tbuckley/cabot-search huggingface dataset:
Arthroscopic Bankart versus open Latarjet as a primary operative treatment for traumatic anteroinferior instability in young males: a randomised controlled trial with 2-year follow-up
Authors: Juha Kukkonen, Sami Elamo, Tapio Flinkkilä, Juha Paloneva, Miia Mäntysaari, Antti Joukainen, Janne Lehtinen, Vesa Lepola, Milja Holstila, Tommi Kauko, Ville Aarimaa
Journal: British Journal of Sports Medicine (2021)

Objectives To compare the success rates of arthroscopic Bankart and open Latarjet procedure in the treatment of traumatic shoulder instability in young males. Design Multicentre randomised controlled trial. Setting Orthopaedic departments in eight public hospitals in Finland. Participants 122 young males, mean age 21 years (range 16–25 years) with traumatic shoulder anteroinferior instability were randomised. Interventions Arthroscopic Bankart (group B) or open Latarjet (group L) procedure. Main outcome measures The primary outcome measure was the reported recurrence of instability, that is, dislocation at 2-year follow-up. The secondary outcome measures included clinical apprehension, sports activity level, the Western Ontario Shoulder Instability Index, the pain Visual Analogue Scale, the Oxford Shoulder Instability Score, the Constant Score and the Subjective Shoulder Value scores and the progression of osteoarthritic changes in plain films and MRI. Results 91 patients were available for analyses at 2-year follow-up (drop-out rate 25%). There were 10 (21%) patients with redislocations in group B and 1 (2%) in group L, p=0.006. One (9%) patient in group B and five (56%) patients in group L returned to their previous top level of competitive sports (p=0.004) at follow-up. There was no statistically significant between group differences in any of the other secondary outcome measures. Conclusions Arthroscopic Bankart operation carries a significant risk for short-term postoperative redislocations compared with open Latarjet operation, in the treatment of traumatic anteroinferior instability in young males. Patients should be counselled accordingly before deciding the surgical treatment. Trial registration number NCT01998048 .
Derivation of the Buffalo Concussion Physical Examination risk of delayed recovery (RDR) score to identify children at risk for persistent postconcussive symptoms
Authors: Mohammad Nadir Haider, Adam Cunningham, Scott Darling, Heidi N Suffoletto, Michael S Freitas, Rajiv K Jain, Barry Willer, John J Leddy
Journal: British Journal of Sports Medicine (2021)

Objective The Buffalo Concussion Physical Examination (BCPE) is a brief, but pertinent physical examination designed for the subacute, outpatient assessment of concussion. The purpose of this study was to perform the BCPE on a larger sample and derive a scoring system to identify children at risk for Persistent Post-Concussive Symptoms (PPCS, recovery ≥30 days). Methods This prospective, observational cohort study from September 2016 to March 2019 was performed at three university-affiliated concussion clinics. Male and female children (n=270, 14.92±1.86 years, range 8–18, 38% female) were diagnosed with a concussion within 14 days of injury and followed-up until recovery. Logistic regression was used with history and physical examination variables to predict PPCS and a weighted scoring metric was derived. Results Out of 15 predictor variables, the main effects of 1 preinjury variable (≥3 previous concussions), 2 injury characteristic variables (days-since-injury and type-of-injury), 3 physical examination variables (orthostatic intolerance (OI), vestibulo-ocular reflex (VOR) and tandem gait) and 2 interaction terms (OI/VOR and tandem gait/type-of-injury) produced a score that was 85% accurate for identifying children with low-risk, medium-risk and high-risk for PPCS on cross-validation. Conclusion The Risk for Delayed Recovery (RDR)-Score allows physicians in an outpatient setting to more accurately predict which children are at greater risk for PPCS early after their injury, and who would benefit most from targeted therapies. The RDR-Score is intended to be used as part of a comprehensive assessment that should include validated symptom checklists, mental health history and adjunct testing (eg, cognitive or physical exertion) where clinically indicated.
NK cells and lipoxin A<sub>4</sub> promote resolution of eosinophilic inflammation after nasal allergen challenge
Authors: Anh Poirot, Guillaume Wacht, Christine Lehalle, Philippe Saas, Nelly Frossard, Bernard Geny, Fréderic de Blay, Cindy Barnig
Journal: Allergy (2021)

Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory nervous system.It is accompanied by neuronal and non-neuronal alterations, including alterations in intracellular second messenger pathways.Cellular levels of 3 ′ ,5 ′ -cyclic adenosine monophosphate (cAMP) and 3 ′ ,5 ′ -cyclic guanosine monophosphate (cGMP) are regulated by phosphodiesterase (PDE) enzymes.Here, we studied the impact of PDE inhibitors (PDEi) in a mouse model of peripheral nerve injury induced by placing a cuff around the main branch of the sciatic nerve.Mechanical hypersensitivity, evaluated using von Frey filaments, was relieved by sustained treatment with the non-selective PDEi theophylline and ibudilast (AV-411), with PDE4i rolipram, etazolate and YM-976, and with PDE5i sildenafil, zaprinast and MY-5445, but not by treatments with PDE1i vinpocetine, PDE2i EHNA or PDE3i milrinone.Using pharmacological and knock-out approaches, we show a preferential implication of delta opioid receptors in the action of the PDE4i rolipram and of both mu and delta opioid receptors in the action of the PDE5i sildenafil.Calcium imaging highlighted a preferential action of rolipram on dorsal root ganglia non-neuronal cells, through PDE4B and PDE4D inhibition.Rolipram had anti-neuroimmune action, as shown by its impact on levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) in the dorsal root ganglia of mice with peripheral nerve injury, as well as in human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides.This study suggests that PDEs, especially PDE4 and 5, may be targets of interest in the treatment of neuropathic pain.
Predictors of mortality and outcomes of liver transplant in spur cell hemolytic anemia
Authors: Zain M. Virk, Arpan A. Patel, Rebecca K. Leaf, Hanny Al‐Samkari
Journal: American Journal of Hematology (2021)

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Sixty-nine patients with SCHA met eligibility for inclusion. The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Thirty-nine patients (56.5%) were red blood celltransfusion-dependent. All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with improvement in median hematocrit from 22.1% to 34.6% post-transplant (p = .001) and excellent post-transplant outcomes. In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an odds ratio (OR) for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality. Model for end-stage liver disease (MELD)-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)]. In conclusion, SCHA is associated with substantial excess mortality than predicted by MELD-Na or Child-Turcotte-Pugh scores and uniformly resolves with liver transplant, without recurrence. Multiple parameters of hemolytic anemia severity independently predict higher 90-day mortality.
Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer’s disease-like neuroinflammation and cognitive impairment
Authors: Shulan Qiu, Juan Pablo Palavicini, Jianing Wang, Nancy S. Gonzalez, Sijia He, Elizabeth Dustin, Cheng Zou, Lin Ding, Anindita Bhattacharjee, Candice E. Van Skike, Veronica Galvan, Jeffrey L. Dupree, Xianlin Han
Journal: Molecular Neurodegeneration (2021)

Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aβ) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aβ accumulation. To date, it remains unclear if changes in specific brain lipids are sufficient to drive AD-related pathology.
P10.01 Effect of mesenchymal cells on infiltration and phenotype of T cells in a 3D glioblastoma spheroid model
Authors: T Svablova, N Ternerova, M Houdova Megova, P Busek, A Sedo
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM), the most malignant primary brain tumor with a median survival less than two years, is characterized by aggressive invasive growth, presence of hypoxic and necrotic regions, and T-cell dysfunction. Mesenchymal cells with characteristics of cancer associated fibroblasts are present in GBMs, but it remains to be established whether they contribute to T cell sequestration in the tumor stroma and functional inactivation similarly to extracranial tumors. Murine models do not reflect several aspects of human immune system and 2D cell culture systems often fail to recapitulate complex interactions in the tumor microenvironment. 3D spheroids prepared from patient-derived cell cultures offer higher degree of complexity and biological relevance. The aim of this study was to establish a 3D GBM spheroid model to determine the effect of patient derived mesenchymal cells on human T cell infiltration and phenotype. MATERIAL AND METHODS Glioma stem-like cell and mesenchymal cell cultures were derived from human GBMs. Naïve T lymphocytes were isolated from buffy coats of healthy donors by Ficoll paque gradient separation, followed by negative magnetic isolation techniques using Naïve Pan T Cell Isolation Kit (Miltenyi Biotec). 3D spheroids were prepared by embedding the cells in 20 µl of Geltrex (Thermo Fisher Scientific). T cells activated by magnetic beads with anti-CD2, anti-CD3 and anti-CD28 antibodies (Miltenyi Biotec) and IL-2 were subsequently added to the spheroids. After 5 days of co-culture, spheroids were dissociated, and viable cells were counted using automated cell counter (Biorad). Expression of a T-cell activation marker CD69 and immune checkpoint molecules LAG3, and PD-1 in CD3+ cells was analyzed by flow cytometry. Mesenchymal, stem cell and lymphocyte markers TE-7, Nestin and CD45 respectively, were analyzed by immunohistochemistry (IHC) on frozen spheroid sections. RESULTS We prepared spheroids comprising glioma stem-like cells with and without mesenchymal cells. Glioblastoma-derived cells were evenly dispersed throughout the spheroids as demonstrated by IHC. T cells infiltrated into both types of spheroids, but their number in spheroids containing mesenchymal cells was about 40% (p=0.002) lower compared to the ones without mesenchymal cells. In both types of spheroids, the presence of activated allogeneic T cells led to more than a 50% reduction of the glioblastoma-derived cells. Ongoing studies evaluate the effect of mesenchymal cells on the phenotype of spheroid infiltrating T cells. CONCLUSION We have successfully established a 3D spheroid model to study the role of mesenchymal cells in GBM microenvironment. Our results indicate that mesenchymal cells may influence the infiltration of T cells and modulate their phenotype. SUPPORT Project was financed by the Center for Tumor Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785).
Estimated effect of increased diagnosis, treatment, and control of diabetes and its associated cardiovascular risk factors among low-income and middle-income countries: a microsimulation model
Authors: Sanjay Basu, David Flood, Pascal Geldsetzer, Michaela Theilmann, Maja E Marcus, Cara Ebert, Mary Mayige, Roy Wong-McClure, Farshad Farzadfar, Sahar Saeedi Moghaddam, Kokou Agoudavi, Bolormaa Norov, Corine Houehanou, Glennis Andall-Brereton, Mongal Gurung, Garry Brian, Pascal Bovet, Joao Martins, Rifat Atun, Till Bärnighausen, Sebastian Vollmer, Jen Manne-Goehler, Justine Davies
Journal: The Lancet Global Health (2021)

Given the increasing prevalence of diabetes in low-income and middle-income countries (LMICs), we aimed to estimate the health and cost implications of achieving different targets for diagnosis, treatment, and control of diabetes and its associated cardiovascular risk factors among LMICs.
Sunscreen use is not associated with increased blood concentrations of benzene among adults in the United States: Data from the National Health and Nutrition Examination Survey 2003-2006 and 2009-2018
Authors: Michael S. Chang, Kevin J. Moore, Nicole Trepanowski, Tulay Koru-Sengul, Rebecca I. Hartman
Journal: Journal of the American Academy of Dermatology (2021)
P14.34 Long-term seizure outcomes and tumor recurrence after glioneural tumor surgery: A single-center retrospective cohort
Authors: M Tomschik, E Horner, G Kasprian, C Dorfer, K Roessler
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNET) are glioneural tumors associated with treatment refractory seizures, especially in younger patients. Because there is a relative paucity of data on which factors predispose patients for recurrences, we analyzed our own cohort treated over the last 25 years. MATERIAL AND METHODS We performed a retrospective analysis of all patients undergoing resection of a glioneural tumor with a minimum follow up of one year. Surgery type, histological findings, and seizure outcome were extracted from patient records. Recurrence was defined as new tumor lesions in previously unremarkable parenchyma or tumor growth of a residual lesion. We performed a Mann-Whitney-U test to determine statistical significance of differences in continuous variables and Fisher’s exact test in categorical. RESULTS In total, 109 patients were operated between March 1994 to March and followed for a median of 62.4 months (range 12–281 months). The average age of patients at the time of surgery was 21.2 years with 60 patients belonging to the pediatric population. Complete lesionectomies were the goal in 72 cases, extended resections in 10, and partial resection due to proximity of eloquent areas was performed in 27 cases. 77 tumors were classified histologically as a GG and 32 as a DNET. The temporal lobe was the most common site of origin with 65 tumors (59.6%) being found there. On postoperative MRI, complete resection was achieved in 76 cases. Local tumor recurrences were seen in 14 patients (12 GG and 2 DNET), 9 of which occurred in patients with apparently complete resection. Overall, only one malignant transformation of a GG was observed. Age at surgery was significantly lower for patients with later recurrence (11.9 yrs vs. 22.6 yrs for patients without recurrence, p=0.0047). A second surgery was performed in 11 patients with previously incomplete resections (33%) and 7 patients with complete resection (9.2%), p=0.0038. 95 patients (87.2%) had preoperative seizures for a median of 26 months before surgery. One year after surgery, a documented ILAE outcome was available for 90 of these patients and 63 (70%) were seizure free one year after surgery. While 45 patients with epilepsy (47.4%) had at least one seizure relapse after surgery - most often associated with AED withdrawal or tumor recurrence - medical therapy and repeat resection allowed 76 patients (80%) to be seizure free for over one year at their last follow up. Age at surgery was not a significant predictor of seizure freedom. CONCLUSION Glioneural tumors are highly epileptogenic but neurosurgical resection allows seizure freedom in the large majority of these patients. Tumor recurrences were more likely in younger patients and incomplete resections predisposed patients to need another surgery. Resection extent on MRI does not appear to be a reliable marker for future recurrence risk.
Hyperexcitable interneurons trigger cortical spreading depression in an Scn1a migraine model
Authors: Eva Auffenberg, Ulrike B.S. Hedrich, Raffaella Barbieri, Daniela Miely, Bernhard Groschup, Thomas V. Wuttke, Niklas Vogel, Philipp Lührs, Ilaria Zanardi, Sara Bertelli, Nadine Spielmann, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Michael Pusch, Martin Dichgans, Holger Lerche, Paola Gavazzo, Nikolaus Plesnila, Tobias Freilinger
Journal: Journal of Clinical Investigation (2021)

