tbuckley/cabot-search huggingface dataset:
Association of Prospective Risk for Chronic PTSD Symptoms With Low TNFα and IFNγ Concentrations in the Immediate Aftermath of Trauma Exposure
Authors: Vasiliki Michopoulos, Eleonore Beurel, Felicia Gould, Firdaus S. Dhabhar, Katharina Schultebraucks, Isaac Galatzer-Levy, Barbara O. Rothbaum, Kerry J. Ressler, Charles B. Nemeroff
Journal: American Journal of Psychiatry (2019)

Although several reports have documented heightened systemic inflammation in posttraumatic stress disorder (PTSD), few studies have assessed whether inflammatory markers serve as prospective biomarkers for PTSD risk. The present study aimed to characterize whether peripheral immune factors measured in blood samples collected in an emergency department immediately after trauma exposure would predict later chronic development of PTSD.Participants (N=505) were recruited from a hospital emergency department and underwent a 1.5-hour assessment. Blood samples were drawn, on average, about 3 hours after trauma exposure. Follow-up assessments were conducted 1, 3, 6, and 12 months after trauma exposure. Latent growth mixture modeling was used to identify classes of PTSD symptom trajectories.Three distinct classes of PTSD symptom trajectories were identified: chronic (N=28), resilient (N=160), and recovery (N=85). Multivariate analyses of covariance revealed a significant multivariate main effect of PTSD symptom trajectory class membership on proinflammatory cytokines. Univariate analyses showed a significant main effect of trajectory class membership on plasma concentrations of proinflammatory tumor necrosis factor α (TNFα) and interferon-γ (IFNγ). Concentrations of proinflammatory TNFα and IFNγ were significantly lower in individuals in the chronic PTSD class compared with those in the recovery and resilient classes. There were no significant differences in interleukin (IL) 1β and IL-6 concentrations by PTSD symptom trajectory class. Anti-inflammatory and other cytokines, as well as chemokines and growth factor concentrations, were not associated with development of chronic PTSD.Overall, the study findings suggest that assessing the proinflammatory immune response to trauma exposure immediately after trauma exposure, in the emergency department, may help identify individuals most at risk for developing chronic PTSD in the aftermath of trauma.
Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract. Selective Decontamination of the Digestive Tract Trialists' Collaborative Group.
Journal: BMJ (1993)

OBJECTIVE--To determine the clinical benefits of selective decontamination of the digestive tract in patients treated in intensive care units. DESIGN--Meta-analysis of 22 randomised trials that compared different combinations of oral non-absorbable antibiotics, with or without a systemic component, with no treatment in controls. SUBJECTS--4142 patients seen in general and specialised intensive care units around the world. 2047 received some form of antibiotic treatment, the remainder no prophylaxis. DATA ANALYSIS--Each trial was reviewed through direct contact with study investigators. Data collected were: the randomisation procedure, number of patients, number excluded from the analysis, and numbers of respiratory tract infections and deaths. Data were combined according to an intention to treat analysis with the Mantel-Haenszel-Peto method. MAIN OUTCOME MEASURES--Respiratory tract infections and total mortality. RESULTS--Selective decontamination of the digestive tract significantly reduced respiratory tract infections (odds ratio 0.37; 95% confidence interval 0.31 to 0.43). The value of the common odds ratio for total mortality (0.90; 0.79 to 1.04) suggested at best a moderate treatment effect, reaching statistical significance only when the subgroup of trials of topical and systemic treatment combined was considered separately (odds ratio 0.80; 0.67 to 0.97). No firm conclusions could be drawn owing to large variations in patient mix and severity within and between trials. CONCLUSIONS--The findings strongly indicate that selective decontamination significantly reduces infection related morbidity in patients receiving intensive care. They also highlight why definite conclusions about the effect of prophylaxis on mortality cannot be drawn despite the large number of trials available. Based on the most favourable results obtained by pooling data from trials in which combined topical and systemic treatment was used it may be estimated that 6 (range 5-9) and 23 (13-139) patients would need to be treated to prevent one respiratory tract infection and one death respectively.
End-of-life care and immune checkpoint inhibitors.
Authors: Hazel O'Sullivan, Dearbhaile Collins, Deirdre O'Mahony, Derek Power, Richard Bambury, Seamus O'Reilly
Journal: Journal of Clinical Oncology (2019)

