tbuckley/cabot-search huggingface dataset:
OP03 Effects of two years of liraglutide treatment on fatty liver disease in patients with type 2 diabetes: analysis of the Liraglutide Effect and Action in Diabetes-2 extension trial
Authors: M Armstrong, A Falahati, D D Houlihan, B Elbrand, W E Schmidt, S Gough, P N Newsome
Journal: Gut (2010)

Introduction  Currently there are no established treatment options for fatty liver disease. Glucagon-like peptide 1 (GLP-1) analogues have been shown to reduce hepatic steatosis and markers of liver inflammation in rodents.  Aim  To determine the efficacy of 2 years treatment with 1.8 mg liraglutide, a once-daily human GLP-1 analogue, on fatty liver disease and body composition in patients with poorly controlled type 2 diabetes (T2D).  Method  Analysis was performed on the “Liraglutide Effect and Action in Diabetes-2” (LEAD-2) study cohort. LEAD-2 was a 26-week, double blind phase III trial with a 1.5-year open-label extension. Patients were randomised (2:2:2:2:1) to liraglutide 1.8, 1.2 or 0.6 mg/day, glimepiride 4 mg/day or placebo, all in combination with metformin 1.5–2 g/day. DEXA (n=160) and computerised tomography (CT) (n=154) sub-studies were performed to measure body fat composition and hepatic steatosis (defined by a liver-to-spleen attenuation ratio   Repeated measure and ANCOVA analysis was performed using last observation carried forward on the intention-to-treat population to estimate change from baseline. Values expressed as mean (SD).  Results  529/1091 patients (58% male; 87% white; age 56.7 years (9.5); body mass index 31 kg/m 2  (4.7); HbA1c 8.4% (0.9); male alanine aminotransferase (ALT) 32.0 IU/L (17.9); female ALT 27.3 IU/L (14.9)) completed 2 years treatment. Of the subjects enrolled in the sub-study 75% had the metabolic syndrome (ATP III classification) and 65.7 % (90/137) had hepatic steatosis on CT at baseline.  Patients with elevated ALT levels (53%) at baseline (males >30, female >19 IU/L) had a significant reduction of ALT with liraglutide (−8.53 from baseline 40.9 IU/l, p  Liver-to-spleen attenuation ratio significantly increased with liraglutide (+0.10, p  Conclusion  Two years treatment with liraglutide significantly improves liver enzymes and hepatic steatosis in patients with T2D and associated fatty liver disease. Significant improvements in % body fat, in particular central adiposity support the role of liraglutide in reducing hepatic steatosis and cardiovascular morbidity.
The Consult Guys - VTE: Is There Cancer?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 January 2016The Consult Guys - VTE: Is There Cancer?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W16-0001 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Geno J. Merli, MD; Howard H. Weitz, MDDisclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorrection: The Consult Guys - A Real Headache: Anticoagulation and a Subdural Hematoma 19 January 2016Volume 164, Issue 2 Page: CG1 Keywords Disclosure Research grants Research reporting guidelines ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Ignorance about sepsis was a factor in child’s death, says report
Authors: Ingrid Torjesen
Journal: BMJ (2016)

England’s health secretary, Jeremy Hunt, has said that he will look into whether more clinicians are needed to staff the urgent care service NHS 111, after a report into the death of 1 year old William Mead from septicaemia in December 2014 found that four opportunities for preventing his death were missed.

The family’s general practice in Cornwall and the NHS 111 telephone helpline failed to diagnose and act on the septicaemia that was responsible for his death and the pneumonia that led to it, says the report, seen by The BMJ . Although the review panel concluded that “these did not constitute serious failings by the individuals involved,” had different courses of action been taken, even those at a late stage, William would probably have survived.

In particular, the report concluded that GPs and parents need more information on the key signs of septicaemia and that NHS 111 call advisers should get more training in what questions to ask and when to escalate cases.

