tbuckley/cabot-search huggingface dataset:
Does timing of initiation influence acceptance and adherence to NIV in patients with ALS?
Authors: M. Vitacca, P. Banfi, A. Montini, M. Paneroni
Journal: Pulmonology (2019)

The role of nocturnal non invasive ventilation (NIV) to prolong tracheostomy-free survival, is still controversial in amyotrophic lateral sclerosis (ALS) patients and the best timing to initiate NIV is unclear. As NIV acceptance and adherence can be influenced by many factors, we aimed to compare immediate acceptance and short-term NIV adherence between NIV initiated very early and NIV initiated later. This is a post hoc analysis of our previous cohort retrospective study of 88 ALS patients: 53 under later NIV (late group – LG) (forced vital capacity [FVC] < 80% pred. at NIV prescription) and 35 under very early NIV (very early group – VEG) (FVC > 80%). We compared hours of NIV use as immediate acceptance of NIV (use ≥4 h/night) and dherence at 4 months post-initiation (defined as use ≥4 h/night or 120 h/month). No differences were found between VEG and LG in use of NIV (>5 h/night in both groups), immediate acceptance (85.7% vs. 85.0%, p = 0.927) and short-term adherence (81.3% vs. 87.2%, p = 0.469); 39.7% of patients increased their NIV use (35% by >60 min/night). A decline in adherence was observed in 12.5% of patients irrespective of group affiliation. In ALS patients, initiation of very early NIV does not reduce its immediate acceptance or the short-term adherence. However, at least 1 in 10 patients may be at risk of reducing their adherence irrespective of early or late NIV prescription. As still under debate and not conclusive, further literature on early NIV benefit is welcomed.
"The Old Swimmin'-Hole"
Authors: E.J. H.
Journal: Annals of Internal Medicine (1971)

Editorial Notes1 June 1971"The Old Swimmin'-Hole"E.J. H.E.J. H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-6-1009_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the nineteenth century James Whitcomb Riley could look back to the summer skinny-dip with untroubled pleasure ( 1 ):Oh! the old swimmin'-hole! In the happy days of yore,When I ust to lean above it on the old sickamore,Oh! it showed me a face in its warm sunny tideThat gazed back at me so gay and glorified,It made me love myself, as I leaped to caressMy shadder smilin' up at me with sich tenderness.If Riley were a twentieth-century physician he might now see the "gay and glorified" face wrinkled a bit by the...References1. RILEY J: The Old Swimmin'-Hole, in The Complete Works of James Whitcomb Riley, Biographical Ed., vol 2, Indianapolis, The Bobbs-Merrill Co., 1913, pp. 414-416 Google Scholar2. PLORDEFELDMANBENNETT JHI: Infections due to Hartmannella, in Harrison's Principles of Internal Medicine, 6th ed., edited by WINTROBE MW, THORN GW, ADAMS RD, et al. New York, McGraw-Hill Book Co., 1970, p. 1030 Google Scholar3. DUMAROSENBLUMMCGEHEE RWR: Primary amoebic meningoencephalitis caused by Naegleria. Two new cases, response to amphotericin B, and a review. Ann Intern Med 74:923-931, 1971 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1971Volume 74, Issue 6Page: 1009-1009 ePublished: 1 December 2008 Issue Published: 1 June 1971 PDF downloadLoading ...
The influence of diabetes severity on guideline-concordant treatment for stage I-III breast cancer in the National Program of Cancer Registries (NPCR) patterns of care for breast and prostate cancer study (POCBP).
Authors: Susan A. Sabatino, Trevor Thompson, Xiao-cheng Wu, Gretchen Genevieve Kimmick, Steven Fleming, Amy Trentham-Dietz, Rosemary Cress, Roger T. Anderson
Journal: Journal of Clinical Oncology (2013)

