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1.  Moderate intra-abdominal hypertension is associated with an increased lactate-pyruvate ratio in the rectus abdominis muscle tissue: a pilot study during laparoscopic surgery 
Annals of Intensive Care  2012;2(Suppl 1):S14.
Background
The development of intra-abdominal hypertension [IAH] in critically ill patients admitted to the ICU is an independent predictor of mortality. In an attempt to find an early, clinically relevant metabolic signal of modest IAH, we investigated abdominal wall metabolite concentrations in a small group of patients undergoing laparoscopic surgery. We hypothesized that elevated intra-abdominal pressure [IAP] due to pneumoperitoneum leads to an increased lactate/pyruvate [L/P] ratio in the rectus abdominis muscle [RAM], indicating anaerobic metabolism.
Method
Six patients scheduled for elective laparoscopic gastric fundoplication were studied. Two hours before surgery, a microdialysis catheter (CMA 60, CMA Small Systems AB, Solna, Sweden) was inserted into the RAM under local anaesthesia. Catheter placement was confirmed by ultrasound. The microdialysis perfusion rate was set at 0.3 μL/min. Dialysate was collected hourly prior to pneumoperitoneum, during pneumoperitoneum, and for 2 h after pneumoperitoneum resolution. IAP was maintained at 12 to 13 mmHg during the surgery. The glucose, glycerol, pyruvate and lactate contents of the dialysate were measured.
Results
The median (interquartile range) L/P ratio was 10.3 (7.1 to 15.5) mmol/L at baseline. One hour of pneumoperitoneum increased the L/P ratio to 16.0 (13.6 to 35.3) mmol/L (p = 0.03). The median pneumoperitoneum duration was 86 (77 to 111) min. The L/P ratio at 2 h post-pneumoperitoneum was not different from that at baseline (p = 1.0). No changes in glycerol or glucose levels were observed.
Conclusions
IAH of 12 to 13 mmHg, even for a relatively short duration, is associated with metabolic changes in the abdominal wall muscle tissue of patients undergoing laparoscopic surgery. We suggest that tissue hypoperfusion occurs even during a modest increase in IAP, and intramuscular metabolic monitoring could therefore serve as an early warning sign of deteriorating tissue perfusion.
doi:10.1186/2110-5820-2-S1-S14
PMCID: PMC3390303  PMID: 22873415
microdialysis; intra-abdominal pressure; intra-abdominal hypertension; lactate-to-pyruvate ratio; muscle ischemia; early clinical sign
2.  Tibial Intervention for Critical Limb Ischemia 
ABSTRACT
Diagnosis and treatment of critical limb ischemia (CLI) is increasingly important as the average age of the world population and the incidence of diabetes and metabolic syndrome increases. Fortunately, most patients will not progress to this stage of peripheral arterial disease, yet if left untreated, there is a high risk of future cardiovascular events. At the point of ischemic rest pain or tissue loss, there are significant implications for morbidity and mortality. There is a high prevalence of multisegment occlusive disease in the CLI patient with the infrapopliteal vessels frequently involved. Revascularization of the affected limb is of utmost importance as the prospects of wound healing and relief of ischemic rest pain are poor without reestablishing continuous flow to the distal extremity. With the advent of endovascular devices designed to treat this vexing problem, the ability to successfully treat this difficult patient population with less procedural morbidity has been greatly enhanced.
doi:10.1055/s-0029-1242205
PMCID: PMC3036465  PMID: 21326541
Peripheral arterial disease; angioplasty; endovascular therapy; ischemic rest pain
3.  Axillofemoral bypass with local anesthesia: a way forward to enable limb salvage in high-risk patients 
For an active, ambulant patient with critical, lower limb ischemia, amputation can lead to a poor quality of life. A small group of older people with critical limb ischemia are considered at high risk for revascularization under conventional anesthesia owing to their comorbid conditions. In these cases, when endovascular therapy is not an option, the decision to amputate or revascularize presents a dilemma, especially in ambulant patients. In this article, we present 2 cases in which the individuals had diabetic foot gangrene, rest pain, and multiple comorbidities, and were unfit to undergo conventional anesthesia. In addition, they had severe aortoiliac occlusive disease, which cannot be managed by endovascular methods. Both patients were living independently and were ambulant before their foot ulcer and ischemia. They underwent an axillofemoral bypass under local anesthesia. The postoperative course was uneventful. After a 3-year follow-up, both patients continue to be ambulant and have no complaints. With selective use of local anesthetic techniques, surgical teamwork to shorten the procedure time, and close meticulous postoperative care, an axillofemoral bypass can enable limb salvage for ambulant patients who are considered unfit for conventional anesthesia.
doi:10.2147/LRA.S13928
PMCID: PMC3417959  PMID: 22915880
limb salvage; axillofemoral bypass; local anesthesia; high-risk patients
4.  Disparity in Outcomes of Surgical Revascularization for Limb Salvage 
Circulation  2008;119(1):123-130.
Background
Vein bypass surgery is an effective therapy for atherosclerotic occlusive disease in the coronary and peripheral circulations; however, long-term results are limited by progressive attrition of graft patency. Failure of vein bypass grafts in patients with critical limb ischemia results in morbidity, limb loss, and additional resource use. Although technical factors are known to be critical to the success of surgical revascularization, patient-specific risk factors are not well defined. In particular, the relationship of race/ethnicity and gender to the outcomes of peripheral bypass surgery has been controversial.
