tbuckley/cabot-search huggingface dataset:
Hospitalizations During Systemic Therapy for Metastatic Lung Cancer
Authors: Rebecca M. Prince, Eshetu G. Atenafu, Monika K. Krzyzanowska
Journal: JAMA Oncology (2015)

Understanding the risk of hospitalization due to treatment-related toxic effects is essential for patients, their clinicians, and health systems. Unplanned hospitalizations represent potential gaps in patient care; definition of these gaps allows characterization and identification of areas for quality improvement.To compare the rates of hospitalization in patients with metastatic non-small-cell lung cancer (mNSCLC) receiving chemotherapy in the "real world" vs clinical trial settings and to identify factors associated with hospitalization.A systematic review of Medline and EMBASE was conducted for records dating from database inception (1946 and 1974, respectively) through December 2014 to identify articles reporting rates of hospitalization during chemotherapy in patients with cancer. Both observational studies and clinical trials were eligible. This report focuses on patients with mNSCLC receiving chemotherapy because data were available for this clinical scenario in both the clinical trial and observational setting, allowing comparison. Summary statistics were used to describe results, and the χ2 test was used to compare hospitalization rates.Of the 74 articles reporting hospitalization rates during chemotherapy, 10 studies, all published after 2004, examined chemotherapy in mNSCLC, 5 randomized clinical trials (3962 patients) and 5 observational studies (8624 patients). Chemotherapy regimens included doublet therapy, single-agent therapy, or chemotherapy type unspecified. The real world cohort was older (71 vs 63 years). All real world studies reported on comorbidities, while clinical trials reported performance status. The aggregate hospitalization rate among real world patients was significantly higher than among trial patients (51% vs 16%) (odds ratio, 7.7; 95% CI, 7.0-8.4; P < .001). Performance status and type of chemotherapy were associated with hospitalization during chemotherapy in clinical trials, while type of chemotherapy was a risk factor in observational studies.Clinical trials in mNSCLC consistently report significantly lower rates of hospitalization than reports of real world cohorts of patients undergoing similar therapies. However, very few clinical trials report hospitalization information.
A compare between two models of cigarette smoke co-exposition in ovalbumin-sensitized mice
Authors: Thayse Regina Brüggemann, Paula Fernandes, Jessica Marques Saez Oliveira, Beatriz Mangueira Saraiva-Romanholo, Milton Arruda Martins, Fernanda Magalhaes Arantes-Costa
Journal: European Respiratory Journal (2014)

Introduction: Asthmatics smokers have an accelerated decline in lung function compared with non-smokers. However, some clinical trials suggest that smokers have a lower risk of developing asthma symptoms when compared with nonsmokers and ex-smokers. Objective: To compare the effects of twelve or thirty days of exposition to cigarette smoke in a model of chronic allergic pulmonary inflammation. Methods: Balb/c mice were sensitized and challenged with ovalbumin (OVA) following two different experimental protocols: a short (28 days) or a long protocol (50 days). Mice were co-exposed to cigarette smoke daily for twelve (short protocol) or thirty days (long protocol). Twenty-four hours after the last challenge, we evaluated the lung responsiveness, lung inflammation and the production of cytokines and OVA-specific antibodies (IgG1, IgG2a and IgE). Results: Longer protocol of sensitization showed an increase in lung responsiveness as well as in the levels of IL-4 and OVA-specific antibodies. While, the shorter protocol lead to an increase in the production of IL-5, IL-13, IL-10 as well as TGF-β and OVA-specific antibodies. The co-exposition of sensitized mice to cigarette smoke for thirty days increased the IL-10 level and reduced the lung responsiveness although increased IL-13 production. Additionally, after twelve days of co-exposition to cigarette smoke, sensitized mice increased IL-10 production and decreased IgG2a level. Conclusion: Co-exposition of cigarette smoke for twelve days worse lung inflammation by decreasing humoral regulation while thirty days of co-exposition increased cellular response although reverting lung hyperresponsiveness.
A Large National Cohort of French Patients With Chronic Recurrent Multifocal Osteitis
Authors: J. Wipff, F. Costantino, I. Lemelle, C. Pajot, A. Duquesne, M. Lorrot, A. Faye, B. Bader‐Meunier, K. Brochard, V. Despert, S. Jean, M. Grall‐Lerosey, Y. Marot, D. Nouar, A. Pagnier, P. Quartier, C. Job‐Deslandre
Journal: Arthritis & Rheumatology (2014)

