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

Osteochondral Allograft Implantation Using the Smith–Peterson (Anterior) Approach for Chondral Lesions of the Femoral Head

Management of chondral lesions of the femoral head can be challenging. Previously described approaches include arthroscopic surgery for small lesions and open surgical dislocation for larger lesions. In 2001, Ganz popularized the trochanteric flip osteotomy for surgical dislocation, and this remains the workhorse for treatment of large chondral lesions. However, by using a Smith–Peterson (direct anterior) approach and a femoral head allograft, large lesions may be treated while avoiding both trochanteric osteotomy and donor-site morbidity. We present our technique using a Smith–Peterson approach and osteochondral implantation of fresh femoral head allograft for surgical treatment of a femoral head chondral lesion

Hip Labral Augmentation With Tibialis Anterior Tendon Allograft Using the Knotless Pull-Through Technique

The importance of the labrum in the biomechanics of the hip joint is well documented. Labral tears are the most common pathology in patients undergoing hip arthroscopy and therefore appropriate labral management is vital. Labral preservation has been advocated as a superior alternative to labral excision in terms of clinical outcomes. While reconstruction of the labrum is recommended for irreparable tears, labral augmentation is a viable alternative for labral function restoration under certain indications. This Technical Note will describe a method for arthroscopic hip labral augmentation using an anterior tibialis tendon allograft and the pull-through technique

Do Not Take for Granted! The Art of Elevating the Capsule in Hip Arthroscopy: A Stepwise Approach

Different techniques have been described to close or plicate the capsule. To perform these procedures, however, the capsule must be preserved, a consideration unfortunately often overlooked. This Technical Note describes in a stepwise manner the initial capsular management necessary to preserve the capsule for further procedures such as closure or plication. Level of Evidence: I (hip), II (impingement, labrum, other)

Microfracture in Hip Arthroscopy. Keep It Simple!

Despite all the advances in hip arthroscopy, microfracture is still the workhorse for treating focal and full-thickness cartilage lesions. The success of this treatment is owed to its reliability and simplicity. Given the structure of the hip joint, however, there are challenges to this procedure using a conventional microfracture pick. This note presents our current and preferred microfracture technique using a curve drill guide and flexible drill. This method offers greater range of access to different regions of the joint with ease, thus ensuring a reproducible and quicker procedure with less risk

Forget the Greater Trochanter! Hip Joint Access With the 12 O’clock Portal in Hip Arthroscopy

Most surgeons rely on the greater trochanter as the reference point to establish the anterolateral portal. Nevertheless, we believe that the anterosuperior iliac spine is a more reliable landmark. Unlike the greater trochanter, it is unaffected by leg rotation and is more easily identified by palpation. Abiding by the central tenet of medicine to “do no harm,” the technique described herein presents in detail the concept of the 12 o’clock portal placement, a hip joint access method based on identifying specific anatomic points under fluoroscopy and by palpation. To accomplish this goal, this Technical Note presents a step-by-step approach, including tips and pearls for patient positioning and fluoroscopic guidance. We believe this method ensures a reproducible and safe way to start hip arthroscopy in the supine position

Arthroscopic Ligamentum Teres Reconstruction Using Anterior Tibialis Allograft and the Tension-Slide Technique

Once perceived to be a vestigial structure, the ligamentum teres (LT) is now increasingly understood to be critical to providing stability in the adult hip. Surgical treatment with arthroscopic debridement is usually the procedure of choice to treat LT tears. However, reconstruction is a possible alternative in select cases. The authors of a recent systematic review concluded that LT debridement may provide short-term relief of hip pain in patients with partial-thickness tears in whom conservative management has failed whereas reconstruction may be more beneficial in cases of full-thickness tears. This Technical Note describes a method for arthroscopic LT reconstruction using the tension-slide technique to fixate an anterior tibialis tendon allograft to the acetabulum