tbuckley/cabot-search huggingface dataset:
Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: A randomized, double‐blind, placebo‐controlled study
Authors: Martin Metz, Rebecca Torene, Sergio Kaiser, Michael T. Beste, Petra Staubach, Andrea Bauer, Randolf Brehler, Janine Gericke, Martin Letzkus, Nicole Hartmann, Veit J. Erpenbeck, Marcus Maurer
Journal: Allergy (2018)

Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment-refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double-blind, placebo-controlled study.Chronic spontaneous urticaria patients (18-75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.c. every 4 weeks for 12 weeks (NCT01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers (HVs). Gene expression data were generated using Affymetrix HG-U133Plus2.0 microarrays. Statistical analyses were performed using R packages.At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two-thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P < 0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration (FCER1G, C3AR1, CD93, S100A8, and S100A9), increased oxidative stress, vascularization (CYR61), and skin repair events (KRT6A, KRT16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS7 longitudinal changes ≥16).Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/HV expression levels; this is consistent with observed omalizumab-mediated clinical improvement observed in patients with CSU.
EUS GUIDED COIL PLACEMENT FOR THE MANAGEMENT OF ACUTE GASTRIC VARICES BLEEDING FOLLOWING UNSUCCESSFUL GLUE INJECTION
Authors: T Mazzawi, CE Markhus, R Flesland Havre, KDC Pham
Journal: Endoscopy (2018)

Endoscopic ultrasound (EUS) guided coil placement is a new emerging technique for the management of gastric varices. In this video case report, we describe the EUS guided single coil placement for managing acute gastric varices (GVs) bleeding following glue injection.
Role of (myo)fibroblasts in the development of vascular and connective tissue structure of the C38 colorectal cancer in mice
Authors: Edina Bugyik, Vanessza Szabó, Katalin Dezső, András Rókusz, Armanda Szücs, Péter Nagy, József Tóvári, Viktória László, Balázs Döme, Sándor Paku
Journal: Cancer Communications (2018)

Abstract Background It remains unclear if the vascular and connective tissue structures of primary and metastatic tumors are intrinsically determined or whether these characteristics are defined by the host tissue. Therefore we examined the microanatomical steps of vasculature and connective tissue development of C38 colon carcinoma in different tissues. Methods Tumors produced in mice at five different locations (the cecal wall, skin, liver, lung, and brain) were analyzed using fluorescent immunohistochemistry, electron microscopy and quantitative real‐time polymerase chain reaction. Results We found that in the cecal wall, skin, liver, and lung, resident fibroblasts differentiate into collagenous matrix‐producing myofibroblasts at the tumor periphery. These activated fibroblasts together with the produced matrix were incorporated by the tumor. The connective tissue development culminated in the appearance of intratumoral tissue columns (centrally located single microvessels embedded in connective tissue and smooth muscle actin‐expressing myofibroblasts surrounded by basement membrane). Conversely, in the brain (which lacks fibroblasts), C38 metastases only induced the development of vascularized desmoplastic tissue columns when the growing tumor reached the fibroblast‐containing meninges. Conclusions Our data suggest that the desmoplastic host tissue response is induced by tumor‐derived fibrogenic molecules acting on host tissue fibroblasts. We concluded that not only the host tissue characteristics but also the tumor‐derived fibrogenic signals determine the vascular and connective tissue structure of tumors.
Using photoplethysmography data to estimate heart rate variability and its association with organ dysfunction in pediatric oncology patients
Authors: Anoop Mayampurath, Samuel L Volchenboum, L. Nelson Sanchez-Pinto
Journal: npj Digital Medicine (2018)

