Search

Background: We evaluated the noncontrast MRA as an alternate method to CT angiography in assessment of patients with lower limb ischemia, 30 patients were included in a prospective cohort study; they underwent quiescent interval slice selective magnetic resonance angiography (QISS-MRA) and computed tomographic angiography (CTA). The assessment of images was evaluated by two independent consultants. The overall subjective image quality, interobserver and intermodality concordance were calculated. Results: The median acquisition time in QISS-MRA was 20 min (range 18–30 min), The overall subjective image quality was rated similarly with QISS-MRA (3.13 [95% CI 2.84–3.42]) and CTA (3.23 [95% CI 2.94–3.52]; p = 0.08) with interobserver concordance for lesion ratings in QISS-MRA reached (κ = 0.987 (SD 0.006)), while for CTA it was (κ = 0.99 (SD 0.006)), while the intermodality concordance between QISS-MRA and CTA in lesion ratings were calculated on a per segment basis and was (κ = 0.944 (SD 0.013)) for reader 1 and (κ = 0.947 (SD 0.013)) for reader 2, with sensitivity 100% and specificity 97.6% Conclusions: QISS-MRA is a reliable modality for assessment of patients with critical limb ischemia. [ABSTRACT FROM AUTHOR]

The most common complications after percutaneous vascular interventions are complications at the site of access. The use of retrograde tibial-pedal access could reduce the risks of significant complications at the puncture site compared to traditional femoral access. Purpose: In this study, we aimed to determine the efficacy and safety of primary tibial-pedal access for revascularization of chronic total occlusion of the femoral-popliteal and infrapopliteal segments in patients with critical lower limb ischemia. Materials and Methods: We conducted a retrospective analysis of 18 patients from January 2022 to August 2024. Patients were selected according to the following criteria: patients with categories 3, 4, 5 according to the Rutherford classification and stages 3,4 according to the Fontaine classification; femoropopliteal (FP) lesion with or without involvement of the infrapopliteal (IP) segment; the presence of blood flow in one or more distal or pedal segments of the main arteries of the leg and foot; informed consent of patients for the intervention. Results: The overall procedural success rate of the intervention was 100%. The average age of patients was 74±5 years. The majority of the subjects were women (66.7%). Comorbidities such as diabetes mellitus (66.7%), arterial hypertension (55.5%), coronary artery disease (38.9%), and hyperlipidemia (77.8%) were diagnosed. The artery of choice in the majority of cases was the anterior tibial artery 13 (72.2%) Balloon angioplasty combined with stent placement was performed in 14 cases (77.8%). Minor bleeding at the puncture site occurred in 1 case (5.5%). There were no signs of major bleeding, hematomas, MALE, MACE, or death in any case. All patients experienced relief of pain of ischemic origin. Conclusion: Retrograde tibial-pedal access is technically easier with a tendency to fewer complications. This technique can be used as a primary procedure or as an alternative to antegrade femoral access in complex patients with a high risk of hematoma formation.

Peripheral arterial disease (PAD) prevalence and diabetes mellitus (DM) prevalence are continuously increasing worldwide. The strong relationship between DM and PAD is highlighted by recent evidence. PAD diagnosis in diabetic patients is very important, particularly in patients with diabetic foot disease (DFD); however, it is often made difficult by the characteristics of such diseases. Diagnosing PAD makes it possible to identify patients at a very high cardiovascular risk who require intensive treatment in terms of risk factor modification and medical therapy. The purpose of this review is to discuss the diagnostic methods that allow for a diagnosis of PAD in diabetic patients. Non-invasive tests that address PAD diagnosis will be discussed, such as the ankle-brachial index (ABI), toe pressure (TP), and transcutaneous oxygen pressure (TcPO2). Furthermore, imaging methods, such as duplex ultrasound (DUS), computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA), are described because they allow for diagnosing the anatomical localization and severity of artery stenosis or occlusion in PAD. Non-invasive tests will also be discussed in terms of their ability to assess foot perfusion. Foot perfusion assessment is crucial in the diagnosis of critical limb ischemia (CLI), the most advanced PAD stage, particularly in DFD patients. The impacts of PAD diagnosis and CLI identification in diabetic patients are clinically relevant to prevent amputation and mortality. [ABSTRACT FROM AUTHOR]

Background: Critical limb ischemia (CLI) is the end stage of peripheral artery disease (PAD), and around 30% of CLI patients are ineligible for current treatments. The angiogenic benefits of c-Kit have been reported in the ischemia scenario; however, the present study demonstrates the effects of specific endothelial c-Kit signaling in arteriogenesis during hindlimb ischemia. Methods: We created conditional knockout mouse models that decrease c-Kit (c-Kit VE-Cadherin CreERT2—c-Kit) or its ligand (SCF VE-Cadherin CreERT2—SCF) specifically in endothelial cells (ECs) after tamoxifen treatment. These mice and a control group (wild-type VE-Cadherin CreERT2—WT) were subjected to hindlimb ischemia or aortic crush to evaluate perfusion/arteriogenesis and endothelial barrier permeability, respectively. Results: Our data confirmed the lower gene expression of c-Kit and SCF in the ECs of c-Kit and SCF mice, respectively. In addition, we confirmed the lower percentage of ECs positive for c-Kit in c-Kit mice. Further, we found that c-Kit and SCF mice had better limb perfusion and arteriogenesis compared to WT mice. We also demonstrated that c-Kit and SCF mice had a preserved endothelial barrier after aortic crush compared to WT. Conclusions: Our data demonstrate the deleterious effects of endothelial SCF/c-Kit signaling on arteriogenesis and endothelial barrier integrity. [ABSTRACT FROM AUTHOR]

The aim of the study is to evaluate the safety and effectiveness of rotational atherectomy-assisted balloon angioplasty (BTK-RA) for the treatment of isolated below the knee (BTK) atherosclerotic lesions and to compare the outcomes to plain old balloon angioplasty (POBA). Between January 2020 and September 2023, 96 consecutive patients with chronic limb threatening ischemia (CTLI) and isolated BTK-lesions underwent POBA (group A) or BTK-RA (group B). The primary outcome measures were: periprocedural technical success, primary patency, postoperative increase of the ankle branchial index (ABI), target lesion revascularization (TLR), limb salvage, minor amputation and death. Both techniques had similar technical success, operative time, intraprocedural complications and bailout stent implantations, independently of the operator's experience. Group B had significantly higher primary patency rates (93.5% vs. 72.0%, respectively, p = 0.006), TLR (2.1% vs. 24%, p = 0.057), lower in-hospital stay (2.0–3.0 vs. 4.0–6.0 days, respectively, p < 0.001) and higher postoperative ABI (0.8–0.2 vs. 0.7–0.1, respectively, p = 0.008), compared to group A. Significant differences (POBA n: 20, 40%, BTK-RA n = 3, 6.5%) were found in minor amputation rates between the two groups (p < 0.001), while the respective limb salvage rates were similar in both groups (94.0% vs. 97.8%, p = 0.35). The use of BTK-RA for the treatment of BTK-lesions in patients with CTLI showed significant clinical advantages in comparison to POBA. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) prevalence and diabetes mellitus (DM) prevalence are continuously increasing worldwide. The strong relationship between DM and PAD is highlighted by recent evidence. PAD diagnosis in diabetic patients is very important, particularly in patients with diabetic foot disease (DFD); however, it is often made difficult by the characteristics of such diseases. Diagnosing PAD makes it possible to identify patients at a very high cardiovascular risk who require intensive treatment in terms of risk factor modification and medical therapy. The purpose of this review is to discuss the diagnostic methods that allow for a diagnosis of PAD in diabetic patients. Non-invasive tests that address PAD diagnosis will be discussed, such as the ankle-brachial index (ABI), toe pressure (TP), and transcutaneous oxygen pressure (TcPO2). Furthermore, imaging methods, such as duplex ultrasound (DUS), computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA), are described because they allow for diagnosing the anatomical localization and severity of artery stenosis or occlusion in PAD. Non-invasive tests will also be discussed in terms of their ability to assess foot perfusion. Foot perfusion assessment is crucial in the diagnosis of critical limb ischemia (CLI), the most advanced PAD stage, particularly in DFD patients. The impacts of PAD diagnosis and CLI identification in diabetic patients are clinically relevant to prevent amputation and mortality.

Background: Critical limb ischemia (CLI) is the end stage of peripheral artery disease (PAD), and around 30% of CLI patients are ineligible for current treatments. The angiogenic benefits of c-Kit have been reported in the ischemia scenario; however, the present study demonstrates the effects of specific endothelial c-Kit signaling in arteriogenesis during hindlimb ischemia. Methods: We created conditional knockout mouse models that decrease c-Kit (c-Kit VE-Cadherin CreERT2—c-Kit) or its ligand (SCF VE-Cadherin CreERT2—SCF) specifically in endothelial cells (ECs) after tamoxifen treatment. These mice and a control group (wild-type VE-Cadherin CreERT2—WT) were subjected to hindlimb ischemia or aortic crush to evaluate perfusion/arteriogenesis and endothelial barrier permeability, respectively. Results: Our data confirmed the lower gene expression of c-Kit and SCF in the ECs of c-Kit and SCF mice, respectively. In addition, we confirmed the lower percentage of ECs positive for c-Kit in c-Kit mice. Further, we found that c-Kit and SCF mice had better limb perfusion and arteriogenesis compared to WT mice. We also demonstrated that c-Kit and SCF mice had a preserved endothelial barrier after aortic crush compared to WT. Conclusions: Our data demonstrate the deleterious effects of endothelial SCF/c-Kit signaling on arteriogenesis and endothelial barrier integrity.

Recognizing written languages using symbols written in cuneiform is a tough endeavor due to the lack of information and the challenge of the process of tokenization. The Cuneiform Language Identification (CLI) dataset attempts to understand seven cuneiform languages and dialects, including Sumerian and six dialects of the Akkadian language: Old Babylonian, Middle Babylonian Peripheral, Standard Babylonian, Neo-Babylonian, Late Babylonian, and Neo-Assyrian. However, this dataset suffers from the problem of imbalanced categories.

Bringing to the field of third language (L3) research a new population of speakers, namely heritage speaker (HS) L3 learners, this study investigates the accents of 19 German-Italian HSs in L3 English. In an accent rating experiment, the speech samples of the HSs and three control groups (monolingual speakers of English, Italian, and German) were rated for 'degree of foreign accent' and 'source of accent'. The role of 'Italian use' and 'phonetic-phonological proficiency in Italian' was also investigated for patterns of cross-linguistic influence (CLI) into English. For 'degree of foreign accent', the HSs were rated as moderately accented, on par with German controls, but as weaker accented than Italian controls. For 'source of accent', the HSs were perceived as German-sounding in most ratings (66.8%), while an Italian-sounding accent was detected in certain HSs (9.5% of ratings). Regression analyses showed CLI from Italian to be significantly predicted by the amount of 'Italian use', measured using a detailed background questionnaire. We conclude that, while accent in L3 English is predominantly affected by German, the typologically closer and majority language, CLI from Italian co-occurs in speakers who used their heritage language frequently. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to determine prognostic factors of limb salvage after iliac angioplasty ± stenting for chronic limbthreatening ischemia patients with iliac artery disease alone or with concomitant other lesion (femoro-popliteal or infrapopliteal disease). Methods: In this prospective interventional study, 32 patients with symptomatic steno-occlusive iliac artery disease treated by balloon angioplasty ± stenting. Patients’ data & comorbidities are collected and they are followed up for 1 month after iliac artery angioplasty ± stenting for above the knee amputation. Results: Comparison of data for final outcomes of limb salvage versus above-the- knee amputation showed that amputation is more likely with the increase in age with p value 0.035. Moreover, medical comorbidities were of no statistical significance regarding amputation however, angiographic characteristics and TASC classification were statistically significant regarding limb salvage. All the patients with total iliac artery occlusion (5 patients) underwent above-the-knee amputation within 1 month following the intervention while the limb was salvaged in patients with iliac artery stenosis with p value < 0.001. In addition, limbs with diseased both CIA and EIA were more prone to above-the-knee amputation than limbs with diseased CIA only with p value 0.009. State of profunda femoris artery was a statistically significant prognostic factor for limb salvage as limbs with diseased PFA were more prone to above-the-knee amputation than limbs with healthy PFA with p value 0.023. Limbs with TASC D were more prone to above-the- knee amputation than TASC A, B, C with p value < 0.001. Limb salvage was more reported in patients who underwent iliac artery angioplasty & stenting than in patients who underwent angioplasty only with p value 0.002. Conclusion: Above-the-knee amputation 30 days post iliac artery angioplasty ± stenting is significantly associated with increasing age, total iliac artery occlusion, concomitant CIA & EIA lesions, diseased PFA, TASC D lesions & in patients who underwent iliac artery angioplasty only than in patients who underwent angioplasty & stenting. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of intractable toe ulcer with critical limb ischemia (CLI) is a challenge because of its poor blood flow and the wound. Here, a novel fixation technique for artificial dermis with negative pressure wound therapy (NPWT) was reported. Method: After the amputation of toe, artificial dermis made of collagen-gelatin sponge (CGS) was grafted onto the wound where human recombinant basic fibroblast growth factor (bFGF) was sprayed. The foot was put on adhesive iodine-impregnated drape, the artificial-dermis area was covered with a sponge dressing of which another end reached to the drape, and the vacuum port was applied on the dressing sponge sandwiched with two drapes and connected to an NPWT system. Since the shape of sponge-dressing was similar to that of elephant-trunk, the technique in this study was named an “Elephant-trunk” technique. Result: During NPWT period, no complications such as air leakage, skin erosion, ischemic around tissue were confirmed. The artificial dermis was engrafted completely at one week after surgery, and the wound was confirmed to close completely. Conclusion: This NPWT technique with bFGF and CGS accelerated the healing of wound treated conservatively with artificial dermis in CLI patients.

Introduction: Individual dosimetry makes Yttrium - 90(90Y) Transarterial Radioembolization (TARE) safer and more effective. Cherenkov Luminescence Imaging (CLI) has been employed as a novel approach for 90Y imaging. While this technique is straightforward and effectively tackles specific limitations in current nuclear medicine systems, its broad application is hindered by its constrained penetration range and low light yield. The predominant wavelength of Cherenkov radiation falls within the ultraviolet spectrum. As a result, it is strongly absorbed by the medium. The intensity of generated Cherenkov radiation is directly dependent on the refractive index of the medium. Introducing nanoparticles (NPs) with a high refractive index into the medium makes it possible to increase the penetration depth and the number of Cherenkov radiation. Objective: This study aimed to overcome limitations in CLI by utilizing TiO2 NPs during the 90Y TARE. Materials: The simulation of CLI was performed using the Monte Carlo codes GATE (version 9) and GEANT4 (version 10.6). TiO2 NPs (with a diameter of 100 nm) were modeled to be randomly distributed within 90Y - loaded glass microspheres at concentrations of 0, 1.2 mol/L, 2.4 mol/L, and 4.8 mol/L. The Cerenkov radiation spectra emitted from the glass microsphere were computed using GEANT4. The obtained spectra were uniformly distributed within the liver tumor of the MOBY mouse phantom. Subsequently, Cherenkov luminescence images of the tumor were captured using GATE. The dosimetry accuracy was assessed by determining the Root Mean Square Errors (RMSEs) in Cherenkov luminescence image - based Dose Volume Histograms (DVHs) and the reference DVHs. Results: The in - silico results showed that RMSE values decreased significantly as the TiO2 NP concentration increased in the glass microspheres. The maximum RMSE reduction was observed at the TiO2 NP concentration of 4.8 M (17%). Conclusions: Our investigation has provided evidence that integrating TiO2 NPs into the glass microspheres enhances the precision of individual dosimetry in Y - 90 - TARE. [ABSTRACT FROM AUTHOR]

Chronic limb-threatening ischemia (CLTI) is on the rise due to the increasing prevalence of diabetes, which is a significant cause of morbidity and mortality worldwide. Due to diabetes, many patients with CLTI present with a predominance of tibial and pedal artery disease. Despite best care, limb amputation cannot always be prevented. Surgical bypass has always been the mainstay in distal revascularization and limb salvage; however, many patients with CLTI have comorbidities, insufficient vein, and anatomic abnormalities that prevent them from undergoing surgery. As a result, endovascular therapies have increased over the last 2 decades and are providing revascularization options in these patients. Although most of the current endovascular literature has focused on above-ankle arterial interventions, recent studies have highlighted the feasibility, safety, and clinical importance of pedal artery interventions. These endovascular techniques hold promise in relieving ischemic pain, healing foot ulcers, reducing rates and extent of amputation, and improving patient functionality and quality of life. This review aims to comprehensively detail pedal artery interventions in terms of anatomy, technique, intraprocedural imaging, and outcomes. In addition, suggestions of when to perform pedal artery interventions and post-intervention surveillance options will be discussed. [ABSTRACT FROM AUTHOR]

Critical limb ischemia (CLI) is a severe disease which affects about 2 million people in the US. Its prevalence is assessed at 800/100,000 population. However, no reliable tools are currently available to assess perfusion defects at the muscle tissue level. DCE-MRI is a technique that holds the potential to be effective in achieving this goal. However, preclinical studies performed with DCE-MRI have indicated low sensitivity assessing perfusion at resting state. To improve these previous results, in this work we propose new methodologies for data acquisition and analysis and we also revisit the biological model used for evaluation. Eleven rabbits underwent embolization of a lower limb. They were imaged at day 7 after embolization using DCE-MRI, performed on a 4.7 T small imaging device. Among them, n = 4 rabbits were used for MRI sequence optimization and n = 6 for data analysis after one exclusion. Normalized Areas under the curve (AUCn), and kinetic parameters such as K trans and V d resulting from the Tofts-Kety modeling (KTM) were calculated on the embolized and contralateral limbs. Average and heterogeneity features, consisting on standard-deviation and quantiles, were calculated on muscle groups and whole limbs. The Wilcoxon and Fisher-tests were performed to compare embolized and contralateral regions of interests. The Wilcoxon test was also used to compare features of parametric maps. Quantiles of 5 and 95% in the contralateral side were used to define low and high outliers. A P -value <0.05 was considered statistically significant. Average features were inefficient to identify injured muscles, in agreement with the low sensitivity of the technique previously reported by the literature. However, these findings were dramatically improved by the use of additional heterogeneity features (97% of total accuracy for group muscles, P < 0.01 and 100% of total accuracy for the total limbs). The mapping analysis and automatic outlier detection quantification improvement was explained by the presence of local hyperemia that impair the average calculations. The analysis with KTM did not provide any additional information compared to AUCn. The DCE technique can be effective in detecting embolization-induced disorders of limb muscles in a CLI model when heterogeneity is taken into account in the data processing, even without vascular stimulation. The simultaneous presence of areas of ischemia and hyperemia appeared as a signature of the injured limbs. These areas seem to reflect the simultaneous presence of infarcted areas and viable peripheral areas, characterized by a vascular response that is visible in DCE. • Microbead embolization induced ischemia in the limbs visible with DCE-MRI mapping. • Embolization also induced hyperemia compatible with peripheral vasoreactivity. • Hyperemia prevented detection of ischemia in standard average perfusion values. • The detection was efficient with heterogeneity features that involve both phenomena. [ABSTRACT FROM AUTHOR]

Chronic limb-threatening ischemia (CLTI) is prevalent and associated with morbidity and mortality. The published research concerning CLTI therapeutics is evolving. The goals of this review are to: 1) summarize the endpoints that are being used in trials assessing interventions for patients with CLTI; and 2) review gaps and discrepancies in current outcome definitions. A search was conducted of the PubMed database and ClinicalTrials.gov to identify studies published between January 2000 and March 2020 that evaluated treatment options for patients with CLTI. Meta-analyses, case series, case reports, abstracts, and expert opinion were excluded. Forty-nine studies (n = 11,667) were identified that fulfilled the inclusion criteria. Most trials reported clinical outcomes (mortality, 69.4%; limb events, 87.8%; target lesion revascularization, 83.7%). Mean follow-up duration was 23.7 months. In investigational device exemption trials, total follow-up and follow-up to primary outcomes were discordant (12 months vs 6 months; P = 0.0018). Hemodynamic testing was reported in 71.4%, usually ankle-brachial index. Patency was assessed in 89.8% of trials; ultrasound was used in 65.3% and invasive angiography in 85.7%, at baseline and/or during follow-up. Wound assessment was performed in 49.0% of studies, qualitative in 28.6% and quantitative in 20.4%. Finally, quality of life assessment was performed in 55% of studies. Definitions for many outcomes varied across studies. Consensus regarding which outcomes to study, uniform definitions, and optimal methods to measure some of these outcomes are yet to be established. A comprehensive effort by all stakeholders is needed to move the field of CLTI forward. [Display omitted] • Variability in CLTI trial outcomes hinders the study of this devastating condition. • A core group of outcomes should be assessed in every CLTI trial. • A coordinated multistakeholder effort is needed to advance the field of CLTI. [ABSTRACT FROM AUTHOR]

In the spirit of Hjorth's turbulence theory, we introduce "unbalancedness": a new dynamical obstruction to classifying orbit equivalence relations by actions of Polish groups which admit a two-sided invariant metric (TSI). Since abelian groups are TSI, unbalancedness can be used for identifying which classification problems cannot be solved by classical homology and cohomology theories. In terms of applications, we show that Morita equivalence of continuous-trace C*-algebras, as well as isomorphism of Hermitian line bundles, are not classifiable by actions of TSI groups. In the process, we show that the Wreath product of any two non-compact subgroups of S∞ admits an action whose orbit equivalence relation is generically ergodic against any action of a TSI group and we deduce that there is an orbit equivalence relation of a CLI group which is not classifiable by actions of TSI groups. [ABSTRACT FROM AUTHOR]

The aim of this work is detection of the effect of PRP on wound healing on diabetic wound in ischemic patients, this study is randomized controlled clinical trial that was conducted on ( 30 ) patients who was divided in 2 groups; group (A) received PRP, and group (B) received the traditional dressing after revascularization of the previous ischemic diabetic limbs, both groups were divided randomly by randomization block at the department of Vascular and General surgery, Beni - Suef University Hospital. Results: There was no significant association between the both groups regarding the post-operative complication (p value; 0.698). There was significant strong inverted correlation between rate of healing and size of ulcers. And there was significant strong proportional correlation between size of ulcers and treatment time (p=0.002) and there was significant strong proportional correlation between size of ulcers and the number of injections (p=0.040). However, the cost of the PRP technique was much higher than the traditional technique and p value was statistically significant.

Objective: Major surgery may induce an inflammatory response, which results in an increased level of C-reactive protein (CRP) and represented in albumin loss to extravascular area due to increased capillary permeability. Our study was to evaluate the association between capillary leak index (CLI) and intensive care unit (ICU)-related mortality in patients underwent major abdominal surgery. Design: This was a prospective study with cohort analytic design. Patients and participants: We included adult patients aged 18 and older who were treated in ICU after underwent major abdominal surgery. Patients who were pregnant, having menstruation, relaparotomy, diabetes mellitus, and idiopathic systemic capillary leak syndrome were excluded from this study. Blood was collected before surgery and at 48 and 72 hours after surgery. Patients were observed for mortality incidence during treatment in the unit. The CRP level was measured using ABX Pentra 400 (HORIBA, Germany), whereas the albumin level was measured using HumaStar 80 (HUMAN, Germany). CLI was measured by dividing CRP level by albumin level. Data were analyzed using SPSS Statistics version 21.0 (IBM, New York, U.S.). Results: CLI at hour 72 was associated with increased risk of ICU-related mortality (RR 21.667; 95% CI 2.938-159.763; p<0.001). Discussion: Acute inflammation normally resolved within three days. Systematic response to tissue injury, including major surgery, is marked by increased proinflammatory cytokines, which promotes CRP production and capillary leakage. CRP production will increase to its peak level 3650 hours after inflammation. However, if the injury still exists, inflammatory process will continue. Conclusions: High CLI at hour 72 can be considered as the risk factor to ICU-related mortality. [ABSTRACT FROM AUTHOR]

Objective: The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI. Methods: We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007–2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson’s correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients. Results: Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n= 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R=-0.61, P = 0.39). Conclusions: Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management. [ABSTRACT FROM AUTHOR]

Communication is indispensible in human population. This study investigated the effect of communication literacy intervention (CLI) on sign language knowledge (SLK) among special needs deaf and dumb college students (SNDDCS) in Nigeria. The study adopted experimental research design involving a purposive sampling of 48 SNDDCS in Nigeria between March and June, 2021. The eligible participants were randomly assigned either in treatment (n=24) or control (n=24) group respectively. Only the participants in the treatment group were exposed to CLI manual while both groups participated in pre-posttest measures of sign language knowledge questionnaire -SLKQ with reliability index (r=0.87). The IBM SPSS version 22 was applied for all statistical computations. The results were deemed significant at p≥0.05. The findings showed that the participants in the treatment group recorded very high SLK scores in the posttest (80.6%) and follow-up (81.7%) measures when compared to the pretest low SLK score (46.2%), implying a significant increase in SLK. Statistically, significant differences were reported within demographic variables and intervals. Thus, no significant difference existed on gender (p=0.090>0.05) and location (p=0.680>0.05) while differences were observed on age by birth (p=0.002<0.05) and school type (p=0.011<0.05). Also, significant difference was observed on pretest (p=0.001<0.05) and follow-up (p=0.010<0.05) intervals while none was recorded on posttest measure (p=0.061>0.05). Therefore, the CLI has significant effect on SLK of SNDDCS in Nigeria. The adoption of language intervention such as CLI in special needs colleges is crucial in improving knowledge and use of sign languages by deaf and dumb students. [ABSTRACT FROM AUTHOR]

We have analyzed in a retrospective study of consecutive diabetic patients affected by no-option critical limb ischemia (CLI) the efficacy of the dermal substitute Integra Dermal Regeneration Template for treatment of complicated foot lesions. The primary end point was limb salvage and 1-year amputation-free survival. The secondary end point was healing time of surgical site. Between October 2014 and October 2017, 1024 patients with diabetic foot ulcer (DFU) and CLI were admitted. In 84 patients (8.2%), there was a failure in distal revascularization with a persistent CLI after the procedure. Despite the persistent CLI, a group of 26 patients of this cohort obtained complete wound healing. Among them, 13 patients were treated with surgical debridement or open amputations and application of dermal substitute Integra Dermal Regeneration Template and the other 13 patients were treated without any dermal substitute. The Integra group healed within a mean time of 83.5 days, and the control group healed within a mean of 139 days (P =.028). No major amputation was carried out at 1-year follow-up in the Integra group versus 15% in the control group. A conservative foot surgery or an approach with minor amputation in diabetic patients with no-option CLI may achieve limb salvage. The use of Integra Dermal Regeneration Template in patients with DFU and no-option CLI may be a useful option in a limb salvage program. [ABSTRACT FROM AUTHOR]

Introduction: Accurate post-treatment dosimetry is essential for evaluating the effectiveness of the Yttrium-90 Transarterial Radioembolization (TARE) treatment. Y-90 Positron Emission Tomography (PET) imaging is acknowledged as the premier modality for post-TARE dosimetry. The low positron yield of Y-90 is a significant challenge for Y-90 PET image - based dosimetry. Recently, Cherenkov Luminescence Imaging (CLI) has been used as a new technique for Y - 90 imaging. CLI is simple and resolves some limitations with the Y-90 PET imaging. Objective: This work aimed to improve personalized dosimetry in TARE using Cherenkov Luminescence Imaging. Methods: The Monte Carlo codes GATE (version 9.2) were employed to simulate post - TARE PET imaging and CLI in the MOBY mouse phantom. The liver tumor with a 5 mm diameter was modeled in the phantom, and Y-90 was distributed uniformly within the tumor. The quality of PET and Cherenkov luminescence images was evaluated by calculating contrast and Coefficient of Variance (CV). The personalized dosimetry accuracy was estimated as Root Mean Square Errors (RMSEs) in the acquired imagebased Dose Volume Histograms (DVHs) and the reference DVHs. Results: The findings indicated that the Cherenkov luminescence image exhibited approximately 39% higher contrast and 44% lower Coefficient of Variation (CV) values than the PET image. The RMSE in Cherenkov luminescence image-based dosimetry, in comparison to PET image - based dosimetry, demonstrated a significant reduction of 51.4%. Conclusions: Our research offers compelling evidence supporting the superior precision of personalized dosimetry using CLI over PET imaging in the TARE. Our approach is readily applicable in preclinical studies and is characterized by its simplicity and effectiveness. [ABSTRACT FROM AUTHOR]

Objective: Peripheral arterial disease (PAD) is a chronic arterial occlusive disease which mostly affects the arteries of the lower extremities. PAD morbidity generally ranges from 3% to 10%, although it increases with advancing age and can be greater than 15% in subjects over 60 years of age. In small trials, autologous bone marrow aspirate stem cell concentrate (BMAC) has proven to be safe and effective in promoting angiogenesis in patients with PAD. In this small pilot, open-label, non-randomized, non-controlled study, we assessed the safety and feasibility of intramuscular BMAC injection and implantation for treatment of patients with PAD who are not susceptible to conventional endovascular or open revascularization. Patients and Methods: A total of 27 patients with non-revascularizable CLI (Fontaine stages III and IV) were enrolled between 2015 and 2019. Comorbidities and risk factors for PAD such as diabetes, hypertension, dyslipidemia and cigarette smoking were also evaluated. Results: A total of 27 patients (M/F: 25/2) with non-revascularizable critical limb ischemia (stages III and IV according to Fontaine classification) were enrolled between 2015 and 2019. Comorbidities and risk factors for PAD such as type 2 diabetes, hypertension, cigarette smoking and dyslipidemia were also evaluated. The prevalence of cigarette smoking was high (74%; 20 patients). During the follow-up, only 4 patients underwent amputation of the limb affected by critical ischemia. In such subgroup, all patients had a Fontaine stage IV PAD. The remaining 23 patients showed a remarkable improvement in clinical features and ankle-brachial index (ABI) values, without undergoing lower-limb amputation. Computed tomography angiography (CTA) performed 3 months after the intramuscular BMAC injection confirmed the presence of neovascularization in 24 out of 27 patients. The procedure was well-tolerated by all patients. Conclusions: Our study showed that intramuscular BMAC injection is a safe and feasible approach for obtaining clinical improvement and short-term induction of neovascularization in patients with severe PAD.

Antegrade crossing techniques via transfemoral access are often challenging and may be associated with technical and clinical failure when treating patients with critical limb ischaemia (CLI). The objective of this study was to summarise all available literature regarding retrograde endovascular treatment of patients with CLI and to investigate the technical success and complication rate of retrograde access. A systematic literature search was performed in PubMed, Scopus, and Cochrane Central until May 2020. A meta-analysis of 31 observational studies (29 retrospective and two prospective; 26 and five studies with low and moderate risk of bias, respectively) was conducted with random effects modelling. The incidence of adverse events peri-procedurally and during follow up were calculated. The 31 studies enrolled 1 910 patients who were treated endovascularly for femoropopliteal and/or infrapopliteal lesions causing CLI. Most of the patients had diabetes while more than half of the overall population had coronary artery disease and dyslipidaemia. All lesions were located in the infra-inguinal segment and most were chronic total occlusions (96%; 95% CI 85%–100%). Seven studies reported moderate or severe calcification in approximately half of the cases (45%; 95% CI 30%–60%). The overall technical success of the retrograde approach was 96% (18 studies; 95% CI 92%–100%). Perforation, flow limiting dissection, distal embolisation, and local haematoma at the retrograde access site were infrequent and observed in 2.1%, 0.6%, 0.1%, and 1.3% of the patients, respectively. The six month primary patency rate was 78% (five studies; 95% CI 46%–99%), the six month limb salvage rate was 77% (four studies; 95% CI 70%–84%). The results indicated that the retrograde or bidirectional antegrade/retrograde approach is safe and effective and facilitates angioplasty when antegrade treatment fails. However, prospective studies with standardised wound care and surveillance protocols are needed to investigate retrograde techniques in patients with CLI who failed antegrade revascularisation, to improve long term limb salvage and survival. [ABSTRACT FROM AUTHOR]

Since 2013, the Japanese Society for Vascular Surgery has started the project of nationwide registration and tracking database for patients with critical limb ischemia (CLI) who are treated by vascular surgeons. The purpose of this project is to clarify the current status of the medical practice for the patients with CLI to contribute to the improvement of the quality of medical care. This database, called JAPAN Critical Limb Ischemia Database (JCLIMB), is created on the National Clinical Database and collects data of patients' background, therapeutic measures, early results, and long-term prognosis as long as 5 years after the initial treatment. The limbs managed conservatively are also registered in JCLIMB, together with those treated by surgery and/or endovascular treatment. In 2020, 1299 CLI limbs (male 890 limbs: 69%) were registered by 85 facilities. Arteriosclerosis obliterans has accounted for 99% of the pathogenesis of these limbs. In this manuscript, the background data and the early prognosis of the registered limbs are reported. (This is a translation of Jpn J Vasc Surg 2023; 32: 363-391.)., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Peripheral vascular disease is a common affliction in the diabetic patient, and its presence adds great complexity to limb salvage efforts. While many patients with critical limb ischemia may be relegated to a major amputation, especially in the setting of a failed minor amputation, worthwhile salvage efforts may be possible. We present a case of limb salvage by way of a Chopart's amputation performed after a failed amputation at the transmetatarsal level. In this patient, pedal circulation was supplied only by collateral vessels, as occlusion affected all 3 major below-knee arteries. To our knowledge, limb salvage has not been previously described in this scenario. Given the favorable outcome presented in this piece, we hope to raise awareness of the potential for salvage in this patient population, and spur continuous research into the complex entity of peripheral vascular disease. Additionally, we present our operative and perioperative pearls as a resource for the limb salvage surgeon. [ABSTRACT FROM AUTHOR]

When diabetes mellitus is not properly controlled with drugs and a healthy lifestyle, it exposes patients with advanced peripheral arterial disease or critical limb ischaemia (CLI) to the most serious complications, in particular lower limb ulcers. Surgical or endovascular treatments represent the first line of intervention; in addition, the adequate management of ulcers can guarantee not only a faster wound healing but also the improvement of the patient's prognosis. To speed up this process, negative pressure wound therapy (NPWT), platelet‐rich plasma (PRP), and other advanced moist wound dressing have been proposed. During Coronavirus disease 2019 (COVID‐19) pandemic, many patients with CLI and diabetes mellitus had difficult access to advanced treatments with a significant reduction in life expectancy. We report the cases of patients with non‐healing ulcers and CLI treated with an empiric multistage approach after successful endovascular revascularisation; the postoperative course was eventful in all patients, and foot ulcers are currently in an advanced state of healing. The association between adequate revascularisation, systemic anti‐inflammatory, and antibiotic therapy with the multistage advanced medications ensures healing of ulcers, limb salvage, and improvement of patient prognosis. [ABSTRACT FROM AUTHOR]

An altered balance between metalloproteinases (MMPs) and their inhibitor tissue inhibitor of metalloproteinases (TIMPs) may influence the healing process of a minor amputation following a successful vein graft. To speed up this process, negative pressure wound therapy (NPWT) and advanced moist wound dressing have been proposed. We determined the systemic and local release of MMP‐1, ‐2, ‐3, ‐9, TIMP‐1, and TIMP‐2 by enzyme linked immunosorbent assay (ELISA) technique and their influences in the healing process in 26 patients who underwent minor amputation after a successful revascularisation procedure. Twelve patients (group 1) were medicated with NPWT and 14 (group 2) with advanced moist wound dressing. Plasma samples were collected on the morning of surgery and thereafter at 1, 3, and 5 months; exudates were collected 3 days after surgery when amputation was performed and thereafter at 1, 3, and 5 months. Fifteen age‐matched healthy male volunteers served as controls. All wounds healed in 5 ± 0.5 months. Follow‐up plasma and local release of MMP‐1, ‐2, ‐3, and ‐9 were overall significantly lower when compared with the preoperative levels, while those of TIMP‐1 and ‐2 were significantly higher with no differences among the groups. Despite no differences in the healing process being observed among the two types of medications, at 1 month the local release of MMP‐2 and ‐9 was significantly lower (P =.013 and.047, respectively) and that of TIMP‐1 was significantly higher (P =.042) in group 1 as compared to group 2. A correct and aggressive local approach to the wound is able to promote the healing of the lesion stimulating the extracellular matrix turnover with local MMP/TIMP adequate balance and favouring the creation of granulation tissue. However, a successful restoration of an adequate blood flow remains the key point of a durable and rapid wound healing. [ABSTRACT FROM AUTHOR]

Background: High-risk patients with advanced peripheral artery disease (PAD), including critical limb ischemia (CLI), are often excluded from peripheral endovascular device intervention clinical trials, leading to difficulty in translating trial results into real-world practice. There is a need for prospectively assessed studies to evaluate peripheral endovascular device intervention outcomes in CLI patients.Methods: LIBERTY 360 is a prospective, observational, multi-center study designed to evaluate the procedural and long-term clinical outcomes of peripheral endovascular device intervention in real-world patients with symptomatic lower-extremity PAD. One thousand two hundred and four patients were enrolled and stratified based on Rutherford Classification (RC): RC2-3 (N=501), RC4-5 (N=603), and RC6 (N=100). For this sub-analysis, RC5 and RC6 patients (RC5-6; N=404) were pooled and 1-year outcomes were assessed.Results: Procedural complications rarely (1.7%) resulted in post-procedural hospitalization and 89.1% of RC5-6 patients were discharged to home. Considering the advanced disease state in RC5-6 patients, there was a high freedom from 1-year major adverse event rate of 65.5% (defined as target vessel revascularization, death to 30 days, and major target limb amputation). At 1 year, freedom from major amputation was 89.6%. Wounds identified at baseline on the target limb had completely healed in 172/243 (70.8%) of the RC5-6 subjects by 1 year. Additionally, the overall quality of life, as measured by VascuQoL, improved from baseline to 1 year.Conclusion: LIBERTY investigated real-world PAD patients with independent oversight of outcomes. This analysis of LIBERTY RC5-6 patients demonstrates that peripheral endovascular device intervention can be successful in CLI patients, with low rates of major amputation and improvement in wound healing and quality of life through 1-year follow-up.LIBERTY 360, https://clinicaltrials.gov/ct2/show/NCT01855412, ClinicalTrials.gov Identifier: NCT01855412. [ABSTRACT FROM AUTHOR]

Ostial lesions of the superficial femoral artery preclude the use of ipsilateral common femoral artery antegrade approach. Access via either the contralateral common femoral or the brachial arteries are the 2 alternative classical approaches. Conversely, using an ipsilateral antegrade approach, through a partially inserted sheath, usually leaves the sheath insecure and frequently hits ostial lesion itself during insertion. Dislodgment from the artery frequently occurs, resulting in loss of access. We describe a technique whereby we insert 2 to 3 cm of the sheath into the common femoral artery and the remaining part of the sheath resides in a fashioned subcutaneous tunnel of the lowermost abdomen. Technical details are provided as well as the results of using this technique on 37 patients. The technique is safe, easy to perform, and reproducible. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: We are presenting three cases (out of similar several cases) where tibio-pedal approach was performed as an initial primary approach for limb salvage in patients with CLI secondary to Infra-popliteal (IP) disease. We consider this approach to be a necessary evolution in endovascular intervention. Discussion: Retrograde pedal access is safe, feasible with high technical success rate and a relatively low procedural complication rate, with low 30 days mortality and low rate of major adverse cardiac events. Freedom from major adverse limb events and limb salvage are both high at 1 year follow up. It allows quick therapy and short procedure time with less observation time in the hospital. A retrograde approach utilizing pedal access improves the crossing success of lesions as well as facilitates the use of some atherectomy devices to remove large plaque burden and modify the compliance of severely calcified infra-popliteal vessels. Using the retrograde approach will minimize the classic complications of the antegrade femoral approach. Conclusion: Retrograde tibio-pedal arterial access, as an initial primary approach for endovascular intervention in CLI patients confined to IP vessels, is an effective, safe, and feasible approach with a high technical success rate and a relatively low procedural complication rate.

Background: Certain patients with critical limb ischemia (CLI) experience significant decline in activities of daily living (ADL) during hospitalization. The prognosis of decline in ADL during hospitalization remains unknown. Methods: A retrospective analysis was performed on collected data of patients with CLI treated by endovascular treatment between April 2007 and December 2015. We evaluated CLI in patients ADL at the time of hospitalization and after discharge using the Barthel index. We classified all patients into patients with decline in ADL and stable in ADL and compared clinical outcomes (cumulative incidence of wound healing, amputation-free survival at 1 year) between the 2 groups. Results: Two hundred and fifty-five consecutive patients with CLI (221 limbs), who underwent successful endovascular intervention, were enrolled in this study. Of all patients, 22 patients were classified into the decline group. The prevalence of wound, Ischemia, foot infection (WIfI) classification high grade was higher in the decline group (30.7% vs 63.6%; P < .01). The wound healing rates were worse in the decline group than in the stable group (40% vs 78% at 1 year; P < .01). The same trends were observed in the amputation-free survival (37% vs 78%; P < .01). After multivariate analysis, decline in ADL was an independent predictor of wound healing and amputation-free survival (odds ratio [OR]: 2.85, 95% confidence interval [CI]: 1.61-3.35, P < .01; OR: 2.46, 95% CI: 1.26-4.53, P = .01). Conclusions: Patients with CLI with decline in ADL during hospitalization were found to have a poor prognosis suggesting that a decline in ADL may affect the clinical outcomes. [ABSTRACT FROM AUTHOR]

Critical limb ischemia (CLI) is the most advanced form of peripheral artery disease. It is associated with significant morbidity and mortality and high management costs. It carries a high risk of amputation and local infection. Moreover, cardiovascular complications remain a major concern. Although it is a well-known entity and new technological and therapeutic advances have been made, this condition remains poorly addressed, with significantly heterogeneous management, especially in nonexperienced centers. This review, from a third-level dedicated inpatient and outpatient cardioangiology structure, aims to provide an updated summary on the topic of CLI of its complexity, encompassing epidemiological, social, economical and, in particular, diagnostic/imaging issues, together with potential therapeutic strategies (medical, endovascular, and surgical), including the evaluation of cardiovascular risk factors, the diagnosis, and treatment together with prognostic stratification. [ABSTRACT FROM AUTHOR]

This study examines three L3 transfer proposals, namely the L1 Factor (Hermas, 2010, 2014a, 2014b), the CEM (Flynn et al., 2004) and the TPM (Rothman, 2010, 2011, 2013, 2015) as well as investigates the role of the language of dominance in L3 acquisition of English attributive adjectives. Three groups of bilinguals took part in this study: L1 Mazandarani/L2 Persian, with Mazandarani as the dominant language of communication, L1 Mazandarani/L2 Persian, with Persian as the dominant language of communication and L1 Persian/L2 Mazandarani, with Persian as the dominant language of communication. The results of a grammaticality judgment task and an element rearrangement task show that the predictions of the above-mentioned L3 transfer proposals were not realized. Instead, the dominant language of communication turns out to be the main source of syntactic crosslinguistic influence at the initial stages of L3 acquisition, irrespective of its status as an L1 or L2. [ABSTRACT FROM AUTHOR]

Objectives The “angiosome” concept as a model for decision making in revascularisation of patients with critical limb ischaemia (CLI) has been subject to lively discussion in recent years. The aim of this prospective pilot study was to use intra-operative fluorescence angiography to provide further data on the angiosome concept on the level of microcirculation after tibial bypass surgery. Design, materials, and methods This was a prospective analysis of 40 patients presenting with CLI Rutherford stage IV to VI before and after tibial bypass surgery. The macrocirculation was measured by the ankle brachial index. Skin microcirculation was assessed by intra-operative fluorescence angiography. The alteration of microcirculation was compared in direct and indirect revascularised angiosomes. Clinical follow-up investigations were performed and the wound healing rate was compared between the different revascularisation methods. Results Cumulated microcirculation parameters showed a significant improvement after surgery (ingress, ingress rate p <.001). Likewise, general microcirculatory improvement was observed in each foot angiosome after revascularisation, regardless of the tibial artery revascularised. Furthermore, a comparison of the direct (DR) and the indirect revascularised (IR) angiosomes did not show a significant difference concerning the improvement of microcirculation (difference DR-IR, ingress: 1.69, 95% CI 71.73–75.11; ingress rate: 0.08, 95% CI −12.91 to 13.07). The wound healing rate was similar in both groups, although the time to wound healing was faster by on average 2.5 months in the DR group ( p =.083). Conclusion Microcirculatory improvement was seen over the whole foot after tibial bypass. Therefore, fluorescence angiography is a promising tool to evaluate the angiosome concept in future larger studies. Clinicaltrials.gov : NCT03012750 . [ABSTRACT FROM AUTHOR]

Purpose: To identify possible risk factors in predicting clinical outcome in critical limb ischemia (CLI) patients undergoing percutaneous transluminal angioplasty (PTA).Materials and Methods: PubMed and EMBASE were searched for studies analyzing CLI and clinical outcome after PTA from January 2006 to April 2017. Outcome measures were ulcer healing, amputation free survival (AFS)/limb salvage and overall survival. Data on predictive factors for ulcer healing, AFS/limb salvage and survival were extracted.Results: Ten articles with a total of 2448 patients were included, all cohorts and based on prospective-designed databases. For ulcers, it seems that complete healing can be achieved in most of the patients within 1 year. No significant predictive factors were found. AFS/limb salvage: AFS rates for 1, 2 and 3 years ranged from 49.5 to 75.2%, 37 to 58% and 22 to 59%, respectively. Limb salvage rates for 1, 2 and 3 years ranged from 71 to 95%, 54 to 93.3% and 32 to 92.7%, respectively. All studies had different univariate and multivariate outcomes for predictive factors; however, age and diabetes were significant predictors in at least three studies. Survival: Survival rates for 1, 2 and 3 years ranged from 65.4 to 91.5%, 45.7 to 76% and 37.3 to 83.1%, respectively. Different predictive factors were found; however, age was found in 2 out of 5 studies reporting on predictive factors.Conclusions: In several studies two factors, age and diabetes, were found as predictive factors for AFS/limb salvage and survival in patients with CLI undergoing PTA. Therefore, we believe that these factors should be taken into account in future research.Level Of Evidence: Level 2a. [ABSTRACT FROM AUTHOR]

The slimming product Mysimba®, a combination of naltrexon and bupropion, was recently included in the Dutch drug reimbursement system (Geneesmiddelenvergoedingssysteem, GVS). The drug is fully reimbursed under the national basic health insurance package, though with specific preconditions, including its use together with the Dutch programme known as combined lifestyle intervention (CLI). Its inclusion in the GVS was reported in the Dutch TV news on Tuesday 24 May 2022. Despite what this media attention suggests, results achieved with naltrexon/bupropion in terms of weight loss have been disappointing, and it is to be expected that over a third of users will discontinue the treatment for this reason. A study using cardiovascular endpoints yielded no conclusions, as it was prematurely ended. There is therefore no reason to recommend this drug to obese patients in practice. [ABSTRACT FROM AUTHOR]

Human mesenchymal/stromal stem cells (hMSC) are the most promising cell source for adult cell therapies in regenerative medicine. Many clinical trials have reported the use of autologous transplantation of hMSCs in several disorders, but with limited results. To exert their potential, hMSCs could exhibit efficient homing and migration toward lesion sites among other effects, but the underlying process is not clear enough. To further increase the knowledge, we studied the co-regulation between hypoxia-regulated genes and miRNAs. To this end, we investigated the miRNA expression profile of healthy hMSCs in low oxygen/nutrient conditions to mimic ischemia and compared with cells of patients suffering from critical limb ischemia (CLI). miRNAs are small, highly conserved, non-coding RNAs, skilled in the control of the target’s expression level in a fine-tuned way. After analyzing the miRNOme in CLI-derived hMSC cells and healthy controls, and intersecting the results with the mRNA expression dataset under hypoxic conditions, we identified two miRNAs potentially relevant to the disease: miR-29b as a pathological marker of the disease and miR-638 as a therapeutic target. This study yielded a deeper understanding of stem cell biology and ischemic disorders, opening new potential treatments in the future.

This paper presents a fully computerized method to backup the router configuration file. The method consists of a friendly graphical interface programmed by Java programming language The proposed method is compared with the two existing methods, namely: TFTP server method and Copy/Paste method. The comparison reveals that the proposed method has many advantages over the existing ones. The proposed method has been implemented on Cisco routers (series 2500, 2600 and 2800)

This Special Issue of Higher Learning Research Communications (HLRC) is dedicated to research in content language integrated learning (CLIL) and English-medium instruction (EMI). A we make our way in the 21st century, higher education institutions are faced with multiple challenges as they try to prepare future professionals. Issues such as globalization and internationalization, technology, access to information, interculturality, and the like pose challenges for future generations. And, higher education institutions play a fundamental role in shaping how that future will look like. In the face of multiculturalism and the communication barriers that are bound to happen, many countries and educational systems are incorporating English, not only as a means to facilitate contact among cultures, but as a means of instruction in itself. The groundwork laid down during the past decades by several researchers, such as David Marsh, has paved the way to promote multilingualism, not just by learning a language but also by using the second or foreign language as a content delivery method. Most research in this area has focused on primary and secondary education; thus, the research regarding CLIL and EMI in tertiary education is limited at the moment. However, in recent years there has been a boom in English-taught programs in non-English speaking countries. This means the need for research is this area is bound to grow exponentially as faculty, students, and institutions, and even governments and the labor market, take on the challenges of English-mediated instruction. It is out hope that with this Special Issue, which features research from Japan and Spain, we can contribute meaningful research to the field.

This volume of HLRC is dedicated to the emergent and rapidly growing interest in English Medium Instruction as a major driver in the internationalization of higher education. It focuses on sharing knowledge and experience in CLIL (Content and Language Integrated Learning) and EMI (English Medium Instruction) from different universities in Eastern and European countries as a means to reflect and improve upon teaching and learning. As editors, we would like to kick this volume off with a review of one of the most comprehensive and relevant publications on the topic in recent times, The Higher Education Language Landscape: Ensuring Quality in English Language Degree Programmes, (2013). Following the book review is a short question and answer section with its authors and renowned experts in the field, David Marsh, Victor Pavón Vázquez, and María Jesús Frigols Martín. We would like to extend our gratitude to all three for providing us with their insights, which are, no doubt, of great use to higher education institutions considering embarking upon or improving English-taught degree programs.

OBJECTIVE: Fibroblast growth factor 23 (FGF23) was demonstrated to be involved in the occurrence and development of cardiovascular disease (CVD). The aim of this study was to investigate the potential role of FGF23 on presence and severity of peripheral arterial disease (PAD) in type 2 diabetic patients. PATIENTS AND METHODS: In this study, we analyzed FGF23 serum levels in 413 type 2 diabetic patients with PAD and in 598 diabetic controls without lower limbs atherosclerosis. RESULTS: We found that FGF23 median serum levels were significantly higher in patients than in diabetic controls (69.3 (58.8-75.1) pg/mL in PAD and 42.98 (37.1-49.8) pg/mL in subjects without PAD (p < 0.001) and were significantly and independently associated with critical limb ischemia (CLI) [OR, 7.69 (2.64-16.31); p = 0.001]. CONCLUSIONS: We have found, for the first time, that FGF23 could be associated with presence and severity of PAD in Italian patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abrasiveness of rocks plays an important role in the wear of TBM tunnelling. Cerchar Abrasivity Index (CAI) test is the most commonly used method to estimate rock abrasiveness due to its simple, fast test procedure and economic benefits. This study investigated the correlation between CAI and geomechanical properties of igneous and metamorphic rocks. Single and multiple regression analysis were performed and predictive models for the CAI from geomechanical properties were developed. It is found that single parameter alone is not suitable to predict the value of CAI. The result of the multiple regression analysis shows that quartz content is less influencing factor to predict the value of CAI. Also, the correlation between CAI and NTNU’s Cutter Life Index (CLI) was examined and a predictive model for the CLI from CAI and geomechanical properties was suggested. Finally, the influence of CAI on disc cutter life prediction models was investigated and it was found that the variation of CAI has the maximum effect on the predicted disc cutter life in Gehring model. [ABSTRACT FROM AUTHOR]

Although L1 has been treated as a rigid system which is more likely to act as a sender than a receiver of CLI in bilinguals and multilinguals, recent studies have provided some evidence of the influence of both L2 and L3 on L1. The study is aimed at shedding further light on how Lns can influence the native language and how these changes can be explained by means of the Speech Learning Model. The first and second formant of L1 Polish vowels of three groups of multilinguals were compared. Evidence of a systemic influence of L2 on L1 was observed in the raising and backing of L1 Polish vowels due to L2 English and lowering and backing or fronting of L1 Polish vowels due to L2 German. No systemic influence of L3 on L1 was observed. The predictions derived from equivalence classification of SLM were tested for the Polish vowel /ɛ/ and the closest vowels from Lns. The majority of predictions regarding the convergence or divergence of the particular diaphone were supported by the data. [ABSTRACT FROM AUTHOR]

Objective/Background Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. Methods The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. Results Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65–1.27), survival (RR 1.00; 95% CI 0.95–1.06), and amputation free survival (RR 1.03; 95% CI 0.86–1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07–0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73–21.02), and pain score (mean difference –0.72; 95% CI –1.37 to –0.07) were significantly better in the treatment group than in the placebo group. Conclusions This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials. [ABSTRACT FROM AUTHOR]