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IntroductionSerine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.MethodsTo evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity).ResultsAccording to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02).DiscussionOur data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Background/purpose(s): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. Methods: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. Results: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04–3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02–2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04–3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21–4.9) with deceased outcomes. Conclusion: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Transforming the orthopedic landscape, hip arthroscopy pioneers a minimally invasive surgical approach for diagnosing and addressing hip pathologies. With its origins dating back to Burman’s 1931 cadaveric study, this groundbreaking technique gained clinical relevance in 1939 through Takagi’s report. However, the 1980s marked the actual emergence of hip arthroscopy for treating a wide range of hip disorders. Now, a staple in modern orthopedics, hip arthroscopy empowers patients with previously undiagnosed and untreated hip conditions, enabling them to obtain relief and reclaim their lives. By employing a compact camera and specialized tools, surgeons expertly navigate the hip joint, performing procedures from excising loose bodies and mending labral tears to addressing femoroacetabular impingement and tackling other intricate issues. This innovative approach has dramatically elevated patients’ quality of life, allowing them to embrace targeted treatments and resume daily activities without resorting to lifestyle alterations.

IntroductionSevere acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization–triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

The preservation of the chondrogenic phenotype and hypoxia-related physiological microenvironment are major challenges in the 2D culture of primary human chondrocytes. To address this problem, we develop a 3D culture system generating scaffold-free spheroids from human chondrocytes. Our results highlight the chondrogenic potential of cultured human articular chondrocytes in a 3D system combined with hypoxia independently of the cartilage source. After 14 days of culture, we developed spheroids with homogenous diameter and shape from hyaline cartilage donors. Spheroids generated in hypoxia showed a significantly increased glycosaminoglycans synthesis and up-regulated the expression of SOX9, ACAN, COL2A1, COMP, and SNAI1 compared to those obtained under normoxic conditions. Therefore, we conclude that spheroids developed under hypoxic conditions modulate the expression of chondrogenesis-related genes and native tissue features better than 2D cultures. Thus, this scaffold-free 3D culture system represents a novel in vitro model that can be used for cartilage biology research.

Common peroneal nerve injury is present in 40% of knee dislocations, and foot drop is the principal complication. Posterior tibial tendon transfer is a viable solution to replace the function of the anterior tibial tendon (ATT) in the mid-foot. Several techniques for posterior tibial tendon transfer exist today, with variable results reported. However, adding augmentation with side-to-side tenorrhaphy of ATT to the transferred posterior tibial tendon (PTT) enhances anterior tissue balance and load sharing stress between native ATT enthesis and PTT tenodesis, allowing early rehabilitation and improving functional outcomes. Side-to-side tenorrhaphy is performed after PTT tenodesis in the lateral cuneiform to improve reliability in foot drop. This technique allows shorter immobilization time (from 6 to 2 weeks), earlier rehabilitation, sooner weight-bearing, and decreased risk of arthrofibrosis, scar formation, and muscle atrophy.

Hamstring tendon autograft remains a popular graft choice for anterior cruciate ligament reconstruction. Although the technique of hamstring autograft harvest is relatively straightforward, it is critical to pay attention to several technical steps to avoid iatrogenic anatomic or neurovascular damage as well as to reduce the risk of premature amputation of the graft when using a tendon stripper. We describe a technique of hamstring autograft harvesting using only 2 anatomic references that makes it a simple and reproducible technique for surgeons, especially those in training.

Entrapment of the sciatic nerve is considered a challenging problem for orthopaedic surgeons. Many surgical interventions (open or endoscopic) have been described as treatments. We describe an endoscopic technique for release of the piriformis tendon and sciatic nerve exploration by the lateral approach through an incision on the iliotibial band.

This article describes the arthroscopic approach and management of a “reverse contre-coup” injury to the hip labrum. The injury occurs in the setting of posterolateral acetabular rim over-coverage impinging on the distal femoral neck in extension causing the femoral head to lever out anteriorly against the labrum. Ligamentous laxity and associated loss of anterior capsular restraint allow increased femoral head translation, adding further insult to the anterior labrum. The arthroscopic approach entails not only a labral repair with correction of the osseous conflict but also restoration of soft-tissue stability to minimize anterior femoral translation.

Extra-articular hip impingement refers to a variety of hip disorders causing pain and limited function in young, non-arthritic patients. Recently, there has been an increased focus on analyzing the degree of anterior inferior iliac spine (AIIS) dysmorphism and its correlation with subspine impingement (SSI), defined as abutment between a prominent distal aspect of the AIIS and the anterior aspect of the femoral head-neck junction. Arthroscopic decompression of the AIIS is recognized as an effective treatment for SSI. However, there may be some inherent risks of performing this procedure arthroscopically that require further investigation.

To perform a proper labral repair, most surgeons use anchors to secure the labrum to the acetabular bone. We aim to describe a technique for labral repair with a knotless tensionable suture anchor. This technique uses a looped suture configuration, allowing selective tensioning of the repair to maintain the anatomic suction seal of the hip. The use of this technique is easily reproducible and reduces the surgical time compared with previous techniques.

Microfracture is a marrow-stimulation technique in which damaged cartilage is drilled or punched, perforating the subchondral bone and generating a blood clot within the defect that matures into fibrocartilage. Microfracture for the treatment of small cartilage defects of the hip has shown good results. Arthroscopic procedures are less invasive than open procedures and have a reduced incidence of complications such as infection or avascular necrosis of the femoral head. Furthermore, arthroscopic procedures allow for a shorter recovery time, resulting in not only lower overall treatment costs but also higher patient satisfaction. Medial and parafoveal cartilage defects of the femoral head can be challenging to effectively microfracture using standard arthroscopy portals because of the acute angles required for instrument manipulation. This report describes a technique for microfracturing these challenging areas of the femoral head using a 2.7-mm K-wire and drilling in a transtrochanteric direction using arthroscopic and imaging guidance to target the area of chondral damage.

Recalcitrant osteitis pubis presents a challenging problem for orthopaedic surgeons. Various surgical interventions have been described for treatment, including opening-wedge resection, symphysiodesis, and curettage. We propose that endoscopic pubic symphysectomy offers an effective method of treating such a challenging problem. This article describes in detail the technique used to perform endoscopic pubic symphysectomy, and a companion video demonstrating the procedure is included. Our experience suggests that removal of the interpubic fibrocartilaginous lamina and resection of approximately 1 cm of bone can successfully eliminate all sources of pain and dysfunction caused by the recalcitrant osteitis pubis.

Atraumatic instability or microinstability of the hip is a recognized cause of groin pain and hip instability. Risk factors include female sex, ligamentous laxity, and borderline dysplasia. Arthroscopically, the joint may distract easily, and there may be associated ligamentum teres tears and laxity of the capsule on manual probing. The use of arthroscopic capsular plication in this cohort of patients has shown good to excellent results. Biomechanically, a capsular plication aims to create an imbrication and inferior shift of the capsule to augment the screw-home mechanism of the capsuloligamentous structures and thereby improve stability in extension and external rotation. The purpose of this article is to detail the step-by-step surgical technique of arthroscopic capsular plication, in addition to the indications, pearls, and pitfalls of the technique.