Hunt has made a public apology to William’s parents and pledged that lessons would be learnt from the incident. Responding to an MP’s question about the death in the House of Commons on 26 January, …
Predictive factors of outcome and clinical management of adjuvant S-1 chemotherapy for gastric cancer
Authors: S. Iwasa, Y. Yamada, T. E. Nakajima, K. Kato, T. Hamaguchi, S. Morita, M. Saka, T. Fukagawa, H. Katai, Y. Shimada
Journal: Journal of Clinical Oncology (2009)

e15676 Background: Adjuvant S-1 chemotherapy has become a standard treatment for stage II and III gastric cancer, following the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC). This study was designed to identify factors that can be used for predicting the outcome and clinical management of adjuvant S-1 chemotherapy in patients with stage II and III gastric cancer. Methods: We retrospectively examined 97 consecutive patients with stage II or III gastric cancer who received S-1 chemotherapy after gastrectomy to investigate factors associated with outcome and clinical management. S-1 (80 mg/m 2 /day) was orally administered twice daily for 28 consecutive days, followed by a 14-day rest period. As a rule, this protocol was continued for one year after gastrectomy. According to toxicity profiles, dose reduction or dose schedule modification was performed. Results: Patients consisted of 63 males and 34 females (median age, 59 years; range, 35–80 years), and those undergoing total gastrectomy/subtotal gastrectomy = 40/57. The median follow-up period after gastrectomy was 43.0 months (range, 5.3–73.4 months). As for adjuvant S-1 chemotherapy, dose reduction and dose schedule modification were conducted in 59% and 40% of the patients, respectively. Of the patients needing dose reduction, 79% underwent reduction within three months of treatment. The most common reason for dose reduction during the treatment period was anorexia (47%), followed by diarrhea (32%), leukopenia (24%) and rash (16%) with overlapping reasons. The duration period of the treatment was at least 3 months in 88%, at least 6 months in 82%, and scheduled 12 months in 73%. Twenty six patients discontinued treatment due to adverse event (20 patients), recurrent disease (2 patients) and other reasons (4 patients). The median duration until treatment discontinuation was 4.0 months. To date, 15 patients have recurrent disease. Significant predictive factors for recurrence were not statistically identified. Conclusions: Most patients (73%) could complete the scheduled treatment duration by dose reduction and dose schedule modification. No significant financial relationships to disclose.
A Placebo-Controlled Study of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Administered During and After Induction Treatment for De Novo Acute Myelogenous Leukemia in Elderly Patients
Authors: F Witz, A Sadoun, M C Perrin, C Berthou, J Brière, J Y Cahn, B Lioure, B Witz, S François, B Desablens, B Pignon, P Y Le Prisé, B Audhuy, D Caillot, P Casassus, M Delain, B Christian, Z Tellier, V Polin, P Hurteloup, J L Harousseau
Journal: Blood (1998)
Induction of clinical and immunological responses in patients with metastatic renal cell carcinoma after vaccinations with peptide pulsed dendritic cells
Authors: J. Wierecky, M. R. Müller, M. S. Horger, W. Brugger, L. Kanz, P. Brossart
Journal: Journal of Clinical Oncology (2005)

