Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis.

Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.

Expression profiles of the internal jugular and saphenous veins: Focus on hemostasis genes.

INTRODUCTION: Venous bed specificity could contribute to differential vulnerability to thrombus formation, and is potentially reflected in mRNA profiles. MATERIALS AND METHODS: Microarray-based transcriptome analysis in wall and valve specimens from internal jugular (IJV) and saphenous (SV) veins collected during IJV surgical reconstruction in patients with impaired brain outflow. Multiplex antigenic assay in paired jugular and peripheral plasma samples. RESULTS: Most of the top differentially expressed transcripts have been previously associated with both vascular and neurological disorders. Large expression differences of HOX genes, organ patterning regulators, pinpointed the vein positional identity. The "complement and coagulation cascade" emerged among enriched pathways. In IJV, upregulation of genes for coagulation inhibitors (TFPI, PROS1), activated protein C pathway receptors (THBD, PROCR), fibrinolysis activators (PLAT, PLAUR), and downregulation of the fibrinolysis inhibitor (SERPINE1) and of contact/amplification pathway genes (F11, F12), would be compatible with a thromboprotective profile in respect to SV. Further, in SV valve the prothrombinase complex genes (F5, F2) were up-regulated and the VWF showed the highest expression. Differential expression of several VWF regulators (ABO, ST3GAL4, SCARA5, CLEC4M) was also observed. Among other differentially expressed hemostasis-related genes, heparanase (HPSE)/heparanase inhibitor (HPSE2) were up-/down-regulated in IJV, which might support procoagulant features and disease conditions. The jugular plasma levels of several proteins, encoded by differentially expressed genes, were lower and highly correlated with peripheral levels. CONCLUSIONS: The IJV and SV rely on differential expression of many hemostasis and hemostasis-related genes to balance local hemostasis, potentially related to differences in vulnerability to thrombosis.

[Integrated management method in the prevention department of a COVID-19 epidemic outbreak in a large meat processing plant in Bari province]. / Modalità di gestione integrata nel dipartimento di prevenzione di un focolaio epidemico di COVID-19 in un grande stabilimento di lavorazione di carni della provincia di Bari.

Aim of this paper is to describe the management of an outbreak of COVID-19 in a slaughtering and meat processing plant in Bari Province (Southern Italy). At the end of the outbreak investigation, 18.4% of the employees were positive to the molecular test for SARS-CoV-2. Higher prevalence has been reported in the bovine slaughtering house and swine meat processing plant.In addition to lack of physical distancing and correct use of personal protective equipment, the spread of the virus has been eased by low level of literacy, indoor microclimate, intensive working time, and aerosol-generating procedures in specific areas of the processing plant where more positive cases have been detected. The analysis of this cluster may suggest specific actions to prevent similar outbreaks in the future.

Rehabilitative Exercise Reduced the Impact of Peripheral Artery Disease on Vascular Outcomes in Elderly Patients with Claudication: A Three-Year Single Center Retrospective Study.

The study retrospectively evaluated the association between rehabilitative outcomes and risk of peripheral revascularizations in elderly peripheral artery disease (PAD) patients with claudication. Eight-hundred thirty-five patients were enrolled. Ankle-brachial index (ABI) and maximal walking speed (Smax) were measured at baseline and at discharge from a structured home-based rehabilitation program. For the analysis, patients were divided according to a baseline ABI value (severe: ≤0.5; moderate: ≥0.5) and according to hemodynamic or functional rehabilitative response (responder: ABI ≥0.10 and/or Smax >0.5 km/h). Three-year outcomes were collected from the regional registry. According to the inclusion criteria (age 60⁻80, ABI <0.80; program completion) 457 patients, 146 severe and 311 moderate, were studied. The whole population showed significant functional and hemodynamic improvements at discharge, with 56 revascularizations and 69 deaths at follow-up. Compared to the moderate group, the severe group showed a higher rate of revascularizations (17% vs. 10%, p < 0.001) and deaths (29% and 8%, respectively; p < 0.001). However, patients with severe PAD who were ABI responders after rehabilitation showed less revascularizations than non-responders (13% vs. 21%; hazard ratio (HR): 0.52) and were not different from patients with moderate disease (9%). Superimposable rates were observed for Smax responders (13% vs. 21%; HR: 0.55; moderate 10%). In conclusion, elderly patients with severe PAD empowered by better rehabilitation outcomes showed lower rates of peripheral revascularizations and deaths that were comparable to patients with moderate PAD.