Objective To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors. Methods One hundred seventy‐eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years. Results Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome. Conclusion This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.
Bone Marrow Features Improve Prognostic Efficiency in Multivariate Risk Classification of Chronic-Phase Ph<sup>1+</sup> Chronic Myelogenous Leukemia: A Multicenter Trial
Authors: Hans Michael Kvasnicka, Juergen Thiele, Annette Schmitt-Graeff, Volker Diehl, Rudolf Zankovich, Norbert Niederle, Lutz-Dietrich Leder, Hans Eckart Schaefer
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Multivariate risk classifications for chronic (stable)-phase Ph 1+ chronic myelogenous leukemia (CML) are generally focused on hematologic variables, and the putative prognostic property of bone morphology has been neglected or even contested so far. PATIENTS AND METHODS: A total of 510 consecutively recruited patients in first chronic phase Ph 1+ CML and pretreatment bone marrow biopsy specimens were entered onto this multicenter observational trial to evaluate the effect of bone marrow histopathology. According to generally accepted criteria, patients with any signs of accelerated disease were excluded. Treatment modalities included administration of interferon alfa-2b (IFN) and chemotherapy with hydroxyurea (HU) or busulfan. Immunohistochemical and morphometric techniques were applied to identify marrow cells and to quantify fiber density. Patients were separated into learning and validation samples, and classification and regression tree (CART) analysis was performed to establish a prognostic decision tree. RESULTS: CART analysis of the validation sample (123 patients with HU therapy) revealed the amount of erythroid precursors in the bone marrow, myelofibrosis, and splenomegaly as the most important prognostic features. Three risk profiles with significantly different survival patterns were established, with median survival times ranging from 33 to 108 months (two-sided log-rank test, P = .0001). The new score was confirmed by application to the learning sample with IFN therapy (two-sided log-rank test, P = .0002). Furthermore, risk status defined by the new score was significantly correlated with the occurrence of blast transformation. CONCLUSION: Our data strongly implicate that prognostic classification of chronic-phase Ph 1+ CML can be significantly improved by the inclusion of morphologic parameters. The variables of the presented scoring system may be easily assessed by routinely processed aspirates and bone marrow trephines.
Risk analysis of non-invasive ventilation outside the intensive care unit in the Netherlands
Authors: Anna van Gemert, Folkert Brijker, Ron Vaartjes, Michiel Wagenaar
Journal: European Respiratory Journal (2014)

Objective It is crucial to ensure patient safety in patients treated with non-invasive ventilation (NIV) on general wards. Previous studies have focused on patient characteristics associated with NIV failure, but not on technical and management aspects. Therefore, we performed a risk analysis to assess these technical and management aspects and to describe preventive measures.

Methods A risk assessment of NIV was performed on the two general wards in a Dutch general hospital in 2008. Riskfactors for (1) NIV failure and (2) the unavailability of NIV were determined. Risk quantification and prioritization was performed by calculating a riskcoefficient (RC; scale: 1-25) based on the Healthcare Failure Model en Effect analysis. Riskfactors with a RC of eight and higher had a moderate to high priority for which preventive measures were identified.

Results The most important riskfactors for NIV failure and the unavailability of NIV were: absence of mask/tubes (RC 8), mask leaking (RC 12), insufficient cleaning (RC 8), equipment malfunction (RC 8), inappropriate indication (RC 10), unfitting (RC 9), incorrect initial settings (RC 9), incorrect NIV adjustment (RC 12), decubitus (RC 12), aerophagia (RC 9), weaning too early (RC 8), delayed intubation (RC 10). The following measures might prevent these factors: preparing a program of requirements, staff training, protocol drafting, periodic patient monitoring, the use of alarms, adequate stock keeping and periodic equipment monitoring.

