tbuckley/cabot-search huggingface dataset:
Outcome with stereotactic radiosurgery (SRS) and ipilimumab (Ipi) for malignant melanoma brain metastases.
Authors: Sana Shoukat, David Mitchell Marcus, Monica Rizzo, David H. Lawson, Yuan Liu, Mohammad Khurram Khan
Journal: Journal of Clinical Oncology (2013)

3032 Background: SRS with Ipi for brain metastases from malignant melanoma has been explored for overall survival (OS) (Knisely JP, Yu JB, Flanigan J, et al. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117:227-33). We present the first retrospective analysis to determine if this combination is safe and improves OS, while accounting for lactate dehydrogenase (LDH). Methods: Patients with melanoma brain metastases who underwent SRS between 1998-2010 (n=124) were compared with those who additionally received Ipi (n=11). The primary endpoint was median OS from time of SRS, calculated using Kaplan-Meier method. Cox proportional hazard model was carried out for univariate and multivariable survival analysis. The secondary endpoints were local control at initial site of SRS, anywhere intra-cranial failure, need for repeat SRS, and toxicity. Results: Median OS for the entire cohort was 6.9 months. Patients in the Ipi group had an improved median OS of 28.3 months vs. 6.8 months in the non-Ipi group (p = 0.013). No difference was noted in local control, anywhere intracranial failures, toxicity (radionecrosis, hemorrhage, patient reported memory deficits), or need for repeated SRS. MVA (Table) showed that Ipi independently predicted for improved OS even when taking into account LDH and ECOG performance status. The only confounding factor within the Ipi group was younger age of the Ipi cohort (43 vs. 55 yrs, p = 0.006). Conclusions: Use of SRS with Ipi appears to be safe and associated with an impressive increase in median OS in patients with brain metastases from malignant melanoma; this combination should be further investigated. [Table: see text]
A novel 3-dimensional (3D) microfluidics device to model the tumor microenvironment (TME).
Authors: Bradley A. Krasnick, Ye Bi, Maddy Goedegebuure, Peter S. Goedegebuure, Venktesh S. Shirure, Steven George, Ryan Fields
Journal: Journal of Clinical Oncology (2018)

704 Background: In vitro models of cancer have led to significant therapeutic advances. Despite the widespread use of in vitro tissue culture, the ability to directly evaluate human biology is limited by the inability to model the complex, 3D nature of the TME. We introduce a novel, microfluidic-based system of 3D human micro-tumors perfused with a network of human micro-vessels which could overcome the shortcomings of current in vitro systems. Methods: The micro-device was created by casting polydimethylsiloxane (PDMS) onto master molds, which are then bonded to a flat PDMS sheet using air plasma. Normal human lung fibroblasts (NHLF) and GFP labelled endothelial colony forming cell derived endothelial cells (EC-FCECs) were loaded in a fibrin gel at a 1:2 ratio into the central tissue chamber. Media was introduced through the microfluidic lines. The vascular network was developed with complete EGM2 media under nominal interstitial flow. Colorectal tumor cell lines labelled with mCherry were loaded to the side chambers on the seventh day after NHLF and EC loading. Bevacizumab or TGF- β were added on the second day after tumor cell loading. Results: Micro-vessels formed in the central chamber in 5-7 days after loading. The vessels were perfused with 70KDa fluorescent (red) dextran, and displayed intact vessel wall barrier. A suspension of a colorectal tumor cell line was loaded into the device side chambers, next to a fully developed vasculature. The tumor cells drove angiogenesis into the side chambers, and at the same time tumor began to migrate into the central chamber and within the vessel lumen. The angiogenesis induced by tumor cells can be pharmacologically inhibited, and the migration/ intravasation of tumor cells can be stimulated by TGF-β. Conclusions: Our novel micro-device system can be used as a functional in vitro system that can model the tumor micro-environment. This system has the advantage over current in vitro and in vivo systems in that it is high-throughput, rapid, cost-effective, and recreates many features of the 3D TME. We are currently expanding the platform to incorporate immune cells and designing a completely autologous system to test cancer immunotherapeutics.
a proof-of-concept Phase 2a clinical trial with Hbv/hdv entry inhibitor Myrcludex B : lb-20
Authors: Pavel Bogomolov, Natalia Voronkova, Lena Allweiss, Maura Dandri, Matthias Schwab, Florian A. Lempp, Mathias Haag, Heiner Wedemeyer, Alexander Alexandrov, Stephan Urban
Journal: Hepatology (2014)
TCTAP A-018 Unrestricted Use of Biolimus-eluting Stents(Biomatrix®, NOBORI) in Patients with Acute Myocardial Infarction
Authors: Ji Young Park, Seung-Woon Rha, Myung-Ho Jeong, Youngkeun Ahn, Taehoon Ahn, Ki-Bae Seung, In-Ho Chae, Hyo-Soo Kim, In-Whan Seong, Kwon-Bae Kim
Journal: Journal of the American College of Cardiology (2018)
Prognostic value of 2D-shear wave elastography for staging cirrhosis in chronic liver diseases in two severity classes according to liver-related complications
Authors: P. Pollo-Flores, M. Munteanu, A. Ngo, Y. Ngo, E. Luckina, T. Phim, H. Perazzo, L. Bonyhay, M. Rudler, P. Lebray, D. Thabut, V. Ratziu, T. Poynard
Journal: Journal of Hepatology (2018)
Phase II study of panitumumab in KRAS wild-type metastatic adenocarcinoma of the small bowel or ampulla of vater.
Authors: Pat Gulhati, Kanwal Pratap Singh Raghav, Rachna T. Shroff, Gauri R. Varadhachary, Milind M. Javle, Wei Qiao, Huamin Wang, Jeffrey Morris, Robert A. Wolff, Michael J. Overman
Journal: Journal of Clinical Oncology (2017)

e15799 Background: Given the benefit noted with epidermal growth factor receptor (EGFR) antibodies in KRAS wild-type colorectal cancer, we conducted a phase II trial to evaluate the efficacy of panitumumab in metastatic small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Methods: This is a single-center open-label single arm two-stage phase II study. The primary objective was response rate (RR). Secondary objectives included overall progression-free survival (PFS), overall survival (OS) and toxicity. Eligibility included: KRAS exon 2 wild-type, ECOG PS 0-1, metastatic disease, adequate organ function and prior progression or intolerance to fluoropyrimidine with oxaliplatin. Panitumumab was administered at a dose of 6mg/kg IV every 14 days. Next generation sequencing panels were used for genomic analysis. Results: 9 patients [M/F 7/2, median age: 61 yrs (range: 40-74), ECOG PS 0/1: 2/7] were enrolled from September 2013 to October 2015. 1 pt had AAC (pancreaticobiliary subtype) and 8 pts had SBA (duodenal in 3, jejunal/ileal in 5). The most common toxicity was grade 1 acneiform rash in all patients. The most common grade 2/3 toxicities were anemia (33%), fatigue (22%), hypomagnesemia (22%) and skin infection (22%). None of the patients had a response, 2 patients had SD while the remaining 7 patients had PD. At a median follow-up time of 16.6 months, the median PFS and median OS were 2.4 months and 5.6 months, respectively. Extended RAS mutational testing identified 0/9 patients with mutations in extended KRAS or NRAS. Further genomic analysis of genes relevant to anti-EGFR activity (BRAF, PIK3CA and ERBB2) identified 2/9 patients with BRAF G469A mutation, 1/9 patients with PIK3CA H1047R mutation, and 0/9 patients with ERRB2 mutations. Conclusions: Although well tolerated, panitumumab had minimal clinical activity in patients with metastatic SBA and AAC. Given recent findings suggesting that right-sided colon cancers (hindgut derivation) benefit less from anti-EGFR therapy compared to left-sided colon cancers (midgut derivation), we propose that our findings may relate to the primarily foregut (proximal duodenum) and midgut (distal duodenum to ileum) derivation of the small bowel. Clinical trial information: NCT01202409.
Hepatitis B virus entry in primary human hepatocytes initiates toll-like receptor 2-dependent immune signaling
Authors: Z. Zhenhua, M. Trippler, C. Real, M. Werner, T. Kemper, H. Baba, J.-W. Treckmann, A. Paul, G. Gerken, J. Schlaak, M. Lu, R. Broering
Journal: Journal of Hepatology (2018)
Interventions to Prevent Falls in Community-Dwelling Older Adults
Authors: David C. Grossman, Susan J. Curry, Douglas K. Owens, Michael J. Barry, Aaron B. Caughey, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, Alex R. Kemper, Alex H. Krist, Martha Kubik, Seth Landefeld, Carol M. Mangione, Michael Pignone, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng
Journal: JAMA (2018)

