tbuckley/cabot-search huggingface dataset:
Disease severity and complexity in patients with acute exacerbation of chronic obstructive pulmonary disease in Lazio, Italy
Authors: Ursula Kirchmayer, Nera Agabiti, Mirko Di Martino, Lisa Bauleo, Luigi Pinnarelli, Danilo Fusco, Riccardo Pistelli, Vittoria Colamesta, Marina Davoli
Journal: European Respiratory Journal (2012)

Population based estimates of disease severity and comorbidities in patients with acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) give insight into the burden of this degenerating condition on patients and health care systems.

Hospitalized COPD patients were characterized in terms of COPD severity and complexity.

A cohort of 21,144 residents in Lazio, discharged after acute COPD exacerbation in 2006-9 was enrolled from the Hospital Information System. Disease severity was defined as presence of admissions during 12 months prior to index admission with diagnosis of COPD, respiratory failure (RF), invasive respiratory procedures, transfer to intensive care, COPD emergency visits, or oxygen therapy (O2), linked from drug claims register. Comorbidities were retrieved from index admission and admissions during 24 months before.

More than half of patients were men (53.9%), mean age was 74.6 years for men and 76.8 years for women. RF and O2 were the two factors detected more often (46.9% and 21.9%, respectively), with higher values in men (RF: 48.5%, O2: 24.5%). Most important comorbidities were hypertension (24.8%), diabetes (20.4%), ischemic heart disease (13.0%), heart failure (12.6%), arrhythmias (12.3%), pulmonary infections (10.3%), and cerebrovascular disease (9.5%), with higher prevalence in men for all but diabetes and hypertension.

Patients admitted for acute exacerbations are typically old and more often men. Almost half of patients are affected by respiratory failure, more than a fifth is treated with oxygen. Many patients suffer from cardiovascular disease or diabetes.

Partially funded by National Medicines Agency; Prot. FARM8ZBT93.
Telehealth for chronic disease management
Authors: Aarash Saleh
Journal: Thorax (2013)

Telehealth for chronic disease managementIn this cluster randomised controlled trial, Cartwright et al 1 evaluated the outcomes of telehealth on patient reported outcomes in a primary care population with chronic disease.Telehealth is the use of remote data exchange between patients at home and health professionals to assist management of long-term conditions.It is heralded as a solution to our growing elderly population with its significant chronic disease burden.The Department of Health has commissioned Whole Systems Demonstrator (WSD) to analyse the efficacy and cost-effectiveness of telehealth.The WSD study consists of a series of nested analyses in a chronic disease population.This paper looks specifically at patient reported anxiety, depression and health-related quality of life.A total of 1573 patients at 154 practices across three sites were recruited and had to have at least one chronic disease (chronic obstructive pulmonary disease, heart failure or diabetes), a broadband internet connection, English literacy and sufficient cognitive ability to complete the questionnaire unaided.Telehealth systems varied and included blood pressure, blood glucose, weight and pulse oximetry measurement as appropriate for the patient and at individualised intervals, symptom data entry and educational support.Monitoring centres were staffed by nursing and support staff with a variety of possible interventions such as physical or telephone consultation.The main endpoints were health-related quality of life, depression and anxiety at 12 months measured via home interview with a trained researcher using widely accepted inventories.Neither the intention to treat analysis nor the per protocol analysis found any significant difference between the treatment and control arms in terms of health-related quality of life, anxiety or depression.This is the largest and most comprehensive investigation of telehealth to date, and the authors suggest that previous trials which have found a beneficial or inconclusive effect on patient reported outcomes were frequently small or methodologically weak.The authors postulate that patients may prefer face-to-face consultations and dislike continual self-monitoring.Further analyses on cost-effectiveness, admission prevention and disease outcomes from the WSD trial are awaited, but this constitutes strong evidence that psychological outcomes are not improved by telehealth.
Combined <i>GADD45A</i> and <i>Thymidine Phosphorylase</i> Expression Levels Predict Response and Survival of Neoadjuvant-Treated Gastric Cancer Patients
Authors: Rudolf Napieralski, Katja Ott, Markus Kremer, Katja Specht, Holger Vogelsang, Karen Becker, Martina Müller, Florian Lordick, Ulrich Fink, Jörg Rüdiger Siewert, Heinz Höfler, Gisela Keller
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We evaluated the expression of seven therapy-related genes to predict the clinical outcome of advanced gastric cancer patients treated with a neoadjuvant chemotherapeutic protocol. Experimental Design: Pretherapeutic, formalin-fixed, and paraffin-embedded biopsies of 61 patients, who received a 5-fluorouracil (5-FU)– and cisplatin-based chemotherapy were studied. The expressions of the 5-FU–related genes TS, DPD, and TP and of the cisplatin-related genes ERCC1, ERCC4, KU80, and GADD45A were analyzed by quantitative real-time PCR. The expression levels of single genes and of various combinations were tested for an association with response and overall survival. Results: High DPD levels were more frequently found in nonresponding patients and were associated with worse survival. GADD45A and TP levels showed weak associations with response, but GADD45A expression correlated with survival. There was no association with response for TS expression, but tumors with a high TS level were associated with worse survival. The combination of GADD45A and TP revealed the strongest predictive effect. High expression values of TP and/or GADD45A were exclusively found in nonresponding patients (P = 0.002) and were associated with a significantly poorer survival (P = 0.04). Conclusions: Combined gene expression levels of TP and GADD45A represent a new variable to predict the clinical outcome after neoadjuvant chemotherapy in gastric cancer. The association of DPD expression with response and survival underlines a predominant role of DPD to predict 5-FU sensitivity. The association of TS expression levels with survival but not with response suggests an importance of this gene for tumor progression.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Authors: James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean Jacques Grob, C. Lance Cowey, Christopher D. Lao, Dirk Schadendorf, Reinhard Dummer, Michael Smylie, Piotr Rutkowski, Pier F. Ferrucci, Andrew Hill, John Wagstaff, Matteo S. Carlino, John B. Haanen, Michele Maio, Ivan Marquez-Rodas, Grant A. McArthur, Paolo A. Ascierto, Georgina V. Long, Margaret K. Callahan, Michael A. Postow, Kenneth Grossmann, Mario Sznol, Brigitte Dreno, Lars Bastholt, Arvin Yang, Linda M. Rollin, Christine Horak, F. Stephen Hodi, Jedd D. Wolchok
Journal: New England Journal of Medicine (2015)

Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.
The Evolution of Melanoma Diagnosis: 25 Years Beyond the ABCDs
Authors: D. S. Rigel, J. Russak, R. Friedman
Journal: CA A Cancer Journal for Clinicians (2010)

Early detection of malignant melanoma remains the key factor in lowering mortality from this cancer. Recognizing the importance of this issue 25 years ago, our group at New York University published in CA: A Cancer Journal for Clinicians the mnemonic "ABCD" to facilitate the early diagnosis of melanoma. Studies have demonstrated the usefulness of this paradigm in enhancing early melanoma diagnosis as a part of clinical examinations, mass screenings, and public education programs. Approaches to melanoma diagnosis have dynamically evolved during the ensuing quarter century. In the 1990s, dermoscopy enabled the recognition of new subsurface features to differentiate between malignant and benign pigmented lesions. During the last decade, new computer-based technologies have improved diagnostic sensitivity and specificity and may result in optimizing lesion selection for biopsy and pathology review. Despite all of the advances in melanoma diagnosis, timely recognition, detection, and rapid treatment of melanoma remain critical. Although pathologic examination remains the gold standard for diagnosis, this cancer has the potential to be diagnosed through noninvasive approaches because of its cutaneous location. From the development of the ABCDs through current attempts that use complex computer algorithms and genetic markers, a clinician's ability to detect melanoma in its earliest form has been augmented. However, a "good clinical eye" is still fundamental to selecting the lesions for evaluation among the sea of those that are prevalent. As current approaches are refined and new techniques are developed, the improved ability to diagnose this cancer will hopefully enhance reaching the goal of reducing melanoma mortality.
Enhanced Peroxynitrite Formation Is Associated with Vascular Aging
Authors: Bernd van der Loo, Ralf Labugger, Jeremy N. Skepper, Markus Bachschmid, Juliane Kilo, Janet M. Powell, Miriam Palacios-Callender, Jorge D. Erusalimsky, Thomas Quaschning, Tadeusz Malinski, Daniel Gygi, Volker Ullrich, Thomas F. Lüscher
Journal: The Journal of Experimental Medicine (2000)

Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-associated enhanced superoxide (·O2−) production with concomitant quenching of NO by the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels, which also increased with age. Thus, vascular aging appears to be initiated by augmented ·O2− release, trapping of vasorelaxant NO, and subsequent peroxynitrite formation, followed by the nitration and inhibition of MnSOD. Increased eNOS expression and activity is a compensatory, but eventually futile, mechanism to counter regulate the loss of NO. The ultrastructural distribution of 3-nitrotyrosyl suggests that mitochondrial dysfunction plays a major role in the vascular aging process.
Monitoring performance, pituitary–adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players
Authors: Sándor L Schmikli, Wouter R de Vries, Michel S Brink, Frank JG Backx
Journal: British Journal of Sports Medicine (2011)