Pediatric oncology patients are at high risk of developing clinical deterioration and organ dysfunction during their illness. Heart rate variability (HRV) measured using electrocardiography waveforms is associated with increased organ dysfunction and clinical deterioration in adult and pediatric patients in the intensive care unit (ICU). Here, we explore the feasibility of using photoplethysmography (PPG)-derived integer pulse rate variability (PRVi) to estimate HRV and determine its association with organ dysfunction in pediatric oncology patients in the ward and pediatric ICU. The advantage of using PPG sensor data over electrocardiography is its higher availability in most healthcare settings and in wearable technology. In a cohort of 38 patients, reduced median daily PRVi was significantly associated with increase in two pediatric organ dysfunction scores after adjusting for confounders (
Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery
Authors: Catherine Cukras, Henry E. Wiley, Brett G. Jeffrey, H. Nida Sen, Amy Turriff, Yong Zeng, Camasamudram Vijayasarathy, Dario Marangoni, Lucia Ziccardi, Sten Kjellstrom, Tae Kwon Park, Suja Hiriyanna, J. Fraser Wright, Peter Colosi, Zhijian Wu, Ronald A. Bush, Lisa L. Wei, Paul A. Sieving
Journal: Molecular Therapy (2018)

This study evaluated the safety and tolerability of ocular RS1 adeno-associated virus (AAV8-RS1) gene augmentation therapy to the retina of participants with X-linked retinoschisis (XLRS). XLRS is a monogenic trait affecting only males, caused by mutations in the RS1 gene. Retinoschisin protein is secreted principally in the outer retina, and its absence results in retinal cavities, synaptic dysfunction, reduced visual acuity, and susceptibility to retinal detachment. This phase I/IIa single-center, prospective, open-label, three-dose-escalation clinical trial administered vector to nine participants with pathogenic RS1 mutations. The eye of each participant with worse acuity (≤63 letters; Snellen 20/63) received the AAV8-RS1 gene vector by intravitreal injection. Three participants were assigned to each of three dosage groups: 1e9 vector genomes (vg)/eye, 1e10 vg/eye, and 1e11 vg/eye. The investigational product was generally well tolerated in all but one individual. Ocular events included dose-related inflammation that resolved with topical and oral corticosteroids. Systemic antibodies against AAV8 increased in a dose-related fashion, but no antibodies against RS1 were observed. Retinal cavities closed transiently in one participant. Additional doses and immunosuppressive regimens are being explored to pursue evidence of safety and efficacy (ClinicalTrials.gov: NCT02317887).
PER-ORAL ENDOSCOPIC PYLOROMYOTOMY (G-POEM) IN THE TREATMENT OF REFRACTORY GASTROPARESIS – A SINGLE CENTRE EXPERIENCE
Authors: R Hustak, Z Vacková, J Spicak, L Jurgos, J Martinek
Journal: Endoscopy (2018)

Gastroparesis is a chronic, debilitating motility disorder. Effective treatment is challenging especially in patients with severe symptoms. G-POEM is an emerging modality for refractory gastroparesis with promising preliminary results. The aim of this prospective case series was to assess our first experience with G-POEM. Main outcomes were: the efficacy defined by improvement of GCSI ≥40% from baseline; GES evolution and safety.
The Emerging Role of Inhaled Heroin in the Opioid Epidemic
Authors: Vilakshan Alambyan, Jonathan Pace, Benjamin Miller, Mark L. Cohen, Sankalp Gokhale, Gagandeep Singh, Ming-Chieh Shun, Anthony Hammond, Ciro Ramos-Estebanez
Journal: JAMA Neurology (2018)