Cortical spreading depression (CSD), a wave of depolarization followed by depression of cortical activity, is a pathophysiological process implicated in migraine with aura and various other brain pathologies, such as ischemic stroke and traumatic brain injury. To gain insight into the pathophysiology of CSD, we generated a mouse model for a severe monogenic subtype of migraine with aura, familial hemiplegic migraine type 3 (FHM3). FHM3 is caused by mutations in SCN1A, encoding the voltage-gated Na+ channel NaV1.1 predominantly expressed in inhibitory interneurons. Homozygous Scn1aL1649Q knock-in mice died prematurely, whereas heterozygous mice had a normal lifespan. Heterozygous Scn1aL1649Q knock-in mice compared with WT mice displayed a significantly enhanced susceptibility to CSD. We found L1649Q to cause a gain-of-function effect with an impaired Na+-channel inactivation and increased ramp Na+ currents leading to hyperactivity of fast-spiking inhibitory interneurons. Brain slice recordings using K+-sensitive electrodes revealed an increase in extracellular K+ in the early phase of CSD in heterozygous mice, likely representing the mechanistic link between interneuron hyperactivity and CSD initiation. The neuronal phenotype and premature death of homozygous Scn1aL1649Q knock-in mice was partially rescued by GS967, a blocker of persistent Na+ currents. Collectively, our findings identify interneuron hyperactivity as a mechanism to trigger CSD.
Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles
Authors: Canhao Wu, Qin Xu, Huiyuan Wang, Bin Tu, Jiaxin Zeng, Pengfei Zhao, Mingjie Shi, Hong Qiu, Yongzhuo Huang
Journal: Acta Pharmaceutica Sinica B (2021)

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.
Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018
Authors: Valérie Bouchez, Sophie Guillot, Annie Landier, Nathalie Armatys, Soraya Matczak, Julie Toubiana, Sylvain Brisse
Journal: Eurosurveillance (2021)

BackgroundBordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough.AimWe aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996-2018).MethodsIsolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing.ResultsThe proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p < 0.0001), whereas only 5 PT-, 5 FHA- and 9 FIM-deficient isolates were found. Impairment of PRN production was predominantly due to IS481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3.ConclusionsB. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.
Doctors leaders endorse Green New Deal and will lobby for climate action
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The BMA has endorsed the Green New Deal for climate action and will lobby NHS trusts and health boards to embed sustainability criteria into their tendering processes, after representatives passed a motion at their annual meeting this week.

The meeting, held on 14 September, declared that the climate emergency is a health emergency, and called on the BMA to commit to a range of actions to …