A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells.

BACKGROUND AIMS: Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs). METHODS: From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression. No experimental treatment (CAT) was administered to the control arm. We investigated the functional and the immunophenotypical features of the harvested CAT-derived stem cells. The primary outcome measures were healing time and safety of the cell treatment. Secondary outcomes were pain evaluated by numeric rating scale (NRS), complete wound healing at 24 weeks by Margolis Index and wound-healing process expressed in square centimeters per week. The various immunophenotypic and functional characteristics of CAT-derived stem cells were then correlated with the clinical outcomes. RESULTS: No major adverse events were recorded. The healing time was significantly faster by applying CAT, 17.5 ± 7.0 weeks versus 24.5 ± 4.9 weeks recorded in the control arm (P < 0.036). NRS dropped after the first week to 2.7 ± 2.0 in the experimental arm versus 6.6 ± 3.0 in the control group (P < 0.01). The rate of healing at the 24th week was not significantly different between arms. Interestingly, we found a strong reverse correlation between the percent of CD34+/CD45- non-hematopoietic cells, respectively, with the healing time (r = -0.894, P < 0.041) and NRS (r = -0.934, P < 0.020). CONCLUSIONS: CAT is safe and may accelerate healing time in VLUs as well as reduce wound pain. The percentage of CD34+/CD45- cells in stromal vascular fraction (SVF) seems to be a predictive biomarker of successful CAT treatment in these patients.

Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.

The role of deconditioning in the end-stage renal disease myopathy: physical exercise improves altered resting muscle oxygen consumption.

BACKGROUND: Skeletal muscle dysfunction and poor exercise tolerance are hallmarks of end-stage renal disease (ESRD). Noninvasively measured (near-infrared spectroscopy, NIRS) resting muscle oxygen consumption (rmVO2) is a biomarker of muscle dysfunction, which can be applied to study the severity and the reversibility of ESRD myopathy. We tested the hypothesis that deconditioning is a relevant factor in ESRD myopathy. METHODS: The whole dialysis population (n = 59) of two of the eight centers participating into the EXCITE study (ClinicalTrials.gov NCT01255969), a randomized trial evaluating the effect of a home-based exercise program on the functional capacity of these patients was studied. Thirty-one patients were in the active arm (exercise group) and 28 in the control arm (no intervention). Normative data for rmVO2 were obtained from a group of 19 healthy subjects. RESULTS: rmVO2 was twice higher (p < 0.001) in ESRDs patients (0.083 ± 0.034 ml/100 g/min) than in healthy subjects (0.041 ± 0.020 ml/100 g/min) indicating substantial skeletal muscle dysfunction in ESRD. rmVO2 correlated with resting heart rate (r = 0.34, p = 0.009) but was independent of age, dialysis vintage, biochemical, vascular and nutrition parameters. After the 6-month exercise program, rmVO2 reduced to 0.064 ± 0.024 ml/100 g/min (-23%, p < 0.001) in the exercise group indicating that skeletal muscle dysfunction is largely reversible but remained identical in the control group (0.082 ± 0.032 to 0.082 ± 0.031 ml/100 g/min). CONCLUSION: Deconditioning has a major role in ESRD myopathy. rmVO2 is a marker of physical deconditioning and has the potential for monitoring re-conditioning programs based on physical exercise in the ESRD population.

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.

Changes of cine cerebrospinal fluid dynamics in patients with multiple sclerosis treated with percutaneous transluminal angioplasty: a case-control study.

PURPOSE: To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis. RESULTS: At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group. CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.

An ultrasound model to calculate the brain blood outflow through collateral vessels: a pilot study.

