The application of a multidisciplinary approach in the diagnosis of Castleman disease and Castleman-like lymphadenopathies: A 20-year retrospective analysis of clinical and pathological features.

BACKGROUND: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8-MCD, POEMS-MCD and idiopathic-MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists. METHODS: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD-like histological features. RESULTS: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8-MCD, three POEMS-MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4-related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma. CONCLUSIONS: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD-like features in order to achieve a definitive diagnosis and choose the appropriate treatment.

Incidence and Fate of Refractory Type II Endoleak after EVAR: A Retrospective Experience of Two High-Volume Italian Centers.

Introduction: The aim of the present study is to report the outcome of patients presenting an isolated type II endoleak (TIIEL) requiring reintervention and to identify clinical and anatomical characteristics potentially implicated in refractory TIIEL occurrence and fate. Materials and Methods: A multicenter retrospective study on TIIEL requiring reintervention was conducted between January 2003 and December 2020. Demographic and clinical characteristics, procedural technical aspects, reinterventions, and outcomes were recorded. TIIEL determining sac expansion greater than 10 mm underwent a further endovascular procedure aiming to exclude aneurismal sac. Redo endovascular procedures were performed via endoleak nidus direct embolization and/or aortic side branches occlusion. TIIELs responsible for persisting aneurysmal sac perfusion 6 months after redo endovascular procedures were classified as "refractory" and submitted to open conversion. Results: A total of 102 TIIEL requiring reintervention were included in the final analysis. Eighty-eight (86.27%) patients were male, the mean age was 77.32 ± 8.08 years, and in 72.55% of cases the American Society of Anaesthesiologists (ASA) class was ≥3. The mean aortic diameter was 64.7 ± 14.02 mm, half of treated patients had a patent inferior mesenteric artery (IMA), and 44.11% ≥ 3 couples of patent lumbar arteries (LA). In 49 cases (48.03%) standard endovascular aneurysm repair (EVAR) procedure was completed without adjunctive maneuvers. All enrolled patients were initially submitted to a further endovascular procedure once TIIEL requiring reintervention was diagnosed; 57 patients underwent LAs or IMA embolization (55.87%), 42 transarterial aneurismal sac embolization (41.17%), and three (2.96%) laparoscopic ostial ligations of the inferior mesenteric artery. During a mean follow-up of 15.22 ± 7.57 months (7−48), a redo endovascular approach was able to ensure complete sac exclusion in 52 cases, while 50 patients presented a still evident refractory TIIEL and therefore a surgical conversion or semiconversion was conducted. At the univariate analysis refractory TIIEL patients were significantly different from those who did not develop the complication in terms of preoperative clinical, morphological characteristics, and initial EVAR procedures: coronary artery disease occurrence (p = 0.005, OR: 3.18, CI95%: 1.3−7.2); preoperative abdominal aortic aneurysm (AAA) sac diameter (p = 0.0055); IMA patency (p = 0.016, OR: 2.64, CI95%: 1.18−5.90); three or more patent LAs; isolated standard EVAR without adjunctive procedures (p > 0.0001; OR: 9.48, CI95%: 3.84−23.4). Conclusions: Our experience seems to demonstrate that it is reasonable to try to preoperatively identify those patients who will develop a refractory TIIEL after EVAR and those with a TIIEL requiring reintervention for whom a simple endovascular redo will not be enough, needing surgical conversion.

Antiphospholipid antibodies and idiopathic infertility.

OBJECTIVE: The aim of our study was to evaluate obstetric outcome of women affected by idiopathic infertility showing persistently positive antiphospholipid antibodies (aPL). METHODS: : From 2000 consecutive patients undergoing ART, we selected 151 (7.55%) clinical records of patients affected by idiopathic infertility undergoing ICSI and showing positive aPL. RESULTS: Persistently positive aPL were found in 64/151 (42.38%) of the patients: in 34/64 (53.12%) at medium/high titers (group A) and in 30/64 (46.87%) at low titers (group B). Primary or secondary antiphospholipid syndrome (APS) was diagnosed in 25% of the patients, whereas 37.5% women showed clinical and/or laboratory features suggestive of APS, but not fulfilling clinical or laboratory classification criteria. Idiopathic infertility was the sole symptom in 31.25%. In 55% of these infertile patients, a history of recurrent failures of assisted reproductive techniques (ART) was also observed. Eighty-eight percent (88.88%) of women became pregnant and 77.77% gave birth. During pregnancy, an increase of aPL values was observed in 29.41% women of group B. CONCLUSIONS: A careful selection of patients allowed us to confirm that women affected by idiopathic infertility show a high prevalence of aPL, suggesting that these autoantibodies can also affect conception. Considering pregnancy complications and thrombotic risk related to ovarian stimulation, measuring aPL can represent a valid tool to identify among infertile women undergoing ART those at higher risk of pregnancy complications potentially life-threatening for mother and the fetus. In such patients, an accurate diagnosis and an adequate therapy are related to a better ART outcome.