Changes in expression profiles of internal jugular vein wall and plasma protein levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disorder of the central nervous system (CNS). Several observations support interactions between vascular and neurodegenerative mechanisms in multiple sclerosis (MS). To investigate the contribution of the extracranial venous compartment, we analysed expression profiles of internal jugular vein (IJV), which drains blood from CNS, and related plasma protein levels. METHODS: We studied a group of MS patients (n = 19), screened by echo-color Doppler and magnetic resonance venography, who underwent surgical reconstruction of IJV for chronic cerebrospinal venous insufficiency (CCSVI). Microarray-based transcriptome analysis was conducted on specimens of IJV wall from MS patients and from subjects undergoing carotid endarterectomy, as controls. Protein levels were determined by multiplex assay in: i) jugular and peripheral plasma from 17 MS/CCSVI patients; ii) peripheral plasma from 60 progressive MS patients, after repeated sampling and iii) healthy individuals. RESULTS: Of the differentially expressed genes (≥ 2 fold-change, multiple testing correction, P < 0.05), the immune-related CD86 (8.5 fold-change, P = 0.002) emerged among the up regulated genes (N = 409). Several genes encoding HOX transcription factors and histones potentially regulated by blood flow, were overexpressed. Smooth muscle contraction and cell adhesion processes emerged among down regulated genes (N = 515), including the neuronal cell adhesion L1CAM as top scorer (5 fold-change, P = 5 × 10- 4). Repeated measurements in jugular/peripheral plasma and overtime in peripheral plasma showed conserved individual plasma patterns for immune-inflammatory (CCL13, CCL18) and adhesion (NCAM1, VAP1, SELL) proteins, despite significant variations overtime (SELL P < 0.0001). Both age and MS disease phenotypes were determinants of VAP1 plasma levels. Data supported cerebral related-mechanisms regulating ANGPT1 levels, which were remarkably lower in jugular plasma and correlated in repeated assays but not between jugular/peripheral compartments. CONCLUSIONS: This study provides for the first time expression patterns of the IJV wall, suggesting signatures of altered vascular mRNA profiles in MS disease also independently from CCSVI. The combined transcriptome-protein analysis provides intriguing links between IJV wall transcript alteration and plasma protein expression, thus highlighting proteins of interest for MS pathophysiology.

Fixing the jugular flow reduces ventricle volume and improves brain perfusion.

