The Combined Delivery of the Vegf, Ang, and Gdnf Genes Stimulates Angiogenesis and Improves Post-Ischemic Innervation and Regeneration in Skeletal Muscle.

In this study, the effects of different combinations of the genes Vegf, Ang, and Gdnf injected both using direct virus-mediated injection (adenovirus, Ad5) and umbilical cord blood mononuclear cells (UCBCs) on the processes of stimulation of post-ischemic innervation, angiogenesis, and regeneration in skeletal muscle were investigated in a rat hindlimb chronic ischemia model. It was shown that more pronounced stimulation of angiogenesis and restoration of post-ischemic innervation were achieved both in the early (28 days post-ischemia, dpi) and late (42 dpi) terms of the experiment in the calf muscle when UCBCs delivered the combination of Ad5-Vegf and Ad5-Ang compared to the direct injection of the same vector combination into the area of ischemia. At the same time, the inclusion of Ad5-Gdnf in the combination of Ad5-Vegf and Ad5-Ang directly injected or administered by UCBCs provided a significant increase in the number of centronuclear muscle fibers, indicating stimulation of post-ischemic reparative myogenesis. This study allowed us to determine the most effective gene combinations for angiogenesis and neurogenesis, which, in the future, may serve as the basis for the development of gene and gene cell products for the treatment of chronic lower limb ischemia.

Influence of endogenous and exogenous hormones on the cardiovascular response to lower extremity exercise and group III/IV activation in young females.

Oral contraceptive (OC) use can increase resting blood pressure (BP) in females as well as contribute to greater activation of group III/IV afferents during upper body exercise. It is unknown, however, whether an exaggerated BP response occurs during lower limb exercise in OC users. We sought to elucidate the group III/IV afferent activity-mediated BP and heart rate responses while performing lower extremity tasks during early and late follicular phases in young, healthy females. Females not taking OCs (NOC: n = 8; age: 25 ± 4 yr) and those taking OCs (OC: n = 10; age: 23 ± 2 yr) completed a continuous knee extension/flexion passive stretch (mechanoreflex) and cycling exercise with subsystolic cuff occlusion (exercise pressor reflex), which was followed by a 2-min postexercise circulatory occlusion (PECO) (metaboreflex). Data collection occurred on two occasions: once during the early follicular phase (days 1-4) and once during the late follicular phase (days 10-14) of their menstrual cycle (NOC) or during the placebo and active pill phases (OC). Resting mean arterial BP and heart rate were not different between phases in NOC and OC participants (P > 0.05). Hemodynamic responses to metaboreflex, mechanoreflex, and collective exercise pressor reflex activation were not different between phases in both groups (P > 0.05). In conclusion, although OCs are known to increase BP at rest, our findings indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during large, lower limb muscle exercise with or without group III/IV afferent activation in young, healthy females.NEW & NOTEWORTHY Sex differences in the cardiovascular response to exercise have been demonstrated and may be dependent on sex hormone levels. Furthermore, oral contraceptives (OCs) have been shown to exaggerate the blood pressure response to upper extremity exercise. The results of this study indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during lower extremity dynamic exercise or with group III/IV afferent activation in young, healthy females.

Independent association of history of diabetic foot with all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study.

BACKGROUND: Foot ulcers and/or infections are common long-term complications of diabetes and are associated with increased mortality, especially from cardiovascular disease, though only a few studies have investigated the independent contribution of these events to risk of death. This study aimed at assessing the association of history of diabetic foot with all-cause mortality in individuals with type 2 diabetes, independent of cardiovascular risk factors, other complications, and comorbidities. METHODS: This prospective cohort study enrolled 15,773 Caucasian patients in 19 Italian centers in the years 2006-2008. Prior lower extremity, coronary, and cerebrovascular events and major comorbidities were ascertained by medical records, diabetic retinopathy by fundoscopy, diabetic kidney disease by albuminuria and estimated glomerular filtration rate, cardiovascular risk factors by standard methods. All-cause mortality was retrieved for 15,656 patients on 31 October 2015. RESULTS: At baseline, 892 patients (5.7%) had a history of diabetic foot, including ulcer/gangrene and/or amputation (n = 565; 3.58%), with (n = 126; 0.80%) or without (n = 439; 2.78%) lower limb revascularization, and revascularization alone (n = 330; 2.09%). History of diabetic foot was associated with all-cause death over a 7.42-year follow-up (adjusted hazard ratio, 1.502 [95% confidence interval, 1.346-1.676], p < 0.0001), independent of confounders, among which age, male sex, smoking, hemoglobin A1c, current treatments, other complications, comorbidities and, inversely, physical activity level and total and HDL cholesterol were correlated independently with mortality. Both ulcer/gangrene and amputation alone were independently associated with death, with a higher strength of association for amputation than for ulcer/gangrene (1.874 [1.144-3.070], p = 0.013 vs. 1.567 [1.353-1.814], p < 0.0001). Both ulcer/gangrene/amputation and lower limb revascularization alone were independently associated with death; mortality risk was much higher for ulcer/gangrene/amputation than for revascularization (1.641 [1.420-1.895], p < 0.0001 vs. 1.229 [1.024-1.475], p = 0.018) and further increased only slightly for combined ulcer/gangrene/amputation and revascularization (1.733 [1.368-2.196], p < 0.0001). CONCLUSIONS: In patients with type 2 diabetes, an history of diabetic foot event, including ulcer/gangrene, amputation, and lower limb revascularization, was associated with a ~ 50% increased risk of subsequent death, independent of cardiovascular risk factors, other complications and severe comorbidities, which were also significantly associated with mortality. The association with mortality was greatest for amputation, whereas that for revascularization alone was relatively modest. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Safety and efficacy of mechanical aspiration thrombectomy for patients with acute lower extremity ischemia.

