mtDNA Activates cGAS Signaling and Suppresses the YAP-Mediated Endothelial Cell Proliferation Program to Promote Inflammatory Injury.

Cytosolic DNA acts as a universal danger-associated molecular pattern (DAMP) signal; however, the mechanisms of self-DNA release into the cytosol and its role in inflammatory tissue injury are not well understood. We found that the internalized bacterial endotoxin lipopolysaccharide (LPS) activated the pore-forming protein Gasdermin D, which formed mitochondrial pores and induced mitochondrial DNA (mtDNA) release into the cytosol of endothelial cells. mtDNA was recognized by the DNA sensor cGAS and generated the second messenger cGAMP, which suppressed endothelial cell proliferation by downregulating YAP1 signaling. This indicated that the surviving endothelial cells in the penumbrium of the inflammatory injury were compromised in their regenerative capacity. In an experimental model of inflammatory lung injury, deletion of cGas in mice restored endothelial regeneration. The results suggest that targeting the endothelial Gasdermin D activated cGAS-YAP signaling pathway could serve as a potential strategy for restoring endothelial function after inflammatory injury.

ZFP36L1 controls KLF16 mRNA stability in vascular smooth muscle cells during restenosis after vascular injury.

The RNA-binding zinc finger protein 36 (ZFP36) family participates in numerous physiological processes including transition and differentiation through post-transcriptional regulation. ZFP36L1 is a member of the ZFP36 family. This study aimed to evaluate the role of ZFP36L1 in restenosis. We found that the expression of ZFP36L1 was inhibited in VSMC-phenotypic transformation induced by TGF-ß, PDGF-BB, and FBS and also in the rat carotid injury model. In addition, we found that the overexpression of ZFP36L1 inhibited the proliferation and migration of VSMCs and promoted the expression of VSMC contractile genes; whereas ZFP36L1 interference promoted the proliferation and migration of VSMCs and suppressed the expression of contractile genes. Furthermore, the RNA binding protein immunoprecipitation and double luciferase reporter gene experiments shows that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16. Finally, our research results in the rat carotid balloon injury animal model further confirmed that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16 and further plays a role in vascular injury and restenosis in vivo.

Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1ß-evoked signaling in vascular smooth muscle cells and vascular inflammation.

Reversible lysine-63 (K63) polyubiquitination regulates proinflammatory signaling in vascular smooth muscle cells (SMCs) and plays an integral role in atherosclerosis. Ubiquitin-specific peptidase 20 (USP20) reduces NFκB activation triggered by proinflammatory stimuli, and USP20 activity attenuates atherosclerosis in mice. The association of USP20 with its substrates triggers deubiquitinase activity; this association is regulated by phosphorylation of USP20 on Ser334 (mouse) or Ser333 (human). USP20 Ser333 phosphorylation was greater in SMCs of atherosclerotic segments of human arteries as compared with nonatherosclerotic segments. To determine whether USP20 Ser334 phosphorylation regulates proinflammatory signaling, we created USP20-S334A mice using CRISPR/Cas9-mediated gene editing. USP20-S334A mice developed ∼50% less neointimal hyperplasia than congenic WT mice after carotid endothelial denudation. WT carotid SMCs showed substantial phosphorylation of USP20 Ser334, and WT carotids demonstrated greater NFκB activation, VCAM-1 expression, and SMC proliferation than USP20-S334A carotids. Concordantly, USP20-S334A primary SMCs in vitro proliferated and migrated less than WT SMCs in response to IL-1ß. An active site ubiquitin probe bound to USP20-S334A and USP20-WT equivalently, but USP20-S334A associated more avidly with TRAF6 than USP20-WT. IL-1ß induced less K63-linked polyubiquitination of TRAF6 and less downstream NFκB activity in USP20-S334A than in WT SMCs. Using in vitro phosphorylation with purified IRAK1 and siRNA-mediated gene silencing of IRAK1 in SMCs, we identified IRAK1 as a novel kinase for IL-1ß-induced USP20 Ser334 phosphorylation. Our findings reveal novel mechanisms regulating IL-1ß-induced proinflammatory signaling: by phosphorylating USP20 Ser334, IRAK1 diminishes the association of USP20 with TRAF6 and thus augments NFκB activation, SMC inflammation, and neointimal hyperplasia.

