R by regulating GLUT4 translocation and glucose uptake.   Hypothesis:  TUG is one of the downstream targets of AMPK, which can be phosphorylated by hypoxia/ischemia induced AMPK activation. Phosphorylation accelerates TUG cleavage and increases GLUT4 translocation during ischemia/reperfusion in the heart.   Methods:  In vitro  hypoxia chamber and  ex vivo  isolated mouse heart perfusion Langendorff system were used to test the hypothesis. Antithrombin (AT) is an endogenous AMPK agonist in the heart, which was used to define the role of TUG in regulating GLUT4 trafficking during ischemia and reperfusion in the heart.   Results:  The  ex vivo  heart perfusion data demonstrated that AT triggered AMPK activation and significantly increase glucose uptake and GLUT4 translocation during ischemia and reperfusion (p   Conclusions:  Cardiac AMPK activation stimulates TUG cleavage and causes the dissociation between TUG and GLUT4 in the intracellular vesicles. TUG is a critical mediator that modulates cardiac GLUT4 translocation to cell surface and enhances glucose uptake by AMPK signaling pathway.
Smoking control policy and legislation.
Authors: Leppo K
Journal: BMJ (1978)

To achieve a reduction in smoking and its associated health hazards 4 major sets of measures were proposed by Finlands Ministry of Social Affairs and Health:  health education price policy restrictive measures and research and development.  In health education the main problems were lack of resources deficiencies in organization and a lack of defined responsibilities leadership and coordination.  The main needs were for funds and other resources and for coordinating activities among separate branches of administration.  Provisions concerning funding and organization of health education activities could be incorporated in any wider legislation.  2 measures were considered to be paramount in price policies:  obligatory price checks on cigarettes at least twice a year and a differential taxation based on the content of  substances.  Both measures required new legislation.  Only limited restrictions on industry and trade could have been carried out without new legislation.  Apart from differential taxation the best way to influence the type of cigarettes produced seemed to be to set upper limits for  constituents to phase out the brands with greatest hazards and to classify the remaining products as either very  or harmful according to their constituents.  Health warnings and declaration of contents on the packets would reinforce the health education messages.  This policy would not be possible without legislation giving new powers to the authorities concerned.  Critical evaluation and monitoring of responses to the implementation of policies are of the utmost importance.  The following are among the main regulations embodied in the new law:  1) except for excise duties the administration of tobacco affairs is mainly in the hands of the health authorities; 2) the government is responsible for fixing the limits of  components of tobacco products; 3) a warning of  effects of smoking shall be printed on retail packages; and 4) smoking is prohibited in all public spaces and public transport facilities except in separate areas allowed for it.  There is growing evidence on the importance of price policy as a determinant of cigarette consumption especially among young people.  On the whole the new strategy and legislation has been well received by the public and its implementation has proceeded smoothly.  The philosophy in this approach has been one of  switching.  Instead of allowing smoking unless specifically forbidden the general rule now is that smoking in all public places is prohibited unless specifically allowed and then it must be in separate areas provided for it.  The provisions for no smoking areas have been overwhelmingly welcomed even though they restrict individual liberty.
Role of class IIa histone deacetylases in the pathogenesis of pulmonary hypertension
Authors: Elisabetta Gamen, Friedrich Grimminger, Werner Seeger, Soni Savai Pullamsetti
Journal: European Respiratory Journal (2014)

Introduction:  Pulmonary hypertension (PH) is a progressive disease resulting in right heart dysfunction and failure. It is characterized by pulmonary vascular remodeling, which is mediated by dysregulation of proliferation, migration and apoptosis of vascular cells. Epigenetic changes, such as histone acetylation, influence gene expression and play a role in several cellular processes. The balance between the acetylated/deacetylated states of histones is partly mediated by histone deacetylases (HDACs).   Aim:  We intend to study the role of classIIa HDACs (HDAC4, HDAC5, HDAC7, HDAC9) in the pathogenesis of PH, focusing on pulmonary arterial smooth muscle cells (PASMCs).   Methods:  Analysis of HDACs expression in human samples from donors and idiopathic PAH patients as well as in chronic hypoxia-induced PH murine model was carried out by RT-PCR, Western blotting and immunohistochemistry. The effects on proliferation and apoptosis of selective siRNA on cultured PASMCs were investigated.   Results:  The expression levels of HDAC7 and HDAC9 are upregulated in human PH samples as well as in the murine model. Immunohistochemistry showed different localization pattern, with HDAC7 mostly expressed in PASMC and HDAC9 in PASMCs, adventitial fibroblasts and infiltrating cells.  In vitro  experiments suggest that the expression and cellular localization of these HDACs are regulated by hypoxia. Selective siRNAs are able to block cellular responses to hypoxia, interfering with HIF1α signaling pathway. In addition, they increase the apoptosis of PASMCs under hypoxia.   Conclusions : Our findings suggest that classIIa HDACs are involved in PH pathogenesis and their specific inhibition may represent a therapeutic target.
Synergistic Effects of Prothrombotic Polymorphisms and Atherogenic Factors on the Risk of Myocardial Infarction in Young Males
Authors: Aida Inbal, Dov Freimark, Baruch Modan, Angela Chetrit, Shlomi Matetzky, Nurit Rosenberg, Rima Dardik, Zvia Baron, Uri Seligsohn
Journal: Blood (1999)
High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome
Authors: Francesca De Filippis, Nicoletta Pellegrini, Lucia Vannini, Ian B Jeffery, Antonietta La Storia, Luca Laghi, Diana I Serrazanetti, Raffaella Di Cagno, Ilario Ferrocino, Camilla Lazzi, Silvia Turroni, Luca Cocolin, Patrizia Brigidi, Erasmo Neviani, Marco Gobbetti, Paul W O'Toole, Danilo Ercolini
Journal: Gut (2015)

