Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients.

BACKGROUND: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. METHODS: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). RESULTS: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1). CONCLUSIONS: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

Severity and Changes in OCD Dimensions during COVID-19: A Two-Year Longitudinal Study.

BACKGROUND: The COVID-19 pandemic appears to be associated with a worsening of obsessive-compulsive symptoms in both young people and adults with OCD and it is necessary to analyze the variables involved in this worsening over time. The main aim of this study was to examine long-term changes in total severity and obsessive-compulsive dimensions in obsessive-compulsive patients during the COVID-19 pandemic. METHOD: A total 250 OCD patients were selected from various associations, clinical centers and hospitals. We discarded 75 as they did not meet the inclusion criteria. A total of 175 obsessive-compulsive participants aged between 16 and 58 years old (M = 33.33, SD = 9.42) were evaluated in obsessive-compulsive symptom severity and dimensions OCD assessed using the Y-BOCS and D-YBOCS scales in T1 (April-June 2020) and in T2 (March-April 2022). The evaluation was carried out through an online survey and face-to-face with a professional clinician at both time points. RESULTS: Intragroup differences in severity were observed, reaching higher scores for patients with contamination, somatic, aggressive and religious. Some patients changed their main dimension, increasing the percentage of patients with contamination and somatic obsessions. CONCLUSIONS: COVID-19 was associated with both changes in severity and also affected some dimensions more than others, particularly those related to the virus itself (contamination and somatic).

Are all patients with sapheno-femoral junction incompetence the same? An ultrasound analysis to potentially predict recurrence after invasive treatments.

The sapheno-femoral junction (SFJ) and the great saphenous vein (GSV) are recognized as one of the main sources of reflux in chronic venous disease. Moreover, reflux time is considered as the main parameter to characterize GSV disease. Despite this, it is well-known in the clinical practice that not all patients with SFJ/GSV reflux are similar, in terms of disease severity and degree. Some other anatomical findings, such as SFJ and GSV diameters, as well as the absence/incompetence of suprasaphenic femoral valve (SFV) might be of interest to better "quantify" the disease severity. The aim of this paper is to describe, through a duplex scan analysis, the relationship between SFJ incompetence, GSV/SFJ diameter and SFV absence/incompetence, to identify if there are patients with "severe" GSV disease and a potential higher recurrence rate after invasive treatments.

A Single Center Retrospective Cohort Study Comparing Different Anticoagulants for the Treatment of Catheter-Related Thrombosis of the Upper Extremities in Women With Gynecologic and Breast Cancer.

Background: Catheter-related thrombosis (CRT) of the upper extremities is a frequent complication among cancer patients that carry a central venous catheter (CVC) and may lead to pulmonary embolism (PE) and loss of CVC function. Despite its clinical impact, no anticoagulant treatment scheme has been rigorously evaluated in these patients. In addition, there is no proven evidence that direct oral anticoagulants (DOACs) are efficacious and safe in this setting because cancer patients with CRT of the upper extremities were not included in the clinical trials that led to the approval of DOACs for the treatment of cancer-associated venous thromboembolism (VTE). Methods: We performed a single center retrospective cohort study on women with gynecologic or breast cancer treated with either low-molecular-weight heparin, fondaparinux, or DOACs for CRT of the upper extremities. Only patients who received anticoagulation at the proper therapeutic dose and for at least 3 months were included in the analysis. Effectiveness was evaluated in terms of preservation of line function, residual thrombosis, and recurrence of VTE (including PE). Safety was evaluated in terms of death, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB). Results: We identified 74 women who fulfilled the criteria to be included in the analysis. Of these, 31 (41.9%) had been treated with fondaparinux, 21 (28.4%) with enoxaparin, and 22 (29.7%) with the DOAC edoxaban. We found no differences between patients treated with the three different therapeutic approaches, in terms of preservation of line function, incidence of residual thrombosis, and VTE recurrence (including PE). Safety was similar as well, with no MBs recorded in any treatment group. Conclusion: These results, although retrospective and based on a relatively small sample size, indicate that, in women with gynecologic or breast cancer, CRT of the upper extremities may be treated with similar effectiveness and safety with fondaparinux, enoxaparin, and edoxaban. Further studies are needed to substantiate these findings.