α-Hemolysin-mediated endothelial injury contributes to the development of Staphylococcus aureus-induced dermonecrosis.

Staphylococcus aureus α-hemolysin (Hla) is a pore-forming toxin critical for the pathogenesis of skin and soft tissue infections, which causes the pathognomonic lesion of cutaneous necrosis (dermonecrosis) in mouse models. To determine the mechanism by which dermonecrosis develops during S. aureus skin infection, mice were given control serum, Hla-neutralizing antiserum, or an inhibitor of Hla receptor [A-disintegrin and metalloprotease 10 (ADAM10) inhibitor] followed by subcutaneous infection by S. aureus, and the lesions were evaluated using immunohistochemistry and immunofluorescence. Hla induced apoptosis in the vascular endothelium at 6 hours post-infection (hpi), followed by apoptosis in keratinocytes at 24 hpi. The loss of vascular endothelial (VE)-cadherin expression preceded the loss of epithelial-cadherin expression. Hla also induced hypoxia in the keratinocytes at 24 hpi following vascular injury. Treatment with Hla-neutralizing antibody or ADAM10 inhibitor attenuated early cleavage of VE-cadherin, cutaneous hypoxia, and dermonecrosis. These findings suggest that Hla-mediated vascular injury with cutaneous hypoxia underlies the pathogenesis of S. aureus-induced dermonecrosis.

Outcomes of vascular closure devices for femoral venous hemostasis following catheter ablation of atrial fibrillation.

INTRODUCTION: Access site complications remain common following atrial fibrillation (AF) catheter ablation. Femoral vascular closure devices (VCDs) reduce time to hemostasis compared with manual compression, although large-scale data comparing clinical outcomes between the two approaches are lacking. METHODS: Two cohorts of patients undergoing AF ablation were identified from 36 healthcare organizations using a global federated research network (TriNetX): those receiving a VCD for femoral hemostasis, and those not receiving a VCD. A 1:1 propensity score matching (PSM) model based on baseline characteristics was used to create two comparable cohorts. The primary outcome was a composite of all-cause mortality, vascular complications, bleeding events, and need for blood transfusion. Outcomes were assessed during early (within 7 days of ablation) and extended follow-up (within 8-30 days of ablation). RESULTS: After PSM, 28 872 patients were included (14 436 in each cohort). The primary composite outcome occurred less frequently in the VCD cohort during early (1.97% vs. 2.60%, odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.88; p < .001) and extended follow-up (1.15% vs. 1.43%, OR 0.80, 95% CI 0.65-0.98; p = .032). This was driven by a lower rate of vascular complications during early follow-up in the VCD cohort (0.83% vs. 1.26%, OR 0.66, 95% CI 0.52-0.83; p < .001), and fewer bleeding events during early (0.90% vs. 1.23%, OR 0.73, 95% CI 0.58-0.92; p = .007) and extended follow-up (0.36% vs. 0.59%, OR 0.61, 95% CI 0.43-0.86; p = .005). CONCLUSION: Following AF ablation, femoral venous hemostasis with a VCD was associated with reduced complications compared with hemostasis without a VCD.

Vascular complications secondary to resuscitative endovascular balloon occlusion of the aorta placement at a Level 1 Trauma Center.