Methods and Results
We analyzed the Project of Ex Vivo Vein Graft Engineering via Transfection III (PREVENT III) randomized trial database, which included 1404 lower extremity vein graft operations performed exclusively for critical limb ischemia at 83 North American centers. Trial design included intensive ultrasound surveillance of the bypass graft and clinical follow-up to 1 year. Multivariable modeling (Cox proportional hazards and propensity score) was used to examine the relationships of demographic variables to clinical end points, including perioperative (30-day) events and 1-year outcomes (vein graft patency, limb salvage, and patient survival). Final propensity score models adjusted for 16 covariates (including type of institution, technical factors, selected comorbidities, and adjunctive medications) to examine the associations between race, gender, and outcomes. Among the 249 black patients enrolled in PREVENT III, 118 were women and 131 were men. Black men were at increased risk for early graft failure (hazard ratio [HR], 2.832 for 30-day failure; 95% confidence interval [CI], 1.393 to 5.759; P=0.0004), even when the analysis was restricted to exclude high-risk venous conduits. Black patients experienced reduced secondary patency (HR, 1.49; 95% CI, 1.08 to 2.06; P=0.016) and limb salvage (HR, 2.02; 95% CI, 1.27 to 3.20; P=0.003) at 1 year. Propensity score models demonstrate that black women were the most disadvantaged, with an increased risk for loss of graft patency (HR, 2.02 for secondary patency; 95% CI, 1.27 to 3.20; P=0.003) and major amputation (HR, 2.38; 95% CI, 1.18 to 4.83; P=0.016) at 1 year. Perioperative mortality and 1-year mortality were similar across race/gender groups.
Conclusions
Black race and female gender are risk factors for adverse outcomes after vein bypass surgery for limb salvage. Graft failure and limb loss are more common events in black patients, with black women being a particularly high-risk group. These data suggest the possibility of an altered biological response to vein grafting in this population; however, further studies are needed to determine the mechanisms underlying these observed disparities in outcome.
doi:10.1161/CIRCULATIONAHA.108.810341
PMCID: PMC2901839  PMID: 19103988
bypass; grafts; peripheral artery disease; race; women
5.  Critical Limb Ischemia 
Opinion statement
Critical limb ischemia (CLI), defined as chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease, is the most advanced form of peripheral arterial disease. Traditionally, open surgical bypass was the only effective treatment strategy for limb revascularization in this patient population. However, during the past decade, the introduction and evolution of endovascular procedures have significantly increased treatment options. In a certain subset of patients for whom either surgical or endovascular revascularization may not be appropriate, primary amputation remains a third treatment option. Definitive high-level evidence on which to base treatment decisions, with an emphasis on clinical and cost effectiveness, is still lacking. Treatment decisions in CLI are individualized, based on life expectancy, functional status, anatomy of the arterial occlusive disease, and surgical risk. For patients with aortoiliac disease, endovascular therapy has become first-line therapy for all but the most severe patterns of occlusion, and aortofemoral bypass surgery is a highly effective and durable treatment for the latter group. For infrainguinal disease, the available data suggest that surgical bypass with vein is the preferred therapy for CLI patients likely to survive 2 years or more, and for those with long segment occlusions or severe infrapopliteal disease who have an acceptable surgical risk. Endovascular therapy may be preferred in patients with reduced life expectancy, those who lack usable vein for bypass or who are at elevated risk for operation, and those with less severe arterial occlusions. Patients with unreconstructable disease, extensive necrosis involving weight-bearing areas, nonambulatory status, or other severe comorbidities may be considered for primary amputation or palliative measures.
doi:10.1007/s11936-010-0076-7
PMCID: PMC2860564  PMID: 20461120
6.  Continuous assessment of concentrations of cytokines in experimental injuries of the extremity 
Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-α, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.
PMCID: PMC2802052  PMID: 20057979
Blunt trauma; microcirculation; inflammation; microdialysis; rat
7.  Noninvasive management of the diabetic foot with critical limb ischemia: current options and future perspectives 
Foot ulcers are a major complication in patients with diabetes mellitus and involve dramatic restrictions to quality of life and also lead to enormous socio-economical loss due to the high amputation rate. The poor and slow wound healing is often aggravated by the frequent comorbidity of foot ulcers with peripheral arterial disease, making the treatment of this condition even more complicated. While the local treatment of foot ulcers is mainly based on mechanical relief and prevention or treatment of infection, improving perfusion of the impaired tissue remains the major challenge in peripheral arterial disease. While focal arterial stenosis is the domain of interventional angioplasty or vascular surgery, patients with critical limb ischemia and lacking options for revascularization have a much worse prognosis, because current treatment options avoiding amputation are scarce. However, based on recent research efforts, there is rising hope for promising and more-effective therapeutic approaches for these patients. Here, we discuss the current improvements of established therapies aimed at an improvement of limb perfusion, as well as the development of novel cutting-edge therapies based on stem-cell technology. The experiences of a ‘high-volume center’ for treatment of diabetic foot syndrome with a current major amputation rate of 4% are discussed.
doi:10.1177/2042018811427721
PMCID: PMC3474643  PMID: 23148189
autologous bone marrow transplantation; critical limb ischemia; diabetic foot; prostaglandins; therapy; urokinase
8.  The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis 
Hepatology International  2008;3(1):310-315.
