Interventional treatment for post-thrombotic chronic venous obstruction: Progress and challenges.

Chronic venous obstruction, including nonthrombotic iliac vein lesions and post-thrombotic syndrome, presents a significant burden on patients' quality of life and health care systems. Venous recanalization and stenting have emerged as promising minimally invasive approaches, yet challenges in patient selection, procedural techniques, and long-term outcomes persist. This review synthesizes current knowledge on the interventional treatment of post-thrombotic syndrome, focusing on the evolution of endovascular techniques and stenting. Patient selection criteria, procedural details, and the characteristics of dedicated venous stents are discussed. Particular emphasis is given to the role of inflow and other anatomical considerations, along with postoperative management protocols for an optimal long-term outcome.

Endovascular treatment of chronic ilio-femoral vein obstruction with extension below the inguinal ligament in patients with post-thrombotic syndrome.

OBJECTIVE: This study aimed to evaluate postoperative outcomes of patients with chronic iliofemoral venous outflow obstruction and post-thrombotic syndrome (PTS) who underwent endovascular recanalization and stenting across the inguinal ligament. METHODS: All consecutive patients with chronic iliofemoral venous outflow obstruction and PTS were included in the analysis, from January 2018 and February 2022. Preoperative, intraoperative, and postoperative outcomes were assessed. Primary endpoints analyzed were major adverse events (MAEs) at 30 days and primary patency rate at 2 years of follow-up. Secondary endpoints assessed were secondary patency rate, target vessel revascularization, and clinical improvement evaluated with the Venous Clinical Severity Score (VCSS) classification, Villalta scale, and visual analog scale (VAS), respectively. RESULTS: A total of 63 patients (mean age, 48.1 ± 15.5 years; female, 61.9%) were evaluated. No intraoperative and 30-day postoperative complications were documented. The technical success rate was achieved at 100%. Overall, one in-stent occlusion and five in-stent restenosis were detected during follow-up. The primary patency rate was 93.7% (95% confidence interval [CI], 87.8%-99.9%) and 92.1% (95% CI, 85.6%-99%), at 1- and 2-year follow-up, respectively (Kaplan-Meier analysis). Target vessel revascularization was conducted in two cases, resulting in a secondary patency of 98.4% (95% CI, 95.4%-100%) at 2 years of follow-up. Stent fracture and/or migration were not observed during follow-up. A significant clinical improvement in the patient's quality of life was documented. The median improvement of VCSS and Villalta scores were 4 (interquartile range, 2-7; P = .001), and 3 (interquartile range, 1.5-5; P = .001) vs baseline at the last follow-up. Overall, pain reduction of 17 mm on the VAS scale was documented at 2 years of follow-up. At multivariate analysis, presence of trabeculation into the femoral vein and deep femoral vein (odds ratio, 1.89; 95% CI, 0.15-6.11; P = .043), and Villalta scale >15 points at admission (odds ratio, 1.89; 95% CI, 0.15-6.11; P = .043) were predictive for in-stent occlusion during the follow-up. CONCLUSIONS: The use of a dedicated venous stent across the inguinal ligament was safe and effective for the treatment of symptomatic iliofemoral venous disease with acceptable primary and secondary patency rates at 2 years of follow-up.

Factors influencing recurrent varicose vein formation after radiofrequency thermal ablation for truncal reflux performed in two high-volume venous centers.

OBJECTIVE: Recanalization of the saphenous vein trunk after endovenous radiofrequency ablation (RFA) is often associated with recurrent varicose veins (RVVs) or recanalization. This study aimed to assess the long-term results of RFA of the great saphenous vein (GSV) and identify the risk factors for GSV recanalization and RVVs during follow-up for patients presenting to dedicated outpatient vein centers. METHODS: All consecutive patients with incompetent GSVs who underwent RFA between 2009 and 2019 were retrospectively analyzed. The primary study end points were freedom from GSV recanalization and the RVV rate during follow-up. The secondary study end points were the postoperative complication rate and the risk factors for GSV recanalization and RVVs. Univariate and multivariate analyses were performed to identify the potential risk factors for GSV recanalization and RVVs. RESULTS: During the study period, 1568 limbs were treated in 1300 consecutive patients (mean age, 53.5 ± 12.9 years; 71.9% women; CEAP [clinical, etiology, anatomy, pathophysiology] C2-C6; venous clinical severity score >5). Technical success was achieved in 99.7% of cases. At a mean follow-up of 57.2 ± 25.4 months, the GSV occlusion and freedom from reintervention rates were 100% and 100% within 1 week, 97% and 95.7% at 1 year, 95.2% and 93.1% at 3 years, and 92.4% and 92.8% at 5 years, respectively. The recurrence rate was 10% (n = 158) during the follow-up period. On multivariate analysis, a direct confluence of the accessory saphenous vein into the saphenofemoral junction (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.0-7.04; P = .032), a history of pregnancy >2 (OR, 3.68; 95% CI, 1.19-11.36; P = .023), C4 (OR, 6.41; 95% CI, 1.36-30.28; P = .019), and preoperative GSV diameter >10 mm (OR, 1.82; 95% CI, 1.65-4.03; P = .043) were risk factors for GSV recanalization. Moreover, age >70 years (OR, 1.04; 95% CI, 1.01-1.06; P = .014) and incompetent perforator veins (OR, 1.17; 95% CI, 0.65-2.03; P = .018) were also risk factors for RVVs. CONCLUSIONS: RFA is a safe technique to ablate the GSV with a low complication rate and durability during 5 years of follow-up. However, patients with a high clinical score and those with direct confluence of the accessory saphenous vein into the saphenofemoral junction experienced higher long-term GSV recanalization and RVV rates.

International Union of Angiology consensus document on vascular compression syndromes.

Vascular compression syndromes (VCS) are rare diseases, but they may cause significant symptoms interfering with the quality of life (QoL) of patients who are often in their younger age. Given their infrequent occurrence, multiform clinical and anatomical presentation, and absence of dedicated guidelines from scientific societies, further knowledge of these conditions is required to investigate and treat them using modern imaging and surgical (open or endovascular) techniques. This consensus document will focus on known VCS, affecting the arterial and venous system. The position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, will show an overview of pathophysiology, diagnostic, and therapeutical approaches for patients with VCS. Furthermore, this document will provide also unresolved issues that require more research that need to be addressed in the future.

Renal perfusion with histidine-tryptophan-ketoglutarate compared with Ringer's solution in patients undergoing thoracoabdominal aortic open repair.

OBJECTIVE: The objective of this study was to compare the efficacy of renal perfusion with Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) versus enriched Ringer's solution for renal protection in patients undergoing open thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: Ninety consecutive patients scheduled for elective open TAAA repair were enrolled between 2015 and 2017 in a single-center, phase IV, prospective, parallel, randomized, double-blind trial (the CUstodiol versus RInger: whaT Is the Best Agent [CURITIBA] trial), and randomized to renal arteries perfusion with 4°C Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany; n = 45) or 4°C lactated Ringer's solution (n = 45). The incidence of acute kidney injury (AKI) in patients undergoing TAAA open surgery using Custodiol renal perfusion versus an enriched Ringer's solution was the primary end point. RESULTS: Ninety patients completed the study (45 patients in each group). The incidence of postoperative AKI was significantly lower in the Custodiol group (48.9% vs 75.6%; P = .02). In the multivariable model, only the use of Custodiol solution resulted as protective from the occurrence of any AKI (odds ratio, 0.230; 95% confidence interval, 0.086-0.614; P = .003), whereas TAAA type II extent was associated with the development of severe AKI (odds ratio, 4.277; 95% confidence interval, 1.239-14.762; P = .02). At 1-year follow-up, serum creatinine was not significantly different from the preoperative values in both groups. CONCLUSIONS: The use of Custodiol during open TAAA repair was safe and resulted in significantly lower rates of postoperative AKI compared with Ringer's solution. These findings support safety and efficacy of Custodiol in this specific setting, which is currently off-label.

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19.

Background: This study's primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods: This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray's method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results: Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8-11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7-21.0) and 9.3 (95% CI, 7.9-11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018-3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions: In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections.

International Union of Angiology Position Statement on perioperative drug and hemostasis management in vascular surgery.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee, shows an overview of coagulation system and laboratory tests, analysis of medical therapies (older and newer), medication discontinuation/restart recommendations, bridging therapy recommendations, and an overview of hemostatic agents used in the operating room.

Intraoperative neurophysiologic monitoring in thoracoabdominal aortic aneurysm surgery can provide real-time feedback for strategic decision making.

OBJECTIVES: Despite the introduction of several adjuncts to improve spinal perfusion, spinal cord ischemia (SCI) remains a devastating complication of thoracoabdominal aortic aneurysm (TAAA) repair. Our aim was to assess the effects on clinical outcome of interventions triggered by motor evoked potentials (MEP) alerts. Furthermore, we want to assess whether a multimodal intraoperative neurophysiologic monitoring (IONM) protocol is helpful for stratifying patients according to the risk of SCI at the end of the vascular phase of surgery. METHODS: We prospectively studied one-hundred consecutive patients who underwent TAAA repair. We applied a multimodal IONM including MEP, somatosensory evoked potentials (SEP) and peripheral nerve monitoring techniques. Signal deteriorations were classified as reversible/irreversible according to whether they recovered or not at the end of monitoring (EOM), set at the end of the vascular phase of surgery. Significant MEP changes drove a series of corrective measures aimed to improve spinal perfusion. RESULTS: The rate of immediate postoperative motor deficits consistent with SCI was significantly higher with irreversible MEP deteriorations compared to reversible ones. The interpretation of MEP findings at the EOM led to the development of risk categories for SCI, based on the association between MEP results and motor outcome. CONCLUSIONS: Our data seem to justify interventions made to reverse MEP deterioration in order to improve the clinical outcome. A multimodal IONM protocol could improve MEP interpretation at the end of the vascular phase of surgery, supporting the surgeon in their decision-making, before concluding vascular maneuvers.

Late surgical conversion of failed Multilayer Flow Modulator stenting in thoraco-abdominal aneurysms.

OBJECTIVES: The aim of this study was to report the outcomes of open or hybrid repair of failed thoraco-abdominal aortic aneurysm endovascular treatment with Multilayer Flow Modulator (MFM) stents. METHODS: All patients who underwent open or hybrid repair of a failed MFM aortic treatment were retrospectively analysed. Perioperative and postoperative data, as well as midterm survival, were assessed. RESULTS: Between 2013 and 2020, 39 patients received an open or hybrid conversion after endovascular treatment. Five of them [13%; 4 males; median age 68 years (interquartile range 66-76)] were previously treated with aortic MFM stents (Cardiatis, Isnes, Belgium). Among these, the median interval between index repair and conversion was 84 months (interquartile range 75-84). The median aneurysm diameter was 9.6 cm (interquartile range 8-10). Renovisceral vessels steno-occlusion was highly prevalent: 2 renal arteries were occluded; 3 coeliac trunks, 2 renal arteries and 1 superior mesenteric artery had a >70% ostial stenosis. Open standard thoraco-abdominal aneurysm conversion was performed in 3 fit patients, while a hybrid approach with visceral debranching and tube endografting was performed in 2 high-risk patients. Two patients (2 open repairs) died intraoperatively, and 1 (hybrid repair) postoperatively. The 2 successfully treated patients are alive at 4- and 34-month follow-up, respectively, with patent visceral branches. CONCLUSIONS: Open or hybrid thoraco-abdominal aortic aneurysm treatment after failed endovascular aortic repair with MFM stents might be the only surgical option to address sac enlargements and ruptures or branch-related failures. However, both procedures had a poor prognosis due to both the impaired preoperative patient's status and the surgical complexity in the presented series.

A novel evidence-based algorithm to predict thromboembolism in patients with COVID-19: preliminary data from a single-center cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterized by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalized patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19. METHODS: We prospectively followed up 180 hospitalized COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results. RESULTS: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalization. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, P<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, P=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed. CONCLUSIONS: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based on lower Pao2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages.

Comparison of mechanochemical ablation versus ligation and stripping for the treatment of incompetent small saphenous vein.

OBJECTIVE: to compare the outcomes of mechanochemical ablation (MOCA) versus saphenopopliteal junction ligation and stripping (OS) for symptomatic small saphenous vein (SSV) insufficiency. METHODS: This is a retrospective study including symptomatic SSV patients treated with MOCA using the ClariVein catheter (Merit Medical, South Jordan, Utah, USA) or OS from 2015 to 2019. RESULTS: A total of 60 limbs (73.3% women, mean age 54.7 ± 14.4 years) were treated with MOCA and 58 limbs (63.8% women, mean age 54 ± 11.6 years) with OS. At 18 months follow-up, recurrence rates were 7.5% (4/53) for MOCA vs. 5.7% (3/52) for the OS group. MOCA group was associated with less pain at first postoperative day, and an early return to work (MOCA 3.5 ± 2.3 days vs. OS 14.2 ± 3.8 days, p < .0001). No cases of leg paresthesia/dysesthesia were observed in the MOCA group, while two patients (3.4%) presented neurological symptoms after OS treatment. CONCLUSION: MOCA and OS are both safe and effective techniques for symptomatic SSV insufficiency. MOCA group demonstrated to be associated with less postoperative pain and early return to work compared to OS.

Intraoperative completion cone-beam computed tomography for the assessment of residual lesions after primary treatment of proximal venous outflow obstructions.

OBJECTIVE: Report the usefulness of completion cone-beam computed tomography (CBCT) as an adjunct tool during femoro-ilio-caval recanalization post stent placement. METHODS: Data from patients who underwent complex endovenous recanalization for chronic proximal outflow obstruction from January 2018 to May 2020 were analyzed. Two groups of patients were obtained based on the execution or not of completion CBCT. Outcomes, radiation, and contrast doses in the two groups were compared. RESULTS: Fifteen patients (9 female, mean age 46.9 ± 13.3) in the control group and ten patients (7 female, 58.3 ± 14) in the CBCT group were included. In the CBCT group, one patient underwent an intraprocedural revision due to a residual lesion. The median total kerma area product (KAPtotal) and the total volume of contrast injected were not statistically different in the two groups. CONCLUSIONS: Completion CBCT after endovenous procedures might identify residual stenosis or stent malposition without a significant increase of total contrast injected and KAPtotal.

Early and mid-term outcomes of open popliteal artery aneurysm repair with prosthetic grafts.

OBJECTIVE: The aim of the present study was to assess the early and mid-term outcomes of open surgical repair (OSR) for popliteal artery aneurysms (PAAs) with prosthetic grafts. METHODS: The pre-, intra-, and postoperative data for all the patients who had undergone OSR for PAAs with prosthetic grafts at our Institution between January 2009 and July 2019 were included in a prospectively maintained database, which was retrospectively analyzed. Primary patency was defined as uninterrupted flow (<50% stenosis) in the graft with no additional procedures performed. Secondary patency was defined as the restoration of graft patency. RESULTS: A total of 82 patients had undergone OSR for 104 PAAs (median age, 71 years; interquartile range [IQR], 67-78 years; 82 men) with prosthetic grafts. Of the 104 PAAs, 72 (68%) had been asymptomatic. The median diameter was 30 mm (IQR, 24-37 mm). A medial approach was used for 35 PAAs (34%) and a posterior approach for 69 (65%). The repairs consisted of aneurysmectomy or aneurysm ligation without removal with an interposition graft placed and end-to-end anastomoses. The median operative time was 120 minutes (IQR, 103-142 minutes). The estimated blood loss was 281 mL (IQR, 150-281 mL). Only one patient treated with a posterior approach sustained a permanent peroneal nerve lesion. A second patient also treated via the posterior approach had required surgical revision for bleeding on postoperative day 2. No temporary lesions were recorded. No early amputations were required, and no perioperative deaths occurred. The median length of stay was 3 days (IQR, 3-4 days). An expanded polytetrafluoroethylene graft was used in 92 cases (88%) and a Dacron graft in 12 cases (12%). An 8-mm graft was used in 64 cases (62%). The median follow-up was 34.6 months (IQR, 8.5-62.7 months). No related mortality occurred. Of the 104 PAAs, 19 had required reintervention, with primary and secondary patency of 78% and 88% at 3 years, respectively. The median interval to reintervention was 28.3 months. CONCLUSIONS: OSR of PAAs with prosthetic grafts is safe and feasible, with good mid-term results and satisfactory primary and secondary patency at 3 years.

Open or endovascular treatment of downstream thoracic or thoraco-abdominal aortic pathology after frozen elephant trunk: perioperative and mid-term outcomes.

OBJECTIVES: The aim of this study was to evaluate the outcomes of open and endovascular treatment of downstream thoracic or thoraco-abdominal aortic pathology in patients who underwent previous frozen elephant trunk (FET). METHODS: Data were retrieved to evaluate mortality, cardiac, pulmonary, cerebrovascular, renal and spinal cord major adverse events, early- and mid-term reintervention and survival rates. The Society for Vascular Surgery endovascular reporting standards were used. RESULTS: From 2011 to 2020, 48 patients (36 males, median age 60 years) underwent downstream aortic repair at a median of 18 months (interquartile range: 6-57) after the initial FET. Twenty-eight patients (58.3%) received open and 20 (41.7%) endovascular repair. The overall 30-day mortality was 6.3% and the initial clinical success was 88%, with no inter-group differences (P = 0.22 and 0.66 respectively). Six spinal cord deficits were recorded (13%): 3 (6.3%) were permanent. The major adverse events incidence was lower in the endovascular cohort [4 (20%) vs 14 (50%); P = 0.047], mainly due to a lower rate of grade ≥2 respiratory complications (5% vs 42.9%; P = 0.004). Assisted primary clinical success at 5 years was higher in the endovascular group (95% vs 68%, P = 0.022); freedom from reintervention at competing risk analysis (P = 0.3) and overall survival at Kaplan-Meier curves (log-rank P = 0.29) were similar. CONCLUSIONS: Downstream aortic repair after FET is feasible with both open and endovascular repair with acceptable mortality and permanent paraplegia rates. The endovascular approach has potential perioperative and mid-term advantages, but long-term durability has to be further investigated in larger cohorts.

An Uncommon Variant of Nutcracker Syndrome Secondary to Left Renal Vein Compression Between the Right Renal Artery and The Proper Hepatic Artery.

Nutcracker syndrome refers to the compression of the left renal vein between the abdominal aorta and the superior mesenteric artery. The subsequent venous congestion of the left kidney, when symptomatic, could be associated with left flank pain, hematuria, varicocele, dyspareunia, dysmenorrhea, and proteinuria. Here we describe a 42-year-old female patient with simultaneous Dunbar syndrome and a rare variant of nutcracker syndrome in which the left renal vein (LRV) compression is secondary to the unusual path of the vein between the right renal artery and the proper hepatic artery. For both the nutcracker syndrome and the Dunbar syndrome, open approach by median mini-laparotomic access for transposition of LRV, and resection of the diaphragmatic pillars and arcuate ligament was attempted. During the intervention, due to anatomical issues, the LRV transposition was converted to endovascular stenting of the LRV, moreover the implanted stent was transfixed with an external non-absorbable suture to avoid migration. At the 12 months follow-up the patient was asymptomatic, and the duplex scan confirmed the patency of the celiac trunk without re-stenosis and a correct position of the LRV stent with no proximal or distal migration.

Symptomatic internal carotid artery dissection and kinking in a patient with fibromuscular dysplasia.

Isolated dissection of the internal carotid artery (ICA) is rare in young patients and is a cause for strong suspicion of fibromuscular dysplasia (FMD), especially when associated with artery elongation and tortuosity. The natural history of cerebrovascular FMD is unknown and management of symptomatic patients can be challenging. We report the case of a 44-year-old female patient with a history of transient ischemic attack in the absence of cardiovascular risk factors, associated with an isolated left ICA dissection and kinking. Carotid duplex ultrasound confirmed the diagnosis of dissection and demonstrated severe stenosis of the left ICA. The patient underwent surgical repair and histopathological evaluation confirmed the diagnosis of FMD with dissection. An autogenous great saphenous vein bypass was performed and the patient had an uneventful recovery. Cervical carotid artery dissection can be related to underlying arterial pathologies such as FMD, and the presence of ICA tortuosity highlights certain peculiarities for optimal management, which might be surgical.

A dissecção isolada da artéria carótida interna em pacientes jovens é rara, e a displasia fibromuscular deve ser altamente suspeitada principalmente quando estiver associada a alongamento e tortuosidade da artéria. A história natural da displasia fibromuscular cerebrovascular é desconhecida, e o manejo de pacientes sintomáticos pode ser desafiador. Apresentamos o caso de uma paciente de 44 anos com histórico de ataque isquêmico transitório sem fatores de risco cardiovasculares, associado a dissecção e acotovelamento isolados da artéria carótida interna esquerda. O ultrassom duplo das carótidas confirmou o diagnóstico de dissecção e demonstrou estenose grave na artéria carótida interna esquerda. A paciente foi submetida a reparo cirúrgico, e a avaliação histopatológica confirmou o diagnóstico de displasia fibromuscular com dissecção. Foi realizada cirurgia de ressecção do segmento e reconstrução com veia safena magna autógena, e a paciente se recuperou sem complicações. A dissecção da artéria carótida cervical pode estar relacionada a doenças arteriais subjacentes, como a displasia fibromuscular, e a presença da tortuosidade da artéria carótida interna destaca algumas particularidades no manejo ideal, o qual pode ser cirúrgico.

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7.

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.

Doppler Ultrasound Monitoring of Echogenicity in Asymptomatic Subcritical Carotid Stenosis and Assessment of Response to Oral Supplementation of Vitamin K2 (PLAK2 Randomized Controlled Trial).

BACKGROUND: Plaque composition may predict the evolution of carotid artery stenosis rather than its sole extent. The grey scale median (GSM) value is a reproducible and standardized value to report plaque echogenicity as an indirect measure of its composition. We monitored plaque composition in asymptomatic subcritical carotid stenosis and evaluated the effect of an oral modulating calcification factor (vitamin K2). METHODS: Carotid plaque composition was assessed by GSM value. Monitoring the effects of standard therapy (acetylsalicylic acid and low-medium dosage statin) (acetylsalicylic acid (ASA) arm) or standard therapy plus vitamins K2 oral supplementation (ASA + K2 arm) over a 12 months period was conducted using an ultrasound scan in a prospective, open-label, randomized controlled trial (PLAK2). RESULTS: Sixty patients on low-medium dosage statin therapy were enrolled and randomized (30 per arm) to either ASA + K2 or ASA alone. Thirty-seven patients (61.6%) showed at 12 months a stable plaque with a mean increase in the GSM value in respect to the baseline of 2.6% with no differences between the two study arms (p = 0.66). Fifteen patients (25%) showed an 8% GSM value reduction respect the baseline with no differences between the two study arms (p = 0.99). At multivariable analysis, the adjusted mean (95% confidence interval) GSM change per month from baseline was greater in the ASA + K2 arm (-0.55 points, p = 0.048) compared to ASA alone (-0.18 points, p = 0.529). CONCLUSIONS: Carotid plaque composition monitoring through GSM value represents a laborious procedure. Although its use may not be applied to everyday practice, a specific application consists in evaluating the effect of pharmacological therapy on plaque composition. This 12 months randomized trial showed that the majority of subcritical asymptomatic carotid plaque on treatment with low-medium dosage statin presented a stable or increased echogenicity. Although vitamin K2 beyond standard therapy did not determine a significant change in plaque composition, for those who presented with GSM reduction it did enhance a GSM monthly decline.

Pulmonary Vascular Thrombosis in COVID-19 Pneumonia.

OBJECTIVES: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. DESIGN: Observational study. SETTING: Medical and intensive care unit wards of a teaching hospital. PARTICIPANTS: The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. INTERVENTIONS: Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. CONCLUSIONS: The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia.