Evaluation of radiation-induced oral mucositis by optical coherence tomography.

PURPOSE: Optical coherence tomography (OCT) imaging was evaluated to determine if radiation-induced mucosal damage could be noninvasively monitored in real time and correlated with histopathologic findings. EXPERIMENTAL DESIGN: Female C3H mice, ages 7 to 9 weeks, four per group, were immobilized in a custom-made Lucite jig and received 0, 15, 22.5, and 25 Gy in a single fraction to their oral cavity. OCT images were acquired of proximal, middle, and distal aspects of the dorsum of the tongue on days 0, 1, 3, 5, and 7 post-irradiation. Animals were sacrificed on day 7 and samples taken for histologic evaluation. OCT images were visually examined and also quantified by image analysis and compared with histologic findings. RESULTS: Tongues removed 7 days post-irradiation showed no visible damage; however, upon staining with toluidine blue, ulcers at the base of the tongue became visible (100% for 25 Gy, 75% after 22.5 Gy, and 0% after 15 Gy). Visual inspection of OCT images qualitatively compared with histologic findings and quantitative image analysis of the OCT images (effective light penetration depth) revealed significant changes 7 days post-irradiation compared with unirradiated controls for the base of the tongue. CONCLUSIONS: OCT allows for direct noninvasive real-time acquisition of digitally archivable images of oral mucosa and can detect radiation-induced changes in the mucosa before visual manifestation. OCT may be a useful technique to quantify subclinical radiation-induced mucosal injury in experimental chemoradiation clinical trials.     

Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance.

Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin.     

Baseline Brain Metabolism in Resistant Depression and Response to Transcranial Magnetic Stimulation

Neuroimaging studies of patients with treatment-resistant depression (TRD) have reported abnormalities in the frontal and temporal regions. We sought to determine whether metabolism in these regions might be related to response to repetitive transcranial magnetic stimulation (TMS) in patients with TRD. Magnetic resonance images and baseline resting-state cerebral glucose uptake index (gluMI) obtained using ¹⁸F-fluorodeoxyglucose positron emission tomography were analyzed in TRD patients who had participated in a double-blind, randomized, sham-controlled trial of prefrontal 10 Hz TMS. Among the patients randomized to active TMS, 17 responders, defined as having 50% depression score decrease, and 14 nonresponders were investigated for prestimulation glucose metabolism and compared with 39 healthy subjects using a voxel-based analysis. In nonresponders relative to responders, gluMI was lower in left lateral orbitofrontal cortex (OFC), and higher in left amygdala and uncinate fasciculus. OFC and amygdala gluMI negatively correlated in nonresponders, positively correlated in responders, and did not correlate in healthy subjects. Relative to healthy subjects, both responders and nonresponders displayed lower gluMI in right dorsolateral prefrontal (DLPFC), right anterior cingulate (ACC), and left ventrolateral prefrontal cortices. Additionally, nonresponders had lower gluMI in left DLPFC, ACC, left and right insula, and higher gluMI in left amygdala and uncus. Hypometabolisms were partly explained by gray matter reductions, whereas hypermetabolisms were unrelated to structural changes. The findings suggest that different patterns of frontal–temporal–limbic abnormalities may distinguish responders and nonresponders to prefrontal magnetic stimulation. Both preserved OFC volume and amygdala metabolism might precondition response to TMS.     

Role of nuclear receptors and their ligands in human trophoblast invasion

Human implantation involves a major invasion of the uterine wall and complete remodelling of uterine arteries by extravillous cytotrophoblasts (EVCT). Abnormality in these early steps of placental development leads to poor placentation, fetal growth defects and is often associated with preeclampsia, a major and frequent complication of human pregnancy. To study the mechanisms that control trophoblast invasion during early placental development and provide new insight in the understanding of preeclampsia, we have developed in vitro models of human invasive trophoblasts. We have shown that activation of the ligand-activated nuclear receptor PPARgamma with synthetic (rosiglitazone) or natural (15deoxyPGJ(2)) agonists inhibits the trophoblastic invasion process. Analysis of PPARgamma-target genes revealed that placental growth hormone and the protease PAPP-A might be involved in the PPARgamma-mediated effect in an autocrine manner. We next investigated PPARgamma ligands at the materno-fetal interface and have shown that oxidized LDLs are present in EVCT in situ and decrease trophoblast invasion in vitro. Analysis of oxidized LDLs revealed that they contain potent PPARgamma agonists such as eicosanoids and also high levels of oxysterols, which are specific ligands for the liver X receptor (LXR). The isoform beta of LXR was found in EVCT in situ, and activation of LXRbeta with synthetic or natural ligands inhibits trophoblast invasion in vitro. Together, our data underscore a major role for PPARgamma and LXRbeta in the control of human trophoblast invasion and suggest that excess ligands such as oxidized LDLs at the implantation site might contribute to the development of preeclampsia.     

The ‘beating-heart butterfly technique’ for repair of basal post-infarction ventricle septum defect

Ischaemic ventricular septal defect is a serious complication of acute myocardial infarction with poor outcome. We present the ‘beating-heart butterfly’ technique to close the ventricular septal defect with a double-layered pericardial patch sewn to the intact septum under beating-heart cardiopulmonary bypass in 4 highest-risk patients. This technique combined with a liberal postoperative mechanical circulatory support and open-chest treatment allowed excellent results with 12 months of survival in all patients.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.     

Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection

Open in a separate window OBJECTIVESOral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD).METHODSThis was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation.RESULTSBetween January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99).CONCLUSIONSEmergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.     

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.     

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

Journal of Neurology - Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore...