tbuckley/cabot-search huggingface dataset:
Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 — Georgia, March 2020
Authors: Jeremy A. W. Gold, Karen K. Wong, Christine M. Szablewski, Priti R. Patel, John Rossow, Juliana da Silva, Pavithra Natarajan, Sapna Bamrah Morris, Robyn Neblett Fanfair, Jessica Rogers-Brown, Beau B. Bruce, Sean D. Browning, Alfonso C. Hernandez-Romieu, Nathan W. Furukawa, Mohleen Kang, Mary E. Evans, Nadine Oosmanally, Melissa Tobin-D’Angelo, Cherie Drenzek, David J. Murphy, Julie Hollberg, James M. Blum, Robert Jansen, David W. Wright, William M. Sewell, Jack D. Owens, Benjamin Lefkove, Frank W. Brown, Deron C. Burton, Timothy M. Uyeki, Stephanie R. Bialek, Brendan R. Jackson
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

This report characterizes a cohort of hospitalized adults with coronavirus disease 2019 (COVID-19) in Georgia in which black patients were overrepresented and one in four hospitalized patients had no recognized risk factors for severe COVID-19.
The importance of fit testing in decontamination of N95 respirators: A cautionary note
Authors: David Ozog, Angela Parks-Miller, Indermeet Kohli, Alexis B. Lyons, Shanthi Narla, Angeli E. Torres, Martin Levesque, Henry W. Lim, Iltefat H. Hamzavi
Journal: Journal of the American Academy of Dermatology (2020)
Imaging of Atherosclerosis with 18F-FDG PET
Authors: Jan Bucerius
Journal: Clinical Nuclear Medicine (2020)

Despite significant therapeutic advances, myocardial infarction and stroke, as the clinical consequences of atherosclerosis, are the two most common causes of death in Europe and worldwide.In clinical routine, evaluation of atherosclerosis still relies mainly on invasive of non-invasive assessment of the degree of intraluminal stenosis using invasive or CT angiography, which, however, do not provide information on plaque vulnerability, i.e., the risk of plaque rupture. Therefore, there is a clear need for non-invasive, highly sensitive measures to identify those high-risk plaques. In that regard, in vivo molecular imaging of pathological mechanisms in atherosclerosis by using positron emission tomography (PET) gained more and more interest over the last two decades. Numerous studies were published regarding PET imaging in atherosclerosis providing insights into the biological processes within the atherosclerotic plaque, improving risk stratification, and enabling the evaluation of novel therapies and interventions.
Certolizumab pegol has a different profile from other anti-TNFs, including golimumab, in a variety of in vitro assays
Authors: G. Fossati, A. Nesbitt
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Differences in structure and in vitro properties of anti-tumour necrosis factor (TNF) agents may account for different modes of action and clinical outcomes. The activities of certolizumab pegol (CZP), etanercept (ETA), infliximab (IFX) and adalimumab (ADA) have been compared using in vitro assays. However, golimumab (GLM) has not previously been evaluated. The objective of this study was to compare the activity of CZP with other anti-TNFs, including GLM, in a range of in vitro assays. <h3>Materials and methods</h3> Neutralisation of human TNF was assessed in the L929 bioassay. The activity of anti-TNFs at inhibiting lipopolysaccharides (LPS)-driven interleukin 1β (IL-1β) secretion by monocytes was measured by ELISA. To determine apoptosis induction, activated peripheral blood lymphocytes and monocytes were examined by annexin V staining using flow cytometry. The effect on neutrophil necrosis was measured by myeloperoxidase release. An isotype-matched control was used in all assays except the L929 bioassay. <h3>Results</h3> The inhibitory concentration (IC<sub>90</sub>) neutralisation activity in the L929 bioassay was 0.3 ng/ml for ETA, 4 ng/ml for GLM, 15 ng/ml for ADA and 20 ng/ml for IFX, versus 2.5 ng/ml for CZP. CZP was the most potent inhibitor of LPS-driven IL-1β secretion (IC<sub>50</sub> ∼0.1 ng/ml), followed by GLM (20 ng/ml). GLM, ADA, IFX and ETA induced apoptosis of monocytes and lymphocytes to a similar degree. CZP caused no increase in apoptosis above isotype-matched control levels. In the neutrophil necrosis assay, ADA, IFX and GLM caused ∼70% necrosis at 100 μg/ml, and ETA 48%. CZP did not increase the level of necrosis above the level of the control. <h3>Conclusion</h3> The ability of GLM, IFX and ADA to neutralise human TNF was inferior to CZP and ETA. CZP had a different profile to the other anti-TNFs; it was the most potent at inhibiting monocyte LPS-driven IL-1β production, did not induce apoptosis of activated monocytes and lymphocytes and did not cause neutrophil necrosis. The clinical relevance of these in vitro effects is unknown. Nevertheless, these assays show interesting differences between anti-TNFs.
STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies
Authors: Patrick M Bossuyt, Johannes B Reitsma, David E Bruns, Constantine A Gatsonis, Paul P Glasziou, Les Irwig, Jeroen G Lijmer, David Moher, Drummond Rennie, Henrica C W de Vet, Herbert Y Kressel, Nader Rifai, Robert M Golub, Douglas G Altman, Lotty Hooft, Daniël A Korevaar, Jérémie F Cohen
Journal: BMJ (2015)

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting Diagnostic Accuracy (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
The acute respiratory distress syndrome
Authors: Michael A. Matthay, Lorraine B. Ware, Guy A. Zimmerman
Journal: Journal of Clinical Investigation (2012)

The acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure that is often associated with multiple organ failure. Several clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair.
ADTH-10 Efficacy and safety of 1l-PEG and ascorbate bowel preparation NER1006 versus 2l-PEG with ascorbate
Authors: Richard Ng, Raf Bisschops, Jonathan Manning, Marco Antonio Alvarez Gonzalez
Journal: Endoscopy (2018)

<h3>Introduction</h3> PEG based preparations are traditionally seen as the gold standard in cleansing, but they all require a high total fluid intake. NER1006 is the first 1L-PEG 3350 and ascorbate bowel preparation. <h3>Methods</h3> This phase 3, randomised, multicentre, colonoscopist-blinded, non-inferiority study assessed the efficacy, safety and tolerability of NER1006, administered either as a 2 day overnight (N2D) or 1 day morning (N1D) split-dosing regimen versus a 2L-PEG 3350 with ascorbate 2 day overnight split dosing regimen (2LPEG) in patients undergoing a colonoscopy. Two alternative primary endpoints were evaluated: overall bowel cleansing efficacy and `Excellent or Good' cleansing rate in the ascending colon and caecum using the Harefield Cleansing Scale (HCS). Secondary endpoints included hierarchical evaluation of lesion detection rates (key), and cleansing assessment using the Boston Bowel Preparation Scale (BBPS; supportive). Patient tolerability, acceptability and compliance were assessed using questionnaires. Safety was monitored through adverse events and clinical laboratory evaluation. The threshold for statistical significance in this study was p&lt;0.025 and a 10% margin was used to demonstrate non-inferiority vs 2LPEG. Patients were randomised to receive either N2D, N1D, or 2LPEG. <h3>Results</h3> Compliance rates were high in all treatment groups. There were no deaths. NER1006 was not associated with any serious treatment-emergent adverse events (TEAEs). The most frequently reported related TEAEs for NER1006 were nausea and vomiting; and for 2LPEG, nausea and abdominal pain. <h3>Conclusions</h3> When administered as either a 2 day overnight or 1 day morning split-dosing regimen, and compared to 2LPEG, NER1006 was non-inferior in overall bowel cleansing success. It also demonstrated a superior `Excellent or Good' cleansing rate in the ascending colon and caecum. As a 2 day overnight split dosing NER1006 demonstrated a superior polyp detection rate in the ascending colon and caecum. The overall tolerability and safety profile of NER1006 was comparable to that of 2LPEG; most TEAEs were mild or moderate in severity and reflected the expected safety profile of the respective treatments.
PTH-063 Endoscopic resection of dysplastic lesions in colitis
Authors: Asma Al-Khandari, Sreedhari Thayalasekaran, Megha Bhandari, Kesavan Kandiah Hayee, Marek Bugajski, Agnieszka Przybysz, Michal Spychalski, Bu Hayee, Alessandro Repici, Pradeep Bhandari
Journal: Endoscopy (2018)

