Chemokines and eicosanoids fuel the hyperinflammation within the lungs of patients with severe COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to a variety of clinical outcomes, ranging from the absence of symptoms to severe acute respiratory disease and ultimately death. A feature of patients with severe coronavirus disease 2019 (COVID-19) is the abundance of inflammatory cytokines in the blood. Elevated levels of cytokines are predictive of infection severity and clinical outcome. In contrast, studies aimed at defining the driving forces behind the inflammation in lungs of subjects with severe COVID-19 remain scarce. OBJECTIVE: Our aim was to analyze and compare the plasma and bronchoalveolar lavage (BAL) fluids of patients with severe COVID-19 (n = 45) for the presence of cytokines and lipid mediators of inflammation (LMIs). METHODS: Cytokines were measured by using Luminex multiplex assay, and LMIs were measured by using liquid chromatography-tandem mass spectrometry. RESULTS: We revealed high concentrations of numerous cytokines, chemokines, and LMIs in the BAL fluid of patients with severe COVID-19. Of the 13 most abundant mediators in BAL fluid, 11 were chemokines, with CXCL1 and CXCL8 being 200 times more abundant than IL-6 and TNF-α. Eicosanoid levels were also elevated in the lungs of subjects with severe COVID-19. Consistent with the presence chemotactic molecules, BAL fluid samples were enriched for neutrophils, lymphocytes, and eosinophils. Inflammatory cytokines and LMIs in plasma showed limited correlations with those present in BAL fluid, arguing that circulating inflammatory molecules may not be a reliable proxy of the inflammation occurring in the lungs of patients with severe COVID-19. CONCLUSIONS: Our findings indicate that hyperinflammation of the lungs of patients with severe COVID-19 is fueled by excessive production of chemokines and eicosanoids. Therapeutic strategies to dampen inflammation in patients with COVID-19 should be tailored accordingly.

High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID-19). While COVID-19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID-19 and few treatments significantly improved clinical outcome. Dexamethasone and possibly aspirin, which directly/indirectly target the biosynthesis/effects of numerous lipid mediators are among those options. Our objective was to define if severe COVID-19 patients were characterized by increased bioactive lipids modulating lung inflammation. A targeted lipidomic analysis of bronchoalveolar lavages (BALs) by tandem mass spectrometry was done on 25 healthy controls and 33 COVID-19 patients requiring mechanical ventilation. BALs from severe COVID-19 patients were characterized by increased fatty acids and inflammatory lipid mediators. There was a predominance of thromboxane and prostaglandins. Leukotrienes were also increased, notably LTB4 , LTE4 , and eoxin E4 . Monohydroxylated 15-lipoxygenase metabolites derived from linoleate, arachidonate, eicosapentaenoate, and docosahexaenoate were also increased. Finally yet importantly, specialized pro-resolving mediators, notably lipoxin A4 and the D-series resolvins, were also increased, underscoring that the lipid mediator storm occurring in severe COVID-19 involves pro- and anti-inflammatory lipids. Our data unmask the lipid mediator storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipid mediators.

Arthroscopic Latarjet procedure: is optimal positioning of the bone block and screws possible? A prospective computed tomography scan analysis.

HYPOTHESIS: We hypothesized that the arthroscopic Latarjet procedure could be performed with accurate bone block positioning and screw fixation with a similar rate of complications to the open Latarjet procedure. METHODS: In this prospective study, 105 shoulders (104 patients) underwent the arthroscopic Latarjet procedure performed by the same senior surgeon. The day after surgery, an independent surgeon examiner performed a multiplanar bidimensional computed tomography scan analysis. We also evaluated our learning curve by comparing 2 chronologic periods (30 procedures performed in each period), separated by an interval during which 45 procedures were performed. RESULTS: Of the 105 shoulders included in the study, 95 (90.5%) (94 patients) were evaluated. The coracoid graft was accurately positioned relative to the equator of the glenoid surface in 87 of 95 shoulders (91.5%). Accurate bone-block positioning on the axial view with "circle" evaluation was obtained for 77 of 95 shoulders (81%). This procedure was performed in a lateralized position in 7 of 95 shoulders (7.3%) and in a medialized position in 11 shoulders (11.6%). The mean screw angulation with the glenoid surface was 21°. One patient had transient axillary nerve palsy. Of the initial 104 patients, 3 (2.8%) underwent revision. The analysis of our results indicated that the screw-glenoid surface angle significantly predicted the accuracy of the bone-block positioning (P = .001). Our learning curve estimates showed that, compared with our initial period, the average surgical time decreased, and the risk of lateralization showed a statistically significant decrease during the last period (P = .006). CONCLUSIONS: This study showed that accurate positioning of the bone block onto the anterior aspect of the glenoid is possible, safe, and reproducible with the arthroscopic Latarjet procedure without additional complications compared with open surgery.

A convertible shoulder system: is it useful in total shoulder arthroplasty revisions?

PURPOSE: The frequency of total shoulder arthroplasty (TSA) implantation is constantly increasing. This leads to revisions because of stem or glenoid component loosening, infection, instability or glenoid subsidence. Significant rotator cuff lesions and/or bone loss necessitate reverse shoulder arthroplasty (RSA) with bone reconstruction, which is a demanding procedure. Our hypothesis is that a platform system (versatile humeral stem with metal back glenoid component) makes revision surgery less demanding and less time consuming, and helps reduce the risks of complication. The purpose of this study is to analyse our revision experience with such a system to support our hypothesis. METHODS: We present 29 revision cases of a convertible platform shoulder system: five hemi arthroplasties (HA), eight TSA with cemented glenoid (TSACG) and 16 TSA with metal backed glenoid component (TSAMB). Three TSACG were switched to TSAMB, and 26 other arthroplasties were switched to RSA. The pre-operative Constant score was 27 (range, 0-38). Our revision incidence was 5.4 % (29 revisions out of 537 shoulder arthroplasties over five years). RESULTS: At revision, Constant score was 60 (range, 42-85). The humeral stem (versatile with TSA and RSA) was kept in three out of four cases. Most of the time it was changed because of too high a position, making it impossible to reduce the RSA. Nevertheless, 12 PTAMB were switched in 12 RSA without any metal backed revisions. CONCLUSION: A platform shoulder system allows much easier revisions.