Conclusion In patients treated with NIV, it is essential to perform a risk assessment, which focuses not only on patient characteristics but also on technical and management aspects, to ensure patient safety.
Nab-Paclitaxel (Nab-P) and Gemcitabine (G) in Pretreated Advanced Pancreatic Cancer (Apdac) Patients (Pts): a Multicentre Retrospective Analysis
Authors: G. Giordano, M. Milella, D. Melisi, A. Zaniboni, S. Caponi, V. Zagonel, E. Giommoni, M. Santoni, V. Vaccaro, P. Bertocchi, F. Bergamo, E. Molinara, G. Musettini, E. Lucchini, A. Febbraro
Journal: Annals of Oncology (2014)
Noninvasive ventilation in the emergency department: Early predictors of outcome in acute cardiogenic pulmonary oedema
Authors: Rodolfo Ferrari, Fabrizio Giostra, Roberto Lazzari, Mario Cavazza
Journal: European Respiratory Journal (2012)

INTRODUCTION The application of early continuous noninvasive ventilation (NIV) is well established in the Emergency Department (ED) for the treatment of acute respiratory failure (ARF) due to Acute Cardiogenic Pulmonary Oedema (ACPO).

AIMS AND METHODS To critically analyse the impact of NIV in ACPO, about ARF presentation and the treatment efficacy or failure (defined as hospital mortality or need for invasive mechanical ventilation). Observational clinical study in the real life practice of the ED of a University teaching Hospital, during 5 months, including every patient emergently admitted and treated for ACPO according to inclusion criteria referring to an institutional protocol.

RESULTS 214 patients (media 1.42/day). Failure rate 15,5%. Failure versus success groups were similar in many characteristics and parameters. They were mainly different in: comorbid diseases, neurologic status, arterial blood pressure, rates of palliative or “ceiling” NIV, leukocytes, AST, CPKMB, troponinT, LDH, PCR, changes in blood gas analysis parameters after 120 minutes.

CONCLUSIONS We identified early predictors of outcome in the ED: clinical parameters, biomarkers and arterial blood gas analysis data to recognize severe conditions and the response to treatment. Unnecessary delaying tracheal intubation remains the major hazard of NIV in ARF; the overutilization of NIV is also a concern. A pivotal unresolved question is about selection criteria and early choices for patients having preset therapeutic and prognostic limits and acutely reversible processes. RCTs in the ED are necessary to define the subgroups of patients who are most likely to benefit for the early application of NIV.
Localization of a Macrophage Chemokinetic Factor on Neoplastic Cells<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: R D Lane, A M Kaplan, M J Snodgrass, D J Spriggs, A K Szakal
Journal: JNCI Journal of the National Cancer Institute (1984)

A rabbit antiserum was produced against a high-molecular-weight fraction (360,000) of murine Lewis lung carcinoma (LLC)-conditioned media. This fraction contained a factor that increased the rate of random migration (chemokinesis) of activated macrophages (M phi) in male C57BL/6J mice. The specificity of the antiserum was demonstrated by the ability of the antiserum to absorb the chemokinetic activity from tumor-conditioned media. Immunofluorescence studies demonstrated cell surface localization of antigenetically similar material on the LLC, Ehrlich ascites cells, MCA9/14 and MCA64/8 mouse fibrosarcomas, and MBT-2 mouse bladder carcinoma. The antiserum further indicated the presence of the chemokinetic factor (CKF) on the surface of peritoneal M phi previously exposed to tumor media. The CKF was observed on approximately 90% of the Corynebacterium parvum-activated M phi and of the M phi activated by maleic anhydride-divinyl ether copolymer (fraction 2), on 10% of the oyster glycogen-elicited M phi, and on 0% of the unstimulated M phi. these data support the concept that the CKF is a common surface marker of neoplastic cells and that it is bound by activated tumoricidal M phi.
Application of genomics to breakthroughs in the cosmetic treatment of skin ageing and discoloration
Authors: R. Osborne, T. Hakozaki, T. Laughlin, D.R. Finlay
Journal: British Journal of Dermatology (2012)