OBJECTIVE: Acute limb ischemia (ALI) is associated with high rates of amputation and consequent morbidity and mortality. The objective of this study is to report on the safety and efficacy of aspiration thrombectomy using the Indigo Aspiration System in patients with lower extremity (LE) ALI. METHODS: The STRIDE study was an international, multicenter, prospective, study that enrolled 119 participants presenting with LE-ALI. Patients were treated firstline with mechanical thrombectomy using the Indigo Aspiration System, before stenting or angioplasty, or other therapies as determined by treating physician. The primary end point was target limb salvage at 30 days after the procedure. Secondary end points within 30 days included technical success, defined as core laboratory-adjudicated Thrombolysis in Myocardial Infarction (TIMI) 2/3 flow rate immediately after the procedure, changes in modified Society for Vascular Surgery runoff score, improvement of Rutherford classification compared with before the procedure, patency, rate of device-related serious adverse events, and major periprocedural bleeding. Secondary end points that will be evaluated at 12 months include target limb salvage and mortality. RESULTS: Of the 119 participants enrolled at 16 sites, the mean age was 66.3 years (46.2% female). At baseline (n = 119), ischemic severity was classified as Rutherford I in 10.9%, Rutherford IIa in 54.6%, and Rutherford IIb in 34.5%. The mean target thrombus length was 125.7 ± 124.7 mm. Before the procedure, 93.0% (of patients 107/115) had no flow (TIMI 0) through the target lesion. The target limb salvage rate at 30 days was 98.2% (109/111). The rate of periprocedural major bleed was 4.2% (5/119) and device-related serious adverse events was 0.8% (1/119). Restoration of flow (TIMI 2/3) was achieved in 96.3% of patients (105/109) immediately after the procedure. The median improvement in the modified Society for Vascular Surgery runoff score (before vs after the procedure) was 6.0 (interquartile range, 0.0-11.0). Rutherford classifications also improved after discharge in 86.5% of patients (83/96), as compared with preprocedural scores. Patency at 30 days was achieved in 89.4% of patients (101/113). CONCLUSIONS: In the STRIDE (A Study of Patients with Lower Extremity Acute Limb Ischemia to Remove Thrombus with the Indigo Aspiration System) study, aspiration thrombectomy with the Indigo System provided a safe and effective endovascular treatment for patients with LE-ALI, resulting in a high rate (98.2%) of successful limb salvage at 30 days, with few periprocedural complications.

One-year limb salvage and quality of life following mechanical aspiration thrombectomy in patients with acute lower extremity ischemia.

OBJECTIVE: Lower extremity acute limb ischemia (LE-ALI) is associated with high morbidity and mortality rates, and a burden on patient quality of life (QoL). There is limited medium- to long-term evidence on mechanical aspiration thrombectomy (MT) in patients with LE-ALI. The STRIDE study was designed to assess safety and efficacy of MT using the Indigo Aspiration System in patients with LE-ALI. Thirty-day primary and secondary endpoints and additional outcomes were previously published. Here, we report 365-day secondary endpoints and QoL data from STRIDE. METHODS: STRIDE was a multicenter, prospective, single-arm, observational cohort study that enrolled 119 patients across 16 sites in the United States and Europe. Patients were treated first-line with MT using the Indigo Aspiration System (Penumbra, Inc). The study completed follow-up in October 2023. Secondary endpoints at 365 days included target limb salvage and mortality. Additionally, the VascuQoL-6 questionnaire, developed for evaluating patient-centered QoL outcomes for peripheral arterial disease, was assessed at baseline and follow-up through 365 days. RESULTS: Seventy-three percent of patients (87/119) were available for 365-day follow-up. Mean age of these patients was 65.0 ± 13.3 years, and 44.8% were female. Baseline ischemic severity was classified as Rutherford I in 12.6%, Rutherford IIa in 51.7%, and Rutherford IIb in 35.6%. In general, baseline and disease characteristics (demographics, medical history, comorbidities, target thrombus) of these patients are similar to the enrolled cohort of 119 patients. The secondary endpoints at 365 days for target limb salvage was 88.5% (77/87) and mortality rate was 12.0% (12/100). VascuQoL-6 improved across all domains, with a median total score improvement from 12.0 (interquartile range, 9.0-15.0) at baseline to 19.0 (interquartile range, 16.0-22.0) at 365 days. CONCLUSIONS: These 365-day results from STRIDE demonstrate that first-line MT with the Indigo Aspiration System for LE-ALI portray continued high target limb salvage rates and improved patient-reported QoL. These findings indicate Indigo as a safe and effective therapeutic option for LE-ALI.