2507 Background: Pulsing of dendritic cells (DC) with tumor antigens and their applications in immunotherapy of malignant diseases has been shown effective. We analyzed the clinical and immunological responses in patients with metastatic renal cell carcinoma (RCC) using autologous mature monocyte derived DC. Methods: DC were pulsed with two HLA-A2 binding peptides deduced from MUC1. For the recruiting and activation of CD4+ T cells DC were further incubated with the PAN-DR binding peptide PADRE. Vaccinations were performed sc every two weeks four times and repeated monthly until tumor progression. After the fifth DC injection patients additionally received 3 injections/week of low dose IL-2 (1Mio IE/m2) sc. The enhancement of T cell precursor was monitored using IFN-γ ELISPOT and 51Cr-release assays. Furthermore, we tested the ability of PBMC to produce cytokines in response to challenge with vaccine-related epitopes by quantitative real-time PCR. Results: 20 patients were included in this study. In 6 patients regression of metastases was induced with 4 objective responses (OR) (1 CR, 3 PR) and 2 mixed responses. 4 patients had a stabilization of the disease. MUC1 peptide specific T cell responses in vivo were detected in the PBMC of all patients with OR. These in vivo induced T cells were able to recognize target cells pulsed with the cognate peptide or matched allogeneic tumor cells (A498) constitutively expressing MUC1 in an antigen and HLA restricted manner after in vitro restimulation. Interestingly, in patients responding to the treatment, T cell responses to antigens not used for vaccinations like adipophilin, telomerase or OFA could be detected indicating that epitope spreading might occur. Proliferative responses to the PADRE peptide were detectable in 11 out of 16 analyzed patients, in some patients already after the first 2 vaccinations. The treatment was well tolerated with no severe side effects. Conclusions: This study demonstrates that peptide pulsed DC can be effective in the treatment of metastatic RCC. Furthermore, analysis of epitope spreading in vaccinated patients might be a usefull parameter to correlate clinical and immunological responses. No significant financial relationships to disclose.
Follow-up of concomitant treatment with gemcitabine/radiotherapy in locally advanced squamous cell carcinoma of head and neck
Authors: F. Bustamante, R. Villalobos, E. Castillo, A. Calva, F. Gallegos, A. Silva, A. Castruita
Journal: Journal of Clinical Oncology (2006)

15537 Background: The stages of the locally advanced head and neck cancer have a negative prognosis, therefore, new treatments are continuously explored. One of these treatments consists of the use of Gemcitabine concomitant with radiotherapy. We previously evaluated the rate of response and the toxicity profile of this treatment in 15 patients and now we are reporting the follow up of such study. Methods: Fifteen patients, with histological report of locally advanced squamous cell carcinoma of head and neck, initiated treatment of Gemcitabine at intravenously doses of 50 mg\m 2 per application weekly concomitant with radiotherapy. The radiotherapy consisted of an initial photons dose of 3960 cGy in 22 fractions of 180 cGy to the primary site and regional lymph with posterior increments of 2880 cGy in 16 fractions of 180 cGy excluding the spinal cord and electrons increments if necessary. Results: In 9 of the 15 patients complete response was obtained, achieving organ preservation. Four of the 15 patients presented a partial response and two presented progression. The principal severe toxicity presented was mucositis. The mean follow-up is 23 months with a range of 19–27 months. From the 9 patients that presented a complete response, one presented bone recurrence 13 months after achieving the total response; another one of them died because an infectious process without evidence of tumoral activity. The rest 7 patients are to the present date without evidence of tumoral activity. One of the patients with partial response is still alive with tumoral activity in central nervous system. The remaining patients died due to tumoral activity. Conclusions: In our study with 15 patients an overall response of 87% was obtained. With a follow up to 23 months only one recurrence has been presented. We concluded that the treatment is feasible and it could have an impact in the overall survival but studies with a greater number of patients and a larger follow up are needed. No significant financial relationships to disclose.
PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease
Authors: Kuti Baruch, Aleksandra Deczkowska, Neta Rosenzweig, Afroditi Tsitsou-Kampeli, Alaa Mohammad Sharif, Orit Matcovitch-Natan, Alexander Kertser, Eyal David, Ido Amit, Michal Schwartz
Journal: Nature Medicine (2016)
Immune response to tumor budding ratio: A new potential prognostic score to improve risk stratification for patients with colorectal cancer.
Authors: I. Zlobec, L. Terracciano, A. Lugli
Journal: Journal of Clinical Oncology (2010)

e14033 Background: Tumor budding in colorectal cancer is the histologic hallmark of epithelial mesencyhmal transition and is considered an additional prognostic factor by the International Union against Cancer. Abundant tumor budding is associated with lymph node metastasis, vascular invasion and distant metastasis and inversely related to peritumoral lymphocytic inflammation implicating tumor immunity in events occurring at the invasive front. Recently a high CD8+/budding ratio was identified as an independent prognostic factor. The aim of this study was to assess the ratio of various immune cell types to tumor budding ratio in order to define a potential new prognostic score for patients with this disease. Methods: Whole tissue sections from 297 patients with colorectal cancer were cut in series and double immunostaining was performed for CK22 with antibodies directed against CD3, CD8, CD16, CD20, CD21, CD56, CD68, CD138, Foxp3, Granzyme B, and mast cell tryptase. The densest region of tumor budding at the invasive front was identified. Using a 40x objective, the number of tumor buds and positively stained cells for each marker were counted. Results: All protein markers where inversely correlated with the number of tumor buds. After multivariable analysis with pT category, pN category and vascular invasion, a hierarchy of marker/budding ratios identified high Granzyme B+/budding (HR: 0.5 [0.31-0.82; p = 0.006]) as having the strongest positive independent effect on outcome, followed by high CD68+/budding (HR: 0.52 [0.33- 0.84; p = 0.007]), CD8+/budding (HR: 0.54 [0.34-0.84; p = 0.007]), CD16+/budding (HR: 0.56 [0.35-0.9; p = 0.015]), FoxP3+/budding (HR: 0.57 [0.35-0.91; p = 0.019]) and CD3+/budding (HR: 0.58 [0.37-0.9; p = 0.017]). Conclusions: High ratios of CD8+ cytotoxic T- lymphocytes, granzyme B+ or CD68+ cells to tumor budding represent not only a possible mechanism by which budding cells are prevented from disseminating into vessels, but also may lead to an additional prognostic score to improve risk stratification for patients with colorectal cancer. No significant financial relationships to disclose.
A phase II trial of stereotactic radiosurgery boost following surgical resection for solitary brain metastases
Authors: A. Narayana, K. Chan, C. Brennan, J. Chang, V. Higgins, S. Lymberis, J. Yamada, P. H. Gutin
Journal: Journal of Clinical Oncology (2006)

1552 Background: At present there is no standard of care for adjuvant therapy following resection of solitary brain metastases. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a surgery-stereotactic radiosurgery (SRS) combined therapy approach while avoiding upfront whole brain radiation therapy (WBRT). Methods: The eligibility criteria included radiologically proven solitary brain metastases, KPS≥70 and a neurologic function score of 0–2. Following the surgical resection, SRS was delivered to the surgical cavity 4–8 weeks later to a dose of 15–22 Gy in a single fraction using the BrainLAB linear accelerator system. Patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. Results: 25 out of 50 patients needed for the study have been accrued since it opened in August 2004. Four patients have failed locally, with a median time to local failure of 9.5 months. The one year local control at the site of original disease was 35%. Two of the four patients who had local recurrence at the time of relapse also had evidence of leptomeningeal disease. Six additional patients developed new brain metastases, resulting in a 1 year brain relapse free survival of 38% following the combined approach. The median overall survival was 12 months. One patient (4%) developed radiation necrosis that required surgical intervention 6 months following the procedure. Six patients (24%) needed WBRT, two patients (8%) needed further SRS and one patient (4%) needed surgery as salvage following development of new brain lesions with this approach. Conclusions: The preliminary results of surgery-SRS approach appear inferior to surgery-WBRT data for solitary brain metastases in terms of local control and development of new brain metastases. However, relapses can be subsequently managed with WBRT without adversely affecting the overall survival and the morbidity. No significant financial relationships to disclose.
A pooled analysis of demographic characteristics and clinical outcomes of phase I oncology clinical trials, the Mayo Clinic experience
Authors: P. J. Atherton, B. J. Jasperson, J. A. Sloan, S. Mandrekar, D. J. Smith, C. Erlichman, A. A. Adjei
Journal: Journal of Clinical Oncology (2004)

9724 Background: Who participates in clinical trials? This pooled analysis of phase I oncology clinical trials describes the patient population and examines differences in efficacy, toxicity and death in sub-populations. Methods: 609 patients participated in 22 phase I trials from Jan. 1995 to Dec. 2002. Descriptive statistics and correlation analyses were used to summarize and explore relationships between trial characteristics, patient demographics and clinical outcomes. Kaplan-Meier survival curves, log-rank statistics and Cox regression models were used to compare survival data across patient sub-populations and assess the impact of demographics on survival. Results: The average trial involved 28 patients (range 7 to 70) and 4.5 dose levels (range 1 to 13). Patients were most often Caucasian (98%) with high performance score (84%) and few prior therapies. The maximum tolerated dose (MTD) averaged 4-fold the starting dose for single agent studies. In all 22 studies, 37% of patients were treated at the MTD, and 17% were treated above the MTD. Common treatment related toxicities were neutropenia (56%), leukopenia (58%), anorexia (47%), nausea (51%), thrombocytopenia (39%), diarrhea (37%), and vomiting (27%). Objective responses occurred in 13% of the patients. There were no response differences across age, gender, tumor site or performance status. Toxicity was more common and severe in older patients and those with poor performance status (ECOG PS ≥ 1). Conclusions: Patients enrolled in these phase I trials experienced acceptable toxicity and had a higher objective response rate than those previously reported. There are no vulnerable or particularly successful sub-populations. Clinical outcomes were not influenced by age or gender. Good performance status and minimal prior therapy were positive prognostic factors for survival, time to progression and time to toxicity. These data support the belief that good performance patients with little prior therapy are the best candidates for phase I trials (supported in part by CA69912 and CA15083). No significant financial relationships to disclose.
Clinical outcomes of elective nodal irradiation (ENI) compared with involved field radiotherapy (IFRT) in NSCLC
Authors: A. Fernandes, J. Faerber, J. Finlay, J. Shen, L. Lin, T. Evans, J. Stevenson, C. Langer, E. Glatstein, S. Hahn, R. Rengan
Journal: Journal of Clinical Oncology (2009)

7541 Background: Local failure rates in patients treated with definitive radiotherapy for non-small cell lung cancer (NSCLC) remain high. IFRT allows higher radiation doses to the primary tumor with the goal of reducing local failure rates while minimizing toxicity. This approach, however, raises concern for increased nodal failures. Our retrospective analysis evaluates clinical outcomes of patients treated at our institution with ENI or IFRT. Methods: We assessed all patients (pts) with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy (RT) from January 1, 2003 to August 21, 2008. The decision to treat with ENI vs. IFRT was based on physician treatment philosophy. We compared baseline demographics in each group as well as toxicities and therapeutic outcomes. Involved nodal failures (INF) were defined as radiographic progression in lymph nodes that were initially involved at the time of treatment. Elective nodal failures (ENF) were defined as progression in initially uninvolved lymph nodes. Results: A total of 104 consecutive pts (56 ENI vs. 48 IFRT) were assessed. Pts in both groups had similar characteristics with respect to age, baseline KPS, and percentage receiving chemotherapy. The average RT dose was 6,345 cGy in the ENI group and 6988 cGy in the IFRT group. The median follow-up time was 8.4 mos (0.3–43.4) for all pts and 9.7 mos (1.5–40.1) for survivors. The results follow in the table below. Conclusions: Our data suggest that IFRT does not result in increased nodal failures or decreased survival compared to ENI, and may result in increased local control. The majority of patients who experienced a local failure also experienced nodal failure, suggesting that local relapse may be linked to subsequent nodal failure. This may explain the increased nodal failure rates in patients treated with ENI. Decreased esophagitis rates in patients treated with IFRT may allow the integration of concurrent, full dose systemic therapy in a greater proportion of patients, as well as higher RT doses. [Table: see text] No significant financial relationships to disclose.