tbuckley/cabot-search huggingface dataset:
The efficacy and safety of underwater endoscopic mucosal resection for ≥10-mm colorectal polyps: systematic review and meta-analysis
Authors: De-feng Li, Ming-Guang Lai, Mei-feng Yang, Zhi-yuan Zou, Jing Xu, Ru-mei Peng, Feng Xiong, Cheng Wei, Ding-guo Zhang, Zheng-lei Xu, Li-sheng Wang, Jun Yao
Journal: Endoscopy (2020)

Abstract Background Underwater endoscopic mucosal resection (UEMR) is a promising strategy for nonpedunculated colorectal polyp removal. However, the efficacy and safety of the technique for the treatment of ≥ 10-mm colorectal polyps remain unclear. We aimed to comprehensively assess the efficacy and safety of UEMR for polyps sized 10–19 mm and ≥ 20 mm. Methods PubMed, EMBASE, and the Cochrane Library databases were searched for relevant articles from January 2012 to November 2019. Primary outcomes were the rates of adverse events and residual polyps. Secondary outcomes were the complete resection, en bloc resection, and R0 resection rates. Results 18 articles including 1142 polyps from 1093 patients met our inclusion criteria. The overall adverse event and residual polyp rates were slightly lower for UEMR when removing colorectal polyps of 10–19 mm vs. ≥ 20 mm (3.5 % vs. 4.3 % and 1.2 % vs. 2.6 %, respectively). The UEMR-related complete resection rate was slightly higher for colorectal polyps of 10–19 mm vs. ≥ 20 mm (97.9 % vs. 92.0 %). However, the en bloc and R0 resection rates were dramatically higher for UEMR removal of polyps of 10–19 mm vs. ≥ 20 mm (83.4 % vs. 36.1 % and 73.0 % vs. 40.0 %, respectively). In addition, univariate meta-regression revealed that polyp size was an independent predictor for complete resection rate (P = 0.03) and en bloc resection (P = 0.01). Conclusions UEMR was an effective and safe technique for the removal of ≥ 10-mm nonpedunculated colorectal polyps. However, UEMR exhibited low en bloc and R0 resection rates for the treatment of ≥ 20-mm polyps.
Pharmacokinetic/pharmacodynamic considerations for new and current therapeutic drugs for uncomplicated gonorrhoea—challenges and opportunities
Authors: Ursula Theuretzbacher, Lindley Barbee, Kristie Connolly, George Drusano, Prabha Fernandes, Edward Hook, Ann Jerse, John O'Donnell, Magnus Unemo, Françoise Van Bambeke, Brian VanScoy, Peter Warn, Brian J. Werth, François Franceschi, Emilie Alirol
Journal: Clinical Microbiology and Infection (2020)
Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study
Authors: Carlo Visco, Alice Di Rocco, Andrea Evangelista, Francesca Maria Quaglia, Maria Chiara Tisi, Lucia Morello, Vittorio Ruggero Zilioli, Chiara Rusconi, Stefan Hohaus, Roberta Sciarra, Alessandro Re, Cristina Tecchio, Annalisa Chiappella, Ana Marin-Niebla, Rory McCulloch, Guido Gini, Tommasina Perrone, Luca Nassi, Elsa Pennese, Piero Maria Stefani, Maria Christina Cox, Valentina Bozzoli, Alberto Fabbri, Valentina Polli, Simone Ferrero, Maria Isabel Alvarez De Celis, Antonello Sica, Luca Petrucci, Luca Arcaini, Simon Rule, Mauro Krampera, Umberto Vitolo, Monica Balzarotti
Journal: Leukemia (2020)
Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression
Authors: Ming‐Feng Hsueh, Xin Zhang, Samuel S. Wellman, Michael P. Bolognesi, Virginia B. Kraus
Journal: Arthritis & Rheumatology (2020)