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is designed to manage severe hemorrhagic shock. Popularized in medical care during military conflicts, the concept has emerged as a lifesaving technique that is utilized around the United States. Literature on risks of REBOA placement, especially vascular injuries, are not well-reported. Our goal was to assess the incidence of vascular injury from REBOA placement and the risk factors associated with injury and death among these patients at our institution. METHODS: We performed a retrospective cohort study of all patients who underwent REBOA placement between September 2017 and June 2022 at our Level 1 Trauma Center. The primary outcome variable was the presence of an injury related to REBOA insertion or use. Secondary outcomes studied were limb loss, the need for dialysis, and mortality. Data were analyzed using descriptive statistics, χ2, and t-tests as appropriate for the variable type. RESULTS: We identified 99 patients who underwent REBOA placement during the study period. The mean age of patients was 43.1 ± 17.2 years, and 67.7% (67/99) were males. The majority of injuries were from blunt trauma (79.8%; 79/99). Twelve of the patients (12.1%; 12/99) had a vascular injury related to REBOA placement. All but one required intervention. The complications included local vessel injury (58.3%; 7/12), distal embolization (16.7%; 2/12), excessive bleeding requiring vascular consult (8.3%; 1/12), pseudoaneurysm requiring intervention (8.3%; 1/12), and one incident of inability to remove the REBOA device (8.3%; 1/12). The repairs were performed by vascular surgery (75%; 9/12), interventional radiology (16.7%; 2/12), and trauma surgery (8.3%; 1/12). There was no association of age, gender, race, and blunt vs penetrating injury to REBOA-related complications. Mortality in this patient population was high (40.4%), but there was no association with REBOA-related complications. Ipsilateral limb loss occurred in two patients with REBOA-related injuries, but both were due to their injuries and not to REBOA-related ischemia. CONCLUSIONS: Although vascular complications are not unusual in REBOA placement, there does not appear to be an association with limb loss, dialysis, or mortality if they are addressed promptly. Close coordination between vascular surgeons and trauma surgeons is essential in patients undergoing REBOA placement.

In-Hospital Risk Factors for Reintervention and Amputation in Brachial Arterial Trauma.

INTRODUCTION: Brachial artery trauma is a rare but potentially devastating injury. There is little data regarding risk factors for reintervention and amputation prevention in this population, as well as anticoagulant (AC) and antiplatelet (AP) regimens and outcomes after discharge in trauma patients with vascular injuries requiring repair. This study aims to identify in-hospital risk factors for reintervention and amputation and stratify outcomes of follow-up by discharge AC or AP regimen. METHODS: The AAST Prospective Observational Vascular Injury Trial database was queried for all patients who underwent traumatic brachial arterial repair from 2013 to 2022. Patients were evaluated by need for reintervention, amputation, and outcomes at follow-up by AC or AP regimen. RESULTS: Three hundred and eleven patients required brachial repair, 28 (9%) required reoperation, and 8 (2.6%) required amputation. High injury severity score and an increased number of packed red blood cells and platelets showed a significant increase for reoperation and amputation. Damage control and shunt use were significant for the need to reoperate. Seventy-four percent (221/298) of patients were discharged with postoperative AC or AP regimens. There was no significant difference of short-term follow-up by type of AC or AP regimen. CONCLUSIONS: Damage control and temporary shunt may lead to additional operations but not an increase in amputations. However, anticoagulation intraoperatively and postoperatively does not appear to play a significant role in reducing reintervention. It also suggests that there is no increase in short-term follow-up complications with or without AC or AP therapy.

Endothelial dysfunction and cardiovascular risk in post-COVID-19 patients after 6- and 12-months SARS-CoV-2 infection.