<h3>Introduction</h3> Cumulative colon cancer risk is estimated at 2%–18% depending on duration of colitis. Management of flat neoplasia in colitis remains controversial. BSG guidelines recommend colectomy if complete endoscopic resection isn't guaranteed. Aim of this study was to assess need for surgery in the management of flat neoplasia in colitis. <h3>Methods</h3> A multicentre cohort study of all flat neoplasia endoscopically resected in colitis in 5 tertiary European centres from 2008–2017. <h3>Results</h3> 101 flat neoplasia were resected in 85 patients at 5 European centres. Mean age 61 years (range 28–82). Mean size of lesions 34 mm (range 8–120 mm). 40% of the lesions were treated by KAR. There was no difference in lesion location between EMR and KAR. Lesions &gt;20 mm in size were removed more by KAR than EMR. More lesions removed by KAR (26) had fibrosis compared to EMR (15). 7 complications occurred in the cohort; 3 cases of bleeding and 4 perforations. Bleeding was controlled endoscopically. 3 perforations were managed endoscopically and 1 required surgery. 7/86 (8.1%) lesions with follow up data had recurrence. Multi-variate regression analysis concluded; 33. EMR leads to higher recurrence rates, irrespective of size, location and fibrosis (p–value of 0.048) 34. KAR leads to higher complication rates in the colon as compared to rectum (p–value of 0.045) 35. KAR shows a trend towards better en–bloc resection (p–value 0.063). 5 lesions underwent surgery; 3 due to cancer; 1 due to perforation; 1 due to failure of endoscopic resection. Histology; 88 adenoma (low-grade dysplasia), 6 adenoma (high-grade dysplasia), 3 cancers and 4 sessile serrated polyps. <h3>Conclusions</h3> This is the largest reported cohort of endoscopic resection of flat neoplasia in colitis. We demonstrate that both KAR and EMR are feasible in colitis with only 5% of patients requiring surgery. Fibrosis is very common in colitis. Recurrence is higher with EMR and complications higher with KAR. Our data shows that lesions with fibrosis are best treated by KAR, and those with fibrosis and &lt;20 mm can be managed by EMR.
Colonoscopy later than 270 days in a fecal immunochemical test-based population screening program is associated with higher prevalence of colorectal cancer
Authors: Manuel Zorzi, Cesare Hassan, Giulia Capodaglio, Maddalena Baracco, Giulio Antonelli, Emanuela Bovo, Massimo Rugge
Journal: Endoscopy (2020)

Background Colorectal cancer (CRC) screening programs based on fecal immunochemical testing (FIT) generate substantial pressure on colonoscopy capacity in Europe. Thus, a relevant proportion of FIT-positive patients undergo colonoscopy after the recommended 30-day interval, which may be associated with an excess CRC risk. Methods In a cohort of 50–69-year-old patients undergoing biennial rounds of FIT (OC-Hemodia latex agglutination test; cutoff 20 µg hemoglobin/g feces) between 2004 and 2017, we assessed the outcome at colonoscopy (low/high risk adenoma/CRC/advanced stage CRC) among FIT-positive patients, according to different time intervals. The association of each outcome with waiting time, and demographic and clinical factors, was analyzed through multivariable analysis. Results 123 138/154 213 FIT-positive patients (79.8 %) underwent post-FIT colonoscopy. Time to colonoscopy was ≤ 30 days, 31–180 days, and ≥ 181 days in 50 406 (40.9 %), 71 724 (58.3 %), and 1008 (0.8 %) patients, respectively. At colonoscopy, CRC, high risk adenoma, and low risk adenoma were diagnosed in 4813 (3.9 %), 30 500 (24.8 %), and 22 986 (18.7 %) patients, respectively. An increased CRC prevalence at colonoscopy was observed for a time to colonoscopy of ≥ 270 days (odds ratio [OR] 1.75, 95 % confidence interval [CI] 1.15–2.67), whereas it was stable for waiting times of &lt; 180 days. The proportion of advanced CRC also increased after 270 days (OR 2.79, 95 %CI 1.03–7.57). No increase for low or high risk adenomas according to time to colonoscopy was observed. Conclusion In a European FIT-based screening program, post-FIT colonoscopy after 9 months was associated with an increased risk of CRC and CRC progression.
miR-182-3p/Myadm contribute to pulmonary artery hypertension vascular remodeling via a KLF4/p21-dependent mechanism
Authors: Lan Sun, Peirong Lin, Ying Chen, Haoying Yu, Shuyu Ren, Jingrong Wang, Liyun Zhao, Guanhua Du
Journal: Theranostics (2020)

Rationale: There is a continued need for investigating the roles of microRNAs and their targets on the pathogenesis of pulmonary arterial hypertension (PAH) vascular remodeling. We recently identified the association of myeloid miR-182-3p and its new target, Myeloid-Associated Differentiation Marker (Myadm), with vascular remodeling. Here, we aimed to determine the role of miR-182-3p/Myadm on PAH vascular remodeling and the underlying molecular mechanism. Methods: The miR-182-3p/Myadm expression profiles were detected in PAH patients and experimental rodent models. Loss-of-function and gain-of-function studies using gene knock-in or gene knock-out and the combinations of the proteomic technology and genome-wide ChIP-Seq were employed to determine the downstream targets of miR-182-3p/Myadm in response to monocrotaline (MCT)-induced PAH. Results: The miR-182-3p/Myadm expression was altered in PAH patients and experimental rodent models. Both miR-182-3p inhibitor and overexpression of Myadm augmented the pathological progression in rats in response to MCT-induced PAH. In contrast, miR-182-3p mimic and Myadm gene knockout attenuated the changes in the hemodynamics and structure of the cardio-pulmonary system in MCT-induced PAH in rats. Myadm mediated the proliferation of pulmonary artery smooth muscle cells (PASMCs) by altering the cell cycle kinase inhibitor (p21/Cip1) expression through the transcription factor Krüppel-like factor 4 (KLF4) translocation into the cytoplasm. Conclusion: Our findings indicate the prognostic and therapeutic significance of miR-182-3p in PAH and provide a new regulatory model of the myeloid-derived miR-182-3p/Myadm/KLF4/p21 axis in PAH vascular remodeling.
Covid-19: Home testing programme across England aims to help define way out of lockdown
Authors: Ingrid Torjesen
Journal: BMJ (2020)

<h3>Objective</h3> To evaluate enteral feeding practices in neonatal units in different countries and on different continents. <h3>Design</h3> A web-based survey of 127 tertiary neonatal intensive care units in Australia, Canada, Denmark, Ireland, New Zealand, Norway, Sweden and the UK. <h3>Results</h3> 124 units (98%) responded. 59 units (48%) had a breast milk bank or access to donor human milk (Australia/New Zealand 2/27, Canada 6/29, Scandinavia 20/20 and UK/Ireland 31/48). The proportion of units initiating enteral feeding within the first 24 h of life was: 43/124 (35%) if gestational age (GA) &lt;25 weeks, 53/124 (43%) if GA 25–27 weeks and 88/124 (71%) if GA 28–31 weeks. In general, Scandinavian units introduced enteral feeds the earliest, followed by UK/Ireland. Continuous feeding was routinely used for infants below 28 weeks9 gestation in almost half of the Scandinavian units and in approximately one sixth of units in UK/Ireland, but rarely in Australia/New Zealand and Canada. Minimal enteral feeding for 4–5 days was common in Canada, but rare in Scandinavia. Target enteral feeding volume in a ‘stable’ preterm infant was 140–160 ml/kg/day in most Canadian units and 161–180 ml/kg/day or higher in units in the other regions. There were also marked regional differences in criteria for use and timing when human milk fortifier was added. <h3>Conclusions</h3> This study highlights areas of uncertainty and demonstrates marked variability in feeding practices. It provides valuable data for planning collaborative feeding trials to optimise outcome in preterm infants.
Salvage therapy with bendamustine for temozolomide-refractory recurrent anaplastic gliomas: A prospective phase II trial.
Authors: Marc C. Chamberlain, Fereshteh Assadian, Howard Colman, Jeffrey J. Raizer
Journal: Journal of Clinical Oncology (2014)

TPS2104 Background: There is no standard therapy for recurrent anaplastic glioma (AG). Salvage therapies include alkylator-based chemotherapy (temozolomide [TMZ] or lomustine [CCNU]), re-resection with or without carmustine implants, re-irradiation and bevacizumab. Bendamustine is a novel bifunctional alkylator with CNS penetration but never previously evaluated in AG. Objective: Assess response and toxicity of bendamustine in recurrent AG following prior surgery, radiotherapy and TMZ in a prospective Phase II trial. Methods: 26 adults (11 males; 15 females: median age 38 years {range 30-65}) with TMZ refractory recurrent AG (8 anaplastic astrocytoma, 10 anaplastic oligodendroglioma, and 8 anaplastic oligoastrocytoma) were treated with bendamustine. 14 patients were treated at first recurrence and 12 patients were treated at second recurrence. Prior salvage therapy included re-resection in 14 (carmustine implant in 1), TMZ re-challenge in 13 and bevacizumab in 3. A cycle of bendamustine was defined as 2 consecutive days of treatment (100mg/m2/day) administered once every 4 weeks (maximum number of cycles 6). Success of treatment was defined as progression free survival at 6 months of 40% or better. Results: Grade 3 toxicities included lymphopenia (14 patients), myalgia, diarrhea, leukopenia, allergic reaction and thrombocytopenia in 1 patient each. No grade 4 or 5 toxicities were seen. The median number of cycles of therapy was 2 (range 1-7). Best radiographic response was progressive disease in 13 (50%) and stable disease in 13 (50%). Response did not differ by histology. Median progression free survival (PFS) was 3.5 months (range 1-14 months), 6-month PFS was 30.8% and 12 month PFS was 15%. Conclusions: In this small prospective series of patients with recurrent AG refractory to TMZ, bendamustine appears to have modest single agent activity though not meeting pre-specified criteria (40% 6-month PFS) with manageable toxicity. Confirmation in a larger series of similar patients is required. The study was supported in part through research funds provided by TEVA Pharmaceuticals and the National Comprehensive Cancer Network. Clinical trial information: NCT00823797.
Development of a peptide-based delivery platform for targeting malignant brain tumors
Authors: Jennifer J. Rahn, Xueqing Lun, Selina K. Jorch, Xiaoguang Hao, Chitra Venugopal, Parvez Vora, Bo Young Ahn, Liane Babes, Mana M. Alshehri, J. Gregory Cairncross, Sheila K. Singh, Paul Kubes, Donna L. Senger, Stephen M. Robbins
Journal: Biomaterials (2020)

Despite extensive molecular characterization, human glioblastoma remains a fatal disease with survival rates measured in months. Little improvement is seen with standard surgery, radiotherapy and chemotherapy. Clinical progress is hampered by the inability to detect and target glioblastoma disease reservoirs based on a diffuse invasive pattern and the presence of molecular and phenotypic heterogeneity. The goal of this study was to target the invasive and stem-like glioblastoma cells that evade first-line treatments using agents capable of delivering imaging enhancers or biotherapeutic cargo. To accomplish this, a combinatorial phage display library was biopanned against glioblastoma cell model systems that accurately recapitulate the intra- and inter-tumor heterogeneity and infiltrative nature of the disease. Candidate peptides were screened for specificity and ability to target glioblastoma cells in vivo. Cargo-conjugated peptides delivered contrast-enhancing agents to highly infiltrative tumor populations in intracranial xenograft models without the obvious need for blood brain barrier disruption. Simultaneous use of five independent targeting peptides provided greater coverage of this complex tumor and selected peptides have the capacity to deliver a therapeutic cargo (oncolytic virus VSVΔM51) to the tumor cells in vivo. Herein, we have identified a series of peptides with utility as an innovative platform to assist in targeting glioblastoma for the purpose of diagnostic or prognostic imaging, image-guided surgery, and/or improved delivery of therapeutic agents to glioblastoma cells implicated in disease relapse.
Prevalence of therapeutic use exemptions at the Olympic Games and association with medals: an analysis of data from 2010 to 2018
Authors: Alan Vernec, David Healy
Journal: British Journal of Sports Medicine (2020)

Objectives The percentage of athletes with Therapeutic Use Exemptions (TUEs) competing in elite sport and the association with winning medals has been a matter of speculation in the absence of validated competitor numbers. We used International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) data to identify athletes competing with TUEs at five Olympic Games (Games) and a possible association between having a TUE and winning an Olympic medal. Methods We used the IOC’s competition results and WADA’s TUE database to identify the number of TUEs for athlete competitions (ACs, defined as one athlete competing in one event) and any associations with medals among athletes competing in individual competitions. We calculated risk ratios (RR) for the probability of winning a medal among athletes with a TUE compared with that of athletes without a TUE. We also reported adjusted RR (RR adj ) controlling for country resources, which is a potential confounder. Results During the Games from 2010 to 2018, there were 20 139 ACs and 2062 medals awarded. Athletes competed with a TUE in 0.9% (181/20 139) of ACs. There were 21/2062 medals won by athletes with a TUE. The RR for winning a medal with a TUE was 1.13 (95% CI: 0.73 to 1.65; p=0.54), and the RR adj was 1.07 (95% CI: 0.69 to 1.56; p=0.73). Conclusion The number of athletes competing with valid TUEs at Games is &lt;1%. Our results suggested that there is no meaningful association between being granted a TUE and the likelihood of winning a medal.