Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Arthroscopic Acetabular Rim Resection in the Treatment of Femoroacetabular Impingement

Appropriate identification and precise resection of the pincer lesion are integral parts of the arthroscopic surgical treatment of femoroacetabular impingement. Preoperative radiographic planning of the bone resection, as well as executing the plan intraoperatively using both fluoroscopic and arthroscopic cues, is critical to adequately removing the pincer lesion. We present our surgical technique of removing the impinging bone by defining the focal acetabular rim overcoverage, accessing the pincer lesion with labral detachment, and then performing acetabular rim resection

Arthroscopic Femoral Neck Osteoplasty in the Treatment of Femoroacetabular Impingement

Femoral neck osteoplasty is an integral component for successful treatment of femoroacetabular impingement. Current techniques allow this to be performed arthroscopically, and results are equivalent to those of open procedures when typical anterior and anterosuperior lesions are considered. The arthroscopic procedure is dependent on obtaining adequate visualization through capsular management and proper leg positioning, and it requires fluoroscopy to guide and verify an adequate resection. We present our preferred technique for arthroscopic femoral neck osteoplasty

Arthroscopic-Assisted Reduction and Percutaneous Fixation of Tibial Plateau Fractures

Tibial plateau fractures present a difficult range of fractures to treat. Arthroscopy allows for a less invasive option when compared with arthrotomy. Furthermore, visualization of the articular surface arthroscopically can allow for a precise reduction and assessment of any concomitant injuries to the articular cartilage and meniscus. By use of arthroscopy, unicondylar lateral plateaus were traditionally approached through a laterally based metaphyseal window. However, in carefully selected patients and fracture patterns, a medially based, arthroscopic-assisted approach can create long bony tunnels for subchondral support and allow for greater ease in fracture reduction. We present our technique using a medial approach for arthroscopic-assisted fixation of lateral tibial plateau fractures

Arthroscopic Meniscal Root Repair Using a Ceterix NovoStitch Suture Passer

Meniscal root injuries can compromise knee function and lead to early degenerative changes if not appropriately treated. Numerous techniques have been described; however, the technical difficulties in performing these repairs are well known. Furthermore, the relative strengths of various repair techniques have been examined. This article describes a single–working portal meniscal root repair technique using a double-locking loop suture configuration with a novel suture-passing device that offers a strong, reproducible repair construct

Arthroscopic Capsular Repair in the Treatment of Femoroacetabular Impingement

The role of capsular repair in the arthroscopic treatment of femoroacetabular impingement remains poorly defined. Some surgeons rarely repair the capsule, whereas others perform repairs routinely. There is little direct clinical evidence to guide surgeon decision making. When capsular repairs are performed, the procedure requires adequate visualization and careful suture placement either to re-establish the patient's normal capsular volume or to plicate a redundant capsule in a hip with hyperlaxity preoperatively. We present our preferred technique for arthroscopic capsular repair

Creating and Closing the T-Capsulotomy for Improved Visualization During Arthroscopic Treatment of Femoroacetabular Impingement

Treatment of femoroacetabular impingement through an arthroscopic approach has gained widespread popularity in recent years. Although outcomes are generally favorable, one of the most common reasons for failure is incomplete resection of cam lesions of the femoral neck. As a result, the T-capsulotomy has been introduced as a method for improving access to the femoral head-neck junction, which is not always visible through a standard interportal capsulotomy. The T-capsulotomy has the benefits of improving arthroscopic visualization of the femoral neck, reducing overall fluoroscopy exposure for the patient and surgeon, and facilitating capsular plication. We present a reliable and efficient method for creating and repairing the T-capsulotomy. We routinely perform this technique in patients with cam lesions that are too large or too distal to safely visualize and decompress through an interportal capsulotomy

A Simple Technique for Capsular Repair After Hip Arthroscopy

Capsulotomy is typically performed during arthroscopic treatment for femoroacetabular impingement. As the frequency of hip arthroscopy continues to expand rapidly, increased attention is being paid to the implications of interportal capsulotomy and the need for repair. To minimize the risk of postoperative instability, capsular closure has been recommended to restore the anatomy and biomechanical function of the capsule. We present a reliable, efficient, and effective method for arthroscopic closure of the interportal capsulotomy after hip arthroscopy

Reconstruction of the Posterolateral Corner of the Knee With Achilles Tendon Allograft

Posterolateral corner injuries of the knee are relatively rare; however, they can result in significant long-term disability without appropriate treatment. They often occur in the setting of multiligament knee injuries, and as a result, diagnosis and management can be challenging. Severe injuries often require reconstruction, and both anatomic and nonanatomic techniques exist. We describe our preferred operative technique to reconstruct the fibular collateral ligament and posterolateral corner using a single Achilles tendon allograft

Inside-Out Repair for Radial Meniscus Tears

Understanding of meniscal function through basic science, natural history, and biomechanics has highlighted the importance of preserving the meniscus to maintain normal knee biomechanics. Tears that may alter these biomechanics can contribute to the progressive nature of degenerative joint disease in the knee. Radial tears result in the disruption of the circumferential fibers causing inability of the native meniscus to resist normal hoop stresses, thereby leading to increased focal areas of pressure that cause complications such as early onset arthrosis. In this technical note, we describe our preferred operative technique to repair radial meniscal tears using an arthroscopic inside-out approach with satisfactory clinical outcomes and healing response