<h3>Importance</h3> Opioid addiction affects approximately 2.4 million Americans. Nearly 1 million individuals, including a growing subset of 21 000 minors, abuse heroin. Its annual cost within the United States amounts to $51 billion. Inhaled heroin use represents a global phenomenon and is approaching epidemic levels east of the Mississippi River as well as among urban youth. Chasing the dragon (CTD) by heating heroin and inhaling its fumes is particularly concerning, because this method of heroin usage has greater availability, greater ease of administration, and impressive intensity of subjective experience (high) compared with sniffing or snorting, although it also has a safer infectious profile compared with heroin injection. This is relevant owing to peculiar and often catastrophic brain complications. Following the American Medical Association Opioid Task Force mandate, we contribute a description of the pharmacology, pathophysiology, clinical spectrum, neuroimaging, and neuropathology of CTD leukoencephalopathy, as distinct from other heroin abuse modalities. <h3>Observations</h3> The unique spectrum of CTD-associated health outcomes includes an aggressive toxic leukoencephalopathy with pathognomonic neuropathologic features, along with sporadic instances of movement disorders and hydrocephalus. Clinical CTD severity is predominantly moderate at admission, frequently unmodified at discharge, and largely improved in the long term. Mild cases survive with minor sequelae, while moderate to severe presentations might deteriorate and progress to death. Other methods of heroin use may complicate with stroke, seizure, obstructive hydrocephalus, and (uncharacteristically) leukoencephalopathy. <h3>Conclusions and Relevance</h3> The distinct pharmacology of CTD correlates with its specific clinical and radiological features and prompts grave concern for potential morbidity and long-term disability costs. Proposed diagnostic criteria and standardized reporting would ameliorate the limitations of CTD literature and facilitate patient selection for a coenzyme Q10 therapeutic trial.
ENDOSCOPIC AND CLINICAL CHARACTERISTICS OF MICROSCOPIC COLITIS
Authors: O Ilyés, I Iozsef, P Miheller, AV Patai
Journal: Endoscopy (2018)

Microscopic colitis (MC) is a common cause of chronic watery diarrhea. The diagnosis of MC is made by specific histopathological findings, with poor colonoscopic signs. The aim of this study was to identify macroscopic signs and clinical features that can be related to MC in patients, who underwent colonoscopic examination in 2016.
Tackling loneliness with a well stocked community
Authors: Lisa McNally
Journal: BMJ (2018)

The Royal College of General Practitioners’ action plan on tackling loneliness is a positive move.12 It advocates for public campaigns on loneliness and for professional development resources. It also encourages social prescribing and the promotion of local, community based opportunities for social contact.

This last point is crucial. As I’ve said elsewhere, “Just as a doctor’s prescription …
Impact of prehospital medical evacuation (MEDEVAC) transport time on combat mortality in patients with non-compressible torso injury and traumatic amputations: a retrospective study
Authors: Joseph K. Maddry, Crystal A. Perez, Alejandra G. Mora, Jill D. Lear, Shelia C. Savell, Vikhyat S. Bebarta
Journal: Military Medical Research (2018)

In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and non-compressible torso injury (NCTI). We completed a retrospective review of MEDEVAC patient care records for United States military personnel who sustained traumatic amputations and NCTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NCTI (AMP+NCTI), traumatic amputation only (AMP), and neither AMP nor NCTI (Non-AMP/NCTI). Analysis was performed using chi-squared tests, Fisher's exact tests, Cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and Cox proportional hazards regression modeling. We reviewed 1267 records, of which 669 had an injury severity score (ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries (n=104, AMP only), 10.8% sustained amputation and NCTI (n=72, AMP+NCTI), and 73.7% did not sustain either an amputation or an NCTI (n=493, Non-AMP/NCTI). AMP+NCTI had the highest mortality (16.7%) with transport time greater than 60 min. While the AMP+NCTI group had decreasing survival with longer transport times, AMP and Non-AMP/NCTI did not exhibit the same trend. A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NCTI. No significant association between transport time and outcomes was found in patients who did not sustain NCTI. Priority for rapid evacuation of combat casualties should be given to those with NCTI.
Abstract P240: Racial/ethnic Differences in Psychological Distress after Stroke
Authors: Emma K Benn, Kezhen Fei, Eric T Roberts, Leigh Quarles, Bernadette Boden-Albala
Journal: Circulation (2013)

Introduction Psychological distress after stroke has received some attention, but little is known about the impact of race/ethnicity. We conducted a secondary analysis to investigate whether there were racial/ethnic differences in psychological distress among stroke/TIA survivors enrolled in the Stroke Warning Information and Faster Treatment (SWIFT) trial, while taking into account the longitudinal nature of the data. Methods The SWIFT trial was a randomized stroke preparedness educational intervention, which prospectively enrolled mild and moderate stroke/TIA patients able to sign informed consent and identified at the NY Presbyterian Medical Center from 2005 to 2010. Psychological distress, defined as having a CES-D score ≥16, was measured at baseline, 1 month, and 12 months. The multiethnic sample included non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. Additional predictors included treatment assignment, health status, marital status, and SES. Health status included stroke severity, as measu...
Abstract 21301: Modulation of EC Function by miR-155, a Shear Stress-Responsive miRNA
Authors: Martina Weber, Charles D Searles
Journal: Circulation (2010)