Systematic literature review comparing clinical utility of heparin-bonded expanded polytetrafluoroethylene graft with autologous saphenous vein graft for the management of below-the-knee peripheral arterial disease.

BACKGROUND: This systematic literature review compares the clinical outcomes of heparin-bonded expanded polytetrafluoroethylene with autologous saphenous vein in the management of patients undergoing below-the-knee bypass to treat peripheral arterial disease. METHODS: An electronic literature search was conducted in MEDLINE and Embase to identify comparative studies in patients who underwent below-the-knee surgical bypass. Studies were screened at abstract and full text review using predefined inclusion criteria by two independent reviewers and critically appraised for risk of bias. Meta-analyses were conducted using Review Manager 5 software (Nordic Cochrane Centre). RESULTS: Eight retrospective cohort studies were identified. Meta-analysis of primary patency demonstrated no significant difference between heparin-bonded expanded polytetrafluoroethylene and autologous saphenous vein grafts after 1 (odds ratio: 0.91, 95% confidence interval: [0.52-1.59]; P = .74), 2 (1.12 [0.60-2.10]; P = .77), 3 (0.62 [0.26-1.48]; P = .28), and 4 years (0.70 [0.36-1.39]; P = .31). Similarly, for secondary patency, no significant difference was detected at 1 (0.62 [0.33-1.15]; P = .13), 2 (0.83 [0.32-2.13]; P = .69), 3 (0.60 [0.27-1.32]; P = .20), and 4 years (0.66 [0.32-1.36]; P = .26). There was no significant difference between autologous veins and heparin-bonded expanded polytetrafluoroethylene for limb salvage and mortality at all time points. A sensitivity analysis to compare outflow vessels was conducted in only tibial bypass and identified no differences. All analyses were considered at high-risk bias because of heterogeneity in study populations and attrition in follow-up. CONCLUSIONS: This meta-analysis demonstrates similar outcomes between autologous saphenous vein and heparin-bonded expanded polytetrafluoroethylene for patency, limb salvage, and mortality through 4 years. The use of heparin-bonded expanded polytetrafluoroethylene synthetic grafts is a satisfactory option to prevent amputation, particularly when autologous saphenous vein grafts are not available. Controlled clinical studies are needed to further inform future decision-making and economic modeling related to the choice of conduit for below-the-knee graft construction.

Cross-education of lower limb muscle strength following resistance exercise training in males and females: A systematic review and meta-analysis.

Cross-education describes the training of one limb that leads to performance enhancements in the contralateral untrained limb, driven by neural changes rather than muscle adaptation. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of cross-education (vs. a control group) via resistance exercise training (RET) for improving muscle strength in the untrained lower limb of healthy males and females. A literature search from inception to September 2023 was conducted using MEDLINE (via PubMed), the Cochrane Library (CENTRAL), Web of Science (Core Database), Scopus, EBSCO-host, and Ovid-EMBASE. Independent screening, data extraction and quality assessment were conducted. The measured outcomes were change in one-repetition maximum (1-RM) load, maximum voluntary contraction (MVC), and concentric, eccentric and isometric peak torque. Change in muscle structure (pennation angle and muscle thickness) was also analysed. A total of 29 studies were included. The pooled effect size from the random-effects model shows that cross-education significantly increased 1-RM compared to the control group (standardised mean difference (SMD): 0.59, 95% CI: 0.22-0.97; P = 0.002). Cross-education also significantly improved MVC (SMD: 0.55, 95% CI: 0.16-0.94; P = 0.006), concentric (SMD: 0.61, 95% CI: 0.39-0.84; P < 0.00001), eccentric (SMD: 0.39, 95% CI: 0.13-0.64; P = 0.003) and isometric (SMD: 0.45, 95% CI: 0.26-0.64; P < 0.00001) peak torque, each compared to the control group. When RET was categorised as eccentric or concentric, subgroup analysis showed that only eccentric training was associated with significantly increased isometric peak torque via cross-education (SMD: 0.37, 95% CI: 0.13-0.61; P = 0.003) (concentric, SMD: 0.33, 95% CI: -0.09 to 0.74; P = 0.12). This systematic review and meta-analysis emphasise the potency of cross-education for improving lower limb muscle strength. These findings have potential implications for clinical situations of impaired unilateral limb function (e.g., limb-casting or stroke). Future work exploring the mechanisms facilitating these enhancements will help to develop optimised rehabilitation protocols.