OBJECTIVE: Increased ventricle volume and brain hypoperfusion are linked to neurodegeneration. We hypothesized that in patients with restricted jugular flow, surgical restoration may reduce brain ventricle volume, because it should improve the pressure gradient, hence promoting cerebrospinal fluid reabsorption into the venous system. METHODS: The effects of restoring the jugular flow were assessed by means of a validated echocardiography with color Doppler (ECD) protocol of flow quantification, magnetic resonance venography, and single-photon emission computed tomography combined with computed tomography (SPECT-CT). The main outcome measurement was the cerebral ventricle volume blindly assessed at SPECT-CT. Secondary outcomes were brain perfusion in the whole brain and in another 12 cerebral regions. The mean follow-up of the SPECT-CT and ECD parameters was 30 days. Patency rate was subsequently monitored by means of the same ECD protocol every 3 months. RESULTS: Among 56 patients (28 male and 28 female; mean age, 44 ± 10 years) with ECD screening positive for chronic cerebrospinal venous insufficiency due to nonmobile jugular leaflets, 15 patients were excluded from the initial cohort because they did not meet the inclusion and exclusion criteria. Of the remaining 41 patients, 27 patients (14 male, 13 female; mean age, 48 ± 7 years) underwent endophlebectomy and autologous vein patch angioplasty. Omohyoid muscle section was performed when appropriate. The control group comprised 14 patients matched by age and gender (8 male, 6 female; mean age, 44 ± 11 years) who were not treated. Comorbidity was multiple sclerosis without significant differences in relapsing remitting (RR) and secondary progressive (SP) clinical course among groups. In the control group, neither ECD nor SPECT-CT showed any significant changes at follow-up. On the contrary, in the group operated on, the collateral flow index went from 70% to 30% (P < .0003) thanks to improved flow through the internal jugular vein. Correspondingly, ventricle volume dramatically decreased in the treated group (from 34 ± 14 cm(3) to 31 ± 13 cm(3); P < .01). The effect was much more evident in the RR subgroup (P = .009), whereas in the SP subgroup, it was not significant. Perfusion was found to be improved in the surgical group with respect to controls, particularly in the occipital and parietal regions of the RR subgroup (P < .0001 and P = .017, respectively), but not in the SP subgroup. The probability of reducing ventricle size is increased by 13-fold (P < .03) when restoration of the jugular flow achieves a postoperative collateral flow index ≤20%. Finally, the 18-month patency rate was 74%. CONCLUSIONS: Fixing the flow in the jugulars in patients with chronic cerebrospinal venous insufficiency might significantly reduce brain ventricle volume and improve cerebral perfusion. These changes are more evident in patients in the earlier stages of neurodegenerative disease.

The effect of an Enhanced Recovery Program in elective retroperitoneal abdominal aortic aneurysm repair.

OBJECTIVE: Enhanced Recovery Programs (ERPs) have been introduced to accelerate postoperative recovery and are mainly focused on decreasing the surgical stress response. Limited data are available regarding the implementation of ERPs in patients who undergo abdominal aortic aneurysm (AAA) repair using the retroperitoneal approach. The aims of this study were: (1) to evaluate the implementation of an ERP in patients who underwent elective retroperitoneal AAA repair; and (2) to define independent predictors of prolonged hospital length of stay (LOS) in these patients. METHODS: This was a retrospective cohort study on 221 patients who underwent elective AAA repair via a retroperitoneal approach from 2005 through 2013 at an Italian university hospital. Patients who received surgery from 2008 through 2013 and enrolled in an ERP (n = 130) were compared with those who received surgery from 2005 through 2007 and managed with traditional perioperative care (n = 91). RESULTS: Patient characteristics were comparable between groups. Intensive care unit admissions were prevalent among patients who received traditional care vs patients in the ERP (P < .01). ERP patients had fewer major (P < .01) and minor (P = .019) complications, and mortality was similar between groups. Complete functional recovery was achieved earlier in ERP patients vs controls (P < .01). Patients in the ERP group left the hospital earlier than controls (P < .01). No readmission ≤30 days were reported in the ERP group. Age ≥65 years and being in a conventional care protocol were found to be independent predictors of prolonged hospital LOS. CONCLUSIONS: The implementation of an ERP after elective AAA repair using a retroperitoneal approach reduced postoperative intensive care unit admission, accelerated functional recovery, and decreased morbidity and LOS with no readmission ≤30 days. Age ≥65 years and conventional perioperative care were the only independent predictors of prolonged LOS.

Structured Home-Based Exercise Versus Invasive Treatment: A Mission Impossible? A Pilot Randomized Study in Elderly Patients With Intermittent Claudication.

We compared the effects of an original structured home-based exercise program and revascularization in elderly patients with peripheral arterial disease over a 4-month period. Twenty-seven participants (n = 21; age = 68 ± 7 years) with moderate to severe claudication were randomized into (1) a test in-train out group (Ti-To; n = 18) that performed a home-based walking program prescribed and controlled at the hospital or (2) a revascularization group (Rev; n = 9) that underwent an endovascular and/or surgical procedure. The primary end point was quality of life as evaluated by the physical component summary (PCS) score of the Medical Outcomes Study Short Form 36 questionnaire. Secondary outcome measures included initial claudication distance (ICD) and absolute claudication distance (ACD), 6-minute walk distance (6MWD) and pain-free walk distance (PFWD), ankle-brachial index (ABI), and cost per walking meter gained. The PCS score significantly increased for both treatments at follow-up without a significant intergroup difference, as did ICD, ACD, and PFWD. The 6MWD and ABI significantly improved in the Rev group, and the Ti-To group exhibited a markedly lower cost per meter gained. The comparable effects of the 2 treatments need to be confirmed in a larger, randomized controlled trial.