Factors Affecting the Outcome of Symptomatic Carotid Stenosis Surgical Treatment in a Single Center Series.

BACKGROUND: The aim of this study is to evaluate the role of preoperative ischemic brain lesion (IBL) volume, assessed by Diffusion-weighted magnetic resonance brain imaging (DW-MRI) with RAPID® processing, and surgery timing in predicting post-operative neurological outcomes in symptomatic carotid stenosis (SCS) patients treated with carotid endarterectomy (CEA). MATERIALS AND METHODS: All patients with SCS who underwent CEA between January 2010 and June 2020 were considered. IBLs ipsilateral to the stenosis were identified in the preoperative magnetic resonance brain (MRI). The volume was quantified in mL and correlated with 30-day rates of stroke and stroke/death by χ2 and receiver operating characteristic (ROC) curve. RESULTS: One hundred thirty-four patients were surgically treated for SCS during the entire study period. CEA procedures were defined as emergent, urgent, or elective if performed within 48 hr, between 48 hr and 14 days, or after 14 days from symptoms onset, respectively. Cumulative new ipsilateral stroke rate was 4,5%, with a statistically higher neurological complications in emergent patients compared to urgent and elective patients (10,6%, 1,47% and 0% respectively, P 0,039). ROC curve analysis showed a volume of 10 mL was predictive of postoperative stroke with 100% sensitivity and 80% specificity. An IBL volume >10 mL was an independent risk factor for postoperative stroke. In fact, the perioperative neurological complication rate was significantly different in high-IBL volume patients (>10 mL) compared with low-IBL volume patients (<10 mL) (P 0,003) CONCLUSIONS: The present study suggests that the optimal timing for CEA is between 48 hr and 14 days. Furthermore, the present study suggests that the presence of the IBL, by itself, is not definitively related with an unsatisfactory neurological outcome. However, an IBL higher than 10 mL should be as a reliable threshold value adverse neurological result in SCS patients.

Neutrophil-to-Lymphocyte Ratio Could Predict Outcome in Patients Presenting with Acute Limb Ischemia.

INTRODUCTION: Acute limb ischemia (ALI), classified according to Rutherford's classification (RC), is a vascular emergency burdened by high rates of mortality and morbidity. The need of new and different prognostic values for ALI has emerged, and, among all, the neutrophil-to-lymphocyte ratio (NLR) has been proven as a strong outcome predictor in vascular disease. The aim of this study is to investigate the role of preoperative NLR in predicting clinical outcomes in patients presenting acute limb ischemia. MATERIAL AND METHODS: A single-center retrospective study was conducted between January 2015 and December 2019. Demographic and clinical characteristics, procedural technical aspects, postoperative and early (up to 30-day) outcomes were recorded. All enrolled patients were categorized into low- and high-NLR at baseline, using a cut-off value of 5. Study outcomes were 30-day all-cause mortality and amputation rates. RESULTS: A total of 177 ALI patients were included in the final analysis (6 RC I, 44 RC IIA, 108 RC IIB, and 19 RC III), 115 males (65%), mean age 78.9 ± 10.4 years. Mean NLR at hospital presentation was 6.65 ± 6.75 (range 0.5-35.4), 108 (61.1%) patients presented a low-NLR, 69 (38.9%) a high-NLR. Immediate technical success was achieved in 90.1% of cases. At 30 days, freedom from amputation and freedom from death rates were 87.1% and 83.6%, respectively. At the univariate analysis, amputation (p < 0.0001, OR: 9.65, 95%CI: 3.7-25.19), mortality (p = 0.0001, OR: 9.88, 95%CI: 3.19-30.57), and cumulative event rates (p < 0.001, OR: 14.45, 95%CI: 6.1-34.21), were significantly different between the two groups according to NLR value. Multivariate analysis showed that a high baseline NLR value was an independent predictor of unfavorable outcomes in all enrolled patients. Consistently, at ROC analysis, a preoperative NLR > 5 was strongly associated with all outcome occurrences. CONCLUSION: Preoperative NLR value seems to be strongly related to ALI outcomes in this unselected population. The largest series should be evaluated to confirm present results.

Psychological Distress in Patients with Autoimmune Arthritis during the COVID-19 Induced Lockdown in Italy.

Lockdowns imposed by governments worldwide as a way to limit the spread of severe atypical respiratory syndrome-coronavirus-2 (SARS-CoV2) have had heavy psychological and economic consequences. Arthritis patients are a vulnerable population at an increased risk of peritraumatic stress. This could be due to several reasons, including the fear of shortage of medicine and difficulty receiving periodical medical checks. In the present case-control study, psychological distress in patients with autoimmune arthritis during the coronavirus disease 2019 (COVID-19) pandemic were investigated. An electronic survey was conducted to gather information on the perceived change in the emotional state, general health (GH), fatigue, joint pain, and disease activity during the lockdown, in 100 patients with autoimmune arthritis and 100 controls. Mental health status was measured using the Depression, Anxiety and Stress Scale (DASS-21). The COVID-19 Peritraumatic Distress Index (CPDI) was used to assess the frequency of peritraumatic stress disorders related to COVID-19. Patients reported a significant worsening of perceived GH (36% vs. 7%; p < 0.001), a significantly higher mean CPDI score (p < 0.001) than controls. Using multivariate analysis, arthritis patients had significantly higher CPDI scores (+3.67 points; p = 0.019), independent of depression, anxiety, and stress symptoms, comorbidities, and sociodemographic and lifestyle characteristics. Logistic regression analysis showed that the risk of reporting worsened GH was 9-fold higher in patients than controls (p < 0.001). Patients with autoimmune arthritis are at higher risk of psychological distress related to COVID-19 pandemic; thus targeted intervention should be designed to strengthen coping capacity in this vulnerable population.

Coinfection of Tuberculosis Pneumonia and COVID-19 in a Patient Vaccinated with Bacille Calmette-Guérin (BCG): Case Report.

COVID-19 is a respiratory tract infection caused by the new coronavirus SARS-COV2 that can be complicated by acute distress respiratory syndrome and multiorgan failure. In light of the high rate of mortality associated with COVID-19, pharmacological and non-pharmacological strategies to prevent the infection are currently being tested. Among non-pharmacological preventive measures, vaccines represent one of the main resources for public health. It has been suggested that Bacille Calmette-Guérin (BCG) vaccine may protect individuals against infection from COVID-19 virus, and two clinical trials addressing this question are underway. Here, we report the case of a 32-year-old woman, vaccinated with BCG when she was 1 year old, who was diagnosed with apical tuberculous pneumonia of the right lung along with COVID 19 pneumonia.

NLRP12 gene mutations and auto-inflammatory diseases: ever-changing evidence.

Systemic auto-inflammatory diseases (SAID) are a group of rare inherited conditions characterized by a dysregulation of the immune system and associated with recurrent episodes of fever and systemic inflammation. Patients with NLRP12 variants develop a rare autosomal dominant condition known as familial cold-induced autoinflammatory syndrome (FCAS2, OMIM #611762) that has been related to several different clinical manifestations including autoimmunity and immune deficiencies. In past years, several new variants have been described; however, their clinical relevance is sometimes uncertain, especially when they have been detected in healthy subjects. To our knowledge 61 patients with NLRP12 variants have been reported so far in the literature. Here we report the case of a 33-year-old woman with a history of recurrent fever and symmetric and additive poly-arthritis, fulfilling diagnostic criteria for RA, who was found to harbour two variants in the NLRP12 gene (OMIM *609648) and provide a review of the literature on similar cases.

Using INTERCheck® to Evaluate the Incidence of Adverse Events and Drug-Drug Interactions in Out- and Inpatients Exposed to Polypharmacy.

BACKGROUND: Polypharmacy exposes patients with comorbidities (particularly elderly patients) to an increased risk of drug-specific adverse events and drug-drug interactions. These adverse events could be avoided with the use of a computerized prescription support system in the primary care setting. The INTERCheck® software is a prescription support system developed with the aim of balancing the risks and benefits of polytherapy and examining drug-drug interactions. OBJECTIVES: This observational study used the INTERCheck® software to evaluate the incidence of adverse events and of drug-drug interactions in outpatients and inpatients receiving multiple medications. METHODS: Patients were randomly enrolled from the outpatient department (n = 98) and internal medicine ward (n = 46) of S. Andrea Hospital of Rome. Polypharmacological treatment was analyzed using INTERCheck® software, and the prevalence of risk indicators and adverse events was compared between the two groups. RESULTS: Polypharmacy (use of five or more drugs) applied to all except three cases among outpatients and one case among inpatients. A significant positive correlation was found between the number of medications and the INTERCheck® score (ρ = 0.67; p < 0.000001), and a significant negative correlation was found between the drug-related anticholinergic burden and cognitive impairment (r = - 0.30 p = 0.01). Based on the INTERCheck® analysis, inpatients had a higher score for class D (contraindicated drug combination should be avoided) than did outpatients (p = 0.01). The potential class D drug-drug interactions were associated with adverse events that caused hospitalization (χ2 = 7.428, p = 0.01). CONCLUSIONS: INTERCheck® analysis indicated that inpatients had a high risk of drug-drug interactions and a high percentage of related adverse drug events. Further prospective studies are necessary to evaluate whether the INTERCheck® software may help reduce polypharmacy-related adverse events when used in a primary care setting and thus potentially avoid related hospitalization and severe complications such as physical and cognitive decline.

Monocyte Subsets, Stanford-A Acute Aortic Dissection, and Carotid Artery Stenosis: New Evidences.

Monocytes are a heterogeneous cell population distinguished into three subsets with distinctive phenotypic and functional properties: "classical" (CD14++CD16-), "intermediate" (CD14++CD16+), and "nonclassical" (CD14+CD16++). Monocyte subsets play a pivotal role in many inflammatory systemic diseases including atherosclerosis (ATS). Only a low number of studies evaluated monocyte behavior in patients affected by cardiovascular diseases, and data about their role in acute aortic dissection (AAD) are lacking. Thus, the aim of this study was to investigate CD14++CD16-, CD14++CD16+, and CD14+CD16++ cells in patients with Stanford-A AAD and in patients with carotid artery stenosis (CAS). Methods. 20 patients with carotid artery stenosis (CAS group), 17 patients with Stanford-A AAD (AAD group), and 17 subjects with traditional cardiovascular risk factors (RF group) were enrolled. Monocyte subset frequency was determined by flow cytometry. Results. Classical monocytes were significantly increased in the AAD group versus CAS and RF groups, whereas intermediate monocytes were significantly decreased in the AAD group versus CAS and RF groups. Conclusions. Results of this study identify in AAD patients a peculiar monocyte array that can partly explain depletion of T CD4+ lymphocyte subpopulations observed in patients affected by AAD.

Different ST2 Serum Concentrations in Asymptomatic and Symptomatic Carotid Artery Stenosis.

BACKGROUND: ST2 represents an interesting biomarker associated with the progression of atherosclerotic disease. METHODS: This study aims to detect different ST2 serum concentrations, and intraplaque ST2 expression, in patients with symptomatic and asymptomatic carotid artery stenosis. RESULTS: The analysis of ST2 expression in the atheromatous plaque did not show any significant difference between symptomatic and asymptomatic patients (39.61 ± 35.97 vs. 38.49 ± 35.26; P = ns). ST2 serum concentrations of asymptomatic and symptomatic patients were statistically different with a concentration of 11.04 ± 8.95 ng/mL and 13.91 ± 8.01 ng/mL, respectively (P = 0.037). We observed statistical difference in serum ST2 levels between asymptomatic and symptomatic patients for cerebrovascular acute disease. No differences have been obtained in intraplaque ST2 expression. CONCLUSIONS: Soluble serum ST2 levels can be a useful biomarker to identify patients at risk for cerebrovascular events.

Regulatory T CD4 + CD25+ lymphocytes increase in symptomatic carotid artery stenosis.

BACKGROUND: Atherosclerosis is a multifactorial disease characterized by an immune-inflammatory remodeling of the arterial wall. Treg and Th17 subpopulations are detectable inside atherosclerotic plaque; however, their behavior in symptomatic carotid artery stenosis (CAS) is not fully elucidated. The aim of this study was to evaluate Th17 and Treg subsets and their ratio in patients affected by symptomatic and asymptomatic CAS. METHODS: 14 patients with symptomatic CAS (CAS-S group), 41 patients with asymptomatic CAS (CAS-A group), 32 subjects with traditional cardiovascular risk factors (RF group), and 10 healthy subjects (HS group) were enrolled. Th17 and Treg frequency was determined by flow cytometry and by histology and immunohistochemistry. Interleukin (IL)-10, IL-17, and metalloproteinase (MMP)-12 levels were measured by ELISA. RESULTS: Th17 were significantly increased in CAS-A versus RF and versus HS. Tregs were significantly increased in CAS-S versus CAS-A. Tregs/Th17 ratio was significantly reduced in CAS-A versus RF and versus HS, whereas it was significantly increased in CAS-S versus CAS-A. CONCLUSIONS: The results of this study suggest that Th17 are related to the late stages of CAS but not to plaque instability. Moreover, Treg expansion seems to represent a specific cellular pattern displayed by patients with symptomatic CAS and associated with brain injury. KEY MESSAGES Tregs expansion seems to represent a specific cellular pattern displayed by patients with symptomatic CAS and associated with CD4+ effector depletion and brain ischemic injury. Th17 lymphocytes are related to the late stages of CAS but not to plaque instability.

MMP-12 and TIMP Behavior in Symptomatic and Asymptomatic Critical Carotid Artery Stenosis.

OBJECTIVE: The aim of this study was to evaluate the levels of matrix metalloproteinase-12 (MMP-12) and tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2, TIMP-3, and TIMP-4 in patients with symptomatic and asymptomatic critical carotid artery stenosis (CAS). METHODS: We enrolled 10 patients affected by symptomatic CAS within 12 hours from onset of stroke (S group) and 30 patients with asymptomatic CAS (CAS group); 31 patients matched for age, sex, and traditional cardiovascular risk factors were used as controls (RF group). Serum levels of MMP-12, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 were assessed by Luminex. RESULTS: MMP-12 levels were significantly higher both in the S and CAS groups than in the RF group (P < .001). We found a significant decrease of all TIMPs in the CAS group compared with the RF group, whereas a significant increase was observed in the S group compared with the CAS group. A significant increase of TIMP-3 and TIMP-4 levels was observed in the S group compared with all other groups. CONCLUSION: MMP-12 is related to critical CAS both symptomatic and asymptomatic, being mainly released in the late stage of plaque development. Moreover, we suggest that a specific pattern of matrix degrading enzyme inhibitors arises during the early phases of stroke.

Stanford-A acute aortic dissection, inflammation, and metalloproteinases: a review.

Acute aortic dissection (AAD) is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year. Depending on the site of rupture, AAD is classified as Stanford-A when the ascending aortic thoracic tract and/or the arch are involved, and Stanford-B when the descending thoracic aorta and/or aortic abdominal tract are targeted. It was recently shown that inflammatory pathways underlie aortic rupture in both type A and type B Stanford AAD. An immune infiltrate has been found within the middle and outer tunics of dissected aortic specimens. It has also been observed that the recall and activation of macrophages inside the middle tunic are key events in the early phases of AAD. Macrophages are able to release metalloproteinases (MMPs) and pro-inflammatory cytokines which, in turn, give rise to matrix degradation and neoangiogenesis. An imbalance between the production of MMPs and MMP tissue inhibitors is pivotal in the extracellular matrix degradation underlying aortic wall remodelling in dissections occurring both in inherited conditions and in atherosclerosis. Among MMPs, MMP-12 is considered a specific marker of aortic wall disease, whatever the genetic predisposition may be. The aim of this review is, therefore, to take a close look at the immune-inflammatory mechanisms underlying Stanford-A AAD.

FGF-23 levels in patients with critical carotid artery stenosis.