BACKGROUND: The quantification of the flow returning from the head through the cervical veins and the collaterals of the internal jugular vein (IJV), is becoming of prominent interest in clinical practice. We developed a novel model to calculate the cerebral venous return, normalized to the arterial inflow, in the different segments of the IJV. METHODS: We assessed, by established Echo Colour Doppler (ECD) methodology, the head inflow (HBinF) defined as the sum of common carotids and vertebral arteries, as well as the cerebral flow (CBF) defined as the sum of internal carotid and vertebral arteries. We also assessed the head outflow (HBoutF) defined as the sum of the measurements at the junction of the IJV and the vertebral veins. In addition, we also calculated the collateral flow index (CFI) by estimating the flow which re-enters directly into the superior vena cava as the amount of blood extrapolated by the difference between the HBinF and the HBoutF. We preliminarily tested the model by comparing ten healthy controls (HC) with ten patients affected by chronic cerebral spinal venous insufficiency (CCSVI), a condition characterized by some blockages in the IJV which are bypassed by collateral circulation. RESULTS: In HC the HBinF was 956+-105ml/min, whereas the HBoutF was > 90% of the HBinF, leading to a final CFI value of 1%. The last result shows that a very small amount of blood is drained by the collaterals. In upright we confirmed a reduction of the outflow through the IJV which increased CFI to 9%. When we applied the model to CCSVI, the HBinF was not significantly different from controls. In supine, the flow of CCSVI patients in the IJV junction was significantly lower (p < 0.001) while the correspondent CFI value significantly increased (61%, p < 0.0002). CONCLUSIONS: Our preliminary application of the novel model in the clinical setting suggests the pivotal role of the collateral network in draining the blood into the superior vena cava under CCSVI condition.

Muscle oxygen consumption by NIRS and mobility in multiple sclerosis patients.

BACKGROUND: The study of muscle metabolism by near-infrared spectroscopy (NIRS) has been poorly implemented in multiple sclerosis (MS). Aims of the study were to compare resting muscle oxygen consumption (rmVO2) at gastrocnemius in MS patients and in age-matched healthy controls (HC) measured using NIRS, and to evaluate its possible relationship with patients' mobility. METHODS: Twenty-eight consecutively enrolled MS patients (male, n = 16; age = 42.7 ± 14.0 y, Relapsing-Remitting, n = 19; Primary-Progressive, n = 9) and 22 HC (male, n = 13; age = 36.0 ± 8.2 y) were studied during rest applying the NIRS probes at gastrocnemius, producing a venous occlusion at the thigh using a cuff, and analyzing the slope of the total hemoglobin to calculate rmVO2. Mobility was assessed by a 6-Minute Walking Test and 6-Minute Walking Distance (6MWD) was recorded. RESULTS: rmVO2 was higher in MS compared to HC (0.059 ± 0.038 vs 0.039 ± 0.016 mlO2/min/100 g, P < 0.003), not different in clinical subtypes, not correlated to patients' characteristics (age, disease duration, Expanded Disability Status Scale, resting heart rate, skinfold thickness), and significantly higher in patients with lower walking ability (6MWD < 450 m, n = 12) compared to those at better performance (respectively, 0.072 ± 0.043 vs 0.049 ± 0.032 mlO2/min/100 g, P = 0.03). CONCLUSION: rmVO2 values, significantly higher in MS patients compared to HC, and in low versus high performing patients, might represent a marker of peripheral adaptations occurred to sustain mobility, as observed in other chronic diseases.

Physical fitness changes induced by thermal aquatic standardized exercise in chronic venous disease patients.

BACKGROUND: Lack of physical activity represents a risk factor for both cardiovascular and chronic venous diseases (CVD), nevertheless a specific exercise protocol for CVD patient is still missing. This investigation was aimed to assess the impact of a standardized exercise protocol in a thermal water environment on physical fitness and quality-of-life (QoL) in CVD patients. METHODS: Sixteen (16) CVD patients performed 5 standardized exercise sessions in a thermal water pool. Before starting the exercise protocol, the cohort filled International Physical Activity Questionnaire (IPAQ) to determine their physical activity level. At baseline and at the end of the exercise program, leg volume, QoL, musculoskeletal and cardiovascular physical fitness were assessed by means of water plethysmography, validated questionnaire and functional test, blood pressure and heart rate at rest were also reported. RESULTS: All the patients were categorized as physically inactive: average activity time 235.6 (155.2) MET-minutes per week. At the end of the study, a significant leg volume reduction was found (-16%; p < .002). Significant improvement in lower limb strength (p < .0001), endurance (p < .006), rapidity and balance (p < .05) together with decrease in resting heart rate (-1.8%, p < .0001) and systolic blood pressure (-1.1%, p < .04) were reported, significant improvement in bodily pain (p < .0005) and social function (p < .002) QoL items were observed. CONCLUSIONS: The proposed exercise protocol in thermal aquatic environment demonstrated to be an effective treatment modality improving both cardiovascular and musculoskeletal outcomes and QoL in sedentary CVD patients. Aquatic environment investigations require proper analysis of the various factors involved, in a standardized and reproducible way. The herein report can be a reference for further studies on different health related conditions.

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.

Internal Jugular Vein Thrombosis: Etiology, Symptomatology, Diagnosis and Current Treatment.

(1) Background: internal jugular vein thrombosis (IJVthr) is a potentially life-threating disease but no comprehensive reviews on etiology, symptomatology, diagnosis and current treatment guidelines are yet available; (2) Methods: we prospectively developed a protocol that defined objectives, search strategy for study identification, criteria for study selection, data extraction, study outcomes, and statistical methodology, according to the PRISMA standard. We performed a computerized search of English-language publications listed in the various electronic databases. We also retrieved relevant reports from other sources, especially by the means of hand search in the Glauco Bassi Library of the University of Ferrara; (3) Results: using the predefined search strategy, we retrieved and screened 1490 titles. Data from randomized control trials were few and limited to the central vein catheterization and to the IJVthr anticoagulation treatment. Systematic reviews were found just for Lemierre syndrome, the risk of pulmonary embolism, and the IJVthr following catheterization. The majority of the information required in our pre-defined objectives comes from perspectives observational studies and case reports. The methodological quality of the included studies was from moderate to good. After title and abstract evaluation, 1251 papers were excluded, leaving 239 manuscripts available. Finally, just 123 studies were eligible for inclusion. We found out the description of 30 different signs, symptoms, and blood biomarkers related to this condition, as well as 24 different reported causes of IJVthr. (4) Conclusions: IJVthr is often an underestimated clinical problem despite being one of the major sources of pulmonary embolism as well as a potential cause of stroke in the case of the upward propagation of the thrombus. More common symptoms are neck pain and headache, whereas swelling, erythema and the palpable cord sign beneath the sternocleidomastoid muscle, frequently associated with fever, are the most reported clinical signs. An ultrasound of the neck, even limited to the simple and rapid assessment of the compression maneuver, is a quick, economic, cost-effective, noninvasive tool. High quality studies are currently lacking.

A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy.

BACKGROUND: Temporal, i.e., 24-hour, weekly, and seasonal patterns in the occurrence of acute cardiovascular and cerebrovascular events are well documented; however, little is known about temporal, especially seasonal, variation in multiple sclerosis (MS) and its relapses. This study investigated, by means of a validated chronobiological method, whether severe relapses of MS, ones requiring medical specialty consultation, display seasonal differences, and whether they are linked with seasonal differences in local meteorological variables. RESULTS: We considered 96 consecutive patients with severe MS relapse (29 men, 67 women, mean age 38.5 ± 8.8 years), referred to the Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy, between January 1, 2007 and December 31, 2008. Overall, we analyzed 164 relapses (56 in men, 108 in women; 115 in patients aged < 40 years, 49 in patients ≥40 years). Relapses were more frequent in May and June (12.2% each) and the least frequent in September (3.7%). Chronobiological analysis showed a biphasic pattern (major peak in May-June, secondary peak in November-December, p = 0.030). Analysis of monthly mean meteorological data showed a significant seasonal pattern in ambient temperature (peak in July, p < 0.001), relative humidity (peak in January, p < 0.001), and wind speed (peak in June, p = 0.011). CONCLUSIONS: In this Italian setting, we found a biphasic pattern (peaks in spring and autumn) in severe MS relapses requiring medical consultation by doctors of the MS specialty center, apparently unrelated to meteorological variables. Confirmations of the findings on larger multi-center populations residing in different climatic conditions are needed to further explore the potential seasonality of MS relapses and associated environmental triggers.

Central venous pressure estimation from ultrasound assessment of the jugular venous pulse.

OBJECTIVES: Acquiring central venous pressure (CVP), an important clinical parameter, requires an invasive procedure, which poses risk to patients. The aim of the study was to develop a non-invasive methodology for determining mean-CVP from ultrasound assessment of the jugular venous pulse. METHODS: In thirty-four adult patients (age = 60 ± 12 years; 10 males), CVP was measured using a central venous catheter, with internal jugular vein (IJV) cross-sectional area (CSA) variation along the cardiac beat acquired using ultrasound. The resultant CVP and IJV-CSA signals were synchronized with electrocardiogram (ECG) signals acquired from the patients. Autocorrelation signals were derived from the IJV-CSA signals using algorithms in R (open-source statistical software). The correlation r-values for successive lag intervals were extracted and used to build a linear regression model in which mean-CVP was the response variable and the lagging autocorrelation r-values and mean IJV-CSA, were the predictor variables. The optimum model was identified using the minimum AIC value and validated using 10-fold cross-validation. RESULTS: While the CVP and IJV-CSA signals were poorly correlated (mean r = -0.018, SD = 0.357) due to the IJV-CSA signal lagging behind the CVP signal, their autocorrelation counterparts were highly positively correlated (mean r = 0.725, SD = 0.215). Using the lagging autocorrelation r-values as predictors, mean-CVP was predicted with reasonable accuracy (r2 = 0.612), with a mean-absolute-error of 1.455 cmH2O, which rose to 2.436 cmH2O when cross-validation was performed. CONCLUSIONS: Mean-CVP can be estimated non-invasively by using the lagged autocorrelation r-values of the IJV-CSA signal. This new methodology may have considerable potential as a clinical monitoring and diagnostic tool.

A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency.

OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS. METHODS: Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire. RESULTS: Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP. CONCLUSIONS: PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.

Acute and long-term effects of an exercise program for dialysis patients prescribed in hospital and performed at home.

BACKGROUND: Exercise has positive psychophysical effects on dialysis patients, thus effective programs should be identified. We evaluated the effects of an original 6-month walking program on physical capacity, health-related quality of life (HRQL) and postdialysis fatigue (PDF). METHODS: Thirty-one dialysis patients (19 male, mean age 65 -/+ 11 years) were divided into exercise (group E; n=17) and control (group C; n=14) groups, and evaluated upon entry, after the 6-month program and 19 -/+ 3 months later. Outcome measures were 6-minute walking distance (6MWD), SF-36 scale scores, self-reported PDF and recovery time. E group was assigned 2 daily 10-minute home walking sessions on the nondialysis day at a speed 50% below maximal treadmill speed as determined and updated monthly at the hospital. C group: no exercise. RESULTS: Twenty patients (13 from E, 7 from C) completed the study. The E group, unlike the C group, increased 6MWD (308 -/+ 105 m, to 351 -/+ 118 m, p=0.0007), and HRQL, significantly for bodily pain, physical role and mental health (p<0.05), decreased PDF and recovery time (p<0.05). At the follow-up, 15 patients were reevaluated (9 from E, 6 from C). The E group was still active and showed 6MWD similar to baseline, with a decline of 0.13 -/+ 1.72 m/mo. The C group decreased 6MWD (p=0.026) with a decline of 3.43 -/+ 3.2 m/mo. For both groups, HRQL, PDF and recovery time showed slight variations from baseline. CONCLUSIONS: In dialysis patients, a 6-month exercise program prescribed at the hospital and performed at home improved physical capacity, HRQL and PDF symptoms. Patients maintained an active lifestyle after discharge and showed a slow functional decline over a 2-year period.

Femoral vein valve incompetence as a risk factor for junctional recurrence.

Background Recurrent varicose veins occur up to 80% of procedures. The sapheno-femoral junction can be involved in more than 50% of cases. A detailed pathophysiological explanation of the phenomenon is still missing. The aim of the present work is to evaluate the role of femoral vein incompetence as risk factor for sapheno-femoral junction recurrence. Methods Three-hundred-eighty-one patients presenting an incompetent great saphenous vein system and eventually also an incompetent femoral tract (C2-6EpAsdPr) underwent a great saphenous vein high ligation with flush ligation also of the incompetent tributaries along the leg, sparing the saphenous trunk. Pre-operatively, all patients underwent a sonographic evaluation assessing the superficial and deep venous systems, including a detailed analysis of the iliac-femoral vein tract above the sapheno-femoral junction. A retrospective statistical analysis assessed the recurrence risk associated with iliac-femoral vein tract incompetence. Results In a 5.5 ± 1.9 years follow-up, great saphenous vein trunk reflux recurrence was detected in 45/381 (11.8%) cases. The reflux source was found in a reconnected sapheno-femoral stump in 11/45 cases (24.5%), in the pelvic network in 8/45 cases (17.8%), in a neovascularization process in 7/45 (15.5%) and in a newly incompetent great saphenous vein tributary in 19/45 (42.2%). At the pre-operative assessment, iliac-femoral vein tract reflux was present in 7 (26.9%) of the 26 cases who developed a sapheno-femoral junction recurrence and in 25 (7%) of the 355 patients who did not demonstrate sapheno-femoral junction recurrence (odds ratio: 4.8; confidence interval 95%: 1.8-12.6; p < .003). Discussion Despite many technical diagnostic and therapeutic refinements, varicose veins recurrence remains a frequent event. The present investigation points out the association among iliac-femoral vein tract incompetence and sapheno-femoral junction recurrences after high ligation.

Effects of intermittent pneumatic compression treatment on clinical outcomes and biochemical markers in patients at low mobility with lower limb edema.

OBJECTIVE: We aimed to evaluate the effects of intermittent pneumatic compression (IPC) in patients at low mobility with leg edema. METHODS: A pilot, two-arm, randomized controlled clinical trial was performed. Fifty patients (age, 58.4 ± 9 years; male, 14), randomly allocated to a group (IPC) undergoing 1 month (n = 29) of an in-home cycle of IPC and to a control (C) group (n = 21), were studied. Leg edema was evaluated by measuring subcutaneous thickness (high-resolution ultrasound) and circumferences (metric tape), both assessed at different levels of the lower limbs, and volume (water plethysmography). Ankle range of motion (ROM, goniometer), quality of life (QoL) by the 36-Item Short Form Health Survey, and a pool of plasma inflammatory markers were also evaluated. RESULTS: Edema significantly decreased in the IPC group (for all outcome measures, P < .0001), whereas it significantly increased in the C group (P < .0001). Ankle ROM was significantly enhanced in the IPC group (dorsiflexion, P < .0001; plantar flexion, P = .002) and remained stable in the C group. QoL showed an improvement in the IPC group, particularly significant for the general health subscale (P = .004), whereas no changes were highlighted in the C group. The two groups exhibited different trends and variations for some plasma inflammatory markers, mainly for granulocyte colony-stimulating factor. CONCLUSIONS: In a sample of patients at reduced mobility with leg edema, IPC treatment was effective in reducing the edema, improving the ankle ROM, and determining a positive impact on QoL together with a slight modulation of some plasma inflammatory markers.

Lower limbs venous kinetics and consequent impact on drainage direction.

Background Literature concerning the lower limbs physiological venous haemodynamics is still lacking of reference velocity values and consequent impact on drainage direction. Aim of the present study is to assess the flow velocities in the different venous compartments, evaluating the possible Venturi effect role, thus finding clues for the identification of the physical model governing the flow direction. Methods Thirty-six lower limbs underwent a velocity and diameters echo-color-Doppler assessment in several anatomical point of analysis along both the deep and superficial venous systems. The investigation protocol included and compared two different manoeuvres to elicit the flow: manual calf compression/relaxation (CR) and active foot dorsiflexion (AFD). Both peak systolic (PSV) and time average velocities (TAV) were measured. Results The different venous segments demonstrated an overlap among the velocity values and the anatomical subdivision of the deep and superficial compartments. At the CR, TAV was 34 ± 12 cm/s in the deep venous system (N1), 15 ± 7 cm/s in the saphenous system (N2), 5 ± 2 cm/s in the saphenous tributaries (N3); PSV was 89 ± 35 cm/s in N1, 34 ± 16 cm/s in N2, 11 ± 4 cm/s in N3, p < 0.05. At the AFD, TAV was 33 ± 13 cm/s in N1, 15 ± 7 in N2, 9 ± 5 in N3; PSV was 83 ± 35 in N1, 32 ± 17 in N2, 15 ± 4 in N3, p < 0.05. A diameter decrease was reported from N1 to N3 ( p < 0.05). Conclusion This investigation provides evidences of the velocity decrease from the deepest to the most superficial compartments. These data introduce the Venturi effect as potential factor in the flow aspiration from the tributary to the deeper veins. The reported data represent a first step towards an objective evaluation of the physic laws governing the drainage. These values can constitute the basis for further investigations in pathological and post-procedural scenarios.

Ultrasound Monitoring of Jugular Venous Pulse during Space Missions: Proof of Concept.

The jugular venous pulse (JVP) is one of the main parameters of cardiac function and is used by cardiologists in diagnosing heart failure. Its waveform comprises three positive waves (a, c and v) and two negative waves (x and y). Recently, it was found that JVP can be extrapolated from an ultrasound (US) video recording of the internal jugular vein (IJV), suggesting its application in space missions, on which US scanners are already widely used. To date, the feasibility of assessing JVP in microgravity (microG) has not been investigated. To verify the feasibility of JVP assessment in microG, we tested a protocol of self-performed B-mode ultrasound on the International Space Station (ISS). The protocol consisted of a video recording of IJV synchronized with electrocardiogram that produces a cross-sectional area time trace (JVP trace) (in cm2). The scans were acquired in six experimental sessions; two pre-flight (BDC1 and -2), two in space (ISS1 and -2) and two post-flight (Houston PF1, Cologne PF2). We measured the mean and standard deviation of the JVP waves and the phase relationship between such waves and P and T waves on the electrocardiogram. We verified that such parameters had the same accuracy on Earth as they did under microG, and we compared their values. The sensitivity, specificity and accuracy of JVP trace in microgravity are higher than those on Earth. The sequence of (a, c, and v) ascents and (x and y) descents along the cardiac cycle in microG is the same as that on Earth. The cause-and-effect relationship between the P and T waves on the electrocardiogram and a and v waves, respectively, of JVP is also confirmed in microG. Our experiment indicated the feasibility of deriving a JVP trace from a B-mode US examination self-performed by an astronaut in microG.

Intracranial venous haemodynamics in multiple sclerosis.

In multiple sclerosis (MS) plaques are known to be venocentric; in addition, MS lesions and peripheral venous disorders share a number of key features. To date, however, despite the anatomical relationship between MS lesions and the venous system, no information on the intracranial venous haemodynamics of MS is available. Eighty-nine consecutive MS patients (58 relapsing-remitting, 31 secondary progressive) matched with 60 controls underwent transcranial color-coded duplex sonography (TCCS). We assessed, in supine as well as in sitting positions, the direction of flow at the activation of the thoracic pump in the deep middle cerebral veins (dMCVs), and in the transverse sinus (TS). In the dMCVs, we also measured peak systolic velocity (PSV), peak diastolic velocity (PDV), as well as the resistance index (RI). Reflux/bidirectional flow rate was significantly higher in the MS population determining also significant differences in PDV, characterized by negative values (16.2+/-1 cm/sec in controls vs. -1.3 +/-2.6 cm/sec in MS, respectively, p<0.0001). Consequently, RI was dramatically increased in the MS group, affecting impedance of cerebral venous drainage (0.48+/-0.04 in controls vs. 1.1 +/-0.08 in MS, respectively p<0.0001). Therefore, the detection of reflux directed toward the subcortical grey matter was significantly associated to highest disability scores (p < 0.0001). Our study of MS patients demonstrated significant haemodynamic alterations detected in veins anatomically related to plaque disposition. Our findings should contribute towards understanding the role of altered venous flow and tissue drainage in the MS inflammatory chain, as well as in the neurodegenerative process.