INTRODUCTION: SARS-CoV-2 infection causes severe endothelial damage, an essential step for cardiovascular complications. Endothelial-colony forming cells (ECFCs) act as a biomarker of vascular damage but their role in SARS-CoV-2 remain unclear. The aim of this study was to assess whether the number of ECFCs and angiogenic biomarkers remained altered after 6 and 12-months post-infection and whether this imbalance correlated with the presence of long-COVID syndrome and other biological parameters measured. METHODS: Seventy-two patients were recruited at different time-points after overcoming COVID-19 and thirty-one healthy controls. All subjects were matched for age, gender, BMI, and comorbidities. ECFCs were obtained from peripheral blood and cultured with specific conditions. RESULTS: The results confirm the presence of a long-term sequela in post-COVID-19 patients, with an abnormal increase in ECFC production compared to controls (82.8% vs. 48.4%, P < 0.01) that is maintained up to 6-months (87.0% vs. 48.4%, P < 0.01) and 12-months post-infection (85.0% vs. 48.4%, P < 0.01). Interestingly, post-COVID-19 patients showed a significant downregulation of angiogenesis-related proteins compared to controls indicating a clear endothelial injury. Troponin, NT-proBNP and ferritin levels, markers of cardiovascular risk and inflammation, remained elevated up to 12-months post-infection. Patients with lower numbers of ECFC exhibited higher levels of inflammatory markers, such as ferritin, suggesting that ECFCs may play a protective role. Additionally, long-COVID syndrome was associated with higher ferritin levels and with female gender. CONCLUSIONS: These findings highlight the presence of vascular sequela that last up to 6- and 12-months post-infection and point out the need for preventive measures and patient follow-up.

Exploring platelet-derived microvesicles in vascular regeneration: unraveling the intricate mechanisms and molecular mediators.

Microvesicles (MVs) serve as biomarkers and transmitters for cell communication and also act as essential contributors to diseases. Platelets release microvesicles when activated voluntarily, making them a significant source. Platelet-derived microvesicles possess a range of characteristics similar to their parent cells and were shown to exert regulatory impacts on vascular and immunological cells. MVs can alter the activity of recipient cells by transferring their internal components. Furthermore, it has been identified that microvesicles derived from platelets possess the ability to exert immunomodulatory effects on different kinds of cells. Recent research has shown that microvesicles have a bidirectional influence of harming and preventing the receptor cells. Nevertheless, the specific characteristics of the active molecules responsible for this phenomenon are still unknown. The primary focus of this review was to explore the mechanism of vascular tissue regeneration and the specific molecules that play a role in mediating various biological effects throughout this process. These molecules exert their effects by influencing autophagy, apoptosis, and inflammatory pathways.

Macro- and microscopic changes in veins with short-term central venous catheters: an observational autopsy study.

BACKGROUND: Centrally inserted central catheters (CICCs) are indispensable in modern healthcare, but unfortunately, come with complications. Catheter-related thrombosis is a well-known complication reported to occur in 5-30% of patients with CICC. There is a paucity of studies that report the incidence of catheter-related thrombosis after the introduction of real-time ultrasound insertion guidance as clinical practice. This study aimed to demonstrate any pathological macro- or microscopic changes in the vein wall associated with CICCs. METHODS: The study was approved by the Swedish Ethical Review Authority and was conducted at a large university hospital. The study included 12 patients with a short-term CICC who were subject to autopsies. Vessels with inserted catheters were macroscopically and microscopically examined. RESULTS: In total, seven female and five male patients with a median age of 70 (interquartile range 63-76) were included. With one exception, all patients received routine thromboprophylaxis throughout the period with CICC. Most inserted CICCs were 9.5 French (54%) and were inserted in the internal jugular vein (92%). The median time with CICC was seven days (interquartile range 1.8-20). At autopsy, thrombi were observed in all cases (100%), macroscopically and microscopically, attached to the distal portion of the CICC and/or the adjacent vessel wall. Inflammatory changes in the vessel walls were seen in all cases, and varying degrees of fibrosis were demonstrated in eight cases (67%). CONCLUSIONS: This autopsy study demonstrated that catheter-related thrombus formation with adjacent inflammatory and fibrotic vessel wall thickening was very common, despite a limited period of catheter use. The consequences of these findings are important, as thrombi may cause pulmonary embolism and possibly lead to catheter-related infections, and since inflammatory and fibrotic vessel wall thickening may evolve into chronic venous stenosis. Furthermore, the findings are a cause of concern, as CICCs are indispensable in modern healthcare and complications may be masked by the general disease that was the indication for CICC insertion.

A novel surgical approach using the "lateral corridor" for minimally invasive oblique lumbar interbody fusion at L5-S1: a clinical series and technical note.

PURPOSE: The minimally invasive oblique lumbar interbody fusion (MI-OLIF) L5-S1 was introduced to overcome the limitations of conventional fusion techniques, however, MI-OLIF is not possible using the standard method due to vascular structures in some cases. We aimed to introduce the "lateral corridor" and report the details of the surgical technique with a clinical case series. METHODS: We utilized the lateral access route of the left common iliac vein and named it the "lateral corridor", to distinguish the technique from the standard technique (central corridor). The type and frequency of branch vessels that required additional manipulations were reviewed, and the frequency of intraoperative vascular injury was investigated. RESULTS: Among the 107 patients who underwent MI-OLIF L5-S1, 26 patients (24.3%) who received the "lateral corridor" technique were included. Branch vessel ligation was required in 42.3% of the patients. The types of branch vessels that required ligation were seven cases (26.9%) of the iliolumbar vein (ILV) and six cases (23.1%) of ascending lumbar vein (ALV). The ILV and ALV were ligated in two cases. None of the patients developed intraoperative vascular injuries. CONCLUSION: We introduced the "lateral corridor" as an alternative approach for MI-OLIF L5-S1, implemented it in 24.3% of the patient cohort, and reported favorable outcomes devoid of vascular complications. The "lateral corridor" necessitated ligation of the ILV or ALV in 42.3% of cases. The "lateral corridor" approach appears to be a promising surgical technique, offering feasibility even in instances where the vascular anatomy precludes the employment of the conventional approach.

Traumatic proximal tibiofibular fracture and dislocation.

BACKGROUND: Traumatic proximal tibiofibular fracture and dislocation (PTFD) have been rarely studied and are easily missed in clinical practice. PTFD is considered a marker of severely traumatized knees. The purpose of this study was to retrospectively analyze the incidence and impact of PTFD in traumatized knees with vascular injury. METHODS: Patients with knee trauma and vascular injury were included from January 2022 to October 2023. X-rays and CT scans of included patients were retrospectively analyzed to determine the presence of PTFD. Patients were further divided into PTFD group and non-PTFD group for further comparative analysis. RESULTS: A total of 27 patients (28 limbs) were included. Incidence of PTFD was 39.3% (11/28) in traumatic knee with vascular injury, including 8 anterolateral dislocations and 3 posteromedial dislocations. PTFD group had significantly more limbs with open injuries compared with non-PTFD group (10/11 VS 7/17, p<0.05). Amputation rate of PTFD group was as high as 40% (4/10), compared to 23.5% (4/17) in non-PTFD group. However, the difference between two groups was not statistically significant (p>0.05). CONCLUSIONS: PTFD was easily overlooked or missed. In traumatized knees with vascular injury, incidence of PTFD was high. The presence of PTFD might indicate severe knee trauma and the possibility of open injury. Although there was no significant difference compared with non-PTFD group, PTFD group had a relatively high amputation rate of 40%.

Cardiovascular collapse during laparoscopy: a brief overview.

This review article considers the physiology, differential diagnosis and immediate management of vasovagal response, vascular injury and carbon dioxide embolism caused during the creation of the laparoscopic pneumoperitoneum. These pathologies account for over half of all laparoscopic complications and therefore, by taking a systematic approach to these possibly life-threatening events, laparoscopy can become even safer.

Indocyanine green fluorescence visualizes landmark arteries for endoscopic sinus and skull base surgery.