Purpose
Ischemia-reperfusion injury induced by the Pringle maneuver is a well-known problem after liver surgery. The aim of this study was to monitor metabolic changes in the pig liver during warm ischemia and the following reperfusion preceded by ischemic preconditioning (IPC).
Methods
Eight Landrace pigs underwent laparotomy. Two microdialysis catheters were inserted in the liver, one in the left lobe and another in the right lobe. A reference catheter was inserted in the right biceps femoris muscle. Microdialysis samples were collected every 30 min during the study. After 2 h of baseline measurement, IPC was performed by subjecting pigs to 10 min of ischemia, followed by 10 min of reperfusion. Total ischemia for 60 min was followed by 3 h of reperfusion. The samples were analyzed for glucose, lactate, pyruvate, and glycerol. Blood samples were drawn three times to determine standard liver parameters.
Results
All parameters remained stable during baseline. Glycerol and glucose levels increased significantly during ischemia, followed by a decrease from the start of reperfusion. During the ischemic period, lactate levels increased significantly and decreased during reperfusion. The lactate–pyruvate ratio increased significantly during ischemia and decreased rapidly during reperfusion. Only minor changes were observed in standard liver parameters.
Conclusions
The present study demonstrated profound metabolic changes before, during, and after warm liver ischemia under the influence of IPC. Compared with a similar study without IPC, the metabolic changes seem to be unaffected by preconditioning.
doi:10.1007/s12072-008-9104-z
PMCID: PMC2712317  PMID: 19669382
Warm liver ischemia; Portal triad clamping; Preconditioning; Metabolic changes; Microdialysis
9.  Long-term outcome of infrapopliteal catheter-based intervention for critical limb ischemia 
CONTEXT:
Percutaneous treatment of tibioperoneal occlusive disease is associated with decreased morbidity compared with bypass surgery. The long-term patency and limb salvage rates are not well documented.
AIMS:
To evaluate the long-term outcome of endoluminal interventions for tibioperoneal lesions.
METHODS:
A retrospective study was performed to determine the outcomes of patients undergoing infrapopliteal catheter-based intervention for critical limb ischemia. Collected data included demographics, comorbidities, clinical presentation, pre- and postintervention noninvasive vascular measurements (segmental pressure and waveforms, and ankle-brachial index [ABI]), type of intervention, limb loss rate, patient follow-up and need for surgical revascularization. Statistical analysis was performed with the two-tailed t test. P<0.05 was considered significant; results were reported as mean ± SD. Cox regression analysis and Kaplan-Meier limb survival analysis were performed to demonstrate freedom from amputation over time.
RESULTS:
Thirty-five patients underwent intervention from 2003 to 2008; technical success was achieved in 26 patients (75%). Arterial segmental pressure studies revealed a significant increase in ABI – preprocedure ABI was 0.62±0.24 versus a postintervention ABI of 0.81±0.29 (P=0.02). The limb salvage rate was 63% during the follow-up period. Limb salvage was better for patients who underwent isolated infrapopliteal intervention versus combined above and below the knee intervention.
CONCLUSION:
Percutaneous interventions for tibioperoneal occlusive disease offer an acceptable limb salvage rate and may be the preferred initial treatment for critical limb ischemia.
PMCID: PMC2903018  PMID: 22477512
Atherectomy; Critical limb ischemia; Tibioperoneal angioplasty
10.  Elevated Monocytes in Patients with Critical Limb Ischemia Diminish after Bypass Surgery 
The Journal of surgical research  2009;167(1):140-150.
Introduction
Mononuclear cells (MNC) increase neovascularization and ulcer healing after injection into an ischemic extremity. Circulating MNC are composed of lymphocytes (85%), monocytes (15%) and endothelial progenitor cells (EPC; 0.03%). We hypothesized that ischemic limbs secrete paracrine signals to recruit bone marrow-derived monocytes and EPC into the circulation, such that patients with critical limb ischemia (CLI) have increased circulating monocytes compared to control patients. We also hypothesized that circulating monocytes and EPC recruitment decrease after resolution of ischemia with successful revascularization.
Methods
We reviewed the records of all patients at the VA Connecticut Healthcare System undergoing lower extremity peripheral bypass surgery between 2002 and 2007, only including patients with both preoperative and postoperative complete blood counts with differentials.
Results
Patients with CLI (n=24) had elevated preoperative monocyte counts compared to control patients (n=8) (0.753±0.04 vs. 0.516±0.05; p=0.0046), whereas the preoperative lymphocyte counts were not significantly different. After revascularization, ischemic patients had decreased monocyte counts compared to control patients (-20% vs. +55%; p=.0003), although lymphocyte counts were unchanged in both groups. Diabetic patients also had reduced postoperative monocyte counts (-32% vs. +13%; p=0.035). Multivariable logistic regression demonstrated that the only factor that independently predicted reduced postoperative monocyte count was preoperative CLI (p=0.038).