11531 Background: In the era of cytotoxic chemotherapy, aggressive cancer treatment and hospitalization at the end of life (EOL) has been associated with a worse quality of death. Meanwhile, in the era of immunotherapy (IO), little is known of the impact of these novel agents on EOL care. The aim of this study was to evaluate the EOL care of metastatic cancer patients treated with immune checkpoint inhibitors. Methods: We conducted a retrospective analysis of patients prescribedPD1/L1 or CTLA-4 antibodies in Cork University Hospital (CUH) and Mercy University Hospital (MUH) between January 2013 to December 2018. Patients treated on a clinical trial were excluded. Results: We identified 224 patients treated with immune checkpoint inhibitors (outside of a clinical trial) in CUH and MUH over the described 6 year period. 108 of these patients were deceased, 102 electronic files were available for analysis. Of the 102 patients, 57 had metastatic melanoma, 33 non small cell lung cancer, 8 renal cell carcinoma, 4 had other advanced malignancies. 43% were female and 57% were male. 6% of patients had an ECOG performance status (PS) of 0 at diagnosis, 80% PS of 1 and 10% PS of 2. Median age at death was 62 years. 47 patients were treated with pembrolizumab, 26 nivolumab, 25 ipilimumab, 2 nivolumab/ipilimumab and 2 received atezolizumab. 29 patients received IO as first line treatment, 50 as second line, 17 as third line and 6 as fourth line. Median number of IO cycles received was 4 (range 1 - 41). Progression of disease (62%) and declining performance status (14%) were the most common reasons for discontinuation of IO treatment. 16 of the 102 patients received a further line of systemic therapy. Median time from last dose of IO to death was 57 days. 20 patients (20%) died within 30 days of last dose of IO. Of these 20 patients, the median number of cycles of IO received was 2 (range 1-7), 8 of these 20 patients received one cycle of IO only. 39 patients (38%) attended the ED in the last month of life. 47 (46%) patients had at least one hospital admission in the last month of life, the median hospital length of stay was 6 days (range 1-30) and 22 patients died in hospital. 94% of patients were referred to palliative care, the median time from palliative care referral to death was 64 days (range 1- 1010), 62% of patients died in hospice. Conclusions: Patients with advanced cancer treated with immunotherapy have high rates of hospital admissions and ED attendances despite early palliative care involvement. 20% of patients died within 30 days of IO. More research is needed to help physicians identify patients who are least likely to benefit from IO so as not to treat futile cases.
Randomized, double-blind, placebo-controlled proof of concept study of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC) who experience response or stabilization during first-line docetaxel chemotherapy.
Authors: Karim Fizazi, Axel Heidenreich, Gedske Daugaard, Joaquim Bellmunt, Nathalie Germann, Eric Chetaille
Journal: Journal of Clinical Oncology (2013)

TPS5098^ Background: Docetaxel is the standard first-line chemotherapy for mCRPC. Most patients experience disease response or stabilization on docetaxel, although no treatment is currently used to maintain efficacy when docetaxel is stopped. Tasquinimod is an oral, quinoline-3-carboxamide derivative that binds to S100A9, with immunomodulatory, anti-angiogenic and anti-metastatic activity and a manageable safety profile. Tasquinimod demonstrated significantly improved PFS (7.6 v 3.3 mo) in asymptomatic to mildly symptomatic mCRPC (Pili, R. et al. J Clin Oncol 2011; 29: 4022-8) and is in phase III development. The purpose of this study is to assess whether tasquinimod used as a switch maintenance therapy can postpone cancer progression in patients with mCRPC with response or stabilization on first-line docetaxel therapy. Methods: Design: Phase II, multinational, randomized, double-blind, placebo-controlled proof of concept study. Patients with mCRPC will be randomly assigned (ratio 1:1) to receive tasquinimod or placebo. Randomization will be stratified by presence of visceral metastases and opioid analgesic use for cancer-related pain. Patient population: 140 male patients aged ≥18 years with histologically documented mCRPC and ECOG performance status 0 or 1 will be randomized. Before study entry, patients should have received ≥6 cycles of docetaxel and not experienced cancer progression according to PSA and RECIST criteria. Recruitment is ongoing. Dosage: Patients will receive a starting dose of 0.25 mg/day tasquinimod or placebo, with escalation to 0.5 mg/day and 1 mg/day based on individual safety and tolerability. Primary endpoint: Radiological PFS including skeletal-related events, from randomization to the date of radiological progression or death due to any cause. Secondary endpoints: Overall survival, symptomatic PFS, quality of life, pharmacokinetics, safety, PFS on next-line therapy, time to PSA progression, and changes in biomarkers over time. Clinical trial information: NCT01732549.
Body composition changes successfully classify prognosis in patients with mycobacterium avium complex lung disease
Authors: Daisuke Akahori, Yuzo Suzuki, Koushi Yokomura, Masahiro Shirai, Hideki Yasui, Hironao Hozumi, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Naoki Inui, Hiroshi Hayakawa, Takafumi Suda
Journal: Journal of Infection (2019)
Efficacy and Adverse Reactions of Gemcitabine Combined with Cyclophosphamide, Vinblastine and Prednisone Hydrogenation Regiments in Relapse and/or Refractory Non-Hodgkin's Lymphoma
Authors: Baiyan Wang, Jie Liu, Yin-Xia Chen, Xing-Mei Cao, Wan-Hong Zhao, Jian-Li Wang, Xiao-Rong Ma, Yun Yang, Peng-Yu Zhang, Fang-Xia Wang, Liu-Fang Gu, Bo Lei, Jin Wang, Ju Bai, Yi-Lin Zhang, Yan Xu, Ai-Li He, Wang-Gang Zhang
Journal: Blood (2018)
Platelet Activation Is Not Crucial for Platelet-Rich Plasma (PRP), When Used As Autologous Therapeutic Product, and Could be Lyophilized without Any Growth Factor Loss
Authors: Letícia Queiroz da Silva, Stephany Cares Huber, Silmara Aparecida De Lima Montalvão, Fernanda Dutra Santiago Bassora, Erich Vinicius De Paula, Joyce Annichino-Bizzacchi
Journal: Blood (2016)
A multicenter analysis of prognostic factors in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib.
Authors: Alan D. Smith, Kelvin K. Chan, Howard John Lim, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

