tbuckley/cabot-search huggingface dataset:
Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method.
Authors: V Dieras, J M Extra, E Bellissant, M Espie, F Morvan, J Y Pierga, L Mignot, P Tresca, M Marty
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer. PATIENTS AND METHODS As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks. RESULTS Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%. CONCLUSION This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.
Book: Living Proof: A Medical Mutiny
Authors: R. Camidge
Journal: BMJ (2002)

Michael Gearin-Tosh

Scribner, £14.99, pp 327 ISBN 0 7432 0677 0

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A series of articles about Living Proof and its author—an Oxford English tutor “battling” myeloma through diet rather than chemotherapy—appeared recently in the Times . Any doctor reading them could be forgiven for prejudging Gearin-Tosh as an academic revealing nothing more than his ignorance of bell-shaped survival curves (which show that it's totally possible to live longer than the average and still not be cured). Yet one message to glean from both the press coverage and this …

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Managing patient pathways to achieve lung cancer waiting time targets: Mixed method study
Authors: Hugh Ip, Tarik Amer, Michael Dangoor, Affan Zamir, Darryl Gibbings-Isaac, Ranjeev Kochhar, Timothy Heymann
Journal: European Respiratory Journal (2011)

Background: England's NHS introduced a 62-day target, from referral to treatment, to make lung cancer patient pathways more efficient. This study aims to understand pathway delays that lead to breaches of the target when patients need care in both secondary and tertiary setting so more than one institution is involved.

Methods: Mixed method cross case analysis. Qualitative methods include pathway mapping and semi-structured interviews. Quantitative analysis of patient pathway times from cancer services records.

Setting: Two tertiary referral hospitals in London

Participants: Database records of 53 patients were analysed. 19 sets of patient notes were used for pathway mapping. 17 doctors, 4 nurses, 8 managers and administrators were interviewed.

Results: The majority of the patient pathway (68.4%) is spent in secondary centres. There is more variability in the processes of secondary centres but tertiary centres do not have perfect processes either.

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Three themes emerged from discussions: information flows, pathway performance, and the role of the multidisciplinary approach.

Conclusions: The actions of secondary centres have a greater influence on whether a patient breaches the 62-day target, compared to tertiary centres. Nevertheless variability exists in both, with potential for improvement.

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Clinical patterns of severe CAP (sCAP) under NIV in a RICU: A real life study
Authors: Raffaele Scala, Uberto Maccari, Giuseppina Ciarleglio, Carmen Manta, Valentina Granese, Claudia Maggiorelli, Benedetta Campolo
Journal: European Respiratory Journal (2013)

Objective: To study clinical features and outcomes of sCAP receiving an early NIV trial in a RICU. Methods : Consecutive patients with sCAP (CID/ATS 2007) and moderate-severe hypoxemic ARF (PaO2/FiO2:100-300) submitted to NIV in the years 2005-2010 in a 3-bed-RICU were evaluated. Underlying diseases (de-novo vs chronic disorders), blood gases (pure hypoxemic vs hypoxemic-hypercapnic), hospital sources (home vs ED vs step-up vs step up), severity scores (Apache III) and clinical-hospital outcomes (ETI need and hospital mortality) were investigated. Results: Among 643 patients treated with NIV in the study-time, 118 (18.2%) full-filled sCAP criteria (mean values: pH 7.307, PaO2/FiO2 116, PaCO2 70.3 mmHg; APACHE II 69.5). NIV failure and hospital mortality were respectively 28% and 23%. Relative incidence of sCAP was greater in ARDS (10/12: 83.3%) vs other diseases (p<0.05). Absolute incidence of sCAP was greater in COPD (61%) vs other diseases (CWD+Fibrothorax, 9.3%; ARDS 8,5%; ALS/MND, 8.5%; CHF, 6.8%; OHS,3,4%; Diffuse-lung-diseases, 2.5%) (p<0.05), and, accordingly, in hypoxemic-hypercapnic ARF (80.5%) vs pure hypoxemic ARF (19.5%) (p<0.05). More patients came from ED (61%) as compared to those admitted in “step-down” from ICU (18.6%), in “step-up” from wards (11.0%) and home (8.5%) (p<0.05). NIV failure was higher in ALS/MND (60%) and ARDS (40%) vs other diseases; hospital mortality was higher in Diffuse-lung-disease (33.3%), ALS/MND (30%) and ARDS (27.3%) vs other diseases. NIV failure was independently predicted by Apache III, baseline PaO2/FiO2, extra-pulmonary complications. Conclusions: Clinical pattern of sCPAP under NIV in a RICU is heterogeneous with a greater incidence in COPD and higher failure rate in ARDS and ALS/MND. Severity of hypoxemia and of multi-organ dysfunction are strongest predictors of failure.
Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force
Authors: Carrie D. Patnode, Jillian T. Henderson, Jamie H. Thompson, Caitlyn A. Senger, Stephen P. Fortmann, Evelyn P. Whitlock
Journal: Annals of Internal Medicine (2015)

Background: Tobacco use is the leading cause of preventable death in the United States. Purpose: To review the effectiveness and safety of pharmacotherapy and behavioral interventions for tobacco cessation. Data Sources: 5 databases and 8 organizational Web sites were searched through 1 August 2014 for systematic reviews, and PubMed was searched through 1 March 2015 for trials on electronic nicotine delivery systems. Study Selection: Two reviewers examined 114 articles to identify English-language reviews that reported health, cessation, or adverse outcomes. Data Extraction: One reviewer abstracted data from good- and fair-quality reviews, and a second checked for accuracy. Data Synthesis: 54 reviews were included. Behavioral interventions increased smoking cessation at 6 months or more (physician advice had a pooled risk ratio [RR] of 1.76 [95% CI, 1.58 to 1.96]). Nicotine replacement therapy (RR, 1.60 [CI, 1.53 to 1.68]), bupropion (RR, 1.62 [CI, 1.49 to 1.76]), and varenicline (RR, 2.27 [CI, 2.02 to 2.55]) were also effective for smoking cessation. Combined behavioral and pharmacotherapy interventions increased cessation by 82% compared with minimal intervention or usual care (RR, 1.82 [CI, 1.66 to 2.00]). None of the drugs were associated with major cardiovascular adverse events. Only 2 trials addressed efficacy of electronic cigarettes for smoking cessation and found no benefit. Among pregnant women, behavioral interventions benefited cessation and perinatal health; effects of nicotine replacement therapy were not significant. Limitation: Evidence published after each review's last search date was not included. Conclusion: Behavioral and pharmacotherapy interventions improve rates of smoking cessation among the general adult population, alone or in combination. Data on the effectiveness and safety of electronic nicotine delivery systems are limited. Primary Funding Source: Agency for Healthcare Research and Quality.
Doxorubicin-Induced Impairment of Wound Healing in Rats
Authors: W T Lawrence, J A Norton, A K Harvey, C M Gorschboth, T L Talbot, G R Grotendorst
Journal: JNCI Journal of the National Cancer Institute (1986)

The mortality rate induced by 3 doses of iv doxorubicin was evaluated in F344 rats, and a dose of 8 mg doxorubicin/kg body weight was the maximum dose tolerated with an acceptable mortality rate. Rats treated with 8 mg doxorubicin/kg prior to or on the day of wounding demonstrated decreased wound breaking strength in incisional wounds at all intervals after wounding. Decreased amounts of collagen and DNA and less cellularity were noted in wound chambers from rats treated in the same manner. In both the incisional wound and wound chamber models, rats treated with doxorubicin 7 days after wounding showed a less dramatic healing impairment. No difference in collagen types was noted between chambers from the doxorubicin-treated and untreated rats. Doxorubicin also produced a significant reduction in platelet and white blood cell counts 1 week after it was administered. The data indicate that doxorubicin impedes healing by decreasing wound cellularity and collagen synthesis.
Abstract IA05: Circulating tumor cells in lung cancer: Biomarkers, biology, and mouse models to study drug resistance
Authors: Caroline Dive, Chris Morrow, Ged Brady, Fiona Blackhall
Journal: Clinical Cancer Research (2015)