The aim of this study was to evaluate fibroblast growth factor (FGF)-23 serum levels and its tissue expression in patients with critical carotid artery stenosis (CAS). We selected 35 patients with critical CAS undergoing carotid thromboendoarterectomy. In each patient, FGF-23 serum levels were evaluated just prior to the surgery (t0) and 30 min (t1) thereafter. Moreover, macrophage cytokines were measured at baselines. Carotid artery specimens were used for immune histochemistry. On the basis of the histology, the patients were divided into 2 groups: A with complicated plaque and B with uncomplicated plaque. Twenty complicated plaques (57.14%, group A,) and 15 uncomplicated (42.86%, group B) were evaluated: calcifications were present in 16/20 (80%) complicated plaques and in 6/15 (40%) uncomplicated plaques. An inflammatory infiltrate was observed in 26/35 carotid samples: 18/26 (69.23%) complicated and 8/26 (30.76%) uncomplicated. FGF-23(+) cells were present in 17/20 complicated (85%) and in 8 uncomplicated (53%) plaques. The double-staining immunofluorescence confirmed that macrophage cells (CD68(+)) were also positive for FGF-23 staining. Serum levels of FGF-23 were significantly higher in group A versus group B at t0 (p < 0.05) and t1 (p 0.0047). Moreover, in group A patients a significant increase of FGF-23 serum levels was observed at t1 in comparison with t0 (p 0.0011). Our results suggest that FGF-23 acts in the late phases of atherosclerotic disease and may potentially represent a marker of complications in critical CAS.

MMP-12 as a new marker of Stanford-A acute aortic dissection.

BACKGROUND: The study evaluated macrophage cytokines and macrophage metalloprotease (MMP)-12 levels in patients with Stanford-A acute aortic dissection (AAD) and in patients with critical carotid artery stenosis (CAS) compared with patients matched for age, sex, and traditional cardiovascular risk factors (RF). The aim was to identify possible early serum markers of risk for atherosclerotic complications. MATERIALS AND METHODS: We selected 65 patients: 23 AAD patients, 21 CAS patients, 21 RF, and 10 healthy subjects (HS). In each patient and control serum, levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), and MMP-12 were assessed by ELISA. RESULTS: A significant increase of MMP-12, IL-6, and IL-8 levels in AAD versus CAS was found. Moreover, MMP-12 was shown to be significantly higher in AAD versus RF, but not in CAS versus RF. A significant increase of IL-6, IL-8, MCP-1, TNF-α, and VEGF levels was observed both in AAD and CAS versus RF. CONCLUSIONS: The results suggest that MMP-12 may be considered to be a specific marker of Stanford-A AAD. Furthermore, the study confirmed that in AAD and CAS macrophage cytokines play a key role in the progression of the atherosclerotic disease towards complications.

The multitasking role of macrophages in Stanford type A acute aortic dissection.

OBJECTIVES: The aim of the study was to determine whether the release by macrophages of matrix metalloproteinase (MMP)-12 and vascular endothelial growth factor (VEGF) - leading to inflammation, matrix degradation and neoangiogenesis - represents an effective pathway that underlies aortic wall remodeling in Stanford type A acute aortic dissection (AAD). METHODS: Twenty-one consecutive patients with no genetic predisposition, with Stanford type A AAD were selected. In each patient, the levels of serum VEGF, MMP-12, serum interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1 were evaluated using enzyme-linked immunosorbent assay. Ascending aortic specimens were collected for immunohistochemical identification of any presence of inflammatory infiltrate, VEGF and CD31 expression. RESULTS: A significant increase in serum VEGF (p = 0.044), MMP-12 (p = 0.007), IL-6 (p = 0.0001), IL-8 (p = 0.0001) and MCP-1 (p = 0.0001) levels was observed in the AAD group compared to the control group. Furthermore, all AAD samples were positive for VEGF in the tunica media and showed vessel growth and immune-inflammatory infiltrate. A large number of cases (62.79%) showed inflammation at the edge of the dissection and approximately half (51.42%) showed neovessels growing at the edge of the dissection. CONCLUSIONS: The results suggest that VEGF-mediated angiogenesis and matrix degradation play a role in AAD. Finally, we believe that MMP-12 should be considered a marker of AAD.