A Comparative Study of Clinical Outcomes and Functional Status after Knee Fracture and Knee Fracture Dislocation

The aim of this study was to compare outcomes of tibial plateau fracture dislocations (FD) with tibial plateau fractures alone. This study was an analysis of a series of tibial plateau fractures, in which FD was defined as a fracture of the tibial plateau with an associated loss of congruent joint reduction and stability of the knee, and classified by the Moore system. Patient data collected included demographics, injury information, and functional outcomes (short musculoskeletal function assessment [SMFA] score and Pain by the visual analog scale). Clinical outcomes at follow-up were recorded including knee range of motion, knee stability and development of complications. There were a total of 325 tibial plateau fracture patients treated operatively, of which 22.2% were identified as FD (n = 72). At injury presentation there was no difference with regard to nerve injury or compartment syndrome (both p > 0.05). FD patients had a higher incidence of arterial injury and acute ligament repair (both p < 0.005). At a mean follow-up of 17.5 months, FD patients were similar with regard to pain, total SMFA scores, and return to sports than their non-FD counterparts (p = 0.884, p = 0.531, p = 0.802). FD patients were found to have decreased knee flexion compared with non-FD patients by 5 degrees (mean: 120 and 125 degrees) (p < 0.05). FD patients also had a higher incidence of late knee instability and subsequent surgery for ligament reconstruction (p < 0.005 & p < 0.05). However, there was no difference in neurological function between groups at follow-up (p = 0.102). Despite the higher incidence of ligamentous instability and decreased range of motion, FD patients appear to have similar long-term functional outcomes compared with non-FD of the tibial plateau. While FD patients initially presented with a higher incidence of arterial injury, neurovascular outcomes at final follow-up were similar to those without a dislocation.

Platelet ACKR3/CXCR7 Favors Anti-Platelet Lipids over an Atherothrombotic Lipidome and Regulates Thrombo-inflammation

Platelet ACKR3/CXCR7 surface expression is enhanced and influences prognosis in coronary artery disease-(CAD) patients, who exhibit a distinct atherothrombotic platelet lipidome. Current investigation validates the potential of ACKR3/CXCR7 in regulating thrombo-inflammatory response, through its impact on the platelet lipidome. CAD patients-(n=230) with enhanced platelet-ACKR3/CXCR7 expression exhibited reduced aggregation. Pharmacological CXCR7-agonist-(VUF11207) significantly reduced pro-thrombotic platelet response in blood from ACS patients-(n=11) ex vivo. CXCR7-agonist administration reduced thrombotic functions and thrombo-inflammatory platelet-leukocyte interactions post myocardial infarction-(MI) and arterial injury in vivo. ACKR3/CXCR7-ligation did not affect surface availability of GPIbα, GPV, GPVI, GPIX, αv-integrin, β3-integrin, coagulation profile-(APTT, PT), bleeding time, plasma-dependent thrombin generation-(thrombinoscopy) or clot formation-(thromboelastography), but counteracted activation-induced phosphatidylserine exposure and procoagulant platelet-assisted thrombin generation. Targeted-(micro-UHPLC-ESI-QTrap-MS/MS) and untargeted-(UHPLC-ESI-QTOF-MS/MS) lipidomics analysis revealed that ACKR3/CXCR7-ligation favored generation of anti-thrombotic lipids-(dihomo-γ-linolenic acid-DGLA, 12-hydroxyeicosatrienoic acid-12-HETrE) over cyclooxygenase-COX-1-(thromboxane-TxA2), or 12-lipoxygenase-LOX-(12-HETE) metabolized pro-thrombotic, and phospholipase derived atherogenic-(lysophosphatidylcholine-LPC) lipids, in healthy subjects and CAD patients, contrary to anti-platelet therapy. Through 12-HETrE, ACKR3/CXCR7-ligation coordinated with Gαs-coupled prostacyclin receptor-(IP) to trigger cAMP-PKA mediated platelet inhibition. ACKR3/CXCR7-ligation reduced generation of lipid agonists-(arachidonic acid-AA,TxA2), lipid signaling intermediates-(lyophosphatidylinositol-LPI, diacylglycerol-DG), which affected calcium mobilization, intracellular signaling, consequently platelet interaction with physiological matrices and thrombo-inflammatory secretion-(IL1β,IFN-γ,TGF-β,IL-8), emphasizing its functional dichotomy from pro-thrombotic CXCR4. Moreover, CXCR7-agonist regulated heparin-induced thrombocytopenia-(HIT)-sera/IgG-induced platelet and neutrophil activation, heparin induced platelet aggregation-(HIPA), generation of COX-1-(TxA2), 12-LOX-(12-HETE) derived thrombo-inflammatory lipids, platelet-neutrophil aggregate formation, and thrombo-inflammatory secretion (sCD40L, IL-1β, IFN-γ, TNF-α, sP-selectin, IL-8, tissue factor-TF) ex vivo. Therefore, ACKR3/CXCR7 may offer a novel therapeutic strategy in acute/chronic thrombo-inflammation exaggerated cardiovascular pathologies, and CAD.

Predicting the Outcome of Open Type IIIC Tibial Fractures Regarding Union, Osteomyelitis, and Amputation

Backgrounds: This study aimed to assess factors that affect union time and complications in Gustilo IIIC tibial fractures.Methods: Patients who presented to our center with IIIC open tibial fractures from January 2000 to October 2020 were eligible for this retrospective analysis. Patient demographics, fracture characteristics, timing, numbers, and type of surgical intervention were documented. Outcomes of interest included union time, occurrence of osteomyelitis, and amputation. Results: Fifty-eight patients were enrolled and grouped by fracture type; eight union on time (13.8%); 27 late union (46.6%); eight delayed union (13.8%); three nonunion (5.2%); and 12 amputation (20.7%). Nine fractures (15.5%) were complicated by osteomyelitis. Union time was prolonged in cases of triple arterial injury, distal third fractures, multiple trauma with Injury Severity Score (ISS) ≥ 16 points, and increased length of bone defect. Additionally, a bone gap > 50 mm, diabetes mellitus, low body mass index, and triple arterial injury in the lower leg were significant risk factors for amputation. A time from injury to definitive soft tissue coverage of more than 22 days was the major risk factor for osteomyelitis. A scoring system to predict union time was devised and the predicted probability of union within two years was stratified based on this score. Conclusions: IIIC tibial fractures involving the distal third of the tibia, fractures with bone defects, triple arterial injury, and multiple trauma with ISS ≥ 16 points demonstrated delayed union, and an effective prediction system for union time was introduced in this study. Early soft tissue coverage can reduce the risk of osteomyelitis. Finally, diabetes and severe bone and soft tissue defects pose a higher risk of amputation.

Repeated Social Defeat Exaggerates Fibrin-Rich Clot Formation by Enhancing Neutrophil Extracellular Trap Formation via Platelet–Neutrophil Interactions

Depression is an independent risk factor for cardiovascular disease (CVD). We have previously shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular trap (NET) formation. In this study, we investigated the impact of RSD on arterial thrombosis. Eight-week-old male wild-type mice (C57BL/6J) were exposed to RSD by housing with larger CD-1 mice in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. After confirming depression-like behaviors, mice underwent FeCl3-induced carotid arterial injury and were analyzed after 3 h. Although the volume of thrombi was comparable between the two groups, fibrin(ogen)-positive areas were significantly increased in defeated mice, in which Ly-6G-positive cells were appreciably co-localized with Cit-H3-positive staining. Treatment with DNase I completely diminished exaggerated fibrin-rich clot formation in defeated mice. Flow cytometric analysis showed that neutrophil CD11b expression before FeCl3 application was significantly higher in defeated mice than in control mice. In vitro NET formation induced by activated platelets was significantly augmented in defeated mice, which was substantially inhibited by anti-CD11b antibody treatment. Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NET formation, suggesting that NET can be a new therapeutic target in depression-related CVD.

Prospective Study of Serration Angioplasty in the Infrapopliteal Arteries Using the Serranator Device: PRELUDE BTK Study

Purpose: The purpose was to evaluate the safety and efficacy of the Serranator percutaneous transluminal angioplasty serration balloon catheter in patients with infrapopliteal peripheral artery disease. Materials and Methods: A prospective, multicenter, single-arm feasibility study in 46 patients with claudication or chronic limb-threatening ischemia, Rutherford Clinical Category (RCC) 3 to 5, that required treatment of the infrapopliteal arteries above the tibiotalar joint. The primary efficacy outcome was device success—successful insertion, balloon inflation and deflation, and removal of the device(s) with a final diameter stenosis of <50%. The primary safety endpoint was a composite of major adverse limb events (MALE) and perioperative death (POD) through 30 day postprocedure. Other outcomes were change in RCC and ankle-brachial index, wound healing, and clinically-driven target lesion revascularization (CD-TLR). A subset of 9 patients were further evaluated by optical coherence tomography (OCT) or intravascular ultrasound (IVUS) for the presence of serrations in treated lesions. Patient follow-up occurred at 30 days and 6 months. Results: Forty-six patients received treatment with the Serranator device and 55 lesions were treated. Fifty-three lesions were deemed analyzable by the core lab with data and reported hereafter. Device success was 91.7% and freedom from MALE + POD through 30 days was 95.7%. Pretreatment stenosis of 82% was reduced to 21.8% and only 1 lesion (1.9%) required a bailout stent for a grade D dissection. The average maximum balloon inflation pressure was 6 atmospheres. Serrations were present in all treated lesions (n=10) in 9 patients imaged with OCT/IVUS as reviewed by the core laboratory. The RCC score improved by 1 or more level in 70% of patients at 6 months with 42% having a score of 0. The 6 month freedom from CD-TLR was 97.7%. Conclusion: Serranator treatment of infrapopliteal lesions showed excellent lumen gain with minimal evidence of arterial injury and low 6 month CD-TLR. Imaging by IVUS and OCT showed serrations without significant dissection, supporting the device’s proposed mechanism of action.

Management Algorithm of External Fixation in Lower Leg Arterial Injury for Limb Salvages

Purpose: The purpose of this study was to review the roles of using external fixation to rescue the patients who sustained arterial injuries in the lower legs.Methods: Demographics, surgical treatment and outcomes in 88 patients with lower leg arterial injuries treated by external fixation at two trauma centers from 2009 to 2018 were reviewed. The primary outcome was the rate of successful lower leg salvage, while secondary outcomes were complications and functional recovery.Results:80 patients (90 legs) maintained a successful lower leg salvage. The patients were followed up for an average of 15.5±5.5 months. 6 patients (8 pins) experienced pin-tract infection, pins loosening happened in 2 patients (4 pins), 7 patients (7 legs) developed wound superficial infection, 3 patients (3 legs) with a deep infection developed osteomyelitis, 16 patients (17 legs) suffered the bone nonunion or bone defect. The average healing time of fracture was 5.6±4.3months. The maintain of external fixation average time was 5.8±3.6 months. Conclusion: With correctly judging the condition of limb ischemia, mastering reasonably the operation indications, and preventing complications, good clinical effects can be achieved when external fixation is used.Level of evidence: Retrospective cohort, level IV.