30-sit-to-stand power is a better tool than isometric knee extensor strength to detect motor impairment in people with haemophilic arthropathy.

INTRODUCTION: Regular assessment of motor impairments is crucial in people with haemophilic arthropathy (PwHA). This study aimed to determine if there are differences in 30-seconds sit-to-stand (30-STS) power and maximal voluntary isometric contraction (MVIC) of the knee extensors between PwHA and healthy control group (CG). The secondary aims were to investigate the correlation between 30-STS power and MVIC of knee extensors with clinical characteristics and to assess their effectiveness in identifying motor impairment in PwHA. METHODS: A cross-sectional study was conducted by collecting data from PwHA (n = 17) and a sedentary CG (n = 15). MVIC (torque) and 30-STS power were normalised to body mass. Correlation analysis and simple linear regression adjusted for age were used to assess the association between tests and clinical variables. Using z-scores derived from the mean and standard deviation of the CG, we compared the MVIC and the 30-STS power in PwHA. RESULTS: PwHA showed lower MVIC and 30-STS power compared to CG (p < .001; large effect size d > .8). Lower 30-STS power was associated with greater joint impairment and greater fear of movement, whereas MVIC showed no association with clinical variables. 30-STS power showed a lower z-score compared to MVIC (p < .001). In addition, 30-STS power detected 47% of PwHA with motor impairment compared to 0% for MVIC (p = .002). CONCLUSIONS: Our results suggest that 30-STS power may be more effective than knee extensors MVIC in detecting motor impairment in PwHA. Consequently, lower limb skeletal muscle power, rather than maximum knee extensor strength, appears to be more affected in PwHA.

Thiamine deficiency-related neuropathy: A reversible entity from an endemic area.

BACKGROUND AND PURPOSE: Despite thiamine deficiency being a lesser-known entity in modern times, beriberi in various forms, including thiamine deficiency-related neuropathy, remains endemic in Kashmir due to the consumption of polished rice as a staple food. This observational study investigates cases of peripheral neuropathy of unknown etiology and their potential responsiveness to thiamine administration. METHODS: This prospective study enrolled adult patients presenting to the emergency department with weakness consistent with thiamine deficiency-related neuropathy and conducted a therapeutic challenge with thiamine on 41 patients. Response to thiamine therapy was monitored based on subjective and objective improvements in weakness and power. Patients were divided into thiamine responders (n = 25) and nonresponders (n = 16) based on their response to thiamine therapy and nerve conduction studies. RESULTS: Most of the baseline characteristics were similar between responders and nonresponders, except the responders exhibited lower thiamine levels and higher partial pressure of oxygen and lactate levels compared to nonresponders. All patients had a history of consuming polished rice and traditional salt tea. Although weakness in the lower limbs was present in both groups, nonresponders were more likely to exhibit weakness in all four limbs. Clinical improvement was observed within 24 h, but proximal muscle weakness persisted for an extended period of time. CONCLUSIONS: Thiamine deficiency-related neuropathy presents with predominant lower limb weakness, exacerbated by vomiting, poor food intake, psychiatric illness, and pregnancy. Thiamine challenge should be followed by observation of clinical and biochemical response.

Construction of a Prognostic Nomogram for Major Amputation Within 30 Days Postrevascularization in Patients With Acute Lower Limb Ischemia Based on 2D Perfusion Parameters.

PURPOSE: The purpose of the study is to develop a prediction model for major amputation (MA) within 30 days after arterial revascularization in patients with acute lower limb ischemia (ALLI) using 2-dimensional (2D) perfusion imaging parameters. MATERIALS AND METHODS: A retrospective study was performed in ALLI patients undergoing arterial revascularization between October 2015 and May 2022. Patients were randomly assigned into training and validation cohorts in a ratio of 7:3. Variables were selected using univariate and multivariate logistic regression. A nomogram for the MA risk within 30 days after arterial revascularization in ALLI patients was created. Its discrimination, calibration, and clinical effectiveness were reported. RESULTS: A total of 310 ALLI patients (326 limbs) were included. The MA rate within 30 days after arterial revascularization was 11.6%. Skin speckle, myoglobin, and time-to-peak were independent risk factors, while atrial fibrillation was a protective factor (all p<0.05). The nomogram predicted 30-day MA with satisfactory discriminative ability. The integrated discrimination improvement was 0.279 and 0.379 for the training and validation cohorts, respectively (both p<0.001). Calibration curves were close to the standard curve. The decision curve analysis demonstrated net benefits. CONCLUSION: This 2D perfusion imaging parameter-based nomogram could accurately predict the risk of MA within 30 days postrevascularization in ALLI patients. CLINICAL IMPACT: This study introduces a novel nomogram based on 2-dimensional (2D) perfusion imaging that can significantly advance the prognosis prediction in ALLI patients. By calculating the risk of major amputation within 30 days postrevascularization, this nomogram offers an accurate predictive tool and can lead to more informed decision-making on patient management. The innovative aspect of this research lies in its utilization of 2D perfusion parameters, a novel approach that enhances risk assessment accuracy in ALLI patients. This nomogram represents a significant step toward risk stratification and can guide future research for appropriate management on ALLI patients with different risk profiles.