To evaluate the role of immune cells and their effector cytokines in the pathogenesis and progression of knee osteoarthritis (OA) in matched OA synovial fluid (SF) and synovial tissue samples.Cells from matched samples of synovial tissue and SF acquired from individuals undergoing total knee replacement for OA (n = 39) were characterized for immune cell-associated surface markers and intracellular cytokine expression using polychromatic flow cytometry. Additional individuals with radiographic knee OA (Kellgren/Lawrence severity grades ≥1) who had available etarfolatide (inflammatory cell) imaging (n = 26) or baseline and 3-year data on progression of radiographic knee OA (n = 85) were also assessed. SF cytokine concentrations in all cohorts were evaluated for associations with synovial tissue and SF cell phenotypes and severity of radiographic knee OA.Macrophages (predominant in the synovial tissue, 53% of total cells) and neutrophils (predominant in the SF, 26% of total cells) were the major immune cell populations identified in the OA knee joints, exhibiting expression of or association with transforming growth factor β1 (TGFβ1) and elastase, respectively, in the SF. Expression levels of TGFβ1 and elastase were significantly associated with severity of radiographic knee OA. Baseline SF concentrations of TGFβ1 and elastase along with radiographic knee OA severity scores were predictive of knee OA progression, with areas under the receiver operating characteristic curves of 0.810 (for TGFβ1), 0.806 (for elastase), and 0.846 (for both TGFβ1 and elastase combined), with greater stability of prediction when both markers were utilized.Our findings demonstrate the hitherto underappreciated role of neutrophils in the sterile inflammatory process and progression of OA. Two soluble mediators, SF elastase and TGFβ1, are strong predictors of knee OA progression, reflecting a synergistic role of neutrophil and macrophage populations in the pathogenesis and worsening of OA that could potentially be utilized to identify patients who may have a greater risk of more rapid disease progression.
Abstract 249: The Epigenetically Modified Pro-inflammatory Cardiac Fibroblast Drives Cardiomyocyte Dysfunction in Pulmonary Hypertension-induced Right Ventricular Pressure Overload
Authors: Danielle R Bruns, Stephen F Thoemmes, Peter M Buttrick, Lori A Walker
Journal: Circulation Research (2016)

Right ventricular (RV) dysfunction is a strong predictor of survival in a variety of clinical contexts including pulmonary hypertension (PH). Thus elucidating mechanisms that contribute to RV dysfunction is of great importance. Persistent inflammation, a central component of PH-induced RV dysfunction, is regulated in part by cardiac fibroblasts (Cfib). We hypothesized that persistent changes in the Cfib pro-inflammatory phenotype may be mediated through epigenetic processes such as DNA methylation and that secretion of inflammatory signals from activated Cfib drives cardiomyocyte dysfunction and contributes to myofibrillar disarray. Therefore the purpose of this investigation was to assess epigenetic changes to pro-inflammatory Cfib and the contribution of the Cfib secretome on myocyte function. We approached this question using a large animal model with significant resonance with human disease- the neonatal calf exposed to hypobaric hypoxia (HH). HH caused RV Cfib global DNA hypomethylation. RNA-seq identified 2115 genes significantly changed in HH including 193 transcriptional regulators and 21 genes involved in DNA methylation. Further, we identified 105 inflammatory genes with enrichment of IL-1β as a central node of inflammatory signaling. Mass spec profiling of conditioned media (CM) from Cfib isolated from the PH calf (PH-CM) also confirmed significant pro-inflammatory protein secretion. We then examined the effects of PH-CM on adult rat ventricular myocytes (ARVM) in culture. Brief exposure to PH-CM caused marked dedifferentiation of ARVM to a neonatal-like phenotype that exhibited spontaneous contractile behavior. This response was not seen in ARVM exposed to CM from Cfib from the normoxic RV. These data suggest the combination of pressure overload and hypoxia causes epigenetic reprogramming of pro-inflammatory Cfib, signaling a phenotypic transformation in a population of myocytes which likely contributes to RV dysfunction. Therapies that target this inflammatory process have the potential to prevent RV dysfunction.
An Observational Study of the Equivalence of Age and Duration of Diabetes to Glycemic Control Relative to the Risk of Complications in the Combined Cohorts of the DCCT/EDIC Study
Authors: Ionut Bebu, Barbara H. Braffett, David Schade, William Sivitz, John I. Malone, Rodica Pop-Busui, Gayle M. Lorenzi, Pearl Lee, Victoria R. Trapani, Amisha Wallia, William H. Herman, John M. Lachin
Journal: Diabetes Care (2020)