The use of global gene expression profiling, also known as transcriptomics or genomics, provides a means to identify key pathways affected in ageing skin that can be improved with appropriate cosmetic compounds. Aspects of skin ageing that can be addressed include matrix production, barrier, lipid synthesis, antioxidant capacity and hyperpigmentation. Gene expression profiling together with in vitro human skin cell cultures for compound screening and verification have led to the identification of cosmetic compounds and an understanding of the biological effects of compounds such as niacinamide, Pal‐KTTKS, hexamidine, retinyl propionate and sodium dehydroacetate. In addition, understanding of the decreased antioxidant capacity of aged skin has led to the identification of new antiageing ingredients, olive‐derived fatty acid ethoxylates, which have been shown to restore antioxidant enzymes in skin keratinocytes and fibroblasts. Gene expression profiling of age spots has also provided an understanding of the role of undecylenoyl phenylalanine in reducing melanin production by an adrenergic receptor mechanism in melanocytes. The use of these compounds in cosmetic formulations for skin care can aid improvements in the appearance of aged skin, including the improved appearance of fine lines, wrinkles and age spots.
Angiogenesis in Neuroblastoma: Relationship to Survival and Other Prognostic Factors in a Cohort of Neuroblastoma Patients
Authors: A. Cañete, S. Navarro, J. Bermúdez, A. Pellín, V. Castel, A. Llombart-Bosch
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To study angiogenesis in neuroblastoma, using morphometric and computerized image analysis, and correlate the results with survival and other prognostic factors. PATIENTS AND METHODS: Sixty-nine patients from the Spanish Cooperative Study for Neuroblastoma were studied. Tumoral angiogenesis was studied using an avidin-biotin immunoperoxidase technique with an anti-CD34 antibody. Vascular parameters (VPs) were analyzed by a computerized system. Statistical analysis was also performed. RESULTS: Sixty-six samples had adequate tumoral tissue, and their tumoral vessels were counted. Endothelial cells were more prominent in pure neuroblastomas than in maturing and more mature tumors. VPs showed no statistical difference between the groups of patients as defined by the levels of the other prognostic factors in neuroblastoma: age, stage, histopathology, TRK-A, P-glycoprotein expression, or MYCN copy number. In patients who relapsed, tumors did not show statistically significant difference in VPs when compared with tumors from patients who did not relapse. There was also no difference in VPs in tumors from living patients when compared with tumors from deceased patients. Overall survival was 75%, and event-free survival was 55% at 50 months. CONCLUSION: VPs could be adequately determined by a computerized system in neuroblastoma; however, VPs were not predictive of survival for our patients. In our patients, neither disseminated nor local relapses were influenced by the angiogenic characteristics of the tumors.
One- or two-week triple therapy for Helicobacter pylori: questions of efficacy and inclusion of a dual therapy treatment arm * Authors' response
Authors: D. Y Graham, Y. Yamaoka, R. M. Zagari, F. Bazzoli
Journal: Gut (2007)

We read with interest the recent paper comparing 1 and 2 weeks of triple therapy for Helicobacter pylori infection in patients with duodenal ulcer disease. ( Gut 2007; 56 :475–9) H pylori is an infectious disease and the goal of treatment is to cure the infection. In 2007, one would hope to be able to reliably cure ⩾95% of the treated patients (discussed by Graham et al ).1 In 1989, a successful treatment has been defined as one that cures >80% of the patients.2 By 1995, it seemed that 90% was achievable.3 The Maastricht consensus conferences defined a useful therapy as the one with an intention to treat (ITT) cure rate of >80%, which is a relatively low hurdle (ie, those with cure rates of ⩽80% would be unacceptable).5 Although the authors concluded that 7 and 14 days therapy provided essentially equivalent results, the focus should have been on the fact that the cure rates obtained were unacceptably low with either duration (eg, ITT of 79.7 for 7 days and 81.7 for 14 days), especially among patients with duodenal ulcer disease where the cure rates are typically higher than among patients without ulcers.5–8