Multicenter Registry of Common Femoral Artery Disease Treated With Endovascular Revascularization Using Interwoven Nitinol Stents: An Observational Retrospective Study.

PURPOSE: Surgical thromboendarterectomy has been the gold standard treatment for common femoral artery (CFA) disease. However, endovascular therapy (EVT) is conducted in certain patients with CFA lesions because of multiple comorbidities. The interwoven nitinol stent (IWS) has been developed to prevent stent fracture. Thus, this study aimed to evaluate the feasibility of EVT using IWS for CFA lesions in clinical practice. MATERIALS AND METHODS: This retrospective multicenter registry analyzed patients who had symptomatic lower-extremity artery disease due to CFA lesions and underwent EVT using IWS between 2019 and 2021. The primary endpoint was restenosis 2 years after EVT. RESULTS: This study enrolled a total of 177 patients with 196 CFA lesions. The 2-year estimate of freedom from restenosis was 88.0%. The 2-year freedom rates from the target-lesion revascularization, major amputation, and all-cause death were 92.9%, 99.0%, and 75.2%, respectively. The clinical features significantly associated with restenosis risk were the reference vessel diameter (RVD, per 1.0 mm, hazard ratio [HR], 0.24 [0.08-0.70]; p=0.009), external iliac artery (EIA) involvement (HR=4.03 [1.56-10.4]; p=0.004), superficial femoral artery (SFA) involvement (HR=3.05 [1.00-9.25]; p=0.049), body mass index (BMI; per 1.0, HR=0.85 [0.73-0.99]; p=0.032), occlusion of deep femoral arteries (DFAs) at baseline (HR=7.89 [2.04-30.5]; p=0.003), and chronic limb-threatening ischemia (CLTI, HR=2.63 [1.02-6.78]; p=0.045). Their significant association was also confirmed by the random survival forest analysis. During a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases (37.2%), and no patients had cannulation-related complications, such as failed hemostasis, fracture of IWS, and stent occlusion. CONCLUSIONS: Endovascular therapy using IWS in CFA lesions showed acceptable 2-year patency rates at 88.0% and might preserve the arterial access via the ipsilateral CFAs. Small RVD, involving EIA and SFA lesions, emaciation, occluded DFA, and CLTI are associated with poor 2-year patency rates following EVT, thus, IWS implantation in CFA lesions may be an option for patients unsuitable for surgical revascularization. CLINICAL IMPACT: This retrospective multicenter registry enrolled 177 patients with 199 CFA lesions treated with EVT using interwoven nitinol stents, because surgical thromboendarterectomy was difficult due to their multiple comorbidities. The 2-year estimate of freedom from restenosis was acceptable at 88.0%. The 2-year freedom rate from major amputation was also high at 99.0%. Moreover, during a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases, and no patients had cannulation-related complications such as failed hemostasis, fracture of IWS, and stent occlusion.

Systematic Review of Outcome Reporting for Interventions to Treat Patients with Acute Lower Limb Ischaemia.

OBJECTIVE: Inconsistencies in outcome data of therapeutic strategies for acute lower limb ischaemia (ALI) have hindered the synthesis of findings. A core outcome set (COS) may offer a solution to this problem by defining a minimum set of outcomes that are considered essential to all stakeholders involved. The first step in developing a COS is to review the previously reported outcomes on various treatment strategies for ALI. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from inception to August 2023. REVIEW METHODS: This systematic review was conducted in accordance with the Core Outcome Measures in Effectiveness Trials (COMET) initiative framework, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was pre-registered with PROSPERO (CRD42022320073). Abstracts were independently screened by two authors for full text review. All outcomes and their definitions were extracted from selected papers. Outcomes with different terminologies were then categorised into an agreed outcome term. The list of agreed outcomes was given a standardised outcome domain and core area using a 38 item standardised taxonomy. RESULTS: Of 6 184 articles identified, 176 relevant studies were included, yielding 1 325 verbatim outcomes. After deduplication, 72 unique verbatim outcomes were categorised into five broad outcome domains. Outcomes considered key to the evaluation of treatment of ALI were further categorised as delivery of care (19.4%), vascular outcomes (13.8%), and adverse events (12.5%). The three most frequently reported agreed outcomes were amputation (14.1%), death (12.3%), and general bleeding (11.6%). CONCLUSION: This systematic review provides an overview of currently reported outcomes in the literature of interventions for ALI. After categorisation into agreed outcome terms, 72 outcomes were identified that can be used in the development of a COS.

Risk Factors for Surgical Site Infection after Lower Limb Revascularisation Surgery: a Systematic Review and Meta-Analysis of Prognostic Studies.

OBJECTIVE: To systematically review and meta-analyse adjusted risk factors for surgical site infection (SSI) after lower limb revascularisation surgery. DATA SOURCES: MEDLINE, Embase, Evidence Based Medicine Reviews, and the Cochrane Central Register of Controlled Trials (inception to 28 April 2022). REVIEW METHODS: Systematic review and meta-analysis conducted according to PRISMA guidelines. After protocol registration, databases were searched. Studies reporting adjusted risk factors for SSI in adults who underwent lower limb revascularisation surgery for peripheral artery disease were included. Adjusted odds ratios (ORs) were pooled using random effects models. GRADE was used to assess certainty. RESULTS: Among 6 377 citations identified, 50 studies (n = 271 125 patients) were included. The cumulative incidence of SSI was 12 (95% confidence interval [CI] 10 - 13) per 100 patients. Studies reported 139 potential SSI risk factors adjusted for a median of 12 (range 1 - 69) potential confounding factors. Risk factors that increased the pooled adjusted odds of SSI included: female sex (pooled OR 1.41, 95% CI 1.20 - 1.64; high certainty); dependent functional status (pooled OR 1.18, 95% CI 1.03 - 1.35; low certainty); being overweight (pooled OR 1.82, 95% CI 1.29 - 2.56; moderate certainty), obese (pooled OR 2.20, 95% CI 1.44 - 3.36; high certainty), or morbidly obese (pooled OR 1.65, 95% CI 1.08 - 2.52; moderate certainty); chronic obstructive pulmonary disease (pooled OR 1.42, 95% CI 1.17 - 1.71; high certainty); chronic limb threatening ischaemia (pooled OR 1.67, 95% CI 1.22 - 2.29; moderate certainty); chronic kidney disease (pooled OR 2.13, 95% CI 1.18 - 3.83; moderate certainty); intra-operative (pooled OR 1.23, 95% CI 1.02 - 1.49), peri-operative (pooled OR 1.92, 95% CI 1.27 - 2.90), or post-operative (pooled OR 2.21, 95% CI 1.44 - 3.39) blood transfusion (moderate certainty for all); urgent or emergency surgery (pooled OR 2.12, 95% CI 1.22 - 3.70; moderate certainty); vein bypass and or patch instead of endarterectomy alone (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty); an operation lasting ≥ 3 hours (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty) or ≥ 5 hours (pooled OR 1.60, 95% CI 1.18 - 2.17; moderate certainty); and early or unplanned re-operation (pooled OR 4.50, 95% CI 2.18 - 9.32; low certainty). CONCLUSION: This systematic review identified evidence informed SSI risk factors following lower limb revascularisation surgery. These may be used to develop improved SSI risk prediction tools and to identify patients who may benefit from evidence informed SSI prevention strategies.

Infective native aneurysms of the infrapopliteal arteries - A systematic literature review and report of two cases.

Infective native aneurysms (INA) of the infrapopliteal arteries are rare and have previously been poorly described. This systematic review aims to provide an overview of the literature of this entity. Furthermore, two case reports of our own clinical experience are presented. PubMed, ScienceDirect, Cochrane, Ovid Embase, Ovid MEDLINE, and Web of Science were searched for articles on INAs of the infrapopliteal segment from January 1990 to September 2023. Article screening and selection were performed adhering to PRISMA guidelines. A total of 98 articles were screened and 20 were eligible for inclusion, of which all were case reports. In total, 22 patients with 28 infrapopliteal INAs were identified. The majority of INAs were located in the tibioperoneal trunk (n = 10, 36%) followed by the posterior tibial artery (n = 7, 25%). A current, or history of, infective endocarditis (IE) was described in 18 out of 22 patients (82%). Two patients died during hospitalization and one patient required a transfemoral amputation. A conservative antibiotic-only approach was chosen in three out of 28 INAs, two of which were the case reports described in this article; surgical or endovascular intervention was performed in 19 out of 28 aneurysms. No complications occurred in the conservative group, but one complication (transfemoral amputation) occurred in the interventional group. Infrapopliteal INA is a rare entity, and most described cases are precipitated by IE. Surgery or endovascular treatment might be indicated, but more research is warranted to define which patient would benefit and by what surgical approach.

Effects of workload and saddle height on muscle activation of the lower limb during cycling.