Conclusions
Patients with CLI have increased numbers of circulating monocytes, and the monocyte number decreases with resolution of ischemia after successful revascularization. Circulating monocytes may be a clinically useful perioperative marker in patients with CLI undergoing vascular surgery.
doi:10.1016/j.jss.2009.06.014
PMCID: PMC2895962  PMID: 19854451
Blood Cells; Ischemia; Claudication; Monocyte; Peripheral Vascular Disease
11.  Dorsal-Plantar Loop Technique Using Chronic Total Occlusion Devices via Anterior Tibial Artery 
Yonsei Medical Journal  2013;54(2):534-537.
The effectiveness of below-the-knee (BTK) percutaneous transluminal angioplasty to obtain successful revascularization in patients with critical limb ischemia has been well established, and many of these patients with chronic lower-extremity disease have been treated by endovascular intervention as the firstline treatment. Dorsal-plantaer loop technique is one of the new BTK interventional techiniques, and includes recanalization of both pedal and plantar arteries and their anatomical anastomoses. This method generally needs two approaches simultaneously, including antegrade and retrograde. In this report, however, we describe a case in which dorsal-plantar loop technique with only one antegrade approach, using chronic total occlusion devices via anterior tibial artery, was used to successfully recanalize BTK arteries. We think that this new technique, which may represent a safe and feasible endovascular option to avoid more invasive, time-consuming, and riskier surgical procedures, especially in end-stage renal disease and diabetes, should be considered whenever the foot is at risk, and results of above-the-ankle percutaneous transluminal angioplasty remain unsatisfactory or insufficient to achieve limb salvage.
doi:10.3349/ymj.2013.54.2.534
PMCID: PMC3575960  PMID: 23364993
Ischemia; peripheral arterial disease; angioplasty
12.  Subintimal Angioplasty for Peripheral Arterial Occlusive Disease: A Systematic Review 
The objective of this study was to summarize outcomes of subintimal angioplasty (SA) for peripheral arterial occlusive disease. The Cochrane Library, Medline and Embase databases were searched to perform a systematic review of the literature from 1966 through May 2007 on outcomes of SA for peripheral arterial occlusive disease of the infrainguinal vessels. The keywords “percutaneous intentional extraluminal revascularization,” “subintimal angioplasty,” “peripheral arterial disease,” “femoral artery,” “popliteal artery,” and “tibial artery” were used. Assessment of study quality was done using a form based on a checklist of the Dutch Cochrane Centre. The recorded outcomes were technical and clinical success, primary (assisted) patency, limb salvage, complications, and survival, in relation to the clinical grade of disease (intermittent claudication or critical limb ischemia [CLI] or mixed) and location of lesion (femoropopliteal, crural, or mixed). Twenty-three cohort studies including a total of 1549 patients (range, 27 to 148) were included in this review. Methodological and reporting quality were moderate, e.g., there was selection bias and reporting was not done according to the reporting standards. These and significant clinical heterogeneity obstructed a meta-analysis. Reports about length of the lesion and TASC classification were too various to summarize or were not mentioned at all. The technical success rates varied between 80% and 90%, with lower rates for crural lesions compared with femoral lesions. Complication rates ranged between 8% and 17% and most complications were minor. After 1 year, clinical success was between 50% and 70%, primary patency was around 50% and limb salvage varied from 80% to 90%. In conclusion, taking into account the methodological shortcomings of the included studies, SA can play an important role in the treatment of peripheral arterial disease, especially in the case of critical limb ischemia. Despite the moderate patency rates after one year, SA may serve as a “temporary bypass” to provide wound healing and limb salvage.
doi:10.1007/s00270-008-9331-7
PMCID: PMC2515568  PMID: 18414946
Subintimal angioplasty; Peripheral arterial disease; Revascularization; Percutaneous intentional extraluminal recanalization; Systematic review
13.  Catheter-Directed Thrombolysis for Acute Limb Ischemia 
ABSTRACT
Acute limb ischemia is a potentially life-threatening clinical event. Thrombosis in situ, bypass graft thrombosis, and embolic occlusion are the three major precipitating events leading to acute limb ischemia. Management of acute ischemia depends on the clinical status of the affected limb and patient comorbidities. Catheter-directed thrombolysis (CDT) is the treatment of choice for patients with relatively mild acute limb ischemia (Rutherford categories I and IIa) with no contraindications to thrombolytic therapy. Patients with severe acute limb ischemia (Rutherford category IIb) need emergent revascularization. CDT should be considered, nonetheless, if the relative risks compared with primary operation are favorable. CDT is a life- and limb-saving treatment for many patients despite limitations of efficacy and associated complications. This article is a review of the etiology of acute arterial occlusion; clinical triage of patients presenting with acute limb ischemia; catheter guide wire techniques, pharmacological agents, and devices in current use for CDT; as well as the outcomes of CDT.
doi:10.1055/s-2006-948765
PMCID: PMC3036379  PMID: 21326772
Thrombolysis; acute limb ischemia; plasminogen activator; anticoagulation
14.  Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication 
BMC Surgery  2012;12(Suppl 1):S19.
Background
Lower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication.
Methods
236 diabetic patients affected by LE-PAD at stage II of Fontaine’s classification, with ankle/brachial index ≤0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses.
Results
No baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049).
Conclusions
The present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events.
doi:10.1186/1471-2482-12-S1-S19
PMCID: PMC3499211  PMID: 23174008
15.  CoCMA: Energy-Efficient Coverage Control in Cluster-Based Wireless Sensor Networks Using a Memetic Algorithm 
Sensors (Basel, Switzerland)  2009;9(6):4918-4940.
Deployment of wireless sensor networks (WSNs) has drawn much attention in recent years. Given the limited energy for sensor nodes, it is critical to implement WSNs with energy efficiency designs. Sensing coverage in networks, on the other hand, may degrade gradually over time after WSNs are activated. For mission-critical applications, therefore, energy-efficient coverage control should be taken into consideration to support the quality of service (QoS) of WSNs. Usually, coverage-controlling strategies present some challenging problems: (1) resolving the conflicts while determining which nodes should be turned off to conserve energy; (2) designing an optimal wake-up scheme that avoids awakening more nodes than necessary. In this paper, we implement an energy-efficient coverage control in cluster-based WSNs using a Memetic Algorithm (MA)-based approach, entitled CoCMA, to resolve the challenging problems. The CoCMA contains two optimization strategies: a MA-based schedule for sensor nodes and a wake-up scheme, which are responsible to prolong the network lifetime while maintaining coverage preservation. The MA-based schedule is applied to a given WSN to avoid unnecessary energy consumption caused by the redundant nodes. During the network operation, the wake-up scheme awakens sleeping sensor nodes to recover coverage hole caused by dead nodes. The performance evaluation of the proposed CoCMA was conducted on a cluster-based WSN (CWSN) under either a random or a uniform deployment of sensor nodes. Simulation results show that the performance yielded by the combination of MA and wake-up scheme is better than that in some existing approaches. Furthermore, CoCMA is able to activate fewer sensor nodes to monitor the required sensing area.
doi:10.3390/s90604918
PMCID: PMC3291946  PMID: 22408561
wireless sensor network; sensing coverage; energy efficiency; memetic algorithm
16.  Always Contact a Vascular Interventional Specialist Before Amputating a Patient with Critical Limb Ischemia 
Patients with severe critical limb ischemia (CLI) due to long tibial artery occlusions are often poor candidates for surgical revascularization and frequently end up with a lower limb amputation. Subintimal angioplasty (SA) offers a minimally invasive alternative for limb salvage in this severely compromised patient population. The objective of this study was to evaluate the results of SA in patients with CLI caused by long tibial occlusions who have no surgical options for revascularization and are facing amputation. We retrospectively reviewed all consecutive patients with CLI due to long tibial occlusions who were scheduled for amputation because they had no surgical options for revascularization and who were treated by SA. A total of 26 procedures in 25 patients (14 males; mean age, 70 ± 15 [SD] years) were evaluated. Technical success rate was 88% (23/26). There were four complications, which were treated conservatively. Finally, in 10 of 26 limbs, no amputation was needed. A major amputation was needed in 10 limbs (7 below-knee amputations and 3 above-knee amputations). Half of the major amputations took place within 3 months after the procedure. Cumulative freedom of major amputation after 12 months was 59% (SE = 11%). In six limbs, amputation was limited to a minor amputation. Seven patients (28%) died during follow-up. In conclusion, SA of the tibial arteries seem to be a valuable treatment option to prevent major amputation in patients with CLI who are facing amputation due to lack of surgical options.
doi:10.1007/s00270-009-9687-3
PMCID: PMC2868169  PMID: 19688364
Subintimal angioplasty; Tibial arteries; Critical limb ischemia
17.  Incidence of re-amputation following partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy: a systematic review. 
Diabetic Foot & Ankle  2012;3:10.3402/dfa.v3i0.12169.
Diabetes mellitus with peripheral sensory neuropathy frequently results in forefoot ulceration. Ulceration at the first ray level tends to be recalcitrant to local wound care modalities and off-loading techniques. If healing does occur, ulcer recurrence is common. When infection develops, partial first ray amputation in an effort to preserve maximum foot length is often performed. However, the survivorship of partial first ray amputations in this patient population and associated re-amputation rate remain unknown. Therefore, in an effort to determine the actual re-amputation rate following any form of partial first ray amputation in patients with diabetes mellitus and peripheral neuropathy, the authors conducted a systematic review. Only studies involving any form of partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy but without critical limb ischemia were included. Our search yielded a total of 24 references with 5 (20.8%) meeting our inclusion criteria involving 435 partial first ray amputations. The weighted mean age of patients was 59 years and the weighted mean follow-up was 26 months. The initial amputation level included the proximal phalanx base 167 (38.4%) times; first metatarsal head resection 96 (22.1%) times; first metatarsal-phalangeal joint disarticulation 53 (12.2%) times; first metatarsal mid-shaft 39 (9%) times; hallux fillet flap 32 (7.4%) times; first metatarsal base 29 (6.7%) times; and partial hallux 19 (4.4%) times. The incidence of re-amputation was 19.8% (86/435). The end stage, most proximal level, following re-amputation was an additional digit 32 (37.2%) times; transmetatarsal 28 (32.6%) times; below-knee 25 (29.1%) times; and LisFranc 1 (1.2%) time. The results of our systematic review reveal that one out of every five patients undergoing any version of a partial first ray amputation will eventually require more proximal re-amputation. These results reveal that partial first ray amputation for patients with diabetes and peripheral sensory neuropathy may not represent a durable, functional, or predictable foot-sparing amputation and that a more proximal amputation, such as a balanced transmetatarsal amputation, as the index amputation may be more beneficial to the patient. However, this remains a matter for conjecture due to the limited data available and, therefore, additional prospective investigations are warranted.