OBJECTIVE This epidemiological analysis of the pooled Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort describes the equivalence of a 1-percentage point increase in HbA1c (such as from 7% to 8%) and years of additional age or duration of type 1 diabetes (T1D) relative to the risk of complications. RESEARCH DESIGN AND METHODS Separate Cox proportional hazards models determined the number of additional years of age and/or duration of T1D that would result in the same increase in risk of microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications and mortality as a 1-percentage point increase in HbA1c. RESULTS The risk of any cardiovascular disease associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 4.3 (95% CI 2.7–5.9) additional years of age or 5.6 (95% CI 2.7–6.5) additional years’ duration of T1D. The risk of estimated glomerular filtration rate &amp;lt;60 mL/min/1.73 m2 and/or end-stage renal disease associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 12.1 (95% CI 8.3–15.9) additional years of age or 18.0 (95% CI 4.3–31.7) additional years’ duration of T1D. The proliferative diabetic retinopathy risk associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 6.4 (95% CI 5.3–7.4) additional years’ duration of T1D, while for mortality risk, it was equivalent to the risk associated with 12.9 (95% CI 6.6–19.3) additional years of age. CONCLUSIONS Our results help evaluate the impact of glycemia on advanced complications in a way that may be more interpretable to health care providers and individuals with T1D.
The neglect of adult social care during covid-19
Authors: Jon Glasby, Catherine Needham
Journal: BMJ (2020)

<h3>Background</h3> Patients with kidney failure on dialysis or after renal transplantation have a high risk for severe COVID-19 infection, and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in patients with kidney failure, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in patients on dialysis and in kidney transplant recipients (KTRs) are still needed. <h3>Methods</h3> In this prospective, multicentric cohort study, antibody responses to COVID-19 mRNA vaccines (BNT162b2 [BioNTech/Pfizer] or mRNA-1273 [Moderna]) were measured in 32 patients on dialysis and in 28 KTRs. SARS-CoV-2–specific antibodies and neutralization capacity were evaluated and compared with controls (<i>n</i>=78) of a similar age range. <h3>Results</h3> After the first vaccination, SARS-CoV-2–specific antibodies were nearly undetectable in patients with kidney failure. After the second vaccination, 93% of the controls and 88% of patients on dialysis but only 37% of KTRs developed SARS-CoV-2–specific IgG above cutoff. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared with patients on dialysis (503±481 BAU/ml; <i>P</i>&lt;0.01). Both KTRs and patients on dialysis had significantly lower IgG levels compared with controls (1992±2485 BAU/ml; <i>P</i>&lt;0.001 and <i>P</i>&lt;0.01, respectively). Importantly, compared with controls, neutralizing antibody titers were significantly lower in KTRs and patients on dialysis. After the second vaccination, 76% of KTRs did not show any neutralization capacity against SARS-CoV-2, suggesting impaired seroprotection. <h3>Conclusions</h3> Patients with kidney failure show a significantly weaker antibody response compared with controls. Most strikingly, only one out of four KTRs developed neutralizing antibodies against SARS-CoV-2 after two doses of vaccine. These data suggest that vaccination strategies need modification in KTRs and patients on dialysis. <b>Clinical Trial registry name and registration number:</b> Vaccination Against COVID-19 in Chronic Kidney Disease, NCT04743947
MEMSID: Results From a Phase 2 Pilot Study on Memantine Treatment for Sickle Cell Disease
Authors: Inga Hegemann, Clelia Sasselli, Fabio Valeri, Asya Makhro, Rouven Müller, Anna Bogdanova, Markus G. Manz, Max Gassmann, Jeroen S. Goede
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
Covid-19: What’s going on in Leicester?
Authors: Penelope Campling
Journal: BMJ (2020)

As someone who lives and works in Leicester, I was grateful to read the editorial criticising the government about the time it took to get crucial data about cases to the local public health team.1

The strict lockdown came as a shock. Leicester has now been locked down for over a third of the year, longer than anywhere else in the world. …
AB0302 USE OF TNF-INHIBITORS BEFORE, DURING AND THE FIRST YEAR AFTER PREGNANCY AMONG WOMEN WITH RHEUMATOID ARTHRITIS
Authors: H. Bjørngaard, H. Koksvik, B. Jakobsen, M. Wallenius
Journal: Annals of the Rheumatic Diseases (2020)