BACKGROUND: Cycling workload is an essential factor in practical cycling training. Saddle height is the most studied topic in bike fitting, but the results are controversial. This study aims to investigate the effects of workload and saddle height on the activation level and coordination of the lower limb muscles during cycling. METHODS: Eighteen healthy male participants with recreational cycling experience performed 15 × 2-min constant cadence cycling at five saddle heights of 95%, 97%, 100%, 103%, and 105% of greater trochanter height (GTH) and three cycling workloads of 25%, 50%, and 75% of functional threshold power (FTP). The EMG signals of the rectus femoris (RF), tibialis anterior (TA), biceps femoris (BF), and medial gastrocnemius (MG) of the right lower limb were collected throughout the experiment. RESULTS: Greater muscle activation was observed for the RF and BF at a higher cycling workload, whereas no differences were observed for the TA and MG. The MG showed intensified muscle activation as the saddle height increased. The mean and maximum amplitudes of the EMG signals of the MG increased by 56.24% and 57.24% at the 25% FTP workload, 102.71% and 126.95% at the 50% FTP workload, and 84.27% and 53.81% at the 75% FTP workload, respectively, when the saddle height increased from 95 to 100% of the GTH. The muscle activation level of the RF was minimal at 100% GTH saddle height. The onset and offset timing revealed few significant differences across cycling conditions. CONCLUSIONS: Muscle activation of the RF and BF was affected by cycling workload, while that of the MG was affected by saddle height. The 100% GTH is probably the appropriate saddle height for most cyclists. There was little statistical difference in muscle activation duration, which might be related to the small workload.

Sex differences in outcomes after revascularization for acute lower limb ischemia: Propensity score adjusted analysis.

BACKGROUND: Previous reports have suggested higher rates of mortality and amputation for female patients in acute lower limb ischemia (ALI). The aims of the present study were to investigate if there is a difference in mortality, amputation, and fasciotomy between the sexes. METHODS: A retrospective cohort study of consecutive patients undergoing index revascularization for ALI between 2001 and 2018 was conducted. A propensity score was created through a logistic regression with female/male sex as an outcome. Cox regression analyses for 90-day and 1-year mortality, combining major amputation/mortality, and logistic regression for major bleeding and fasciotomy, were performed. All analyses were performed with and without adjusting for propensity score. RESULTS: A total of 709 patients were included in the study of which 45.9% were women. Mean age was 72.1 years. Females were older and had higher rates of atrial fibrillation, embolic disease, and lower estimated glomerular filtration rate, while men more often had anemia and chronic peripheral arterial disease. Mortality at 1 year was 21.2% for women and 14.7% for men. The adjusted hazard ratio for 1-year mortality was 0.99 (95% CI 0.67-1.46). Fasciotomy was performed in 7.1% of female and 12.8% of male patients; the adjusted odds ratio was 0.52 (95% CI 0.29-0.91). CONCLUSION: Sex was not found to be an independent risk factor for mortality or combined major amputation/mortality after revascularization for acute lower limb ischemia, whereas women had lower odds of undergoing fasciotomy. Whether women are underdiagnosed or do not develop acute compartment syndrome in the lower leg as often as men should be evaluated prospectively.

Neuropsychiatric drugs and a neurophysiological marker as predictors of health-related quality of life in patients with phantom limb pain.

OBJECTIVE: To explore the relationship between sociodemographic, clinical, and neurophysiological variables and health-related quality of life (HR-QOL) of patients with phantom limb pain. METHODS: This is a cross-sectional analysis of a previous clinical trial. Univariate and multivariate linear and logistic regression analyses were used to model the predictors of HR-QOL. We utilized a sequential modeling approach with increasing adjustment levels, controlling for age and sex, and other relevant clinical variables (time since amputation, level of amputation, and pain). HR-QOL was assessed by the SF-36 Health Survey and its eight subdomains. RESULTS: We analyzed baseline data from 92 patients with lower-limb amputations. They were mostly male (63%), 45.2 ± 15.6 years, with a mean time since amputation of 82.7 ± 122.4 months, and an overall SF-36 score of 55.9 ± 21.5. We found an association between intracortical facilitation in the affected hemisphere (ICF), gabapentin usage, and HR-QOL. ICF is a predictor of better HRQOL, whereas gabapentin usage was associated with a poorer HR-QOL, with the main model explaining 13.4% of the variance in the outcome. For the SF-36 subdomains, ICF was also a positive predictor for social functioning, bodily pain, and vitality, while medication usage was associated with lower scores in mental health, general health perception, bodily pain, and vitality. CONCLUSION: We found firsthand two new independent predictors of HR-QOL in individuals with PLP, namely, the neurophysiological metric ICF and gabapentin usage. These results highlight the role of the motor cortex excitability in the HR-QOL and stress the need for treatments that favor the neuroplastic adaptation after amputation, for which ICF may be used as a possible marker.

Effectiveness of combined robotics and virtual reality on lower limb functional ability in stroke survivors: A systematic review of randomized controlled trials.

Lower limb impairments are common consequences of stroke. Robotics and virtual reality (VR) play crucial roles in improving lower limb function post-stroke. This review aims to assess the effects of combined robot and VR interventions on lower limb functional ability poststroke and to provide recommendations for future studies in the rehabilitation field. PubMed, SCOPUS, CINAHL, MEDLINE, EMBASE, and Web of Science were searched from inception to March 1, 2024. Randomized controlled trials (RCTs) involving patients with a stroke, administering combined robot and VR compared with passive (i.e., rest) or active (any intervention), and including at least one outcome evaluating lower limb function (i.e., balance, gait, mobility, muscle tone, muscle strength, range of motion) or activities of daily living were selected. The Cochrane Collaboration tool was employed to evaluate the risk of bias in the included studies. Nine studies met the eligibility criteria. In total, 364 stroke survivors (Mean age 55.62 years) were involved in this review. According to the Cochrane Collaboration tool, five studies were classified as "high quality," "moderate quality" (n=3), and "low quality" (n=1). There are mixed findings on the effects of combined robot and VR on lower limb functional ability in stroke survivors. The evidence for the effects of combined robot and VR on lower limb functional ability post-stroke is promising. Further trials with long-term follow-up are strongly warranted to understand the immediate and long-term effect of combined robot and VR intervention on various lower limb impairments and to define the optimal treatment protocols.

The Effect of Prosthetic Limb Sophistication and Amputation Level on Self-reported Mobility and Satisfaction With Mobility.

OBJECTIVE: To determine if lower limb prosthesis (LLP) sophistication is associated with patient-reported mobility and/or mobility satisfaction, and if these associations differ by amputation level. DESIGN: Cohort study that identified participants through a large national database and prospectively collected self-reported patient outcomes. SETTING: The Veterans Administration (VA) Corporate Data Warehouse, the National Prosthetics Patient Database, participant mailings, and phone calls. PARTICIPANTS: 347 Veterans who underwent an incident transtibial (TT) or transfemoral (TF) amputation due to diabetes and/or peripheral artery disease and received a qualifying LLP between March 1, 2018, and November 30, 2020. INTERVENTIONS: Basic, intermediate, and advanced prosthesis sophistication was measured by the accurate and reliable PROClass system. MAIN OUTCOME MEASURE: Patient-reported mobility using the advanced mobility subscale of the Locomotor Capabilities Index-5; mobility satisfaction using a 0-10-point Likert scale. RESULTS: Lower limb amputees who received intermediate or advanced prostheses were more likely to achieve advanced mobility than those who received basic prostheses, with intermediate nearing statistical significance at nearly twice the odds (adjusted odds ratio (aOR)=1.8, 95% confidence interval (CI), .98-3.3; P=.06). The association was strongest in TF amputees with over 10 times the odds (aOR=10.2, 95% CI, 1.1-96.8; P=.04). The use of an intermediate sophistication prosthesis relative to a basic prosthesis was significantly associated with mobility satisfaction (adjusted ß coefficient (aß)=.77, 95% CI, .11-1.4; P=.02). A statistically significant association was only observed in those who underwent a TT amputation (aß=.79, 95% CI, .09-1.5; P=.03). CONCLUSIONS: Prosthesis sophistication was not associated with achieving advanced mobility in TT amputees but was associated with greater mobility satisfaction. In contrast, prosthesis sophistication was associated with achieving advanced mobility in TF amputees but was not associated with an increase in mobility satisfaction.

Validation of Proprietary and Novel Step-counting Algorithms for Individuals Ambulating With a Lower Limb Prosthesis.

OBJECTIVE: To compare the accuracy and reliability of 10 different accelerometer-based step-counting algorithms for individuals with lower limb loss, accounting for different clinical characteristics and real-world activities. DESIGN: Cross-sectional study. SETTING: General community setting (ie, institutional research laboratory and community free-living). PARTICIPANTS: Forty-eight individuals with a lower limb amputation (N=48) wore an ActiGraph (AG) wGT3x-BT accelerometer proximal to the foot of their prosthetic limb during labeled indoor/outdoor activities and community free-living. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Intraclass correlation coefficient (ICC), absolute and root mean square error (RMSE), and Bland Altman plots were used to compare true (manual) step counts to estimated step counts from the proprietary AG Default algorithm and low frequency extension filter, as well as from 8 novel algorithms based on continuous wavelet transforms, fast Fourier transforms (FFTs), and peak detection. RESULTS: All algorithms had excellent agreement with manual step counts (ICC>0.9). The AG Default and FFT algorithms had the highest overall error (RMSE=17.81 and 19.91 steps, respectively), widest limits of agreement, and highest error during outdoor and ramp ambulation. The AG Default algorithm also had among the highest error during indoor ambulation and stairs, while a FFT algorithm had the highest error during stationary tasks. Peak detection algorithms, especially those using pre-set parameters with a trial-specific component, had among the lowest error across all activities (RMSE=4.07-8.99 steps). CONCLUSIONS: Because of its simplicity and accuracy across activities and clinical characteristics, we recommend the peak detection algorithm with set parameters to count steps using a prosthetic-worn AG among individuals with lower limb loss for clinical and research applications.