<h3>Importance</h3> Falls are the leading cause of injury-related morbidity and mortality among older adults in the United States. In 2014, 28.7% of community-dwelling adults 65 years or older reported falling, resulting in 29 million falls (37.5% of which needed medical treatment or restricted activity for a day or longer) and an estimated 33 000 deaths in 2015. <h3>Objective</h3> To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on the prevention of falls in community-dwelling older adults. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the effectiveness and harms of primary care–relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling older adults 65 years or older who are not known to have osteoporosis or vitamin D deficiency. <h3>Findings</h3> The USPSTF found adequate evidence that exercise interventions have a moderate benefit in preventing falls in older adults at increased risk for falls and that multifactorial interventions have a small benefit. The USPSTF found adequate evidence that vitamin D supplementation has no benefit in preventing falls in older adults. The USPSTF found adequate evidence to bound the harms of exercise and multifactorial interventions as no greater than small. The USPSTF found adequate evidence that the overall harms of vitamin D supplementation are small to moderate. <h3>Conclusions and Recommendation</h3> The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians selectively offer multifactorial interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences. (C recommendation) The USPSTF recommends against vitamin D supplementation to prevent falls in community-dwelling adults 65 years or older. (D recommendation) These recommendations apply to community-dwelling adults who are not known to have osteoporosis or vitamin D deficiency.
What Surgeons Should Know About Non–Vitamin K Oral Anticoagulants
Authors: Atul Verma, Andrew C. T. Ha, James T. Rutka, Subodh Verma
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Non–vitamin K oral anticoagulants (NOACs) are increasingly prescribed for patients to treat or prevent arterial or venous thromboembolism. The following 4 NOAC agents are approved by the US Food and Drug Administration for clinical use: dabigatran etexilate, apixaban, edoxaban tosylate, and rivaroxaban. A good understanding of these agents' pharmacologic properties is important for surgeons given their marked differences compared with warfarin sodium. This review highlights key practical issues surrounding the use of NOACs in the perioperative setting. <h3>Observations</h3> The PubMed and Cochrane Library databases were searched for English-language studies from May 1, 2009, until May 1, 2017, for randomized clinical trials, meta-analyses, systematic reviews, observational studies, and clinical guidelines. From a systematic review of the published literature that included 70 articles and 166 404 patients, this study identified 5 key practical issues surrounding the use of NOACs in the perioperative setting. These include patient populations for which NOAC use is indicated and contraindicated, the timing of NOAC treatment cessation before invasive interventions, management of NOAC-treated patients requiring urgent interventions, the need for "bridging," and the timing of NOAC treatment's reinitiation after invasive interventions. Important findings are as follows: NOAC agents are not recommended for patients with mechanical heart valves or advanced kidney disease (creatinine clearance, &lt;15 mL/min); minimal to no anticoagulant effect remains when therapy with a NOAC is withheld for 48 to 72 hours before surgery in the context of normal kidney function; a reversal agent is clinically available for dabigatran, while reversal agents for apixaban, edoxaban, and rivaroxaban are under regulatory review; and laboratory testing of the anticoagulant effects of NOACs are not routinely available. There is a paucity of high-quality data on the optimal timing of NOAC cessation and resumption in the perioperative period, particularly for patients who undergo procedures with high bleeding risk. <h3>Conclusions and Relevance</h3> The anticoagulant effect of NOAC agents is predictable but not readily measurable in routine clinical practice. A number of uncertainties remain surrounding the use of these agents in the perioperative setting. Ongoing prospective studies and randomized clinical trials will provide greater clarity on these management issues in the near future.
Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors <scp>PD</scp>‐1, <scp>TIGIT</scp>, and <scp>TIM</scp>‐3 in Lymphocytes From Patients With Systemic Sclerosis
Authors: Michelle Fleury, Anna C. Belkina, Elizabeth A. Proctor, Christopher Zammitti, Robert W. Simms, Douglas A. Lauffenburger, Jennifer E. Snyder‐Cappione, Robert Lafyatis, Hans Dooms
Journal: Arthritis & Rheumatology (2017)

Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc. Co-IR expression levels on subsets of immune cells were analyzed using a 16-color flow cytometry panel. The functional role of co-IRs was determined by measuring cytokine production after in vitro stimulation of SSc and healthy control peripheral blood mononuclear cells (PBMCs) in the presence of co-IR-blocking antibodies. Supernatants from cultures of stimulated PBMCs were added to SSc fibroblasts, and their impact on fibroblast gene expression was measured. Mathematical modeling was used to reveal differences between co-IR functions in SSc patients and healthy controls. Levels of the co-IRs PD-1 and TIGIT were increased, and each was coexpressed, in distinct T cell subsets from SSc patients compared to healthy controls. Levels of TIM-3 were increased in SSc natural killer cells. PD-1, TIGIT, and TIM-3 antibody blockade revealed patient-specific roles of each of these co-IRs in modulating activation-induced T cell cytokine production. In contrast to healthy subjects, blockade of TIGIT and TIM-3, but not PD-1, failed to reverse inhibited cytokine production in SSc patients, indicating that enhanced T cell exhaustion is present in SSc. Finally, cytokines secreted in anti-TIM-3-treated PBMC cultures distinctly changed the gene expression profile in SSc fibroblasts. The altered expression and regulatory capacity of co-IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine-mediated cross-talk of immune cells and fibroblasts at sites of inflammation and/or fibrosis.
Estimated glomerular filtration rate variations and direct acting antivirals treatment for chronic hepatitis C: a retrospective longitudinal study
Authors: V. Mallet, L. Parlati, O. Dorval, L. Kramer, A. Hernvann, A.V. Pichard, C. Guerin, H. Fontaine, P. Sogni, S. Pol
Journal: Journal of Hepatology (2018)
Identification, by Cold-PCR, of treatment-resistant HCV mutations in baseline samples of patients treated with DAAs
Authors: A. Madejón, I. Francisco-Recuero, M. Romero, A. García-Sánchez, A.O. Martin, J.C. Erdozaín, P. Castillo, R. Mena, F.J.G.-S. Rey
Journal: Journal of Hepatology (2018)
Mixed HCC-ICC liver cancer derives from hepatic progenitor cells- A lineage tracing investigation in mouse liver inflammation models
Authors: N. Rosenberg, N. Barashi, H. Giladi, D. Goldenberg, M. Shoshkes-Carmel, K. Kaestner, M. Van Haele, T. Roskams, E. Galun
Journal: Journal of Hepatology (2018)
Albumin administration in the prevention of hepatorenal syndrome (HRS) and death in patients with advanced cirrhosis and non-SBP infections
Authors: J. Fernandez, P. Angeli, J. Trebicka, M. Merli, T. Gustot, C. Alessandria, N.K. Aagaard, A. De Gottardi, S. Zeuzem, A. Gerbes, G. Soriano, V. Vargas, A. Albillos, F. Salerno, F. Durand, R. Bañares, R.E. Stauber, V. Prado, M. Arteaga, F. Morando, C. Jansen, B. Lattanzi, C. Moreno, A. Risso, H. Grønbæk, R. Garcia, M. Pavesi, V. Arroyo
Journal: Journal of Hepatology (2018)
Conflicts of Interest of Public Speakers at Meetings of the Anesthetic and Analgesic Drug Products Advisory Committee
Authors: Matthew S. McCoy, Olivia Pagán, Gabrielle Donohoe, Genevieve P. Kanter, Ronald S. Litman
Journal: JAMA Internal Medicine (2018)

This data review investigates the characteristics and conflicts of interest of public speakers at Anesthetic and Analgesic Drug Products Advisory Committee meetings.
A Correction to the Research Article Titled: "Neural Stem Cell Engraftment and Myelination in the Human Brain" by N. Gupta, R. G. Henry, J. Strober, S.-M. Kang, D. A. Lim, M. Bucci, E. Caverzasi, L. Gaetano, M. L. Mandelli, T. Ryan, R. Perry, J. Farrell, R. J. Jeremy, M. Ulman, S. L. Huhn, A. J. Barkovich, D. H. Rowitch
Journal: Science Translational Medicine (2012)