Endothelial cells (ECs) respond to changes in shear stress forces by modulating cell morphology, migration, apoptosis, proliferation, and survival. MicroRNAs (miRNAs) are a class of short (19–25 nt...
ENDOSCOPIC TREATMENT OF A SEVERE ANASTOMOTIC LEAK WITH ENDOSCOPIC VACCUM THERAPY AFTER STENT FAILURE
Authors: R Morais, E Rodrigues-Pinto, P Pereira, G Macedo
Journal: Endoscopy (2018)

A 58-year-old man underwent an Ivor-Lewis esophagectomy due to an esophagus squamous-cell carcinoma. Three days later, he presented with subcutaneous emphysema and respiratory insufficiency. Chest computed tomography (CT) with oral contrast revealed a pneumomediastinum with contrast extravasation between the gastric tube and the right pleural cavity at the level of the carina, in relation with an anastomotic leakage. After multidisciplinary discussion, upper endoscopy revealed a severe anastomotic leakage 29 cm from the incisors. A fully covered 28/23/28 × 120 mm SEMS (Wallflex, Boston Scientific, Marlborough, MA) was placed. Nevertheless, SEMS migrated despite 3 clips placement. After SEMS removal, endoscopic vacuum therapy (EVT) was performed (Endo-Sponge system, B. Braun, Melsungen, Germany). The “backpack technique” was first used to place the 7 cm polyurethane foam sponge of this pre-assembled set, however, it could not be inserted into the cavity. With the assistance of two Endo-Sponge encrusted overtubes, the foam was placed well deep in the mediastinal cavity. The sponge was replaced every five days using the technique described above, with progressive clinical and endoscopic improvement (decrease of cavity dimensions, necrotic content improvement and granulation tissue formation). Third sponge replacement was hampered by drainage tube disconnection from the polyurethane foam sponge; the sponge remained inside the wound cavity and required the use of multiple devices (biopsy forceps, baskets, snares and double channel endoscope) to achieve removal. A complete closure of the anastomotic defect was achieved at fifth sponge replacement. Barium swallow and CT with oral contrast showed no leak.
Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge 2018” (28–29 November, 2018, Naples, Italy)
Authors: Paolo A. Ascierto, Carlo Bifulco, Luigi Buonaguro, Leisha A. Emens, Robert L. Ferris, Bernard A. Fox, Greg M. Delgoffe, Jérôme Galon, Cesare Gridelli, Marco Merlano, Paul Nathan, Kunle Odunsi, Hideho Okada, Chrystal M. Paulos, Sandro Pignata, Kurt A. Schalper, Stefani Spranger, Giampaolo Tortora, Hassane Zarour, Lisa H. Butterfield, Igor Puzanov
Journal: Journal for ImmunoTherapy of Cancer (2019)

Immunotherapy is now widely established as a potent and effective treatment option across several types of cancer. However, there is increasing recognition that not all patients respond to immunotherapy, focusing attention on the immune contexture of the tumor microenvironment (TME), drivers of the immune response and mechanisms of tumor resistance to immunity. The development of novel immunotherapeutics and their use in combination with checkpoint inhibitors and other standard of care and novel treatment modalities is an area of particular attention across several tumor types, including melanoma, lung, ovarian, breast, pancreatic, renal, head and neck, brain and non-melanoma skin cancers. The 4th Immunotherapy Bridge meeting (28-29 November, 2018, Naples, Italy) focused on a wide range of evolving topics and trends in the field of cancer immunotherapy and key presentations from this meeting are summarised in this report.
Sensitization of the Neural Salience Network to Repeated Emotional Stimuli Following Initial Habituation in Patients With Borderline Personality Disorder
Authors: Bryan T. Denny, Jin Fan, Samuel Fels, Hayley Galitzer, Daniela Schiller, Harold W. Koenigsberg
Journal: American Journal of Psychiatry (2018)