Objective To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). Design A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. Setting Sporting field and sports medical laboratory. Participants Ninety-four young elite soccer players were monitored during the 2006–2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. Main outcome measures Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. Results Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. Conclusions Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.
Hepatic injury induced by bile salts: Correlation between biochemical and morphological events
Authors: Douglas L. Schmucker, Minoru Ohta, Setsuko Kanai, Yuko Sato, Kenichi Kitani
Journal: Hepatology (1990)

Continuous intravenous infusion of taurochenodeoxycholate at a rate of 0.4 mumol.min-1.100 gm-1 for only 30 min in rats caused threefold to tenfold greater release of proteins (alkaline phosphatase, lactate dehydrogenase and albumin) into bile in comparison with animals infused with tauroursodeoxycholate at much higher rates (1.8 mumol.min-1.100 gm-1) for 2 hr. The simultaneous infusion of tauroursodeoxycholate and taurochenodeoxycholate (0.6 and 0.4 mumol.min-1.100 gm-1, respectively) for 2 hr prevented the marked biochemical changes in the bile induced by taurochenodeoxycholate for 15 to 60 min exhibited significantly more necrotic hepatocytes, especially in zone 1, in comparison with animals infused with tauroursodeoxycholate or a combination of taurochenodeoxycholate and tauroursodeoxycholate. A good correlation was observed between biochemical and morphological indices of bile acid-induced hepatocyte injury. These data suggest that (a) primary events induced by the acute infusion of toxic bile salts responsible for cholestasis include zone 1 hepatocellular necrosis and (b) this can be prevented by the simultaneous infusion of tauroursodeoxycholate.
Tropism of herpes simplex virus type 1 to nonmelanoma skin cancers
Authors: M. Hochberg, N. Kunicher, L. Gilead, A. Maly, H. Falk, A. Ingber, A. Panet
Journal: British Journal of Dermatology (2010)

Current treatments for nonmelanoma skin cancer include surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy, local chemotherapy and application of immunomodulators such as imiquimod. However, all have a 5-year recurrence rate of 1-40%. Gene therapy for the treatment of skin cancers is a promising new approach, as delivery of the vectors to the skin is simple and safety issues can be properly addressed.To develop an ex-vivo organ culture system for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tumours, and to test the feasibility of applying oncolytic viruses to these tumours.We first optimized conditions for the maintenance of BCC and SCC tissues in organ culture, and demonstrated viability of the tissues ex vivo for 3-7 days. The tropism of two potential oncolytic viral vectors, herpes simplex virus type 1 (HSV-1) and adenovirus (AD), was next evaluated.Immunohistological analysis revealed that HSV-1 targeted tumour cells that expressed p63 and did not express keratin 15 or keratin 14 markers of keratinocytes. Further examination indicated that uninfected BCC and SCC tissues express two isoforms of p63 mRNA, and HSV-1 infection specifically enhanced expression of the TAp63 isoform. Furthermore, following infection, both HSV-1 and AD induced apoptosis in the BCC and SCC cells as indicated by the induction of activated caspase-3.The results indicated a specific pattern of viral tropism to skin cancer cells that are critical for maintenance of the tumour. This new experimental system should aid in the analysis of new therapeutic modalities, such as oncolytic viruses, for future treatment of these skin tumours.
Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer
Authors: Gennadi V. Glinsky, Olga Berezovska, Anna B. Glinskii
Journal: Journal of Clinical Investigation (2005)

Activation in transformed cells of normal stem cells’ self-renewal pathways might contribute to the survival life cycle of cancer stem cells and promote tumor progression. The BMI-1 oncogene–driven gene expression pathway is essential for the self-renewal of hematopoietic and neural stem cells. We applied a mouse/human comparative translational genomics approach to identify an 11-gene signature that consistently displays a stem cell–resembling expression profile in distant metastatic lesions as revealed by the analysis of metastases and primary tumors from a transgenic mouse model of prostate cancer and cancer patients. To further validate these results, we examined the prognostic power of the 11-gene signature in several independent therapy-outcome sets of clinical samples obtained from 1,153 cancer patients diagnosed with 11 different types of cancer, including 5 epithelial malignancies (prostate, breast, lung, ovarian, and bladder cancers) and 5 nonepithelial malignancies (lymphoma, mesothelioma, medulloblastoma, glioma, and acute myeloid leukemia). Kaplan-Meier analysis demonstrated that a stem cell–like expression profile of the 11-gene signature in primary tumors is a consistent powerful predictor of a short interval to disease recurrence, distant metastasis, and death after therapy in cancer patients diagnosed with 11 distinct types of cancer. These data suggest the presence of a conserved BMI-1–driven pathway, which is similarly engaged in both normal stem cells and a highly malignant subset of human cancers diagnosed in a wide range of organs and uniformly exhibiting a marked propensity toward metastatic dissemination as well as a high probability of unfavorable therapy outcome.
Failure of thromboxane A2 blockade to prevent attacks of vasospastic angina.
Authors: S Chierchia, R de Caterina, F Crea, C Patrono, A Maseri
Journal: Circulation (1982)

Thromboxane A2 (TxA2), released by aggregating platelets, has been proposed as a potential mediator of coronary vasospasm. We studied six patients with variant angina, a clinical syndrome due to coronary vasospasm, and one patient with frequent recurrent episodes of transient ST-segment depression at rest in whom the spasm was demonstrated angiographically. All patients underwent continuous ECG monitoring for 2 days before and 2 days after a single, low, i.v. dose of aspirin (2 mg/kg), which reduced TxB2 (the stable metabolite of TxA2) to less than 3% of the control values. There were 129 transient ischemic episodes during control and 146 after aspirin, when platelet TxB2 was reduced to negligible levels. The duration, severity and incidence of symptomatic episodes were not significantly affected by TxA2 blockade. We conclude that platelet TxA2 is probably not responsible for the initiation of coronary vasospasm.
Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains
Authors: Justin S Hogg, Fen Z Hu, Benjamin Janto, Robert Boissy, Jay Hayes, Randy Keefe, J Christopher Post, Garth D Ehrlich
Journal: Genome biology (2007)

Abstract Background The distributed genome hypothesis (DGH) posits that chronic bacterial pathogens utilize polyclonal infection and reassortment of genic characters to ensure persistence in the face of adaptive host defenses. Studies based on random sequencing of multiple strain libraries suggested that free-living bacterial species possess a supragenome that is much larger than the genome of any single bacterium. Results We derived high depth genomic coverage of nine nontypeable Haemophilus influenzae (NTHi) clinical isolates, bringing to 13 the number of sequenced NTHi genomes. Clustering identified 2,786 genes, of which 1,461 were common to all strains, with each of the remaining 1,328 found in a subset of strains; the number of clusters ranged from 1,686 to 1,878 per strain. Genic differences of between 96 and 585 were identified per strain pair. Comparisons of each of the NTHi strains with the Rd strain revealed between 107 and 158 insertions and 100 and 213 deletions per genome. The mean insertion and deletion sizes were 1,356 and 1,020 base-pairs, respectively, with mean maximum insertions and deletions of 26,977 and 37,299 base-pairs. This relatively large number of small rearrangements among strains is in keeping with what is known about the transformation mechanisms in this naturally competent pathogen. Conclusion A finite supragenome model was developed to explain the distribution of genes among strains. The model predicts that the NTHi supragenome contains between 4,425 and 6,052 genes with most uncertainty regarding the number of rare genes, those that have a frequency of &lt;0.1 among strains; collectively, these results support the DGH.
Clinical Cardiac Tolerability of Trastuzumab
Authors: Edith A. Perez, Richard Rodeheffer
Journal: Journal of Clinical Oncology (2004)

This review provides an update on the current understanding of the clinical cardiac tolerability of trastuzumab, a humanized monoclonal antibody effective in the treatment of patients with advanced breast cancer overexpressing or amplifying HER2.We produced a summary of currently available information regarding the incidence and natural history of trastuzumab-associated cardiac dysfunction. Data from new, prospective clinical studies that incorporate close cardiac monitoring and standardized follow-up in patients with either advanced or earlier stages of breast cancer are also presented, and hypotheses regarding potential mechanisms of trastuzumab-related cardiotoxicity are discussed. Patients treated with trastuzumab in the pivotal trials were found to have increased risk for cardiac dysfunction, mostly when used concurrent with anthracyclines. Recent trials have required more stringent and consistent cardiac monitoring criteria and excluded patients with abnormal cardiac function, pre-existing heart disease, and/or high cumulative doses of anthracyclines. Decreases of ejection fraction and a few cases of congestive heart failure (CHF) requiring medical therapy have been detected. Improvements in ejection fraction and the symptoms of CHF have been subsequently noted in a significant number of these patients.Trastuzumab is associated with an increased risk of asymptomatic decreases in ejection fraction, and, in a small number of patients, CHF that is almost always responsive to medical management. This risk is greatest in patients receiving concurrent anthracyclines. More data are needed to help elucidate the pathophysiology of this syndrome.