HLA-G is a nonclassical MHC class I (MHCITo date, the structural basis for HLA-G͞LILR recognition remains to be examined. Here, we report the 2.5-Å resolution crystal structure of the LILRB2͞HLA-G complex. LILRB2 exhibits an overlapping but distinct MHCI recognition mode compared with LILRB1 and dominantly recognizes the hydrophobic site of the HLA-G ␣3 domain. NMR binding studies also confirmed these LILR recognition differences on both conformed (heavy chain͞peptide͞ 2m) and free forms of 2m. Binding studies using 2m-free MHCIs revealed differential 2m-dependent LILR-binding specificities. These results suggest that subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression.crystal structure ͉ immune suppression ͉ MHC class I ͉ 2m-free MHC ͉ maternal-fetal interface
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Highlights-Thoracic anesthesiologists might be involved in the perioperative care of patients suspected to have or diagnosed COVID-19 who might undergo thoracic surgery during the acute or convalescence phases of the disease.-Caution should be exercised when securing the airway and performing lung separation (if required), through vigilant donning/doffing of personal protection equipment (PPE), planning ahead, team briefing, proper preparations, systematic approach, and debriefing.-Lung separation / isolation should be individualized using either bronchial blockers or double lumen tubes according to the patient"s status and postoperative care plan.-Optimum PPE donning should be maintained during surgery and anesthesia. One lung ventilation could be challenging in this group of patients.-The anesthesiologists should discuss the feasibility of extubating the patient following thoracic surgery, and procedures for postoperative care andtransferring the patient to the isolation wards or intensive care unit.Abstract 110 words, Manuscript 4935 words Running
Vascular injury plays an important role in the primary and secondary injury mechanisms that cause damage to the acutely traumatized spinal cord. To understand the pathophysiology of human spinal cord injury, the authors investigated the vascular system in three uninjured human spinal cords using silicone rubber microangiography and analyzed the histological findings related to vascular injury in nine acutely traumatized human spinal cords obtained at autopsy. The interval from spinal cord injury to death ranged from 20 minutes to 9 months. The microangiograms of the uninjured human cervical cords demonstrated new information about the sulcal arterial system and the pial arteries. The centrifugal sulcal arterial system was found to supply all of the anterior gray matter, the anterior half of the posterior gray matter, approximately the inner half of the anterior and lateral white columns, and the anterior half of the posterior white columns. Traumatized spinal cord specimens in the acute stage (3-5 days postinjury) showed severe hemorrhages predominantly in the gray matter, but also in the white matter. The white matter surrounding the hemorrhagic gray matter showed a variety of lesions, including decreased staining, disrupted myelin, and axonal and periaxonal swelling. The white matter lesions extended far from the injury site, especially in the posterior columns. There was no evidence of complete occlusion of any of the larger arteries, including the anterior and posterior spinal arteries and the sulcal arteries. However, occluded intramedullary veins were identified in the degenerated posterior white columns. In the chronic stage (3-9 months postinjury), the injured segments showed major tissue loss with large cavitations, whereas both rostral and caudal remote sites showed well-demarcated necrotic areas indicative of infarction mainly in the posterior white columns. Obstruction of small intramedullary arteries and veins by the initial mechanical stress or secondary injury mechanisms most likely produced these extensive white matter lesions. Our studies implicate damage to the anterior sulcal arteries in causing the hemorrhagic necrosis and subsequent central myelomalacia at the injury site in acute spinal cord injury in humans.
Several surgical procedures have been used for the treatment of syringomyelia associated with Chiari I malformation at our institute. The purpose of this article is to evaluate the results of two major surgical procedures, foramen magnum decompression (FMD) and syringosubarachnoid (SS) shunting. The series consisted of 70 patients with syringomyelia associated with Chiari I malformation who were surgically treated. Their ages ranged from 3 to 59 years (median, 29.4 yr). FMD was performed on 33 patients, and SS shunting was performed on 37 patients. The follow-up period ranged from 6 months to 12.5 years, with a mean of 60 months. The clinical and radiological outcomes were analyzed comparing the two groups. We principally performed FMD in patients with symptoms of Chiari I malformation and/or a small syrinx. We prefer to use SS shunting in patients with large syringes. Postoperative magnetic resonance imaging demonstrated that the syrinx had collapsed or decreased in size in 94% of the patients who underwent FMD and in 100% of the patients who underwent SS shunting. Neurological improvements were observed in 82% and in 97% of the patients who underwent FMD and SS shunting, respectively. In particular, the relief of pain was more fully achieved after SS shunting than after FMD. The average time for the syrinx to collapse was 6.3 weeks after surgery in the FMD group and 1.8 weeks in the SS shunting group. These results indicate that clinical symptoms and radiological findings improved much more quickly in the SS shunting group than in the FMD group.(ABSTRACT TRUNCATED AT 250 WORDS)
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