<h3>Objectives</h3> Habitual diet plays a major role in shaping the composition of the gut microbiota, and also determines the repertoire of microbial metabolites that can influence the host. The typical Western diet corresponds to that of an omnivore; however, the Mediterranean diet (MD), common in the Western Mediterranean culture, is to date a nutritionally recommended dietary pattern that includes high-level consumption of cereals, fruit, vegetables and legumes. To investigate the potential benefits of the MD in this cross-sectional survey, we assessed the gut microbiota and metabolome in a cohort of Italian individuals in relation to their habitual diets. <h3>Design and results</h3> We retrieved daily dietary information and assessed gut microbiota and metabolome in 153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD. We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota. We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, <i>Prevotella</i> and some fibre-degrading Firmicutes, whose role in human gut warrants further research. Conversely, we detected higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD. <h3>Conclusions</h3> High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet. <h3>Trial registration number</h3> This study was registered at clinical trials.gov as NCT02118857.
A phase II study of the efficacy and safety of sunitinib in treatment-naïve and pretreated Japanese patients (pts) with metastatic renal cell carcinoma (mRCC)
Authors: H. Uemura, N. Shinohara, S. Naito, H. Akaza
Journal: Journal of Clinical Oncology (2008)

16108 Background: Sunitinib malate (SU) is an oral multitargeted receptor tyrosine kinase inhibitor that is approved multinationally for the treatment of advanced RCC. A multicenter phase II trial of SU in Japanese pts with mRCC has recently been completed; here we report efficacy and safety data from this trial. Methods: mRCC pts with prior nephrectomy received sunitinib 50 mg/day p.o. on a 4-week on, 2-week off schedule in 6-week cycles. Primary efficacy endpoint was objective response rate (ORR) as determined by RECIST. Secondary endpoints included progression-free survival (PFS) and time to tumor response (TTR). Responses were determined every 6 weeks (wks) by computed tomography/magnetic resonance imaging. Toxicity assessments were undertaken every 2 wks (NCI-CTCAE version 3). Results: In total, 51 Japanese pts received SU, comprising 25 treatment-naïve pts (1st-line group) and 26 pts who had received prior cytokine-based therapy (pretreated group), for a median of 4 and 5 cycles, respectively. In the intention-to-treat population, ORR was 48.0% in the 1st-line group, 46.2% in the pretreated group and 47.1% in the overall population (independent review). Median PFS was 46.0, 33.6 and 46.0 wks in the 1st-line, pretreated and overall populations, respectively. Median TTR was 10.0 wks in the overall population, and 7.1 wks and 10.7 wks in the two arms. The most commonly observed grade 3–4 Aes were fatigue (20%), hand-foot syndrome (14%), and hypertension (12%). The most common grade 3–4 laboratory abnormalities were reduced platelet (55%) and neutrophil (51%) levels, and increased lipase levels (39%). In total, 37 pts required dose reductions and 10 pts discontinued SU due to Aes. Conclusions: These data show significant efficacy and tolerability with SU in Japanese mRCC pts. Although Aes were generally manageable and reversible, there was a trend towards higher efficacy and a higher incidence of some Aes in Japanese pts compared with previously reported international phase II/III trials with mostly Western pts; this potential difference remains to be clarified. It is strongly suggested that SU is effective and tolerable for the treatment of Japanese pts in the 1st- and 2nd-line settings. No significant financial relationships to disclose.
A consensus prognostic factor model for survival in patients with metastatic renal cell carcinoma: A Kidney Cancer Association’s International Kidney Cancer Working Group (IKCWG) study
Authors: P. Royston, J. Bacik, P. Elson, J. B. Manola, M. Mazumdar
Journal: Journal of Clinical Oncology (2007)

5109 Background: Numerous well-designed retrospective studies of prognostic factors (pf) for survival (S) in metastatic renal cell carcinoma (mRCC) patients (pts) have been conducted since 1986. However, no single model for describing S in this population has been universally accepted. Methods: Authors of several existing prognostic indices, and others, formed the IKCWG to develop a single validated S model. The IKCWG has established a comprehensive database of previously reported clinical pf from 3748 previously untreated mRCC pts entered on institution review board approved clinical trials conducted by 11 centers in Europe and the United States from 1975–2002. Results: Median age at study entry was 58, 70% of pts were male, 89% had ECOG performance status (PS) 0 or 1; 75% had prior nephrectomy. 72%, 30%, and 19% of pts had lung, bone, and liver metastases (mets), respectively. 72% received interferon-a and/or interleukin-2 based treatments (tx); 25% were txd with chemotherapy/hormones only; 3% received other tx. 88% of pts have died; median S was 11.1 months (m). All examined factors except sex, age, and histology impacted S at p&lt;.001 in univariable analysis. Multivariable analysis using a log-logistic model stratified by center and multivariable fractional polynomials was performed to identify independent predictors of S. Missing data were handled using multiple imputation methods. Using p=.0044 as the criterion for variable selection to avoid overly complex models, a model comprising tx, PS, number of met sites, interval from diagnosis to tx, and pre-tx hemoglobin, WBC, LDH, alkaline phosphatase and calcium was identified. The 25 th and 75 th percentiles of the prognostic index formed by multiplying each factor by its regression coefficient were used as cutpoints to form three risk (r) groups with median S times (SE) of: favorable r (n=937; 27.8 (0.4) m), intermediate r (n=1874; 11.4 (0.2) m), and poor r (n=937; 4.1 (0.1) m). Conclusions: 9 clinical factors can be used to model S in mRCC and form 3 distinct prognostic groups. Additional model building to determine if model complexity can be reduced further, validation in independent data and comparison to existing prognostic models are underway. No significant financial relationships to disclose.