e14532 Background: Established clinical prognostic systems for advanced HCC were previously developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care. It is unclear if these existing models provide useful prognostic information for patients receiving sorafenib. Our aims were to: 1) evaluate the current utility of 4 known prognostic systems, including the Okuda, CLIP, BCLC, and French classification systems; and 2) identify new prognostic factors for patients treated with sorafenib. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 and treated with sorafenib at any 1 of 6 regional cancer cancers in either British Columbia or Ontario, Canada were reviewed. Patients were risk-stratified using each of the 4 established prognostic systems to determine if these correlated with overall survival (OS). Cox proportional hazards models were also constructed to examine for associations between other clinical factors and OS. Results: Of 205 patients identified, 193 were evaluable: median age was 66 years, 79% were men, and 49% / 19 % / 16% had hepatitis B, C, and alcohol-related liver disease, respectively. The mean number of sorafenib cycles was 5.5 and median OS was 7.1 months. Of the 4 known prognostics models, only the French system proved useful where the high, intermediate, and low risk groups demonstrated a median OS of 2.4, 7.0, and 16.8 months, respectively (p&lt;0.0001). Among other clinical factors, univariate analyses showed that poor performance status, presence of ascites, and large tumor size &gt;5cm were associated with worse OS as were an elevated serum AFP, AST, GGT, or ALP level and a low albumin or hemoglobin level (all p&lt;0.05). In multivariate analyses, none of these clinical factors continued to be independently predictive of outcome (all p&gt;0.05). Conclusions: Except for the French classification system, clinical prognostic factors that were identified in the era of conventional chemotherapy were not useful in this Western cohort of advanced HCC patients treated with sorafenib. There is a need for molecular biomarkers that may provide better prognostic information.
Fatty Acid Metabolites Combine with Reduced β Oxidation to Activate Th17 Inflammation in Human Type 2 Diabetes
Authors: Dequina A. Nicholas, Elizabeth A. Proctor, Madhur Agrawal, Anna C. Belkina, Stephen C. Van Nostrand, Leena Panneerseelan-Bharath, Albert R. Jones, Forum Raval, Blanche C. Ip, Min Zhu, Jose M. Cacicedo, Chloe Habib, Nestor Sainz-Rueda, Leah Persky, Patrick G. Sullivan, Barbara E. Corkey, Caroline M. Apovian, Philip A. Kern, Douglas A. Lauffenburger, Barbara S. Nikolajczyk
Journal: Cell Metabolism (2019)
Cautious view on the link between yoghurt consumption and risk of colorectal cancer
Authors: Jiaoyan Ren, Maojin Yao
Journal: Gut (2019)

We read with great interest the recent work by Zheng et al published in the Gut journal titled ‘Yogurt consumption and risk of conventional and serrated precursors of colorectal cancer’.1 This impressive result was widely reported and rapidly disseminated and attracted great public health attention. Although the study was well-explored, the conclusion needs to be carefully interpreted. Below are a few points of concern in relation to the potential influence of this study.