Background: Treat to target is a goal, also in pregnant women with Rheumatoid arthritis (1). There is increasing evidence on safe use with TNF inhibitors during pregnancy. Adjusted use of TNF inhibitors preconception and throughout pregnancy may stabilize disease activity and prevent flares (2). Low disease activity is also beneficial for the fetus. Objectives: To study the use of TNF-inhibitors among women with Rheumatic arthritis during and after pregnancy. Methods: RevNatus is a Norwegian, nationwide quality register that monitors treatment of inflammatory rheumatic diseases before, during and after pregnancy. Data from RevNatus in the period October 2017 to October 2019 was used to map the use of all types of TNF inhibitors among 208 women with rheumatoid arthritis, diagnosed by the ACR/EULAR criteria. The use of medication was reported at the time of visit in outpatient clinic. The frequency of use of TNF inhibitors registered at seven timepoints from pre-pregnancy to twelve months after delivery. Results: The use of medication was reported at each visit for all the women with rheumatoid arthritis. Most of the women were not using TNF inhibitors before and beyond conception. Most of the women continuing TNF inhibitors beyond conception used certolizumab or etanercept. Adalimumab and infliximab were used in pregnancy (tabell 1 ). Tabell 1. certoliz-umab etane-rcept adalim-umab golim-umab inflixi-mab No TNF-inhibitor Before pregnancy n=105 21% (22) 9% (10) 3% (3) 1% (1) 66% (69) 1.trimester n=81 19% (15) 10% (8) 71% (58) 2.trimester n=88 10% (9) 10% (9) 80% (70) 3.trimester n=91 11% (10) 5% (5) 83% (76) 6 weeks post partum n=96 22% (21) 13% (13) 1% (1) 1% (1) 63% (60) 6 months post partum n=88 24% (21) 18% (16) 4% (4) 1% (1) 53% (46) 12 months post partum n=84 21% (18) 17% (15) 7% (6) 2% (2) 53% (43) Conclusion: Most of the women with rheumatic arthritis were not treated with TNF inhibitors before or in pregnancy. Women with rheumatic arthritis that continuing treatment with TNF inhibitors through pregnancy were using certilozumab and etanercept. References: [1]Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. 2016;75(5):795-810. [2]van den Brandt S, Zbinden A, Baeten D, Villiger PM, Ostensen M, Forger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19(1):64. Disclosure of Interests: None declared
What to do with appraisal: the focus of appraisal is supportive and in the service of professional development
Authors: Judith M Neaves
Journal: BMJ (2020)

Gerada states that doctors cannot choose their own learning needs.1 In fact, developing our own learning needs is a fundamental part of appraisal. The only elements that are compulsory are the multi-source feedback and patient satisfaction questionnaires that are done once every five years. Is this …
Plasma protein-based signature predicts distant metastasis and induction chemotherapy benefit in Nasopharyngeal Carcinoma
Authors: Yelin Liang, Junyan Li, Qian Li, Linglong Tang, Lei Chen, Yanping Mao, Qingmei He, Xiaojing Yang, Yuan Lei, Xiaohong Hong, Yin Zhao, Shiwei He, Ying Guo, Yaqin Wang, Panpan Zhang, Na Liu, Yingqin Li, Jun Ma
Journal: Theranostics (2020)

Rationale: Currently, for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), there is no effective blood-based method to predict distant metastasis. We aimed to detect plasma protein profiles to identify biomarkers that could distinguish patients with NPC who are at high risk of posttreatment distant metastasis. Methods: A high-throughput antibody array was initially applied to detect 1000 proteins in pretreatment plasma from 16 matched LA-NPC patients with or without distant metastasis after radical treatment. Differentially expressed proteins were further examined using a low-throughput array to construct a plasma protein-based signature for distant metastasis (PSDM) in a cohort of 226 patients. Results: Fifty circulating proteins were differentially expressed between metastatic and non-metastatic patients and 18 were proven to be strongly correlated with distant metastasis-free survival (DMFS) in NPC. A PSDM signature consisting of five proteins (SLAMF5, ESM-1, MMP-8, INSR, and Serpin A5) was established to assign patients with NPC into a high-risk group and a low-risk group. Patients in the high-risk group had shorter DMFS (P < 0.001), disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001). Moreover, the PSDM performed better than N stage and Epstein-Barr virus (EBV) DNA load at effectively identifying patients with NPC at high risk of metastasis. For patients in the high-risk group, induction chemotherapy significantly improved DMFS, DFS, and OS. Conclusions: The PSDM could be a useful liquid biopsy tool to effectively predict distant metastasis and the benefit of induction chemotherapy in patients with LA-NPC.
Emergence of co-infection of COVID-19 and dengue: A serious public health threat
Authors: Arbab Saddique, Muhammad Suleman Rana, Muhammad Masroor Alam, Aamer Ikram, Muhammad Usman, Muhammad Salman, Rani Faryal, Umair Massab, Habib Bokhari, Muhammad Sufian Mian, Asiya Israr, None Safiullah
Journal: Journal of Infection (2020)
Polypoidal Choroidal Vasculopathy
Authors: Chui M. Gemmy Cheung, Timothy Y.Y. Lai, Kelvin Teo, Paisan Ruamviboonsuk, Shih-Jen Chen, Judy E. Kim, Fumi Gomi, Adrian H. Koh, Gregg Kokame, Janice Marie Jordan-Yu, Federico Corvi, Alessandro Invernizzi, Yuichiro Ogura, Colin Tan, Paul Mitchell, Vishali Gupta, Jay Chhablani, Usha Chakravarthy, Srinivas R. Sadda, Tien Y. Wong, Giovanni Staurenghi, Won Ki Lee
Journal: Ophthalmology (2020)

To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings.Evaluation of diagnostic test results.Panel of retina specialists.As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts.Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD.The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%.We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.
6 The clinical and financial impact of measuring infliximab levels and antibodies to infliximab in inflammatory bowel disease patients
Authors: S O’Reilly, D Keegan, K Byrne, J Sheridan, HE Mulcahy, GA Doherty, G Cullen
Journal: Gut (2017)

Background  Approximately 150 IBD patients are currently on infliximab (IFX) at our centre, costing over €2 million in 2016. IFX drug and antibody level measurement was introduced in 2015.  Aim  To analyse the clinical and financial impact of measurement of IFX levels and antibodies to IFX (ATI) in 2016.  Method  IBD patients with IFX levels and ATI measured between Dec 2015 and Dec 2016 were identified from laboratory records and an IBD database. The results and clinical reaction to the levels were recorded.  Results  93 (55 Crohn’s, 38 UC) patients had levels checked. More than one measurement was made in 25. 37 had subtherapeutic levels ( 7 mg/ml): 12 had dose reduction and six stopped IFX. The remainder were maintained on current dose. 22 had therapeutic levels (3-7mg/ml): 13 were maintained on current dose, two dose escalated, five dose reduced and two stopped IFX. 76% of IBD patients on IFX had supertherapeutic or subtherapeutic levels. Of these, 41% had a medication/dose change in response to these results. 11% stopped IFX. Projected savings in our centre are €85 000 in 2016.  Conclusions  Initial analysis suggests significant cost savings with IFX level measurement, although decisions on IFX dosing are not made on levels in isolation and alternative treatment options may be equally or more expensive. A prospective study would help clarify the true cost savings.
Predicting functional effects of missense variants in voltage-gated sodium and calcium channels
Authors: Henrike O. Heyne, David Baez-Nieto, Sumaiya Iqbal, Duncan S. Palmer, Andreas Brunklaus, Patrick May, Katrine M. Johannesen, Stephan Lauxmann, Johannes R. Lemke, Rikke S. Møller, Eduardo Pérez-Palma, Ute I. Scholl, Steffen Syrbe, Holger Lerche, Dennis Lal, Arthur J. Campbell, Hao-Ran Wang, Jen Pan, Mark J. Daly
Journal: Science Translational Medicine (2020)

Malfunctions of voltage-gated sodium and calcium channels (encoded by