Objective: Borderline personality disorder is the prototypical disorder of emotion reactivity and dysregulation, yet there remains limited understanding of its neurocognitive correlates. Two mechanisms that may underlie anomalous reactivity in response to negative stimuli among patients with borderline personality disorder are impairment in habituation and exaggerated sensitization of activity in the neural salience network, including the amygdala, anterior insula, and dorsal anterior cingulate cortex. The authors aimed to reveal the most plausible mechanism by examining the effect of repeated exposure to emotional images both within and across study sessions. Method: A total of 75 participants (patients with borderline personality disorder, N=26; patients with avoidant personality disorder included as a psychopathological control group, N=25; and healthy control subjects, N=24) were included in the study analyses. All participants viewed five presentations of the same set of negative and neutral images at each of two sessions, separated by approximately 3 days, while functional MRI data were acquired. Salience network activity, as measured by blood-oxygen-level–dependent signal in anatomically defined regions of interest across the salience network, was compared across the three groups for each presentation at each of the two study sessions. Self-reported negative affect was measured for each trial. Results: Salience network activity showed a main effect of within-session habituation across all groups and sessions. However, a group-by-session interaction was present, such that only patients with borderline personality disorder showed increased salience network activity in response to the images reencountered at the second session, and this increased salience network sensitization predicted greater sensitization in self-reported negative affect. Conclusions: These results elucidate the neural mechanisms by which patients with borderline personality disorder appraise negative social situations as exaggeratedly salient and suggest potential neurocognitive intervention targets.
Offshore Exploration in the Arctic: Can Shell’s Oil-Spill Response Plans Keep Up?
Authors: Charles W. Schmidt
Journal: Environmental Health Perspectives (2012)

A ll around the world, oil and gas companies are being forced by resource declines to drill in less accessible areas, and the Arctic is their newest frontier.The geology above the Arctic Circle-that is, everything above latitude 66.56°N-holds an estimated 90 billion barrels of oil and 1,669 trillion cubic feet of natural gas, or 22% of the world's undiscovered 1 conventional resources, according to the U.S. Energy Information Administration. 2 It's thought that these resources lie predominantly under Arctic seas, which have recently become easier to reach due to significant reductions in seasonal ice cover associated with global climate change. 3Norway, Russia, Canada, Denmark, and other northern countries are in various stages of developing offshore Arctic programs, and diplomatic squabbles have broken out over territorial rights extending all the way to the North Pole.Between 1980 and 2000 Alaska accounted for an average one-fifth of U.S. oil production. 4But with oil f lowing through the Trans-Alaska Pipeline falling by more than two-thirds since a peak in 1988, 4 the recent pressure to drill in the Outer Continental Shelf (OCS) off the state's north coast has been relentless.Alaska derives at least 90% of its revenues from oil, 5 so law makers in that state-supported by much of the state's population-have pushed hard for offshore authorization.The federal government has also indicated its support, in 2011 expressing a A second drill rig engaged in Beaufort Sea exploration-the Kullukcould begin drilling a relief well in the Chukchi within a week should attempts to kill a worst-case blowout fail. © Tom DoyleFocus | Offshore Exploration in the Arctic commitment to facilitate development in the OCS region and to expedite offshore permitting in Alaska, assuming that "safety, health, and environmental standards are fully met." 6ow the United States has taken a big step toward opening the seas off Alaska to a new round of oil and gas exploration.In a major breakthrough for the petroleum industry and loss for drilling opponents, the U.S. Department of the Interior (DOI) in February 2012 approved Shell Gulf of Mexico, Inc.'s oil-spill response plan for the Chukchi Sea, which provides habitat for polar bears, walruses, and other wildlife, and a hunting ground for Alaska Natives who still