OBJECTIVE: Landmark arteries during endoscopic sinus surgery are currently identified on the basis of anatomy, CT imaging and navigation, and Doppler flowmetry. However, the advantage of intraoperative fluorescence imaging during endoscopic sinus surgery has not been demonstrated. This study aimed to investigate whether Indocyanine Green (ICG) is useful for visualizing landmark arteries during endoscopic sinus and skull base surgery. METHODS: Eight patients who underwent endoscopic sinus and pituitary surgeries and consented to study participation were included. After planned procedures were performed as usual, landmark arteries were examined by ICG endoscope. Recorded video and preoperative CT images were analyzed for identification of five landmark arteries: anterior ethmoidal artery (AEA), posterior ethmoidal artery (PEA), internal carotid artery (ICA), sphenopalatine artery (SPA), and postnasal artery (PNA). Identification of arteries was evaluated three grades: identifiable, locatable, unrecognizable. RESULTS: Eight patients and eleven sides were evaluated. The ICG dose was 2.5 mg/body and a single shot was sufficient for evaluation. 100 % of AEA was identified (9/9 sides), 86 % of PNA (6/7 sides), 56 % of ICA (5/9 sides), and 25 % of PEA and SPA (2/8 sides). CONCLUSION: ICG could visualize landmark arteries, even thin arteries like AEA, during endoscopic sinus and skull base surgeries. Visualization was affected by thickness of bone or soft tissue above arteries, blood clots, sensitivity setting, and angle and distance of near-infrared light irradiation. ICG visualization of landmark arteries may help avoid vascular injuries during endoscopic sinus and skull base surgeries, particularly of AEA, PNA and ICA.

Flow capabilities of arterial and drainage cannulae during venoarterial extracorporeal membrane oxygenation: A simulation model.

BACKGROUND: Large cannulae can increase cannula-related complications during venoarterial extracorporeal membrane oxygenation (VA ECMO). Conversely, the ability for small cannulae to provide adequate support is poorly understood. Therefore, we aimed to evaluate a range of cannula sizes and VA ECMO flow rates in a simulated patient under various disease states. METHODS: Arterial cannulae sizes between 13 and 21 Fr and drainage cannula sizes between 21 and 25 Fr were tested in a VA ECMO circuit connected to a mock circulation loop simulating a patient with severe left ventricular failure. Systemic and pulmonary hypertension, physiologically normal, and hypotension were simulated by varying systemic and pulmonary vascular resistances (SVR and PVR, respectively). All cannula combinations were evaluated against all combinations of SVR, PVR, and VA ECMO flow rates. RESULTS: A 15 Fr arterial cannula combined with a 21 Fr drainage cannula could provide >4 L/min of total flow and a mean arterial pressure of 81.1 mmHg. Changes in SVR produced marked changes to all measured parameters, while changes to PVR had minimal effect. Larger drainage cannulae only increased maximum circuit flow rates when combined with larger arterial cannulae. CONCLUSION: Smaller cannulae and lower flow rates could sufficiently support the simulated patient under various disease states. We found arterial cannula size and SVR to be key factors in determining the flow-delivering capabilities for any given VA ECMO circuit. Overall, our results challenge the notion that larger cannulae and high flows must be used to achieve adequate ECMO support.

The Modulation of Septic Shock: A Proteomic Approach.

Sepsis poses a significant challenge due its lethality, involving multiple organ dysfunction and impaired immune responses. Among several factors affecting sepsis, monocytes play a crucial role; however, their phenotype, proteomic profile, and function in septic shock remain unclear. Our aim was to fully characterize the subpopulations and proteomic profiles of monocytes seen in septic shock cases and discuss their possible impact on the disease. Peripheral blood monocyte subpopulations were phenotype based on CD14/CD16 expression by flow cytometry, and proteins were extracted from the monocytes of individuals with septic shock and healthy controls to identify changes in the global protein expression in these cells. Analysis using 2D-nanoUPLC-UDMSE identified 67 differentially expressed proteins in shock patients compared to controls, in which 44 were upregulated and 23 downregulated. These proteins are involved in monocyte reprogramming, immune dysfunction, severe hypotension, hypo-responsiveness to vasoconstrictors, vasodilation, endothelial dysfunction, vascular injury, and blood clotting, elucidating the disease severity and therapeutic challenges of septic shock. This study identified critical biological targets in monocytes that could serve as potential biomarkers for the diagnosis, prognosis, and treatment of septic shock, providing new insights into the pathophysiology of the disease.

Endovascular Treatment of Traumatic Vascular Injuries in the Head and Neck Region.

Background and Objectives: Traumatic vascular injuries of the head and neck pose significant treatment challenges due to the complex anatomy, diverse clinical presentation, and mostly emergent nature. Endovascular treatment increasingly complements traditional surgical approaches. This study aimed to report our 10-year experience in treating traumatic vascular injuries of the head and neck with endovascular therapy and to determine the effectiveness of endovascular treatment. Materials and Methods: A retrospective analysis of 21 patients treated for head and neck vascular injuries between May 2011 and April 2021 was performed. Patients' medical histories, clinical presentations, imaging findings, treatment materials, and clinical outcomes were reviewed. Treatments included stenting, coil embolization, and other endovascular techniques focused on hemostasis and preservation of the parent vessel. Results: The most common injuries involved the internal maxillary artery branches (n = 11), followed by the common or internal carotid artery (n = 6), vertebral artery (n = 3), and others. Endovascular treatment achieved successful hemostasis in all but one case. In five of six carotid artery injuries and two of three vertebral artery injuries, we achieved successful hemostasis while preserving the parent vessel using covered and bare stents, respectively. Conclusions: Endovascular therapy might be a useful treatment modality for traumatic vascular injuries in the head and neck region, offering efficacy, safety, and a minimally invasive approach.

Expression pattern of the bone morphogenetic protein-4 and its relationship with inflammation, vascular injury in patients suffered the arterial occlusive diseases. / åŠ¨è„‰é˜»å¡žæ€§ç–¾ç— æ‚£è€ è¡€æµ†éª¨å½¢æ€å‘ç”Ÿè›‹ç™½-4çš„è¡¨è¾¾å˜åŒ–åŠå ¶ä¸Žç‚Žç—‡å’Œè¡€ç®¡æŸä¼¤çš„ç›¸å ³æ€§.

OBJECTIVES: Bone morphogenetic protein-4 (BMP4) has been proved to be an important regulatory factor for the pathological process of atherosclerosis (AS). However, there are few related clinical studies. This study aims to investigate the levels of plasma BMP4 in patients suffering from the arterial occlusive diseases (ACD) characterized by AS, and further to test the relationship between BMP4 and inflammation and vascular injury. METHODS: A total of 38 ACD patients (the ACD group) and 38 healthy people for the physical examination (the control group) were enrolled. The plasma in each subject from both groups was obtained to test the levels of BMP4, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-10, and vascular endothelial cadherin (VE-cadherin), and the relationship between BMP4 and the detected indicators above were further analyzed. RESULTS: Compared with the control group, the patients in the ACD group displayed significant elevations in the neutrophil to lymphocyte ratio [NLR, 1.63 (1.26, 1.91) vs 3.43 (2.16, 6.61)] and platelet to lymphocyte ratio [PLR, 6.37 (5.26, 7.74) vs 15.79 (7.97, 20.53)], while decrease in the lymphocyte to monocyte ratio [LMR, 5.67 (4.41, 7.14) vs 3.43 (2.07, 3.74)] (all P<0.05). Besides, the ACD patients displayed significant elevations in plasma BMP4 [581.26 (389.85, 735.64) pg/mL vs 653.97(510.95, 890.43) pg/mL], TNF-α [254.16 (182.96, 340.70) pg/mL vs 293.29(238.90, 383.44) pg/mL], and VE-cadherin [1.54 (1.08, 2.13) ng/mL vs 1.85 (1.30, 2.54) ng/mL], and decrease in IL-10 [175.89 (118.39, 219.25) pg/mL vs 135.92 (95.80, 178.04) pg/mL] (all P<0.05). While the levels of IL-1ß remained statistically comparable between the 2 groups (P=0.09). Furthermore, the plasma BMP4 levels were further revealed to be positively correlated with the levels of IL-1ß (r=0.35), TNF-α (r=0.31) and VE-cadherin (r=0.47), while they were negatively correlated with the levels of IL-10 (r=-0.37; all P<0.01). CONCLUSIONS: After ACD occurrence, the patients' plasma concentrations of BMP4 would be upregulated, which may serve as a candidate to indicate the levels of inflammation and vascular injury.