6606 Background: Little is known about whether diabetes status or severity affects receipt of guideline-concordant breast cancer treatment, which may impact outcomes. Methods: We used data from a Centers for Disease Control and Prevention NPCR funded 7 state Patterns of Care study for 6912 stage I-III breast cancer cases diagnosed in 2004. We determined diabetes status and severity using the Adult Comorbidity Evaluation Index (ACE 27). We used National Comprehensive Cancer Network guidelines to define guideline concordant locoregional treatment (LR), adjuvant chemotherapy (CTX) and hormonal therapy. Using logistic regression models, we examined the association of diabetes severity with each treatment modality adjusting for age, race/ethnicity, area-level education and income, insurance, registry, BMI, comorbidity, tumor size, nodal status, histology, ER/PR status, HER2 status and grade. Results: Over 10% of women had diabetes (8.6% mild, 1.6% moderate/severe). Before adjustment, diabetes status was associated with lower guideline concordance for both LR treatment (82.1% vs. 86.3%, p=.01) and CTX (56.4% vs. 69.4%, p&lt;.0001), and increasing diabetes severity was associated with decreasing guideline concordance for LR (86.3%, 82.7% and 79.3% for none, mild and moderate/severe respectively, p=.028) and CTX (69.4%, 57.5% and 50.4% respectively, p&lt;.0001). After adjusting for all factors, diabetes severity was not significantly associated with LR treatment (OR 0.93 (95% CI 0.73 - 1.19) for mild and 0.74 (0.46 - 1.20) for moderate/severe vs. none, p=.43) or CTX (0.91 (0.73 - 1.13) for mild and 0.67 (0.41 - 1.10) for moderate/severe vs. none, p=.23). After adjusting first for sociodemographic factors, then adding comorbidity and BMI, and finally tumor characteristics, significance of diabetes severity was lost after adjusting for sociodemographic factors, largely due to age. Conclusions: Breast cancer patients with diabetes are less likely to receive guideline concordant LR treatment and CTX, with increasing severity associated with lower receipt. However differences appear largely due to age.
Abstract LB-117: Increased peripheral glucose levels restores chemotherapeutic efficacy in a mouse model of pancreatic cancer
Authors: Ali Vaziri-Gohar, Imran Khokhar, George Titomihelakis, Jonathan R. Brody, Jordan M. Winter
Journal: Cancer Research (2019)

Abstract Pancreatic cancer is the third leading cause of cancer-related death in the United States. The 5-year survival rate is less than 10% and less than 5% for patients with metastatic disease due to the lack of effective therapy. Therefore, searching for novel therapies or strategies to improve existing therapies is a high priority in the field. The pancreatic cancer microenvironment comprises the majority of the tumor mass, and is characterized by a dense, fibrotic stroma, high interstitial fluid pressure and diminished vascularity. This creates a large nutrient gradient, such that pancreatic cancers must adapt to severely austere conditions to survive. We previously demonstrated that the harsh, nutrient-deprived conditions directly resulted in aggressive pancreatic cancer biology and chemotherapy resistance, in part due to activation of a stress response protein, HuR (ELAVL1). It also followed that higher blood glucose levels (e.g., diabetics) correlated with longer disease-free survival in pancreatic cancer patients who received gemcitabine after tumor resection. Herein, we extend this line of investigation in an in vivo mouse model of pancreatic cancer. First, we induced moderate hyperglycemia using a single dose of streptozotocin (120 mg/kg), which destroys beta islets in the pancreas. Blood glucose levels were titrated to a “non-toxic” level (~300 mg/dL) through daily injections of long-acting insulin, glargine. In a second independent model, we induced mild hyperglycemia by adding dextrose to the drinking water (30% dextrose). In both models, blood glucose levels and body weights were measured weekly, and mice were examined for the signs of distress. Interestingly, low-dose gemcitabine treatment, 50 mg/kg twice per week, significantly inhibited PDA xenograft growth under moderate and mild hyperglycemia. However, gemcitabine had no benefit in euglycemic mice with especially low levels of glucose in the xenograft microenvironment. These results demonstrate that chemotherapeutic efficacy may be potentially enhanced through forced induction of hyperglycemia in patients receiving chemotherapy. Citation Format: Ali Vaziri-Gohar, Imran Khokhar, George Titomihelakis, Jonathan R. Brody, Jordan M. Winter. Increased peripheral glucose levels restores chemotherapeutic efficacy in a mouse model of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-117.
<i>K-Ras</i> mutation (mut), EGFR-related, and exploratory markers as response predictors of cetuximab in first-line advanced NSCLC: Retrospective analyses of the BMS099 trial
Authors: S. Khambata-Ford, C. Harbison, D. Woytowitz, M. Awad, C. Horak, L. A. Xu, S. Dakhil, R. C. Hermann, T. J. Lynch, M. R. Weber
Journal: Journal of Clinical Oncology (2009)