Yoghurt consumption has been associated with obvious health benefits in different populations.2 However, nutritional information and health-related attributes of yoghurt in disease progression are limited. In this study, the researchers followed the yoghurt intake and subsequent development of different types of adenoma among 32 606 men and found that compared with the population who didn't consume yoghurt, …
Integrin α6 targeted positron emission tomography imaging of hepatocellular carcinoma in mouse models
Authors: Guo-Kai Feng, Jia-Cong Ye, Wei-Guang Zhang, Yan Mei, Chao Zhou, Yi-Tai Xiao, Xin-Ling Li, Wei Fan, Fan Wang, Mu-Sheng Zeng
Journal: Journal of Controlled Release (2019)
Differences in survival for metastatic colorectal cancer patients by lines of therapy received.
Authors: Brian S. Seal, Benjamin Chastek, Mahesh Kulakodlu, Satish Valluri
Journal: Journal of Clinical Oncology (2012)

e14016 Background: Improvements in survival for advanced-stage CRC patients who receive chemotherapy have been reported. We compared survival rates for patients with 3+ vs. &lt;3 lines of therapy. Methods: Adult patients with a diagnosis of CRC between 01/01/05 and 05/31/10 were identified from the Impact Intelligence Oncology Management (IIOM) registry. Patients with either stage 4 CRC at original diagnosis or development of metastasis were included. Registry data included original stage and date of diagnosis. Linked healthcare claims from the Life Sciences Research Database, a large US health insurance database affiliated with OptumInsight, were used to identify lines of therapy after metastases and patient characteristics. Death data were obtained from the Social Security Administration’s master death file. Patients were categorized by number of lines of therapy received (0, 1, 2, 3+) and original stage at diagnosis (0-2, 3, 4, unknown). Survival following metastases was evaluated using Cox proportional hazards models controlling for lines of therapy received, stage, and other patient characteristics. Results: 598 patients, followed for a mean of 653 days after becoming metastatic, were included. Mean unadjusted length of follow-up was lowest among patients who received no chemotherapy (516 days) or only 1 line (511 days), and increased to 627 days for those with 2 lines and 930 days for those with 3+ lines. However, multivariate analysis indicated that patients with 3+ lines had comparable survival vs. those with 0 (HR=0.79), 1 (HR=1.59), or 2 (HR=1.15) lines of therapy (p&gt;0.05 for all comparisons). Compared to patients who presented with stage 4 CRC, those who progressed from stage 0-2 (HR=1.22), stage 3 (HR=0.83), or unknown stage (HR=1.18) had similar survival after metastases (p&gt;0.05 for all comparisons). After excluding 94 patients who didn’t receive chemotherapy, patients treated with an oxaliplatin-based regimen (HR=1.28; p=0.24) in first line had similar survival compared to patients treated with an irinotecan-based or anti-EGFR regimen in first line. Conclusions: Lines of therapy received and initial stage were not associated with survival after development of metastases.
Survival outcomes of ovarian cancer patients treated with secondary cytoreductive surgery for isolated lymph node recurrence: A systematic review of the literature
Authors: Vasilios Pergialiotis, Anastasia Androutsou, Eleni Papoutsi, Ioannis Bellos, Nikolaos Thomakos, Dimitrios Haidopoulos, Alexandros Rodolakis
Journal: International Journal of Surgery (2019)
Characterization and Comparison of GITR Expression in Solid Tumors
Authors: Luis Vence, Samantha L. Bucktrout, Irina Fernandez Curbelo, Jorge Blando, Bevin M. Smith, Ashley E. Mahne, John C. Lin, Terrence Park, Edward Pascua, Tao Sai, Javier Chaparro-Riggers, Sumit K. Subudhi, Jorge B. Scutti, Maria G. Higa, Hao Zhao, Shalini S. Yadav, Anirban Maitra, Ignacio I. Wistuba, James P. Allison, Padmanee Sharma
Journal: Clinical Cancer Research (2019)