Pulmonary Embolism in COVID-19 Patients: Which Diagnostic Algorithm Should We Use?

Introduction: Although pulmonary embolism (PE) is a frequent complication of the clinical course of COVID-19, there is a lack of explicit indications regarding the best algorithm for diagnosing PE in these patients. In particular, it is not clear how to identify subjects who should undergo computed tomography pulmonary angiography (CTPA), rather than simply X-ray and/or high resolution computed tomography (HRCT) of the chest. Methods: We retrospectively analyzed COVID-19 patients who presented to the Emergency Department (ED) of our University hospital with acute respiratory failure, or that developed acute respiratory failure during hospital stay, to determine how many of them had a theoretical indication to undergo CTPA for suspected PE according to current guidelines. Next, we looked for differences between patients who underwent CTPA and those who only underwent X-ray and/or HRCT of the chest. Finally, we determined whether patients with a confirmed diagnosis of PE had specific characteristics that made them different from those with a CTPA negative for PE. Results: Out of 93 subjects with COVID-19 and acute respiratory failure, 73 (78.4%) had an indication to undergo CTPA according to the revised Geneva and Wells scores and the PERC rule-out criteria, and 54 (58%) according to the YEARS algorithm. However, in contrast with these indications, only 28 patients (30.1%) underwent CTPA. Of note, they were not clinically different from those who underwent X-ray and/or HRCT of the chest. Among the 28 subjects who underwent CTPA, there were 10 cases of PE (35.7%). They were not clinically different from those with CTPA negative for PE. Conclusions: COVID-19 patients with acute respiratory failure undergo CTPA, X-ray of the chest, or HRCT without an established criterion. Nonetheless, when CTPA is performed, the diagnosis of PE is anything but rare. Validated tools for identifying COVID-19 patients who require CTPA for suspected PE are urgently needed.

Inferior selective crossectomy for great saphenous vein incompetence: Our experience.

OBJECTIVE: To describe the mid-term outcome after inferior selective crossectomy in a subset of patients with symptomatic chronic venous disease and both great saphenous vein and suprasaphenic valve incompetence.Methodsː Retrospective analysis of prospectively collected data was conducted. During an eight-year period, 1095 ligations of all saphenofemoral junction inferior tributaries and great saphenous vein stripping were performed in 814 Clinical, Etiology, Anatomy, Pathophysiology C2-C6 patients. Duplex ultrasound follow-up examinations were performed after 30 days, 6 months, and 2 years, and saphenofemoral junction hemodynamic patterns and varicose veins recurrence rates were evaluated. RESULTS: Two hundred and twenty patients completed the two-year follow-up period. At the 30-day Duplex ultrasound evaluations, two different hemodynamic patterns were described. Type 1, with physiological drainage of saphenofemoral junction superior tributaries, was observed in 214 patients. Type 2, without flow in saphenofemoral junction superior tributaries, was observed in six patients. Overall varicose vein recurrence rates were 0, 2.3, and 2.7% at the 30-day, 6-month, and 2-year follow-up examinations, respectively. At the two-year follow-up, Type 1 patients showed 0% varicose vein recurrence, while Type 2 patients showed 100%.Conclusionsː Inferior selective crossectomy seems to be a valid and safe option in case of both suprasaphenic valve and great saphenous vein incompetence. Duplex ultrasound evaluation, according to our protocol, allows us to identify two different saphenofemoral junction hemodynamic patterns that could predict varicose vein recurrence at mid-term. An optimal stump washing after inferior selective crossectomy, warranted by patency and large caliber saphenofemoral junction superior tributaries, seems to be the key point in preventing varicose vein recurrence in this context. However, large prospective studies regarding saphenofemoral junction modifications and varicose vein recurrence are needed to confirm these preliminary observations.

Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo.

Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker αSMA, with direct connections between αSMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans.