Abstract SCLC patients (∼75%) respond well initially to standard chemotherapy (platinum/etoposide) but drug resistant disease relapse ensues rapidly. Most Small Cell Lung Cancer (SCLC) patients present with metastases, consequently tumor resection is rare and tumor biopsy is rarely obtained at disease relapse to explore drug resistance mechanisms. Targeted therapies have yet to impact SCLC patient outcomes, new drug targets and biomarkers measured in minimally invasive samples are required. Using EpCam dependent CellSearch technology, we showed that CTCs are prevalent in SCLC and CTC number is an independent prognosticator. SCLC CTC number is pharamcodynamic and CTCs are amenable to biomarker assay development (protein expression, omic profiling, FISH etc.) to be applied in clinical trials. We also developed unique patient CTC derived mouse models (CDX) to study SCLC biology, search for new drug targets, develop biomarkers and explore drug resistance mechanisms. Successful CDX engraftment has been observed so far in ∼45% cases. The molecular landscape of CDX can be compared to that of single, isolated CTCs from the same patient. CDX are readily passaged and their response to cisplatin/etoposide closely mimics the donor patient. CDX offer unparalleled opportunity to interrogate drug resistance mechanisms as paired models can be generated at presentation (chemosensitive) and again at relapse (drug resistance). Our data demonstrate that serial blood sampling with CDX and CTC molecular analysis could facilitate delivery of precision medicine to improve outcomes in SCLC. A program of evaluation of novel therapeutics in CDX models, the development of orthotopic CDX SCLC and NSCLC CDX are underway. Citation Format: Caroline Dive, Chris Morrow, Ged Brady, Fiona Blackhall. Circulating tumor cells in lung cancer: Biomarkers, biology, and mouse models to study drug resistance. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA05.
Bronchodilator intake and plasma levels on admission for severe acute asthma
Authors: C Janson, J Boe, G Boman, B Mossberg, N Svedmyr
Journal: European Respiratory Journal (1992)

We have measured the plasma levels of salbutamol, terbutaline and theophylline in 140 patients (70 men, mean age 57 yrs) arriving for emergency treatment with severe acute asthma. The aim of the study was to investigate how the measured plasma levels correlated with the reported bronchodilator intake and whether the pretreatment beta 2-agonist levels influenced the effect of emergency salbutamol treatment. We found a highly significant correlation between the reported 24 h dose and the measured plasma concentrations for all three drugs. A plasma concentration less than 40 mumol.l-1 was found in 63 of the 107 patients who had taken theophylline, while no patient had a plasma concentration greater than 110 mumol.l-1. A plasma concentration above the suggested therapeutic range was found in 23 of the 95 patients who had taken terbutaline (greater than 30 nmol.l-1) and in 12 of the 98 patients who had taken salbutamol (greater than 60 nmol.l-1). A significant negative correlation was found between the initial plasma beta 2-agonist levels and the bronchodilation after i.v. salbutamol treatment (5 micrograms.kg-1), while there was no clear indication that high plasma beta 2-agonist levels reduced the bronchodilator effect of a high dose of inhaled salbutamol (0.15 mg.kg-1 x 2). We conclude that some patients arriving with acute asthma have high blood concentrations of beta 2-agonists, which possibly limit the response to i.v. beta 2-agonist treatment, while the effect of high-dose inhaled beta 2-agonists appears to be related to a lesser degree to the drug concentration on arrival. In this study overtreatment with theophylline appears to be uncommon.
The proteomic profile of hair damage
Authors: R. Sinclair, M.J. Flagler, L. Jones, N. Rufaut, M.G. Davis
Journal: British Journal of Dermatology (2012)