Retroperitoneal access for abdominal aortic aneurysms: a single center experience.

BACKGROUND: Abdominal aortic aneurysms (AAA) may be treated through different surgical techniques. In this endovascular era, surgery remains a mainstay in the management of this disease, especially in patients unsuitable for EVAR. The purpose of this study was to compare retrospectively the postoperative outcomes and survival rates of the transperitoneal and the retroperitoneal approach for the abdominal aortic aneurysm repair in our Unit. METHODS: A retrospective analysis of 840 consecutive patients affected by AAA who were electively admitted in our unit from 1996 to 2011 was performed. Five hundred and sixty patients underwent surgical treatment, 193 through a transperitoneal approach (TP group) and 367 by a retroperitoneal approach (RP group). Short and long-term postoperative outcomes were compared in the two groups. RESULTS: The RP group was characterized by significantly fewer ICU admissions and fewer respiratory and cardiac postoperative complications. Canalization and oral feeding occurred earlier and the mean length of hospital stay for the RP group was shorter compared with that for the TP group. Twelve months survival rate in the RP group was significantly higher comparing with the TP group. Similarly higher survival rates were also observed at 180 months follow-up. CONCLUSIONS: In our study the repair of AAA through a retroperitoneal approach was associated with positive outcomes particularly in high-risk patients. It represents a valid therapeutic option especially in subjects not suitable for endovascular procedures. Surgical training and competence should be maintained to ensure the selection of the appropriate therapy for each patient.

Absorbable suture material in carotid surgery.

BACKGROUND: Absorbable sutures are not generally accepted by most vascular surgeons for the fear of breakage of the suture line and the risk of aneurysmal formation, except in cases of paediatric surgery or in case of infections. Aim of this study is to provide evidence of safety and efficacy of the use of absorbable suture materials in carotid surgery. PATIENTS AND METHODS: In an 11 year period, 1126 patients (659 male [58.5%], 467 female [41.5%], median age 72) underwent carotid endarterectomy for carotid stenosis by either conventional with primary closure (cCEA) or eversion (eCEA) techniques. Patients were randomised into two groups according to the type of suture material used. In Group A, absorbable suture material (polyglycolic acid) was used and in Group B non-absorbable suture material (polypropylene) was used. Primary end-point was to compare severe restenosis and aneurysmal formation rates between the two groups of patients. For statistical analysis only cases with a minimum period of follow-up of 12 months were considered. RESULTS: A total of 868 surgical procedures were considered for data analysis. Median follow-up was 6 years (range 1-10 years). The rate of postoperative complications was better for group A for both cCEA and eCEA procedures: 3.5% and 2.0% for group A, respectively, and 11.8% and 12.9% for group B, respectively. CONCLUSIONS: In carotid surgery, the use of absorbable suture material seems to be safe and effective and with a general lower complications rate compared to the use of non-absorbable materials.

An integrated genomic-transcriptomic approach supports a role for the proto-oncogene BCL3 in atherosclerosis.

Data with border-line statistical significance, copiously generated in genome-wide association studies of coronary artery disease (CAD), could include functionally relevant associations. We propose an integrated genomic and transcriptomic approach for unravelling new potential genetic signatures of atherosclerosis. Fifteen among 91 single nucleotide polymorphisms (SNPs) were first selected for association in a sex- and age-adjusted model by examining 510 patients with CAD and myocardial infarction and 388 subjects with normal coronary arteries (CAD-free) in the replication stages of a genome-wide association study. We investigated the expression of 71 genes proximal to the 15 tag-SNPs by two subsequent steps of microarray-based mRNA profiling, the former in vascular smooth muscle cell populations, isolated from non-atherosclerotic and atherosclerotic human carotid portions, and the latter in whole carotid specimens. BCL3 and PVRL2, contiguously located on chromosome 19, and ABCA1, extensively investigated before, were found to be differentially expressed. BCL3 and PVRL2 SNPs were genotyped within a second population of CAD patients (n=442) and compared with CAD-free subjects (n=393). The carriership of the BCL3 rs2965169 G allele was more represented among CAD patients and remained independently associated with CAD after adjustment for all the traditional cardiovascular risk factors (odds ratio=1.70 with 95% confidence interval 1.07-2.71), while the BCL3 rs8100239 A allele correlated with metabolic abnormalities. The up-regulation of BCL3 mRNA levels in atherosclerotic tissue samples was consistent with BCL3 protein expression, which was detected by immunostaining in the intima-media of atherosclerotic specimens, but not within non-atherosclerotic ones. Our integrated approach suggests a role for BCL3 in cardiovascular diseases.

Reliability of the vascular claudication reporting in diabetic patients with peripheral arterial disease: a study with near-infrared spectroscopy.

We evaluated whether altered reporting of ischemic symptoms occurs in diabetic patients with peripheral arterial disease (PAD) and stable claudication. Patients (n = 152) with claudication were enrolled (120 males; mean age: 71.0 ± 8.6 years): 74 with diabetes (DM-PAD) and 78 without (DMfree-PAD). The degree of muscle oxygenation at symptom onset and maximal speed (Smax) during an incremental treadmill test was recorded at the gastrocnemius by near-infrared spectroscopy (NIRS) and quantified by area under the curve of oxygenated hemoglobin (AUC-Hbo 2) and area under the curve of differential hemoglobin (AUC-dHb). The DM-PAD and DMfree-PAD showed similar exercise capacities inversely correlated with the degree of muscle oxygenation but significantly lower values of AUC-Hbo 2 and AUC-dHb for DM-PAD at symptom onset and Smax (-356 vs -122 and -1200 vs -359, P < .0001). During a NIRS-assisted test, the report of claudication in the presence of diabetes was delayed, occurring at a lower degree of oxygenation than in patients with PAD only, with potential implications for testing, functional staging, and balance disorders.

Acute oxygenation changes on ischemic foot of a novel intermittent pneumatic compression device and of an existing sequential device in severe peripheral arterial disease.

BACKGROUND: Intermittent pneumatic compression (IPC) improves haemodynamics in peripheral arterial disease (PAD), but its effects on foot perfusion were scarcely studied. In severe PAD patients we measured the foot oxygenation changes evoked by a novel intermittent IPC device (GP), haemodynamics and compliance to the treatment. Reference values were obtained by a sequential foot-calf device (SFC). METHODS: Twenty ischemic limbs (Ankle-Brachial Index = 0.5 ± 0.2) of 12 PAD patients (7 male, age: 74.5 ± 10.8 y) with an interval of 48 ± 2 hours received a 35 minute treatment in supine position with two IPC devices: i) a Gradient Pump (GP), which slowly inflates a single thigh special sleeve and ii) an SFC (ArtAssist®, ACI Medical, San Marcos, CA, USA), which rapidly inflates two foot-calf sleeves. MAIN OUTCOME MEASURE: changes of oxygenated haemoglobin at foot (HbO2foot) by continuous near-infrared spectroscopy recording and quantified as area-under-curve (AUC) for periods of 5 minutes. Other measures: haemodynamics by echo-colour Doppler (time average velocity (TAV) and blood flow (BF) in the popliteal artery and in the femoral vein), patient compliance by a properly developed form. RESULTS: All patients completed the treatment with GP, 9 with SFC. HbO2foot during the working phase, considered as average value of the 5 minutes periods, increased with GP (AUC 458 ± 600 to 1216 ± 280) and decreased with SFC (AUC 231 ± 946 to -1088 ± 346), significantly for most periods (P < 0.05). The GP treatment was associated to significant haemodynamic changes from baseline to end of the treatment (TAV = 10.2 ± 3.3 to 13.5 ± 5.5 cm/sec, P = 0.004; BF = 452.0 ± 187.2 to 607.9 ± 237.8 ml/sec, P = 0.0001), not observed with SFC (TAV = 11.2 ± 3.4 to 11.8 ± 4.3 cm/sec; BF = 513.8 ± 203.7 to 505.9 ± 166.5 ml/min, P = n.s.). GP obtained a higher score of patient compliance (P < 0.0001). CONCLUSIONS: A novel IPC thigh device, unlike a traditional SFC device, increased foot oxygenation in severe PAD, together with favourable haemodynamic response and high compliance to the treatment under the present experimental conditions.