8021 Background: This phase III study investigated cetuximab (C) plus taxane/carboplatin (TC) in 1 st -line advanced NSCLC. Progression-free survival (PFS) was not significantly different with the addition of C to TC; response rate (RR) was significantly higher; median overall survival (OS) was longer, with a difference (not statistically significant) similar in magnitude to the significant OS improvement from FLEX (cisplat/vinorelb±C). Potential patient-selection markers were analyzed, including mut in K-Ras, EGFR mut and gene copy number (GCN), EGFR protein expression, and gene expression profiles. Methods: Chemonaïve patients (pts) with stage IIIB/IV NSCLC (any histology or EGFR expression status) were randomized to TC±C. K-Ras gene exon 2, and EGFR exons 18–21 were sequenced bidirectionally using formalin-fixed paraffin embedded tissue-derived genomic DNA. EGFR GCN was measured by fluorescence in situ hybridization (FISH) and EGFR protein expression by immunohistochemistry (IHC). Exploratory expression profiling studies using Affymetrix GeneChip are ongoing. Analyses were blinded to clinical outcome. The relationships between biomarker status and efficacy were assessed with log-rank tests per study arm for treatment-specific effects, and across the total evaluable population. Results: Samples from 225/676 randomized pts were available; 35/202 (17%) had K-Ras mut, 17/167 (10%) had EGFR mut, 54/104 (52%) were EGFR FISH+, 131/148 (89%) were EGFR IHC+. There were no significant treatment-specific correlations between any biomarker assessed and PFS, OS or RR, except superior OS with TC for the EGFR FISH+ group (P=0.03). With all pts combined, OS was longer in the EGFR mut subset vs wt (P=0.09); PFS was longer in EGFR IHC- pts vs IHC+ (P=0.048). Results from gene expression profiling studies, including EGFR ligands, will be presented. Conclusions: There was no significant correlation between patient response to C and any molecular marker evaluated to date (K-RAS mut, EGFR mut, EGFR IHC, EGFR FISH), exploratory analyses are ongoing. Additional predictive-marker studies are needed to optimize cetuximab therapeutic use in NSCLC. [Table: see text]
Elderly subgroup analysis of a randomized phase 3 trial of gemcitabine (G) in combination with carboplatin (Cb) or paclitaxel (P) compared to paclitaxel plus carboplatin in advanced (stage IIIB, IV) non-small cell lung cancer (NSCLC)
Authors: R. H. Ansari, R. Gonin, M. Socinski, M. Edelman, R. Catalano, D. Marinucci, R. Comis, C. Obasaju, J. A. Treat, C. P. Belani
Journal: Journal of Clinical Oncology (2007)

7665 Background: Efficacy and safety of platinum-based chemotherapy doublets in elderly (ELD) NSCLC pts with good PS have been reported to be similar to those in younger pts (N-ELD). However, little data exists about which of the standard regimens are suitable for the ELD. To compare efficacy and safety of doublet regimens in the ELD, we conducted a retrospective age-specific subgroup analysis of our Phase 3 randomized trial comparing 3 regimens for advanced NSCLC (Treat, et al: Abst#7025, Proc ASCO 2005). Methods: A Phase 3 study in advanced (Stage IIIB/IV) NSCLC chemonaive patients with ECOG PS &lt;2 was designed to compare the efficacy of a G-containing platinum regimen GCb (G 1000 mg/m 2 IV D 1, 8 plus Cb AUC 5.5, D 1) to a nonplatinum G doublet GP (G 1000 mg/m 2 IV D 1,8 plus P 200 mg/m 2 , D 1) and a reference regimen of PCb (P 225 mg/m 2 plus Cb AUC 6.0, D 1). Outcome data of ELD pts (age =70) vs. N-ELD pts (age &lt;70) were compared. Survival (OS) was the primary endpoint with secondary endpoints being response rate (RR), time to progression (TTP) and toxicity. Data from all 3 arms were pooled for this analysis. Results: A total of 314 ELD and 746 N- ELD pts were analyzed (GCb 111/245, GP 100/251, PCb 103/250). There were no significant differences in the OS or TTP distributions in ELD compared to N-ELD pts ( Table 1 ). In general, the incidence and grade of toxicity in ELD vs. N-ELD were comparable. ELD experienced moderately higher incidences of Grade 3–4 constitutional (12.6% vs. 7.1%), neurologic (16.1% vs. 8.9%), and pulmonary (12.3% vs. 7.9%) toxicities compared with N-ELD pts. Conclusion: Use of G-containing doublets as first-line chemotherapy showed similar efficacy to the standard PCb regimen in ELD and N-ELD patients with advanced/metastatic NSCLC as defined by OS, RR, and TTP. ELD tolerated these regimens well despite experiencing slightly more toxicity than younger patients. No significant financial relationships to disclose. [Table: see text]
Darbepoetin Alfa for the Treatment of Anemic Patients with Myelodysplastic Syndrome: A Belgian Single-Arm, Companion Trial to the Arcade Phase 3 Study
Authors: Michel Delforge, Dominiek Mazure, Isabelle Vande Broek, Jo Caers, Sejal Badre, Bhakti Mehta, Cisio De Oliveira Brandao
Journal: Blood (2017)
Positron emission tomography for the assessment of survival after subsequent surgery in multimodality treatment for patients with locally advanced esophageal squamous cell carcinoma.
Authors: Manabu Emi
Journal: Journal of Clinical Oncology (2012)

e14636 Background: Recent studies imply that positron emission tomography with fludeoxyglucose F 18(FDG-PET) correlates with histopathologic response and survival in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (CRT) followed by surgical resection. To evaluate the rating system of FDG-PET after the completion of neoadjuvant CRT for the assessment of histopathologic response and prognosis inthe multimodality treatment of patients with esophageal cancer. Methods: Seventy patients (58 men, 12 women; median age, 61 years) with locally advanced esophageal squamous cell carcinoma who received neoadjuvant CRT underwent FDG-PET before chemoradiotherapy and transthoracic en bloc esophagectomy in evaluation of pathologic response to CRT and postoperative survival. Lack of FDG uptake was defined as primary tumors with SUVmax at least 2.5, and FDG-PET complete response after CRT (PET-CR) was defined as SUVmax&lt;2.5 or SUVmax&lt;3 with mild hyper metabolic activity around the primary tumor. Results: After CRT, lack of FDG uptake was noted 34 patients, PET-CR was noted 49 patients and pathological CR was noted 31 patients. PET-CR indicated stronger correlation with postoperative survival than lack of FDG uptake and rate of decrease in SUV. PET-CR and pathologic CR predicted for improved outcomes (3-year disease free survival 70.3% vs 42.6% P=0.0032; log-rank test, 76.4% vs 37.6% P=0.0008; log-lank test). But on multivariate analysis using the Cox proportional hazards model, only pathologic CR was found to be correlated with post-CRT disease free survival (HR 0.190, 95%CI 0.049-0.73, P=0.017). Conclusions: To evaluate the value of FDG-PET for the assessment of prognosis in the multimodality treatment for patients with locally advanced esophageal squamous cell carcinoma, we tried different rating system of FDG-PET but no recommendation was made for the use of FDG-PET.
PM’s £1.8bn pledge for NHS buildings is “drop in the ocean,” say experts
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Boris Johnson has announced that his government will release £1.8bn (€2bn; $2.2bn) to fund new equipment and buildings at selected sites across England.

Twenty hospital trusts and primary care organisations in England (box 1) will receive a share of £850m in new capital funding to enable them to upgrade outdated facilities and equipment. An additional £1bn will be released by the Treasury from surplus reserves to allow existing projects to update facilities and infrastructure to proceed.

Healthcare leaders and experts have welcomed the announcement but said the funding fell well short of what was needed to clear the huge £6bn backlog of NHS maintenance costs.

Johnson made the announcement on Monday 5 August during a visit to Boston Pilgrim Hospital of the United Lincolnshire Hospitals NHS Trust, one of the organisations that will benefit from the funding. It is part of a package of new announcements on the NHS expected this week. On 7 August the government was due to announce a “new, more flexible” consultation on NHS pensions for senior doctors. It said it would issue guidance to all NHS trusts on actions they may take to mitigate the immediate pensions difficulties facing …
Abstract 9790: Endothelin-1 Inhibits Endothelium-Dependent NO-Mediated Dilation of Coronary Arterioles via p38 Kinase Linked Superoxide Production From NAD(P)H Oxidase
Authors: Naris Thengchaisri, Travis W Hein, Yi Ren, Lih Kuo
Journal: Circulation (2011)

Elevated levels of endothelin (ET)-1, a potent constrictor peptide, are associated with higher risk of cardiovascular diseases by promoting vasoconstriction and oxidative stress. However, it remains unknown whether ET-1, at subvasomotor concentrations, exerts adverse effects on coronary vasomotor function. To address this issue without confounding influences from systemic and local factors, porcine coronary arterioles (50-100 μm) were isolated, cannulated and pressurized without flow for in vitro study. Diameter changes were recorded using a videomicrometer. Dihydroethidium (DHE) staining was used to detect superoxide production. Arterioles developed basal tone (60±3 µm) and dilated dose-dependently to the endothelium-dependent NO-mediated vasodilators serotonin (1 nM to 0.1 µM) and adenosine (1 nM to 10 µM). Extraluminal incubation with a clinically relevant subvasomotor concentration of ET-1 (10 pM, 60 minutes) significantly attenuated arteriolar dilation to adenosine and serotonin but not to endothelium-independent vasodilator sodium nitroprusside. The adverse effects of ET-1 on serotonin- and adenosine-induced dilations were prevented by pretreating the vessels with the ETA receptor antagonist BQ123 (1 μM), the superoxide scavenger TEMPOL (1 mM), the NAD(P)H oxidase inhibitor apocynin (100 μM) or the p38 kinase inhibitor SB203580 (0.1 μM). However, the adverse effects of ET-1 were not prevented by pretreating the vessels with ETB receptor antagonist BQ788 (0.1 μM), H2O2 scavenger catalase (1000 units/ml), xanthine oxidase inhibitor allopurinol (10 μM) or c-Jun N-terminal kinase inhibitor SP600125 (5 μM). DHE immunohistochemical staining showed that ET-1 generated TEMPOL- and SB203580-sensitive superoxide production in the arteriolar endothelium. Collectively, our data indicate that exposure of coronary arterioles to a pathophysiological concentration of ET-1 inhibits endothelium-dependent NO-mediated dilation in coronary arterioles by activation of ETA receptors leading to the production of superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase activation.
Phase I study of combination chemotherapy with irinotecan and gemcitabine for taxane/platinum resistant ovarian, fallopian tube, or primary peritoneal cancer.
Authors: Kiyoshi Yoshino, Shoji Kamiura, Haruki Ogawa, Atsushi Tokuhira, Masahiko Takemura, Kenjiro Sawada, Yutaka Ueda, Seiji Mabuchi, Masami Fujita, Tateki Tsutsui, Tadashi Kimura
Journal: Journal of Clinical Oncology (2013)

5538 Background: Development of new regimen is required to overcome platinum resistant ovarian cancer. Irinotecan and gemcitabine have a synergistic effect to inhibit the growth of ovarian cancer cell line in vitro. The objective is to evaluate the feasibility of combination chemotherapy with irinotecan and gemcitabine for taxane/platinum resistant recurrent ovarian, fallopian tube or peritoneal cancer and to determine the recommended dose. Methods: Nine patients with measurable disease (age range 51-70 years) were enrolled. Patients were treated with irinotecan and gemcitabine on days 1 and 8 every 3 weeks with starting dose of level 1. Dose levels included irinotecan/gemcitabine: 65/650 (level 0), 80/800 (level 1), 100/1000 (level 2), mg/m 2 respectively. Level 2 is defined as the maximum dose as used in other malignancies. Dose-limiting toxicity (DLT) was assessed during the first cycle; toxicities were monitored throughout the treatment according to the CTCAE v4.0. Treatment continued until disease progression or unacceptable toxicity. Results: In level 1 (n = 6), grade 3/4 neutropenia was observed in 5 patients. Grade 3 nausea and vomiting was observed in 1, grade 3 diarrhea in 1. One patient of level 1 experienced DLTs. In level 2 (n = 3), grade 3/4 neutropenia are observed in 3, anemia in 1, and thrombocytopenia in one patient. Other toxicities were mild. Three patients who received level 2 did not show DLT. The objective response was CR/PR/SD/PD, 0/2/5/2. Conclusions: The dose level of irinotecan 100 mg/m 2 and gemcitabine 1000 mg/m 2 on day 1 and 8 every 3 weeks is recommended for a phase II study. Clinical trial information: UMIN000005926.