Pelizaeus-Merzbacher disease (PMD) is a rare leukodystrophy caused by mutation of the proteolipid protein 1 gene.Defective oligodendrocytes in PMD fail to myelinate axons, causing global neurological dysfunction.Human central nervous system stem cells (HuCNS-SCs) can develop into oligodendrocytes and confer structurally normal myelin when transplanted into a hypomyelinating mouse model.A 1-year open-label phase 1 study was undertaken to evaluate safety and to detect evidence of myelin formation after HuCNS-SC transplantation.Allogeneic HuCNS-SCs were surgically implanted into the frontal lobe white matter in four male subjects with an early-onset severe form of PMD.Immunosuppression was administered for 9 months.Serial neurological evaluations, developmental assessments, and cranial magnetic resonance imaging (MRI) and MR spectroscopy, including high-angular resolution diffusion tensor imaging (DTI), were performed at baseline and after transplantation.The neurosurgical procedure, immunosuppression regimen, and HuCNS-SC transplantation were well tolerated.Modest gains in neurological function were observed in three of the four subjects.No clinical or radiological adverse effects were directly attributed to the donor cells.Reduced T1 and T2 relaxation times were observed in the regions of transplantation 9 months after the procedure in the three subjects.Normalized DTI showed increasing fractional anisotropy and reduced radial diffusivity, consistent with myelination, in the region of transplantation compared to control white matter regions remote to the transplant sites.These phase 1 findings indicate a favorable safety profile for HuCNS-SCs in subjects with PMD.The MRI results suggest durable cell engraftment and donor-derived myelin in the transplanted host white matter.
In high-risk T1DM, real-time continuous glucose monitoring vs self-monitoring reduced hypoglycemic events
Authors: Hertzel Gerstein
Journal: Annals of Internal Medicine (2018)

Source Citation Heinemann L, Freckmann G, Ehrmann D, et al. Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial. Lancet. 2018 391:1367-77. 29459019
Clinical Knowledge from Observational Studies. Everything You Wanted to Know but Were Afraid to Ask
Authors: Andrea S. Gershon, S. Reza Jafarzadeh, Kevin C. Wilson, Allan J. Walkey
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Well-done randomized trials provide accurate estimates of treatment effect by producing groups that are similar on all measures except for the intervention of interest. However, inferences of efficacy in tightly-controlled experimental settings may not translate into similar effectiveness in real-world settings. Observational studies generally enable inferences over a wider range of patient characteristics and evaluation of a broader range of outcomes over a longer period than randomized trials. However, clinicians are often reluctant to incorporate the findings of observational studies into clinical practice. Reason for uncertainty regarding observational studies include a lack of familiarity with observational research methods, occasional disagreements between results of observational studies and randomized trials, the perceived risk of spurious results from systematic bias, and prior teaching that randomized trials are the most reliable source of medical evidence. We propose that a better understanding...
COMBINED ENDOSCOPIC AND PERCUTANEOUS SELF EXPANDABLE METAL STENT PLACEMENT FOR MALIGNANT HILAR STENOSIS OF THE BILIARY TREE
Authors: A Katzarov, Z Dunkov, I Popadiin, K Katzarov
Journal: Endoscopy (2018)

Patients with malignant hilar biliary strictures, not suitable candidates for surgery are referred for palliative treatment. Following generally accepted guidelines they are managed by placement of uncovered self expandable metal stents (SEMS) for biliary decompression and palliative chemotherapy. Hilar strictures are technically challenging even for experienced endoscopists. In specific cases severity of the stenosis makes it difficult to canulate the affected branch and achieve adequate biliary drainage.
Combinations of inflammatory markers, soluble (s)CD163, mannose receptor (sMR) and neutrophil gelatinase associated lipocalin (NGAL), predicts mortality in patients with acute-on-chronic liver failure
Authors: H. Grønbæk, H.J. Møller, D. Benten, R. Jalan, C. Moreno, A. Alex, P. Marco, P. Ginès, V. Arroyo
Journal: Journal of Hepatology (2018)