The omohyoid muscle entrapment of the internal jugular vein. A still unclear pathogenetic mechanism.

OBJECTIVES: To evaluate the role of the omohyoid muscle anatomic variants as a possible reversible cause of internal jugular vein extrinsic compression. METHOD: We describe a chronic cerebro-spinal venous insufficiency patient, who presented a omohyoid muscle entrapment of the internal jugular vein, confirmed by both magnetic resonance venography and ultrasound investigation. A omohyoid muscle surgical transection together with a patch angioplasty was performed. RESULTS: The surgical procedure led to both IJV flow restoration and neurological improvement. CONCLUSIONS: The omohyoid muscle compression on the internal jugular vein seems to be a possible cause of venous obstruction, but several anatomical and patho-physiological aspects need further investigations. Such picture might cause balloon venous angioplasty inefficacy and needs to be preoperatively considered.

Calmodulin expression distinguishes the smooth muscle cell population of human carotid plaque.

Several observations suggest the expansion of a distinct medial smooth muscle cell (SMC) subset in atherosclerosis and restenosis. We characterized the phenotypic features of SMC subsets in cultures derived from human carotid endarterectomy specimens. Specimens comprised an undiseased portion (thin intimal thickening with the underlying media) and a diseased portion (atherosclerotic plaque with the underlying media). From plaque tissues of the diseased portion, only macrophage-derived foam cells were retrieved. From medial tissues, two SMC phenotypes were isolated: large SMCs (flat with a monolayered growth pattern, from the undiseased portion) and small SMCs (fusiform and growing in multilayers, from the undiseased and diseased portions after co-culture with macrophage-derived foam cells). Small SMCs displayed higher proliferative and migratory activities and were less differentiated than large SMCs. Proteomic analysis showed that calmodulin was predominant in small SMCs. Co-culture of large SMCs with macrophage-derived foam cells induced a transition to the small phenotype with increased calmodulin expression. The calmodulin inhibitor W-7 decreased the proliferation of small SMCs and prevented the large to small phenotypic transition. In vivo, calmodulin was markedly expressed in SMCs of atherosclerotic plaques and was barely detectable in the media. Macrophage-derived foam cells promote selective migration from the media of atheroma-prone SMCs characterized by calmodulin overexpression. Further studies of small SMCs could be instrumental in understanding atherosclerosis pathogenesis and in planning therapeutic strategies.

Altered collagen expression in jugular veins in multiple sclerosis.

INTRODUCTION: Venous abnormalities have been associated with different neurological conditions, and the presence of a vascular involvement in multiple sclerosis (MS) has long been anticipated. In view of the recent debate regarding the existence of cerebral venous outflow impairment in MS due to abnormalities of the azygos or internal jugular veins (IJVs), we have studied the morphological and biological features of IJVs in MS patients. METHODS: We examined (a) IJVs specimens from MS patients who underwent surgical reconstruction of the IJV and specimens of the great saphenous vein used for surgical reconstruction, (b) different vein specimens from an MS patient dead of an unrelated cause, and (c) autoptical and surgical IJV specimens from patients without MS. Collagen deposition was assessed by means of Sirius red staining followed by polarized light examination. The expression of collagen type I and III, cytoskeletal proteins (α-smooth muscle actin and smooth muscle myosin heavy chains), and inflammatory markers (CD3 and CD68) was investigated. RESULTS: The extracranial veins of MS patients showed focal thickenings of the wall characterized by a prevailing yellow-green birefringence (corresponding to thin, loosely packed collagen fibers) correlated to a higher expression of type III collagen. No differences in cytoskeletal protein and inflammatory marker expression were observed. DISCUSSION: The IJVs of MS patients presenting a focal thickening of the vein wall are characterized by the prevalence of loosely packed type III collagen fibers in the adventitia. Further studies are required to determine whether the observed venous alterations play a role in MS pathogenesis.

Near-infrared spectroscopy assessment following exercise training in patients with intermittent claudication and in untrained healthy participants.

Selected near-infrared spectroscopy (NIRS) parameters were assessed in healthy untrained participants and in peripheral arterial disease (PAD) trained patients to evaluate their usefulness in rehabilitative outcome. Forty-five PAD and 15 healthy participants were studied at entry and at 34 ± 2 weeks. Healthy participants performed their usual activities. Patients with PAD performed 2 home-based programs: structured at prescribed pace (S-pre, n = 31) and unstructured at free pace (U-free, n = 14). We measured ankle-brachial index (ABI), NIRS calf oxygen consumption at rest, NIRS dynamic muscle perfusion during an incremental test, and walking capacity. In all patients with PAD the NIRS parameters significantly increased approaching the stable values of untrained healthy participants. Among PAD, only S-pre group showed significant improvements in hemodynamic, functional, and NIRS parameters with selective adaptations in the worse legs. The assessment of NIRS parameters, that were found stable without training in healthy and modified in PAD only following structured training, might outline the local exercise-induced adaptations.

Evaluation of patient compliance, quality of life impact and cost-effectiveness of a "test in-train out" exercise-based rehabilitation program for patients with intermittent claudication.

BACKGROUND: Patients with intermittent claudication (IC) could benefit from low-cost, effective rehabilitative programs. This retrospective study evaluates compliance, impact on Quality of Life (QoL) and cost-effectiveness of a hospital prescribed, at-home performed (Test-in/Train-out) rehabilitative program for patients with IC. METHODS AND RESULTS: Two-hundred and eighty-nine patients with IC (71 ± 10.1 years, M = 210) were enrolled for a 2-year period. Two daily 10-min home walking sessions at maximal asymptomatic speed were prescribed, with serial check-ups at the hospital. Compliance with the program was assessed by assigning a score of 1 (lowest compliance) to 4 (highest compliance). The SF-36 questionnaire and a constant-load treadmill test were used to evaluate QoL and Initial/Absolute Claudication Distance, respectively. Both direct and indirect costs of the program were considered for cost-effectiveness analysis. Two-hundred and fifty patients (70.5 ± 9.2 years, M = 191), at Fontaine's II-B stage (86%), were included in the study. No adverse events were reported. The average compliance score was 3.1. At discharge, both SF-36 domains and walking performance significantly increased (P < 0.0001). A total of 1,839 in-hospital check-ups (7.36 /patient) were performed. Direct and indirect costs represented 93% and 7% of the total costs, respectively. The average costs of a visit and of a therapy cycle were C68.93 and C507.20, respectively. The cost to walk an additional meter before stopping was C9.22. CONCLUSIONS: A Test-in/Train-out program provided favourable patient compliance, QoL impact and cost-effectiveness in patients with IC.

Heparin surface stent-graft for the treatment of a carotid pseudoaneurysm.

Carotid pseudoaneurysms are a rare consequence of carotid surgery, trauma, and infection. Historically, carotid aneurysms and pseudoaneurysms were treated surgically. However, endovascular techniques have recently become a valid alternative for the treatment of carotid pseudoaneurysms. The case of a 57-year-old male patient with a pseudoaneurysm of the right internal carotid artery is described. The patient came to our unit with a painless and pulsatile mass in the neck, which was growing slowly. Five years earlier, he had undergone surgery on a saccular aneurysm located on the distal extracranial segment of the right internal carotid artery. The pseudoaneurysm was successfully treated with a heparin surface Viabahn stent-graft system (Gore AL, Flagstaff, AZ). Heparin surface stent-grafts can be used for the treatment of carotid lesions and may offer protection against intimal hyperplasia and thrombosis. Further studies are needed to evaluate the long-term results.