Anticoagulant therapy in the treatment of splanchnic vein thrombosis associated to acute pancreatitis: a 3-year single-centre experience.

Splanchnic vein thrombosis (SVT) is a possible complication of acute pancreatitis (AP). There are no precise guidelines on the use of anticoagulant therapy (AT) in these patients. The aim of the study was to determine the safety and the efficacy of AT in AP-associated SVT. Two hundred twenty-one patients were retrospectively and consecutively enrolled from the Pancreatic Outpatient Clinic of the "A. Gemelli" hospital. Patients had a diagnosis of AP and a diagnostic imaging to evaluate whether they had or not SVT. Twenty-seven out of 221 AP patients had SVT (12.21%) and AT therapy was administered to 16 patients (59.3%), for 5.2 ± 2.2 months. A therapeutic dose of low molecular weight heparin was administered (100 UI/kg b.i.d.) at the diagnosis, with fondaparinux 7.5 mg/day, or vitamin K antagonist, or the novel direct oral anti-coagulants, upon discharge. The presence of SVT resulted significantly associated to male sex (p = 0.002). The recanalization rates were 11/16 (68.7%) in patients who received AT, and 3/11 (27.3%) in patients who did not receive it. There was a significant difference between the recanalization rates with and without AT (p = 0.03, OR 5.87). No SVT recurrence was registered during follow-up. No treated patient developed haemorrhagic complications after AT. No deaths were recorded, either in the group undergoing AT or in the one that was not. In conclusion, AT in AP-associated SVT appears to be safe and effective; yet prospective clinical trials are needed to confirm our results.

The Hedgehog Signaling Pathway in Ischemic Tissues.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in the ischemic condition is also presented.

Differences in Clinical Presentation, Rate of Pulmonary Embolism, and Risk Factors Among Patients With Deep Vein Thrombosis in Unusual Sites.

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism with heterogeneous signs and symptoms, unknown rate of pulmonary embolism (PE), and poorly defined risk factors. We conducted a retrospective analysis of 107 consecutive cases of USDVTs, discharged from our University Hospital over a period of 2 years. Patients were classified based on the site of thrombosis and distinguished between patients with cerebral vein thrombosis, jugular vein thrombosis, thrombosis of the deep veins of the upper extremities, and abdominal vein thrombosis. We found statistically significant differences between groups in terms of age (P < .0001) and gender distribution (P < .05). We also found that the rate of symptomatic patients was significantly different between groups (P < .0001). Another interesting finding was the significant difference between groups in terms of rate of PE (P < .01). Finally, we found statistically significant differences between groups in terms of risk factors for thrombosis, in particular cancer (P < .01). Unprovoked cases were differently distributed among groups (P < .0001). This study highlights differences between patients with USDVT, which depend on the site of thrombosis, and provides data which might be useful in clinical practice.

The 9p21 Rs 1333040 polymorphism is associated with coronary microvascular obstruction in ST-segment elevation myocardial infarction treated by primary angioplasty.

BACKGROUND: Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) leads to higher incidence of both early and late complications. A number of single nucleotide polymorphisms in 9p21 chromosome have been shown to affect angiogenesis in response to ischaemia. In particular, Rs1333040 with its three genotypic vriants C/C, T/C and T/T might influence the occurrence of MVO after pPCI. METHODS: We enrolled ST-elevation myocardial infarction (STEMI) patients undergoing pPCI. The Rs1333040 polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism using restriction endonucleases (Bsml). Two expert operators unaware of the patients' identity performed the angiographic analysis; collaterals were assessed applying Rentrop's classification. Angiographic MVO was defined as a post-pPCI Thrombolysis In Myocardial Infarction (TIMI)<3 or TIMI 3 with myocardial blush grade 0 or 1, whereas electrocardiographic MVO was defined as ST segment resolution <70% one hour after pPCI. RESULTS: Among our 133 STEMI patients (mean age 63 ± 11 years, men 72%), 35 (26%) and 53 (40%) respectively experienced angiographic or electrocardiographic MVO. Angiographic and electrocardiographic MVO were different among the three variants (p= 0.03 and p=0.02 respectively). In particular, T/T genotype was associated with a higher incidence of both angiographic and electrocardiographic MVO compared with C/C genotype (p=0.04 and p=0.03 respectively). Moreover, Rentrop score <2 detection rate differed among the three genotypes (p=0.03). In particular T/T genotype was associated with a higher incidence of a Rentrop score <2 as compared with C/C genotype (p= 0.02). CONCLUSION: Rs1333040 polymorphism genetic variants portend different MVO incidence. In particular, T/T genotype is related to angiographic and electrocardiographic MVO and to worse collaterals towards the culprit artery.

Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs-produced either by endothelial cells, platelets, leukocytes, and erythrocytes-was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs-which was measured in MP-depleted plasma-was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications.

Radial Artery as a Coronary Artery Bypass Conduit: 20-Year Results.

BACKGROUND: There is a lack of evidence for the choice of the second conduit in coronary surgery. The radial artery (RA) is a possible option, but few data on very-long-term outcomes exist. OBJECTIVES: This study describes 20-year results of RA grafts used for coronary artery bypass grafting and the effects of RA removal on forearm circulation. METHODS: We report the results of the prospective 20-year follow-up of the first 100 consecutive patients who received the RA as a coronary bypass conduit at our institution. RESULTS: Follow-up was 100% complete. There were 64 deaths, 23 (35.9%) from cardiovascular causes. Kaplan-Meier 20-year survival was 31%. Of the 36 survivors, 33 (91.6%) underwent RA graft control at a mean of 19.0 ± 2.5 years after surgery. The RA was found to be patent in 24 cases (84.8% patency). In the overall population, probability of graft failure at 20 years was 19.0 ± 0.2% for the left internal thoracic artery (ITA), 25.0 ± 0.2% for the RA, and 55.0 ± 0.2% for the saphenous vein (p = 0.002 for RA vs. saphenous vein, 0.11 for RA vs. ITA, and p < 0.001 for ITA vs. saphenous vein). Target vessel stenosis >90%, but not location of distal anastomosis, significantly influenced long-term RA graft patency. No patients reported hand or forearm symptoms. The ulnar artery diameter was increased in the operated arm (2.44 ± 0.43 mm vs. 2.01 ± 0.47 mm; p < 0.05) and correlated with the peak systolic velocity of the second palmar digital artery (Pearson coefficient: 0.621; p < 0.05). CONCLUSIONS: The 20-year patency rate of RA grafts is good, and not inferior to the ITA, especially when the conduit is used to graft a vessel with >90% stenosis. RA harvesting does not lead to hand or forearm symptoms, even at a very-long-term follow-up.

Morphological and functional consequences of transradial coronary angiography on the radial artery: implications for its use as a bypass conduit.

OBJECTIVES: To assess the degree of damage to the radial artery (RA) in coronary artery bypass grafting (CABG) patients who underwent preoperative transradial coronary angiography (RA-CA). METHODS: From May 2012 to October 2013, 50 consecutive CABG patients who underwent RA-CA were prospectively enrolled in the study. All patients underwent echo-Doppler evaluation of the RA of the catheterized arm; the contralateral RA was used as control. The distal segment of the RA was submitted to immunohistochemical assessment of endothelial integrity. Patients were divided in three groups according to the time interval from angiography to evaluation: ≤24 h, >24 h to <7 days and ≥7 days. RESULTS: Baseline RA median diameters were 0.25 ± 0.04 cm in the cannulated arm and 0.22 ± 0.04 cm in the non-cannulated arm (P = 0.01). The flow-mediated dilatation (FMD) in the RA in the catheterized arm and in the control arm were 11.6 ± 7.9 and 14.2 ± 8.9 (P = 0.01), respectively. A statistically significant correlation was found between FMD of the catheterized RA and the time from RA-CA (Pearson's r = 0.348). Linear regression analysis confirmed that the FMD of the catheterized RA was dependent on days elapsed from the procedure (P = 0.032; OR 1.11, CI 0.009-0.203). Immunohistochemical evaluation showed extensive endothelial lesion in all examined RAs, with a trend towards reduction of the damage with time. Endothelial function and integrity of the cannulated arm did not reach those of the control arm in any of the study patients. CONCLUSIONS: RA-CA produces extensive damage to the RA. The lesions tend to heal with time but incomplete recovery of endothelial integrity and function is still present more than 30 days after the procedure. After RA-CA, the cannulated RA should not be used for CABG.