Journal Article The proteomic profile of hair damage Get access R. Sinclair, R. Sinclair University of Melbourne and Epworth Hospital, Melbourne, Vic., Australia Search for other works by this author on: Oxford Academic Google Scholar M.J. Flagler, M.J. Flagler Procter & Gamble Beauty Technology Division, 11810 East Miami River Road, Cincinnati, OH 45252, U.S.A Search for other works by this author on: Oxford Academic Google Scholar L. Jones, L. Jones Department of Medicine (Dermatology), University of Melbourne, Melbourne, Vic., Australia Search for other works by this author on: Oxford Academic Google Scholar N. Rufaut, N. Rufaut Department of Medicine (Dermatology), University of Melbourne, Melbourne, Vic., Australia Search for other works by this author on: Oxford Academic Google Scholar M.G. Davis M.G. Davis Procter & Gamble Beauty Technology Division, 11810 East Miami River Road, Cincinnati, OH 45252, U.S.A Michael G. Davis. E‐mail: davis.mg.2@pg.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue s2, 1 June 2012, Pages 27–32, https://doi.org/10.1111/j.1365-2133.2012.10862.x Published: 01 June 2012 Article history Accepted: 17 September 2011 Published: 01 June 2012
The prognostic significance of residual pigmentation following radiotherapy of epidemic Kaposi's sarcoma.
Authors: J S Cooper, A D Steinfeld, I A Lerch
Journal: Journal of Clinical Oncology (1989)

The response to radiotherapy of epidemic Kaposi's sarcoma (EKS) is unusual in that irradiated regions are frequently left with a persistent purple stain, reminiscent of the color of the original tumor, but with no tumor mass. To date there are no published data to indicate whether the persistence of pigmentation can be predicted beforehand or if it has any prognostic import. We reviewed the response to treatment of 118 EKS lesions that were irradiated at New York University (NYU) Medical Center between 1981 and 1986. A total of 86 responded to treatment by complete clearance of the mass. Of these, 29 left residual purple pigmentation within the treatment portal, while 57 did not. Complete response (CR; without residual pigmentation) occurred more often in patients who had higher Karnofsky scores at the time of treatment. However, in terms of ultimate local control or survival, there were no differences between patients whose lesions cleared completely v those in whom pigmentation remained. We conclude that persistent pigmentation represents only a benign remnant of irradiated EKS and has no prognostic import.
Immunopotentiation With BCG. IV. Factors Affecting the Magnitude of an Antitumor Response2
Authors: Eugenia Hawrylko, G. B. Mackaness
Journal: JNCI Journal of the National Cancer Institute (1973)

The immunopotentiating activity of BCG was studied in a test system that measured the capacity of irradiated murine tumor cells (mastocytoma, P815) to provoke systemic Immunity when injected into sites prepared by a prior injection of BCG; a tumor located remotely in the footpad was monitored for evidence of specific resistance. The time of onset and duration of immunity were established, and 3 variables affecting the degree of immunopotentiation were evaluated. The first sign of tumor inhibition occurred 7 days after the tumor-specific immunogenic stimulus was introduced, and maximum tumor immunity was achieved when the irradiated tumor cells were injected 10 days after the priming dose of BCG. The frequency of tumor suppression and overall survival rates were increased by raising the priming dose of BCG, but raising the dose of irradiated tumor cells beyond a certain optimum caused less suppression and lowersurvival rates. As previously observed, a significant level of antitumor immunity developed only when irradiated tumor cells were injected into BCG-infected sites; neither BCG nor irrad iated cells alone had any significant tumor-suppressive effect.
Chest CT-findings after hematopoietic stem cell transplantation
Authors: Caroline Barthels, Adriana Dubbeldam, Johan Coolen, Johny Verschakelen, Walter De Wever
Journal: European Respiratory Journal (2014)

Purpose: 

To evaluate CT-findings of patients after hematopoietic stem cell transplantation (HSCT) and to correlate these findings with the clinical diagnosis.

Methods & Materials: 

Between January 2010 and December 2013, 91 patients (52 male and 39 female patients; mean age 39,7 years) were found in our radiologic database who underwent chest CT after HSCT. Retrospectively 296 CT scans were evaluated. 105 CT scans were performed in follow-up setting after HSCT, 191 CT scans were performed on clinical indication (fever, cough, positive galactomannan test, suspicion of PTLD,…).

CT-examinations were evaluated on the presence of ground glass attenuation (GGO), consolidation, crazy paving pattern, bronchial abnormalities (bronchial dilatation, bronchial wall thickening, tree-in-bud), air-trapping and mosaic attenuation pattern.