doi:10.3402/dfa.v3i0.12169
PMCID: PMC3284264  PMID: 22396832
diabetic foot; hallux; ulceration; osteomyelitis; metatarsal; resection
18.  DISCOVER: Dutch Iliac Stent trial: COVERed balloon-expandable versus uncovered balloon-expandable stents in the common iliac artery: study protocol for a randomized controlled trial 
Trials  2012;13:215.
Background
Iliac artery atherosclerotic disease may cause intermittent claudication and critical limb ischemia. It can lead to serious complications such as infection, amputation and even death. Revascularization relieves symptoms and prevents these complications. Historically, open surgical repair, in the form of endarterectomy or bypass, was used. Over the last decade, endovascular repair has become the first choice of treatment for iliac arterial occlusive disease. No definitive consensus has emerged about the best endovascular strategy and which type of stent, if any, to use. However, in more advanced disease, that is, long or multiple stenoses or occlusions, literature is most supportive of primary stenting with a balloon-expandable stent in the common iliac artery (Jongkind V et al., J Vasc Surg 52:1376-1383,2010). Recently, a PTFE-covered balloon-expandable stent (Advanta V12, Atrium Medical Inc., Hudson, NH, USA) has been introduced for the iliac artery. Covering stents with PTFE has been shown to lead to less neo-intimal hyperplasia and this might lower restenosis rates (Dolmatch B et al. J Vasc Interv Radiol 18:527-534,2007, Marin ML et al. J Vasc Interv Radiol 7:651-656,1996, Virmani R et al. J Vasc Interv Radiol 10:445-456,1999). However, only one RCT, of mediocre quality has been published on this stent in the common iliac artery (Mwipatayi BP et al. J Vasc Surg 54:1561-1570,2011, Bekken JA et al. J Vasc Surg 55:1545-1546,2012). Our hypothesis is that covered balloon-expandable stents lead to better results when compared to uncovered balloon-expandable stents.
Methods/Design
This is a prospective, randomized, controlled, double-blind, multi-center trial. The study population consists of human volunteers aged over 18 years, with symptomatic advanced atherosclerotic disease of the common iliac artery, defined as stenoses longer than 3 cm and occlusions. A total of 174 patients will be included.
The control group will undergo endovascular dilatation or revascularization of the common iliac artery, followed by placement of one or more uncovered balloon-expandable stents. The study group will undergo the same treatment, however one or more PTFE-covered balloon-expandable stents will be placed. When necessary, the aorta, external iliac artery, common femoral artery, superficial femoral artery and deep femoral artery will be treated, using the standard treatment.
The primary endpoint is absence of binary restenosis rate. Secondary endpoints are reocclusion rate, target-lesion revascularization rate, clinical success, procedural success, hemodynamic success, major amputation rate, complication rate and mortality rate. Main study parameters are age, gender, relevant co-morbidity, and several patient, disease and procedure-related parameters.
Trial registration
Dutch Trial Register, NTR3381.
doi:10.1186/1745-6215-13-215
PMCID: PMC3576320  PMID: 23164097
Peripheral arterial occlusive disease; Atherosclerotic disease; Common Iliac Artery; Intermittent Claudication; Critical Limb Ischemia; Endovascular; Stenting; Covered stent
19.  Monitoring of the first stages of bone healing with microdialysis 
Acta Orthopaedica  2013;84(1):76-81.
Background and purpose
Bone healing is a complex process influenced by growth factors, cytokines, and other mediators. The regulation of this process is not well understood. In this pilot study, we used microdialysis technology in a critical-size bone defect in rat femurs to determine the feasibility of measuring cytokines and growth factors in the first 24 h after injury.
Methods
A 5-mm defect, stabilized by a plate, was created in the femurs of 30 male Wistar rats. The microdialysis probe (with 100 kDa molecular weight cutoff) was inserted into the defect and microdialysates were collected continuously for up to 24 h. Total protein concentration, interleukin-6 (IL-6) concentration, and transforming growth factor-β1 (TGF-β1) concentration were assessed under different conditions.
Results
Microdialysis allowed continuous and consistent protein collection over 24 h from a critical-size bone defect starting at the time of injury. IL-6 was secreted within the first 3 h after the injury. The highest IL-6 concentration (344 pg/mL) was measured between 12 and 15 h after surgery. Addition of bovine serum albumin to the perfusate resulted in detectable concentrations of TGF-β1 ranging from 10 to 23 pg/mL.