TNFRSF11B gene polymorphisms increased risk of peripheral arterial occlusive disease and critical limb ischemia in patients with type 2 diabetes.

AIMS: Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. OPG has been hypothesized to modulate vascular functions; however, its role in mediating atherosclerosis is controversial. Epidemiological data in patients with cardiovascular disease (CVD) indicate that OPG serum levels are associated with several inflammatory markers, myocardial infarction events, and calcium scores, suggesting that OPG may be causative for CVD. METHODS: The present study aimed to evaluate whether the OPG gene (TNFRSF11B) polymorphisms are involved in the development of peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI) in patients with type 2 diabetes. This genetic association study included 402 diabetic patients (139 males and 263 females) with peripheral arterial occlusive disease and 567 diabetic subjects without peripheral arterial occlusive disease (208 males and 359 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (27.9 vs. 12.2 %, P < 0.01; 33.6 vs. 10.4 %, P < 0.01 and 24.4 vs. 12.7 %, P < 0.01, respectively) and independently (adjusted OR 4.97 (3.12-6.91), OR 7.02 (4.96-11.67), and OR 2.85 (1.95-4.02), respectively) associated with PAOD. We also found that these three polymorphisms act synergistically in patients with PAOD and are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes carried concomitantly by a given individual. CONCLUSION: The TNFRSF11B gene polymorphisms under study are associated with PAOD, and synergistic effects between these genotypes might be potential markers for the presence and severity of atherosclerotic disorders.

Regression of endothelial dysfunction in patients with endometriosis after surgical treatment: a 2-year follow-up study.

STUDY QUESTION: How does endothelial function change in women with endometriosis after surgical treatment? SUMMARY ANSWER: Surgical treatment of endometriosis leads to endothelial function improvement, resulting in reduction of cardiovascular risk. WHAT IS KNOWN ALREADY: Some recent studies have demonstrated that in young women with endometriosis, even if structural alterations are absent, endothelial dysfunction, expressed as flow-mediated dilation (FMD) impairment, can nevertheless occur. However, there are no data about changes of endothelial function in women with endometriosis after surgical treatment of endometriosis. STUDY DESIGN, SIZE, DURATION: This is a follow-up study carried out in 68 women enrolled in a previous study. Endothelial function was evaluated 2 years after surgical procedure and compared with baseline values. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-two patients who had undergone surgical treatment of endometriosis (named as patients with STE) and 10 control subjects without endometriosis, from the original study sample participated in this follow-up study. Assessment of endothelial function by FMD evaluation and measurements of serum markers of endothelial activation and inflammation were done in all these subjects. MAIN RESULTS AND THE ROLE OF CHANCE: After a 2-year follow-up period, FMD increased significantly with respect to baseline values among patients with STE [average pre- to post-difference: 5.07%, 95% confidence intervals (CI) 3.50, 6.63%; P < 0.001] but not among controls (average pre- to post-difference: 1.56%, 95% CI -0.55, 3.67%; P = 0.13). Follow-up FMD values were not significantly different between patients with STE and controls (average difference 1.50%, 95% CI -1.24, 4.23%; P = 0.27). Follow-up markers of inflammation and endothelial cells activation were similar among patients with STE and controls. LIMITATIONS, REASONS FOR CAUTION: Although this study represents the first in the literature assessing endothelial function after surgical treatment of endometriosis, further longitudinal studies are desirable to define better the real risk that women with a history of endometriosis will develop cardiovascular events. WIDER IMPLICATIONS OF THE FINDINGS: Endothelial dysfunction may be a better predictor of future cardiovascular events than traditional risk factors and the improvement in endothelial function we observed in patients after STE may have significant implications for their future cardiovascular risk. STUDY FUNDING/COMPETING INTEREST(S): No external funding has been either sought or obtained for this study. There are no conflicts of interest to declare.