Determine the differential effect of a FcγR-binding, mIgG2a anti-GITR antibody in mouse tumor models, and characterize the tumor microenvironment for the frequency of GITR expression in T-cell subsets from seven different human solid tumors.Experimental Design: For mouse experiments, wild-type C57BL/6 mice were subcutaneously injected with MC38 cells or B16 cells, and BALB/c mice were injected with CT26 cells. Mice were treated with the anti-mouse GITR agonist antibody 21B6, and tumor burden and survival were monitored. GITR expression was evaluated at the single-cell level using flow cytometry (FC). A total of 213 samples were evaluated for GITR expression by IHC, 63 by FC, and 170 by both in seven human solid tumors: advanced hepatocellular carcinoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, pancreatic carcinoma, head and neck carcinoma, melanoma, and ovarian carcinoma.The therapeutic benefit of 21B6 was greatest in CT26 followed by MC38, and was least in the B16 tumor model. The frequency of CD8 T cells and effector CD4 T cells within the immune infiltrate correlated with response to treatment with GITR antibody. Analysis of clinical tumor samples showed that NSCLC, renal cell carcinoma, and melanoma had the highest proportions of GITR-expressing cells and highest per-cell density of GITR expression on CD4+ Foxp3+ T regulatory cells. IHC and FC data showed similar trends with a good correlation between both techniques.Human tumor data suggest that NSCLC, renal cell carcinoma, and melanoma should be the tumor subtypes prioritized for anti-GITR therapy development.
Induction of hypertrophy of the left hepatic lobe by unilateral right hepatic arterial radioembolization (RE) using 90Y-labeled resin microspheres in patients with right-sided secondary malignant liver tumors.
Authors: Benjamin Garlipp, Max Seidensticker, Romy Irmscher, Robert Damm, Jens Ricke, Patrick Stuebs, Frank Meyer, Hans Lippert
Journal: Journal of Clinical Oncology (2012)

e14630 Background: In patients with unilateral liver tumors who are candidates for extended liver resection but demonstrate insufficient future liver remnant (FLR) size, induction of FLR hypertrophy by contralateral portal vein embolization (PVE) is an established approach but concerns exist regarding tumor progression during the interval from PVE to liver surgery. We hypothesized that unilateral hepatic arterial radioembolization (RE) using 90Y-labelled resin microspheres achieves a similar degree of contralateral hypertrophy as PVE. Methods: 32 patients with right-sided secondary liver cancers (metastases from colorectal [n=20], breast [n=7], head and neck [n=2], and other [n=3] cancers) were treated with unilateral right hepatic arterial RE. Before and 44 (22-81) days following RE MRI-based volumetry of the total liver (TLV), the right (RLV, segments 4-8) and left (LLV, segments 2 and 3) hepatic lobes was performed. TLV, RLV, and LLV as well as the LLV/TLV ratio before and after RE were compared using the Mann-Whitney U-test. Results: Median values for TLV, RLV, LLV, and the LLV/TLV ratio are shown in table. Compared to baseline, RLV and TLV showed no significant change after right hepatic arterial RE (-3.7 [min/max, -37.7/+56.5] per cent [p=0.158] and +3.2 [-16.5/+47.4] per cent [p=0.282], respectively). In contrast, LLV as well as the LLV/TLV ratio were significantly increased after RE (+34.9 [-3.1/+146.2] per cent [p&lt;0.001] and +29.4 [-24.3/+155.3] per cent [p&lt;0.001], respectively). Conclusions: Right hepatic arterial RE achieved superior contralateral liver hypertrophy compared to hypertrophy reported after PVE and may be an alternative to PVE since it provides simultaneous treatment to the liver tumors during the interval from treatment to liver surgery, reducing the risk for tumor progression. These two methods should be directly compared within a prospective trial. [Table: see text]
Automated age estimation from MRI volumes of the hand
Authors: Darko Štern, Christian Payer, Martin Urschler
Journal: Medical Image Analysis (2019)

Highly relevant for both clinical and legal medicine applications, the established radiological methods for estimating unknown age in children and adolescents are based on visual examination of bone ossification in X-ray images of the hand. Our group has initiated the development of fully automatic age estimation methods from 3D MRI scans of the hand, in order to simultaneously overcome the problems of the radiological methods including (1) exposure to ionizing radiation, (2) necessity to define new, MRI specific staging systems, and (3) subjective influence of the examiner. The present work provides a theoretical background for understanding the nonlinear regression problem of biological age estimation and chronological age approximation. Based on this theoretical background, we comprehensively evaluate machine learning methods (random forests, deep convolutional neural networks) with different simplifications of the image information used as an input for learning. Trained on a large dataset of 328 MR images, we compare the performance of the different input strategies and demonstrate unprecedented results. For estimating biological age, we obtain a mean absolute error of 0.37 ± 0.51 years for the age range of the subjects ≤ 18 years, i.e. where bone ossification has not yet saturated. Finally, we validate our findings by adapting our best performing method to 2D images and applying it to a publicly available dataset of X-ray images, showing that we are in line with the state-of-the-art automatic methods for this task.