Incidence of vascular injury associated with knee arthroplasty: series of cases.

INTRODUCTION: The incidence of vascular injury associated with knee arthroplasty is scarce, but, when they occur, the consequences are serious. OBJECTIVES: Describe the incidence of vascular lesions in our center and evaluate time to diagnosis, resolution and follow-up. MATERIALS AND METHODS: Retrospective cohort during the 2010-2019 period of primary arthroplasties and knee revision. The incidence of vascular lesions and their demographic characteristics were analyzed. Type of lesion, diagnostic method and treatment were recorded. It was evaluated in distant follow-up of pain and functionality. RESULTS: 7.940 primary total knee arthroplasty and revision surgeries were recorded, and a report of 7 emergency cases for vascular lesions was also recorded, with an incidence of 0.088%. 3 vascular lesions were caused by direct laceration of the popliteal artery, 1 case of thrombosis of the popliteal artery and 3 cases of pseudoaneurysmal lesion of the superior genicular artery. Three vascular lesions that occurred in primary arthroplasty were immediately repaired by a vascular surgeon. Pseudoaneurysm lesions and thrombosis were resolved by angiographic procedure. DISCUSSION: Vascular complications around the knee are rare. Time to diagnosis and treatment is essential. Digital angiography is a diagnostic and therapeutic tool. There are various repair techniques, whether it's embolization, cauterization, stenting or endoprosthesis; therefore, digital angiography is a safe method with a low complication rate. CONCLUSION: The incidence of vascular lesions in knee arthroplasty in our center is very low. The cases were diagnosed and resolved early, without registering subsequent complications with good functional results in distant follow-up.

Frailty is a predictor of immediate postoperative complications following surgical management of knee dislocations.

PURPOSE: To assess the utility of frailty in predicting outcomes following surgical intervention for KDs. METHODS: The NIS database was queried for non-congenital knee dislocations from 2015 to 2019 that underwent ligament repair or surgical reduction. Patients were assigned frailty scores using the mFI-11, and outcomes were compared. Multivariate regression and ROC curve analysis were used to assess the independent association of obesity, frailty, VI, and age with adverse outcomes. RESULTS: A total of 3797 patients who underwent surgical management were included. Frailty was associated with extended LOS (OR 1.353, 95% CI 1.212-1.510, p < 0.001), adverse discharge (OR 1.716, 95% CI 1.515-1.946, p < 0.001), and complications (OR 1.449, 95% CI 1.352-1.553, p < 0.001). Severely frailty was associated with extended LOS (OR 1.838, 95% CI 1.611-2.097, p < 0.001), adverse discharge (OR 2.756, 95% CI 2.394-3.171, p < 0.001), and complications (OR 1.603, 95% CI 1.453-1.768, p < 0.001). Additionally, VI was a risk factor for extended LOS (OR 7.647 (6.442-9.076) p < 0.001), complications (OR 2.065 (1.810-2.341) p < 0.001), and adverse discharge (OR 1.825 (1.606-2.075), p < 0.001). Obesity was a risk factor for extended LOS (OR 1.599 (1.470-1.739), p < 0.001) and complications (OR 1.235 (1.108-1.377), p < 0.001). AUC analysis showed that frailty was the most accurate predictor of all outcomes when compared to VI, obesity, and age. CONCLUSIONS: Frailty is superior to age and obesity, and comparable to VI, at predicting adverse outcomes following surgical management of KDs. These findings suggest that frailty assessment might play a role in risk stratification and preoperative planning for KD patients that require surgical intervention.