Their results are not unexpected as large studies of this legacy triple therapy (proton-pump inhibitor (PPI), amoxicillin and clarithromycin) have recently yielded unacceptably low eradication rates in Europe and the US, and have only infrequently achieved the minimum 80% success rate (table 1).10–17 Overall, these results suggest that traditional triple therapy should no longer be used in Western populations unless pretreatment susceptibility is …
Late-breaking abstract: Riociguat for the treatment of pulmonary arterial hypertension (PAH): 2-year results from the PATENT-2 long-term extension
Authors: Lewis J. Rubin, Nazzareno Galiè, Friedrich Grimminger, Ekkehard Grünig, Marc Humbert, Zhi-Cheng Jing, Anne Keogh, David Langleben, Arno Fritsch, Flavia Menezes, Neil Davie, Hossein-Ardeschir Ghofrani
Journal: European Respiratory Journal (2014)

In the 12-wk PATENT-1 study, riociguat significantly improved 6MWD and other secondary endpoints in PAH pts. Improvements persisted for a further 1 yr in PATENT-2. We present 2-yr data from PATENT-2, the final analysis before most pts switch to the commercial drug.

PAH pts who were treatment-naive or pretreated with ERAs or prostanoids entered PATENT-2 after completing PATENT-1 without ongoing riociguat-related SAEs. All pts received riociguat adjusted up to 2.5 mg tid. Primary endpoints were safety and tolerability; secondary endpoints included 6MWD and WHO FC.

Of 405 pts completing PATENT-1, 396 (98%) entered PATENT-2. At this cut-off (March 2014), 275 (69%) pts were ongoing, 307 (78%) had received ≥2 yrs of treatment and 13 (3%) had switched to the commercial drug. Riociguat was well tolerated; 10% of pts withdrew due to AEs. The most common drug-related AEs were dizziness (10%), headache (8%) and dyspepsia (9%). There were 13 (3%) drug-related SAEs of syncope and 4 (1%) drug-related SAEs of pulmonary bleeding. Mean±SD 6MWD increased from PATENT-1 baseline by +37±52 m in riociguat 2.5 mg–maximum pts vs +12±58 m in placebo pts at the end of PATENT-1 and by +47±85 m at 2 yrs (n=296). At the end of PATENT-1, WHO FC improved/stabilized/worsened in 21/78/2% of riociguat 2.5 mg–maximum pts vs 16/75/9% of placebo pts; proportions were 33/58/9% at 2 yrs (n=306). At 2 yrs, survival was 93% and 17% of former therapy-naive pts were receiving additional PAH therapy. Analyses of correlation between efficacy endpoints and long-term outcomes will be presented.

Riociguat has a good long-term safety profile and shows sustained clinical effect for up to 2 yrs in PAH pts.
Electron Microscopic Study of Polyoma-Induced Salivary Gland Tumors, With Special Reference to Cell-Virus Interactions&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Masakatsu Imamura
Journal: JNCI Journal of the National Cancer Institute (1968)

Polyoma-induced salivary gland tumors of AKR mice were studied by electron microscopy. Occasionally the tumor cells contained many intranuclear virus particles, approximately 42 mμ in diameter, of less density and with a vague contour. Similar particles were often observed in close contact with the chromosomes of the tumor cells undergoing mitosis. Also, the fine structure of virus-containing tumor cells showed little difference from that of tumor cells with no virus particles. Thus 42 mμ particles (large particles) in the tumor cell nuclei may not play a specific role in the maintenance of the tumor cell and may not be directly responsible for the prevention of tumor cell division. A few macrophages, frequently included in these tumor tissues, contained numerous virus particles 38 mμ in diameter (small particles), i.e., type D particles, within the cytoplasm. These were mainly associated with phagosomes or large vacuoles, frequently showing a crystalline arrangement. The differences between these two types of round particles are discussed in relation to the host cell-virus interaction. In addition, 50–60 mμ particles, with an outer coat, and long filaments were observed. Inasmuch as the long filament is considered a developmental form of the virus, its presence in dividing tumor cells indicates the coexistence of cell mitosis and virus multiplication.