Multiligamentous Knee Injuries: Current Concepts Review.

Multiligamentous knee injuries (MLKI) are rare but devastating injuries that have a potential to cause long-term sequelae and significant morbidity. Frequently occurring concomitantly with knee dislocations (KD), MLKI have many risk factors that influence their incidence and treatment outcomes. Proper understanding of these risk factors can assist the surgeon with evaluation, surgical planning, and managing patient expectations both pre- and postoperatively. The purpose of this review is fourfold: (1) identify the risk factors and injuries associated with MLKI, (2) describe factors implicated in the treatment of MLKI, (3) report the effect of these risk factors on outcomes of MLKI, and (4) provide a brief insight into MLKI at our tertiary referral academic care center. This was a retrospective review of literature relevant to MLKI. Studies that described injuries, risk factors, treatment techniques, or outcomes associated with MLKI were included in our review. A total of 35 studies (consisting of level 3 and 4 evidence) published between 2009 and 2020 were found and included in our analysis. In addition, 25 patients who underwent treatment for MLKI at the University of Chicago Medical Center between December 2015 and December 2019 were included in our analysis. MLKI tend to occur in the younger male population. Increasing age, body mass index, and severity of the injury have been correlated with worse functional and patient-reported outcomes. Operative treatment is indicated for MLKI; however, timing and repair versus reconstruction is still debated, and is often decided on a patient by patient basis. Retrospective cohort studies have indicated that reconstruction may be favored; however, further more rigorous studies are needed to better characterize this finding. MLKIs are devastating injuries with significant variability in presentation, treatment, and outcome. Variations in these are largely attributable to the mechanism and severity of injury, timing, and surgeon preference. A holistic approach, and understanding of the present literature, is required to best optimize patient outcome.

The C-C Chemokine Receptor Type 4 Is an Immunomodulatory Target of Hydroxychloroquine.

The emergence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) in China, reported to the World Health Organization on December 31, 2019, has led to a large global pandemic and is a major public health issue. As a result, there are more than 200 clinical trials of COVID-19 treatments or vaccines that are either ongoing or recruiting patients. One potential therapy that has garnered international attention is hydroxychloroquine; a potent immunomodulatory agent FDA-approved for the treatment of numerous inflammatory and autoimmune conditions, including malaria, lupus, and rheumatoid arthritis. Hydroxychloroquine has demonstrated promise in vitro and is currently under investigation in clinical trials for the treatment of COVID-19. Despite an abundance of empirical data, the mechanism(s) involved in the immunomodulatory activity of hydroxychloroquine have not been characterized. Using the unbiased chemical similarity ensemble approach (SEA), we identified C-C chemokine receptor type 4 (CCR4) as an immunomodulatory target of hydroxychloroquine. The crystal structure of CCR4 was selected for molecular docking studies using the SwissDock modeling software. In silico, hydroxychloroquine interacts with Thr-189 within the CCR4 active site, presumably blocking endogenous ligand binding. However, the CCR4 antagonists compound 18a and K777 outperformed hydroxychloroquine in silico, demonstrating energetically favorable binding characteristics. Hydroxychloroquine may subject COVID-19 patients to QT-prolongation, increasing the risk of sudden cardiac death. The FDA-approved CCR4 antagonist mogalizumab is not known to increase the risk of QT prolongation and may serve as a viable alternative to hydroxychloroquine. Results from this report introduce additional FDA-approved drugs that warrant investigation for therapeutic use in the treatment of COVID-19.