Results: 

91 Patients underwent 296 CT scans. 106 CT-scans were negative, 190 CT-scans showed different CT-findings.

Table 1 showed the distribution of the different CT-findings in correlation with the clinical diagnosis.

View this table:

Table 1: Correlation between CT-findings and clinical diagnosis





Conclusion: 

GGO, consolidation, crazy paving pattern and bronchial abnormalities are CT-findings mostly seen in patients with infection. Air-trapping and mosaic attenuation patterns are signs very suggestive for GVHD.
Smoking Habits in Lung-Cancer Proband Families and Comparable Control Families&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: George K. Tokuhata
Journal: JNCI Journal of the National Cancer Institute (1963)

The pattern of the familial smoking behavior was analyzed and compared between parents, siblings, and children of 270 lung cancer probands and the counterparts of 270 controls selected within the same community. The information regarding lifetime smoking experience was ascertained for 90 percent of all living and dead relatives being studied. The distribution of parents, siblings, and children by year of birth as well as the size of sibship and of family were comparable between the two family populations. With respect to cigarette smoking among the index subjects the following findings may be of interest: 1) Smoking at young ages is related to lung cancer. 2) The amount of daily smoking (one pack or more) is related to lung cancer. 3) The duration of smoking (40 years or more) is related to lung cancer. Three different aspects of cigarette smoking among the relatives were analyzed with the following results: 1) The relatives of the lung cancer probands are more likely to be smokers than those of the controls. 2) About 40 percent of the case relatives are smokers regardless of the smoking status of the probands; in contrast, 40 percent of those control relatives whose index subjects are smokers, as compared with 30 percent of those control relatives whose index subjects are nonsmokers, are smokers. 3) In both proband and control families, children are more likely to be smokers if their parents are smokers. The results of our analyses do not seem to support R. A. Fisher's “common genotype” hypothesis regarding lung cancer and smoking behavior.
Altered imbalance between Th17 and regulatory T-cells and impaired Th1 response in the recovery of multidrug-resistant tuberculosis
Authors: Qi Tan, Rui Min, Hong Wang, Weiping Xie, Zhihui Xu, Weiguo Xu, Mao Huang, Chunyan Shi, Hongqiu Pan
Journal: European Respiratory Journal (2012)

OBJECTIVE: Multidrug-resistant tuberculousis(MDR-TB), a lethal global threat today, requires prolonged and expensive second-line drugs of heightened toxicity. A dysregulation of CD4 + T cell subsets, found in the pathogenesis of TB, is a crucial question still unsolved in MDR-TB. Insights into MDR-TB immune responses are urgent for developing new solutions . METHODS: We phenotypically examined circulating T-helper(Th)17 cells, regulatory T cells(Tregs),Th1,Th2 cells by flow cytometric detection in 26 MDR-TB patients, 26 drug-sensitive TB patients(DS-TBs) and 26 healthy subjects(HCs). The levels of circulating T cell subsets were further analyzed during before/post-treatment phases in MDR-TB patients. RESULTS: We found upregulation of circulating Th17 expression(7.45±1.54)and decreased ratio of Treg/Th17(0.42±0.01) in MDR-TBs compared to HCs and DS-TBs. More remarkble suppression of Th1 cell activation was detected in MDR-TBs(11.99±0.87) than that in DS-TBs compared to HCs. Although clinical signs of MDR-TB patients did not show obvious recovery after 7 month-chemotherapy, the circulating ratio of Treg/Th17(0.88±0.13) and level of Th1(15.1±0.90) in MDR-TB patients tended to normal compared to their previous level before treatment(P<0.05). CONCLUSIONS: These data provided evidence for an unbalanced immune status of Treg/Th17 and inhibition of Th1 type immunity in MDR-TB infection, and suggested a specific role of these T cell-induced immunities during the evolution of MDR-TB. Further study on the immune homeostasis restoration of MDR-TB patients may aid in improving adjuvant immunotherapies and developing potential therapeutic strategies.