Interpretation
Continuous sampling over 24 h of proteins from a bone defect directly after the injury is feasible and provides the opportunity for a detailed analysis of the initial stages of bone healing.
doi:10.3109/17453674.2013.769080
PMCID: PMC3584608  PMID: 23350578
20.  Effect of Lower Extremity Bypass Surgery on Inflammatory Reaction and Endothelial Dysfunction in Type 2 Diabetic Patients 
Mediators of Inflammation  2009;2009:417301.
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia and dyslipidemia. The abnormalities in nutrient metabolism and elevated inflammatory mediators resulting from DM lead to impairment of wound healing and vulnerability to infection and foot ulcers. Diabetic lower limb ischemia often leads to limb necrosis. Lower extremity bypass surgery (LEBS) is indicated to prevent limb loss in patients with critical leg ischemia. This study investigated the alteration of inflammatory and endothelium dysfunction markers before and after LEBS in DM patients. Twenty one type 2 DM patients with LEBS were included. Blood was drawn before and at 1 day and 7 days after surgery in the patients. Plasma soluble cellular adhesion molecule levels and blood leukocyte integrin expressions were measured. Also, plasma concentrations of endothelin-1 and nitric oxide were analyzed to evaluate the vascular endothelial function. The results showed that there were no significant differences in plasma cellular adhesion molecules, endothelin-1 and nitric oxide levels, nor did any differences in leukocyte integrin expressions before and after the operation. These results suggest that the efficacy of LEBS on alleviating inflammatory reaction and improving endothelial function in DM patients was not obvious.
doi:10.1155/2009/417301
PMCID: PMC2665719  PMID: 19360107
21.  The role of atherectomy in the treatment of lower extremity peripheral artery disease 
BMC Surgery  2012;12(Suppl 1):S13.
Background
The incidence of lower extremity peripheral artery disease (LE-PAD) continues to increase and associated morbidity remains high. Despite the significant development of percutaneous revascularization strategies, over the past decade, LE-PAD still represents a unique challenge for interventional cardiologists and vascular surgeons.
Method
Typical features of atherosclerosis that affects peripheral vascular bed (diffuse nature, poor distal runoff, critical limb ischemia, chronic total occlusion) contribute to the disappointing results of traditional percutaneous transluminal angioplasty (PTA). New technologies have been developed in attempt to improve the safety and effectiveness of percutaneous revascularization. Among these, atherectomy, debulking and removing atherosclerotic plaque, offers the potential advantage of eliminating stretch on arterial walls and reducing rates of restenosis.
Conclusions
This review summarizes the features and the current applications of new debulking devices.
doi:10.1186/1471-2482-12-S1-S13
PMCID: PMC3499201  PMID: 23173800
22.  Primary infragenicular angioplasty for diabetic neuroischemic foot ulcers following the angiosome distribution: a new paradigm for the vascular interventionist? 
The angiosome principle was first described by Jan Taylor in 1987 in the plastic reconstructive surgery field, providing useful information on the vascular anatomy of the human body. Specifically concerning foot and ankle pathology, it may help the clinician to select better vascular access and specific strategies for revascularization. This knowledge may be particularly beneficial when treating diabetic neuroischemic foot wounds associated with particularly aggressive atherosclerotic disease and a poor collateral circulation. The implementation of angiosome-based strategies in diabetic infragenicular vascular reconstruction may afford encouraging wound healing and limb preservation rates using both bypass and endovascular techniques. The minimal invasiveness of these novel strategies enables us to perform more specific and more distal tibial and/or foot arterial reconstructions, in one or multiple targeted vessels. This paper reviews the available literature on this revascularization strategy and focuses on the potential benefit of angiosome-guided primary angioplasty for diabetic ischemic foot ulcers.
doi:10.2147/DMSO.S23471
PMCID: PMC3180522  PMID: 21969804
critical limb ischemia; diabetic foot; limb salvage; angiosomes; angioplasty
23.  Impact of Hyperlipidemia and Statins on Ischemic Stroke Outcomes after Intra-Arterial Fibrinolysis and Percutaneous Mechanical Embolectomy 
Background
Endovascular recanalization therapies are an increasingly employed treatment strategy in acute cerebral ischemia. The determinants of the final clinical outcome after endovascular treatment have been understudied. We investigated the effects of hyperlipidemia and statins on acute ischemic stroke outcomes after endovascular procedures.
Methods
An inquiry of a prospectively maintained stroke registry was conducted. Endovascular procedures were performed using recombinant tissue plasminogen activator, prourokinase or the Merci device within 12 hours after symptom onset. The analyzed outcomes were revascularization, hemorrhage and excellent functional outcome (Rankin score of 0–1 at 3 months). The analyses included χ2 and Wilcoxon rank sum, logistic regression (for multivariate analyses with binary outcomes) and linear regression (for continuous outcomes). Significance was set at p < 0.05.
Results
We included 142 patients, 80% treated with intra-arterial fibrinolysis, 22% with percutaneous mechanical embolectomy and 27% treated with intravenous fibrinolysis prior to endovascular intervention. Age (OR = 0.956, 95% CI = 0.927–0.986, p = 0.0041), National Institutes of Health Stroke Scale (NIHSS) score on admission (OR = 0.881, 95% CI = 0.812–0.957, p = 0.0025) and history of hyperlipidemia (OR = 0.284, 95% CI = 0.08–0.99, p = 0.0478) were negatively associated with excellent functional outcome at 3 months. Every 50 mg/dl increment in the total cholesterol level resulted in 64% decrease in the odds of excellent functional outcome (OR = 0.36, 95% CI = 0.447–0.882, p = 0.0253). History of hyperlipidemia decreased the likelihood of neurological improvement (p = 0.0462) and was associated with a higher NIHSS score at 7 days or discharge. Statin use was related to an average 6.5-unit NIHSS decrease at discharge (p = 0.0168). Statins were not associated with increased frequency of recanalization or symptomatic intracerebral hemorrhage.
Conclusions
History of hyperlipidemia may have a negative impact on the outcomes of acute ischemic stroke treated with intra-arterial fibrinolysis or percutaneous mechanical embolectomy. Statin use before and after these procedures may be related to better neurological outcomes. Larger prospective studies are needed to endorse these findings.
doi:10.1159/000235625
PMCID: PMC2909704  PMID: 19713698
Ischemic stroke; Thrombolysis; Percutaneous embolectomy; Statins; Hyperlipidemia
24.  Microdialysis in the femoral head of the minipig and in a blood cloth of human blood 
Acta Orthopaedica  2011;82(2):241-245.
Introduction
Microdialysis can detect ischemia in soft tissue. In a previous study, we have shown the development of ischemia in the femoral head removed from patients undergoing total hip replacement. That study also raised some methodological questions that this study tries to answer: what is happening in the dead space around the catheter in the drill canal, and is there an equilibrium period after the insertion of the catheter?
Material and methods
In an ex-vivo study using 5 syringes with 5 mL human blood, a microdialysis catheter was inserted and microdialysis was performed over 3 h. In an in-vivo study, a drill hole was made in the proximal part of the femur in 6 mature Göttingen minipigs and microdialysis was performed over 3 h. The pigs were kept normoventilated during the experiment.
Results
The ex-vivo microdialysis results showed that lactate kept a steady level and glucose and glycerol both fell; pyruvate fell but leveled out. The mean lactate/pyruvate ratio increased from 13 (SD 4) to 32 (SD 6) (p < 0.001). In vivo, relative recovery was 57% (SD 11). Lactate increased, pyruvate stayed constant, and glucose and glycerol levels fell. The lactate/pyruvate ratio increased from 30 (8) initially to 37 (8) after 1 h (p = 0.007) but no statistically significant change from 1 to 2 h was observed.
Interpretation
The ex-vivo study showed a clear washout pattern, and was different from what we see in bone. The in-vivo study indicated that an equilibrium period is necessary or that a reference measurement in healthy bone must be used when performing short measurements in bone.
doi:10.3109/17453674.2011.566132
PMCID: PMC3235298  PMID: 21428845
25.  Endovascular management of patients with coronary artery disease and diabetic foot syndrome: A long-term follow-up 
Background
To investigate the long-term results of global coronary and peripheral interventional treatment of diabetic foot patients.
Methods
We retrospectively included 220 diabetic patients (78.5 ± 15.8 years, 107 females, all with Fontaine III or IV class) who were referred to our centre for diabetic foot syndrome and severe limb ischemia from January 2006 to December 2010. Patients were evaluated by a team of interventional cardiologists and diabetologists in order to assess presence of concomitant coronary artery disease (CAD) and eventual need for coronary revascularization. Stress-echo was performed in all patients before diagnostic peripheral angiography. Patients with indications for coronary angiography were submitted to combined diagnostic angiography and then to eventual staged peripheral and coronary interventions. Doppler ultrasonography and foot transcutaneous oximetry of transcutaneous oxygen pressure (TcPO2) before and after the procedure were performed as well as stress-echocardiography and combined cardiologic and diabetic examination at 1 and 6 month and yearly.
Results
Stress-echocardiography was performed in 94/220 patients and resulted positive in 56 patients who underwent combined coronary and peripheral angiography. In the rest of 126 patients, combined coronary and peripheral angiography was performed directly for concomitant signs and symptoms of coronary heart disease in 35 patients. Coronary revascularization was judged necessary in 85/129 patients and was performed percutaneously after peripheral interventions in 72 patients and surgically in 13 patients. For Diabetic foot interventions the preferred approach was ipsilateral femoral antegrade in 170/220 patients (77.7%) and contralateral cross-over in 40/220 patients (18.8%) and popliteal retrograde + femoral antegrade in 10/220 patients (4.5%). Balloon angioplasty was performed in 252 legs (32 patients had bilateral disease): the procedure was successful in 239/252 legs with an immediate success rate of 94.8% and a significant improvement in TcPO2 and ABI with ulcer healing in 233/252 legs (92.4%). Freedom from major amputation was 82.8% at a mean follow-up of 3.1 ± 1.8 years (range 1 to 5 years) whereas survival was 88%.
Conclusions
Global coronary and peripheral endovascular management of diabetic foot syndrome patients seems to lead to an high immediate success and limb salvage rates and increasing survival compared to historical series.
doi:10.3724/SP.J.1263.2011.00078
PMCID: PMC3390080  PMID: 22783289
intervention; angioplasty; diabetes; complications

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