Endothelial dysfunction but not increased carotid intima-media thickness in young European women with endometriosis.

BACKGROUND: Atherosclerosis is a chronic and degenerative disease developing typically in the elderly; nonetheless, a condition of accelerated atherosclerosis can be observed precociously in the presence of some diseases. Endometriosis, a chronic benign gynecological disorder, shows some characteristics, such as oxidative stress, systemic inflammation and a pro-atherogenic lipid profile, which could increase the risk of developing accelerated atherosclerosis. The aim of our study was to evaluate markers of subclinical atherosclerosis in young European women with endometriosis. METHODS: This cross-sectional study included 37 women with endometriosis and 31 control subjects. The presence of subclinical atherosclerosis was investigated by ultrasound evaluation of common carotid intima-media thickness (ccIMT) and flow-mediated dilation (FMD); in addition, serum levels of lipids, inflammatory and coagulation parameters, as well as markers of endothelial inflammation and activation, were determined. RESULTS: Women with endometriosis showed significantly lower values of FMD compared with controls [mean difference: -4.62, 95% confidence interval (CI): -6.52, -2.73; P < 0.001], whereas no significant differences in ccIMT values were found between the two groups. As regards markers of endothelial inflammation and activation, women with endometriosis had significantly higher values of inter-cellular adhesion molecule 1 (P < 0.001), vascular cell adhesion molecule 1 (P < 0.001), E-selectin (P < 0.001), von Willebrand factor (P = 0.004) and ristocetin cofactor (P = 0.001) compared with controls. CONCLUSIONS: Our study suggests that women with endometriosis have more subclinical atherosclerosis, resulting in a higher risk of developing cardiovascular disorders. Moreover, our findings demonstrate that endothelial dysfunction can occur in the absence of structural atherosclerotic changes; its evaluation might be helpful in young women with endometriosis.

Endothelial dysfunction in psoriasis patients: cross-sectional case-control study.

Psoriasis is an inflammatory, immunomediated skin disorder associated with an increased risk of cardiovascular disease. Psoriasis patients are at higher risk of atherothrombotic disease independently of the concomitance of traditional cardiovascular risk factors. Inflammation is one of the mechanisms involved in the development of endothelial dysfunction (ED), which is a marker of subclinical atherosclerosis. This study was designed to assess ED in psoriasis patients non-invasively. Flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) of the brachial artery were measured by ultrasonography in 32 psoriasis patients and 31 healthy controls. Diabetes mellitus, renal failure, a history of neoplasm, major cardiovascular and cerebrovascular disease and psoriatic arthritis were exclusion criteria. Psoriasis patients exhibited a significantly lower percent FMD compared with controls, but not a significantly different NID. Our data confirm that psoriasis is associated with impaired endothelial function and suggest that these patients suffer from subclinical atherosclerosis.

Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.

BACKGROUND/AIMS: Prognostic scores currently used in cirrhotic patients do not include thrombotic risk factors (TRFs). Predicting factors of portal vein thrombosis (PVT) development are still unknown. We wanted to describe TRFs as a function of liver disease severity using the MELD score and assess the role of local and systemic TRFs as predictors of PVT development in cirrhotic patients. METHODS: One hundred consecutive patients with liver cirrhosis were included in the study. TRFs, D-dimers, MELD score, portal vein patency and flow velocity were evaluated in all subjects at baseline and every 6 months thereafter. Variables able to predict PVT development within 1 year were identified by means of multiple logistic regression. RESULTS: The plasma levels of protein C and antithrombin were lower and the concentration of D-dimers was higher in patients with advanced disease. Plasma levels of antithrombin, protein C and protein S resulted significantly lower in PVT group at univariate analysis, but reduced portal vein flow velocity was the only variable independently associated with PVT development. CONCLUSIONS: Lower concentrations of natural coagulation inhibitors are frequently detected in patients with liver cirrhosis. A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis.