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&#;The committee recommends that states, with assistance from relevant federal agencies, particularly the Substance Abuse and Mental Health Services Administration, provide universal access to evidence-based treatment for opioid use disorder (OUD), including use of medication, in a variety of settings, including hospitals, criminal justice settings, and substance use treatment programs. Efforts to this end should be carried out with particular intensity in communities with a high burden of OUD. State licensing bodies should require training in treatment for OUD for all licensed substance use disorder treatment facilities and providers (Recommendation ). The committee recommends that schools for health professional education, professional societies, and state licensing boards require and provide basic training in the treatment of opioid use disorder for health care providers, including but not limited to physicians, nurses, pharmacists, dentists, physician assistants, psychologists, and social workers (Recommendation ). The committee recommends that the U.S. Department of Health and Human Services and state health financing agencies remove impediments to full coverage of medications approved by the U.S. Food and Drug Administration for treatment of opioid use disorder (Recommendation ). &#;

In the context of the growing opioid problem, the FDA launched an Opioids Action Plan in early One component of the FDA plan is to reassess the agency’s risk-benefit framework for opioid approval and monitoring. The FDA commissioned this study specifically to inform this reassessment. Read Full Study Here

Peripheral arterial disease (PAD) is defined by atherosclerotic narrowing of the peripheral arteries, leading to progressive ischaemia, intermittent claudication and, in some patients, chronic limb-threatening ischaemia (CLTI), frequently resulting in major amputation.¹ Patients with CLTI suffer an inordinate burden of cardiovascular morbidity and mortality, with major amputation rates of up to 30% at 1 year and mortality rates of 25% and 50% at 1 and 5 years, respectively, which have not changed significantly in 40 years.² Below the knee (BTK) PAD represents a large portion of the CLTI population given the predilection of frequently comorbid conditions, such as diabetes and chronic kidney disease, for the small artery vascular territories.³ The small vessel size and frequently long lesions of BTK PAD have made the optimal treatment of this patient population elusive from both a surgical and an increasingly endovascular perspective.⁴ In patients with intermittent claudication, the mainstay of therapy has been and continues to be, monitored exercise programs along with optimal medical therapy.⁵ However, in patients with CLTI secondary to BTK PAD, both surgical and endovascular options exist for revascularisation with the goal of improving long-term patency, limb salvage and, possibly, ultimately mortality. The best treatment strategy for any individual patient is frequently dictated by anatomy and the comorbid risk of treatment via either surgery or endovascular techniques. Frequently, endovascular techniques are chosen and, in all cases, straight in-line flow to the target angiosome is required. As such, in the absence of distal bypass targets, as is often the case, endovascular therapy of the tibial vessels may become the preferred strategy if primary patency can be preserved. The BASIL trial, performed to compare percutaneous transluminal angioplasty (PTA) with surgical revascularisation, demonstrated no significant difference in overall and amputation-free survival between angioplasty-first and surgery-first strategies in patients with CLTI.⁶ Further studies, including BASIL-2 (ISRCTN) and BEST-CLI (NCT), aim to fully delineate the optimal strategy for the treatment of patients with CLTI. The global vascular guidelines on the management of CLTI recommend an endovascular-first approach in most patients with aortoiliac and infra-inguinal CLTI, recognising that surgical revascularisation may be more appropriate for certain high-risk populations or those with severe common femoral disease.⁷

PTA has been the standard of care for the endovascular treatment of BTK PAD over the past 30 years; however, major limitations to the overall success of PTA in BTK disease include flow-limiting dissection caused by balloon dilatation and heavily calcified lesions. Vascular scaffolds, including bare metal stents (BMS), drug-eluting stents (DES), bioresorbable vascular scaffolds (BVS), and other more novel strategies have been used to treat flow-limiting dissections resulting from PTA in BTK lesions with varying levels of success. Due to the small-vessel, long-segment and multivessel nature of BTK PAD, stenting with either metallic or bioresorbable scaffolds has not been nearly as successful as it has been in the coronary, aortoiliac and femoropopliteal vasculature. However, clinical trials appraising the efficacy of scaffolds in BTK PAD are allowing for continuous iterations and improvements in patient care. In this review, we focus on the more novel scaffolds, including DES, BVS and tacks, and several newer technologies being used and studied in the BTK PAD population.

Drug-eluting Stents

The use of BMS for revascularisation in BTK PAD has been associated with poor mid-term outcomes due to in-stent restenosis, likely secondary to stent arterial wall inflammation, neointimal hyperplasia and smooth muscle cell proliferation.⁸ Consequently, DES technology has emerged in an attempt to prevent stent restenosis. Most DES comprise a metal stent platform covered in a polymer matrix that is saturated with an antiproliferative drug, such as sirolimus (or its analogue) or paclitaxel. In small series, the use of DES has been associated with significant improvements in the prevention of lesion restenosis and limb amputation in patients with BTK PAD.^9,10

Many single- and multi-centre clinical trials have been conducted to evaluate the utility of DES in patients with CLTI secondary to BTK PAD. In one of the first such single-centre trials, 60 patients with symptomatic PAD (Rutherford Class [RC] 3–6) and angiographically proven BTK stenosis or occlusion were treated with either a BMS or sirolimus-eluting stent (SES) Despite the small sample size of that study, significantly favourable outcomes were observed in patients treated with the SES compared with those treated with a BMS. At a mean follow-up of approximately 10 months for both groups of patients, 7 (%) patients treated with a BMS required clinically driven total lesion revascularisation (CD-TLR), compared with no patients in the SES group (p=).¹¹ Similarly, the total number of major adverse events was lower in the SES than BMS group (3 [10%] versus 14 [%], respectively; p=). At a mean angiographic follow-up time of approximately 6 months for both groups, no patients in the SES group had stent occlusion or restenosis of the treated vessel >50%, compared with 4 (%; p=) and 9 (%; p=) patients, respectively, in the BMS group.¹¹ In addition, the mean degree of in-stent restenosis in patients in the SES group was only %, compared with % in the BMS group (p<) However, due to the limited sample size and follow-up time, there was no statistically significant difference in the rate of limb amputation between the two groups, although a numerically greater number of patients in the BMS than SES group experienced a major limb amputation (3 [10%] versus 0 patients, respectively).¹¹

Another two small single-centre randomised clinical trials were early to evaluate the efficacy of DES in BTK PAD. Falkowski et al. randomised 50 RC 3–5 patients with stenosis of one of the infrapopliteal arteries into treatment with an SES (n=25) or BMS (n=25).¹² Of note, only 32% of patients included in that study had CLTI. The primary endpoint of the study was the angiographically determined restenosis rate. At the 6-month follow-up, patients in the SES group performed significantly better than the patients in the BMS group; the restenosis rate for patients in the SES group was 16% (4/25 patients), compared with 76% (19/25 patients; p<) in the BMS group In the BELOW study, 60 patients with CLTI were randomised to receive treatment with either PTA, abciximab plus PTA, abciximab plus a BMS, or abciximab plus an SES; after 6 months, the restenosis rates in these groups were 58%, 75%, 67% and 9%, respectively, with the SES group having the lowest restenosis rate.¹³

Several large multicentre trials have provided further evidence for the utility of multiple different DES in the prevention of stent restenosis after placement. One of the first of these larger multicentre trials was the Yukon-BTK trial.^14,15 In that trial, patients were randomised to either a polymer-free SES (n=82) or BMS (n=79). Of these patients, 75 were classified as RC 4–5. At the 1-year follow-up, there was a statistically significant difference in primary patency rate, the primary endpoint, between the two groups, favouring treatment with an SES; of the patients who reached the 1-year follow-up, the primary patency rate was % (n=50) in the SES group, compared with % (n=35; p=) in the BMS group At a mean follow-up time of approximately 1, days, the event-free survival rate was % in the SES group, compared with % (p=) in the BMS group.¹⁵ In addition, the rate of limb amputation was significantly lower in the SES than BMS group; 2 (%) patients with CLTI who underwent SES placement experienced any type of limb amputation, compared with 7 (%; p=) patients who underwent BMS placement.

Alternatively, the DESTINY trial evaluated the benefit of everolimus-eluting stent (EES) placement versus BMS in the setting of CLTI In that trial, patients with CLTI (63 patients with RC 4 and 77 patients with RC 5) were randomised for treatment with either the Multi-Link Vision BMS (Abbott Vascular, Chicago, IL, US; n=66) or the XIENCE V DES (Abbott; n=74). The primary endpoint was primary patency at 1 year, defined as the absence of angiographically imaged in-stent restenosis ≥50%. At the 1-year follow-up, the primary patency in the EES group was % (n=50), compared with only % (n=32; p=) in the BMS group Patency was superior in the EES group for patients who had both proximal and distal lesions. At the 1-year follow-up, % of patients in the EES group were free from target lesion revascularisation, compared with % in the BMS group (p=). There was no difference in survival between the two groups at 1 year.¹⁶

The ACHILLES trial was another multicentre randomised clinical trial comparing SES with PTA in RC 3–5 patients.¹⁷ In that study, 99 patients were randomised to the SES group and were randomised to the PTA group. The primary endpoint was 1-year in-segment binary restenosis, as determined by quantitative angiography. In the intention-to-treat analysis, % of patients in the PTA group (n=31) had in-segment restenosis, compared with % (n=15) in the SES group (p=) Statistically significant reductions in restenosis rate were also apparent in the ‘as treated’ population (p=) and in the subset of patients with diabetes (p<) Other angiographic endpoints, including percentage diameter stenosis (p=) and minimal lumen diameter (p=), favoured intervention with the SES The clinical endpoint of vessel patency, defined as the absence of haemodynamically relevant restenosis and/or CD-TLR, also favoured treatment with the SES (n=54/72; %) over PTA (n=44/77; %; p=) Freedom from a composite endpoint of death, target lesion revascularisation, bypass, amputation and RC ≥4 also favoured the SES over PTA group at 1 year (log-rank p=).¹⁷

Finally, paclitaxel-eluting stents (PES) were compared to PTA with or without (±) BMS in the PADI trial In that trial, patients with CLTI (RC ≥4) were randomised to either the PES group (n=73) or the PTA ± BMS group (n=64). At the 6-month follow-up, a signal towards benefit for the PES treatment was seen, with significantly worse treatment failure noted in the PTA ± BMS than PES group, as graded by an ordinal score of both angiographic and clinical endpoints (modified intention-to-treat p=).¹⁸ The lesion patency rate at 6 months showed a trend towards better outcomes in the PES group than in the PTA ± BMS group (% versus %, respectively), but this did not reach statistical significance (p=) Similarly, there was a trend towards a reduction in amputations for those treated with a PES by 2 years of follow-up, although, again, this did not reach statistical significance (p=).¹⁸ At the 5-year follow-up, the differences in outcomes between patients treated with a PES or BMS became more pronounced; there was a statistically significant improvement in the composite endpoint of major amputation or death rate (p=) and in the event rate per patient (p=) The rate of amputations in patients in the PTA ± BMS group (%) remained numerically higher than in the PES group (%), although this, again, did not reach statistical significance (p=).¹⁹ The survival rate at 5 years remained comparable between the PTA ± BMS and PTA groups (% and %, respectively; p=).¹⁹

In the setting of continued controversy^{20, 21} regarding mortality associated with paclitaxel-coated devices (discussed above), the investigators of the PADI study examined the long-term (year) mortality associated with PES in their cohort.²² In the PADI study, investigators noted poor mortality outcomes in both the PTA ± BMS and PES groups, with no statistically significant difference between the two groups at 10 years (log-rank p=).²² Similarly, the authors reported no total dose-related mortality associated with paclitaxel (unadjusted HR , p=).²² Despite the poor long-term survival of this very high-risk cohort of patients, regardless of treatment option for critical limb ischaemia, treatment with PES is theorised to offer additional economic benefits, at least through 5 years, due to the increased incidence- and event-free survival associated with the PES.²³

The SAVAL trial is a recently completed multicentre trial studying a DES designed specifically for use in infrapopliteal critical limb ischaemia (NCT). The SAVAL DES (Boston Scientific) is a paclitaxel-coated self-expanding stent measuring mm × 80 mm, longer than coronary artery stents, specifically engineered to be durable in infrapopliteal arteries. The SAVAL stent was designed based on the Eluvia stent, a self-expanding PES designed and tested for use in femoropopliteal PAD.²⁴ The SAVAL stent uses a similar dual-layer drug-coating design to that of the Eluvia with a modified paclitaxel dosing scheme specifically designed for the peripheral vascular bed.²⁵ Eligibility criteria for the SAVAL trial include RC 4–5 disease with a target lesion at least 4 cm above the ankle joint, two or fewer infrapopliteal lesions, reference vessel diameter of – mm, life expectancy >1 year and no prior stent or surgery in the target vessel. Phase A randomised subjects into receiving the SAVAL DES or PTA alone, in a fashion, with the primary endpoint being primary patency at 12 months. Phase B involves non-randomly administering the SAVAL DES to patients to gather further safety and efficacy data, with the primary outcome being the assessment of major adverse events at 12 months. Patients are being followed for 3 years, with periodic clinical and ultrasound follow-up. Preliminary data from the SAVAL trial was presented at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual meeting by Hans van Overhagen. Disappointingly, at 12 months, the patency of the SAVAL DES (%) was not superior to PTA alone (%, 95% CI for difference −, %, p=). Similarly, non-inferiority analysis for major adverse events showed that the SAVAL DES was not noninferior to PTA alone; the MAE-free rate at 12 months was % in the DES cohort and % in the PTA cohort (non-inferiority p=). Despite these results, patient follow-up is continuing through three years in-office with vital status assessment through 5 years, as defined in the study protocol. It is not immediately clear why the SAVAL trial is not showing as efficacious a result as previous BTK paclitaxel-eluting stent trials (e.g. the PADI trial). Perhaps differences in the stent systems themselves may play a role in explaining this discordance. However, it is also worth noting that a significantly greater proportion of patients in the SAVAL DES group had moderate or severe calcification (%) than in the PTA group (%, p=). More severe lesions at baseline may falsely minimize the benefit of the stent in this patient cohort.

Bioresorbable Scaffolds

DES used in BTK PAD have shown promising results in terms of short-term patency rates, freedom from CD-TLR and major amputation, as described above. However, there is still concern over the long-term effects of indwelling metal scaffolds in small BTK arteries, specifically the ongoing nidus of arterial wall inflammation represented by the remaining scaffold long after the antiproliferative drug has been delivered.^{26, 27} Therefore, as with the coronary vasculature, bioresorbable scaffolds have been developed and studied in BTK PAD to provide a scaffold that maintains vessel patency after PTA and enables sustained antiproliferative drug delivery, but one that will ultimately be reabsorbed with time.

Bioresorbable scaffolds were first developed and used in coronary vasculature. Early data from the ABSORB II trial comparing an everolimus-eluting bioresorbable scaffold with the XIENCE DES (Abbott) in de novo coronary lesions were promising, with no significant difference in the composite endpoint of 1-year cardiac death, MI or target lesion revascularisation.²⁸ However, the 3-year results of the ABSORB II trial showed significantly higher target lesion failure with the everolimus-eluting bioresorbable scaffold, and the scaffold was subsequently taken off the market for coronary indication.²⁹

The first developed bioresorbable drug-eluting scaffold for BTK indications was reported in with the absorbable metal stent (AMS; Magic, Biotronik, Berlin, Germany). Bosiers et al. reported the month outcomes of AMS use in BTK PAD.³⁰ In that pilot study, 15 of 20 patients were RC 4–5. Procedural success was achieved in % of patients. The 1-year primary patency, limb salvage and survival rates were %, % and 85% respectively This led to the subsequent AMS Insight trial, a large multicentre randomised trial comparing AMS with PTA alone in patients with BTK PAD and CLTI In that trial, patients with RC 4–5 symptoms were enrolled from across four countries in Europe and randomised (57 to PTA, 60 to AMS). Procedural success was achieved in % of AMS patients and % of PTA patients.³¹ There was no significant difference in the primary safety endpoint of day freedom from major amputation or death between the two groups. Unfortunately, likely due, in part, to high rates of procedural cross-over, loss to follow-up and incomplete 6-month data, in the intention-to-treat analysis of that study, AMS failed to outperform and, in fact, was inferior to PTA alone, with 6-month primary patency rates of % in the AMS arm and 58% in the PTA-alone arm (p=).³¹

The largest body of literature to date exists for the Absorb BVS (Abbott Vascular, Santa Clara, CA, US).^{32, 33} In , Varcoe et al. presented the month results of their prospective, single-centre experience using the Absorb BVS in BTK PAD.³³ The Absorb BVS comprises a poly L-lactic acid coated with a poly(d,l-lactide) polymer that controls the release of everolimus from the BVS, which is fully resorbable. The dose of everolimus delivered by the Absorb BVS ( µg/mm2) is equivalent to that of the XIENCE Prime DES (Abbott Vascular). The primary efficacy endpoint in the study of Varcoe et al. was the freedom from binary restenosis rate, defined by a peak systolic velocity ratio > Secondary endpoints included CD-TLR, amputation, bypass surgery, cardiovascular and all-cause mortality and ‘any related morbidity within 30 days of the index procedure’.³³ Primary patency was defined by freedom from CD-TLR and binary restenosis. In all, 33 patients with severe claudication to CLTI (RC 3–5) were enrolled (% CLTI, % severe claudication); 50 scaffolds were used to treat 43 distinct lesions, with 34% of patients receiving treatment of inflow lesions either preceding their BVS procedure or concomitantly. Procedural success, defined by the successful deployment of the Absorb BVS with <30% residual stenosis and no evidence of acute thrombosis, was achieved in % of patients.³³ One patient underwent CD-TLR on day 2 after the procedure and was found to have occlusions in two of the three BVSs placed. Three patients developed femoral pseudoaneurysms during follow-up; two of these patients required covered stent placement and one required open surgical repair. Twelve-month survival was %. Freedom from CD-TLR was 96% at 6, 12 and 24 months. Primary patency was 96%, 96% and % at 6, 12 and 24 months respectively. Seventy-nine per cent of patients showed clinical improvement, defined as either wound healing or improvement in RC. Sixty-four per cent of patients with RC 5–6 had complete healing of their wounds during the follow-up period Varcoe et al. have recently reported the 5-year outcomes of these data with an additional 15 patients added to their series for a total of 48 patients with 71 scaffolds in 61 lesions.³⁴ Impressively, the authors report binary restenosis in only % of BVS at 5 years, primary patency in % at 5 years and freedom from CD-TLR of % at 5 years.³⁴ After a mean follow-up period of ± months, % of patients were alive.³⁴

In a retrospective case series, Dia et al. reported the results of their institutional experience with the Absorb BVS in BTK PAD, demonstrating % procedural success with 1-year freedom from clinically driven target vessel failure of %, primary patency of %, improvement in RC in % of patients and no deaths at 1 year.³² In , Kum et al. subsequently reported the results of the DISAPEAR registry, a retrospective registry of Asian patients treated with Absorb BVS in BTK PAD.³⁵ In 41 patients with CLTI due to BTK PAD, the authors reported % technical success, 6- and month primary patency of 95% and 86%, respectively, 1-year freedom from CD-TLR and major amputation of 93% and 98%, respectively, and amputation-free survival of 85% at 1 year.³⁵ Seventy-nine per cent of patients with RC 5–6 symptoms had wound healing by 12 months.³⁵

In , Huizing et al. published a pooled analysis of three separate real-world cohorts using the ABSORB BVS in BTK PAD.³⁶ The primary endpoint in this analysis was freedom from restenosis, with secondary endpoints of freedom from CD-TLR, major amputation and survival. In all, patients received ABSORB BVS, with 75% of patients in RC 5–6. The primary endpoint of freedom from restenosis was achieved in % and % of patients at 12 and 24 months, respectively.³⁶ Freedom from CD-TLR was % and % at 12 and 24 months, respectively, with major amputation in only % of limbs at 24 months. Overall survival was 85% at 24 months.³⁶

Ipema et al. recently published a systemic review and meta-analysis of the existing literature surrounding bioresorbable scaffolds in BTK PAD with month data available. That analysis indicated a pooled 1-year primary patency rate of 90%, freedom from CD-TLR of 96%, limb salvage rate of 97% and survival of 90%.³⁷

These data are compelling and offer the first potentially tenable solution to the question of how to deliver antiproliferative drugs to target vessels in BTK PAD, maintaining left main patency with a vascular scaffold while avoiding the negative long-term effects of metallic scaffolds. Although compelling, the data apart from Insight AMS all come from non-randomised prospective and retrospective case series. The ongoing LIFE-BTK trial (NCT) is a prospective randomised multicentre global trial assessing the safety and efficacy of the Esprit bioresorbable scaffold in BTK PAD compared with PTA. We eagerly await the results of this trial to better define the role of bioresorbable scaffolds in the management of BTK PAD.

Tacks

In this section, we discuss the most recent addition to the armamentarium of tools for the treatment of BTK PAD, the Tack Endovascular System. Flow-limiting dissections remain one of the primary limitations to successful PTA and often necessitate the placement of an endovascular scaffold to maintain vessel patency. As discussed in the preceding sections, deploying vascular scaffolds in BTK arteries has been fraught with low long-term patency rates with BMS, concerns regarding long-term failure secondary to external crush forces on repurposed coronary DES and a lack of prospective randomised data in the area of bioresorbable scaffolds. The Tack endovascular system uses short (<6–10 mm)-segment, open-cell metallic stents to tack up dissection flaps to maintain vessel patency after PTA. The Tack Endovascular System for BTK lesions uses a 4 Fr system with four independent Tack implants (Figure 1) for vessels ranging in diameter from to mm.

The 6-month data of the TOBA II BTK study, in which the Tack Endovascular System was used for the treatment of angiographically confirmed dissections after PTA in BTK arteries, were published in ³⁸ In that study, patients with RC 3–5 symptoms were enrolled. The primary safety endpoint was a composite of day major adverse limb events (MALE) and all-cause postoperative death (POD). The primary efficacy endpoint was a composite 6-month of MALE and day POD. These same endpoints were evaluated at 12 months, along with amputation-free survival (AFS), freedom from CD-TLR, vessel patency, and changes in clinical and quality-of-life-measures. The authors reported impressive results, with % of patients free of the composite endpoint of MALE and POD, a tacked segment patency of %, a limb salvage rate of %, freedom from CD-TLR of % and AFS of % In addition, % and % of patients had sustained improvements in RC and in wound healing, respectively. This trial’s 6-month data led to the US Food and Drug Administration’s (FDA) approval of this device in BTK PAD, the first vascular scaffold to receive an indication in BTK PAD.

Devices in Development

The landscape of endovascular interventions for BTK PAD continues to change rapidly. In this section, we review the current therapies in various stages of development and how they may fit into the treatment paradigm for BTK PAD. Ongoing trials with a novel scaffold for BTK PAD are described in Supplementary Material Table 1.

Micro Medical Solutions has developed an integrated platform of microstent, microcatheter and microballoon specifically designed for use in the BTK PAD population. The microstent, a self-expanding woven nitinol stent, is designed to conform to complex tibial lesions and exert lower radial force than balloon-expandable stents while maintaining luminal gain and vessel patency after PTA. The FDA granted investigational device exemption status to the MICROSTENT platform in following the report of its safety and feasibility study in 15 patients across three centres with RC 4–5 symptoms.³⁹ One hundred per cent of patients were free from the primary safety endpoint of MALE or POD at 30 days, and % of patients maintained primary patency at 30 days, with % of patients free from CD-TLR (unpublished data; presented by Robert Beasley at the Leipzig Interventional Course in ). These results were carried out to 6 months, with % of patients achieving primary patency, ultimately paving the way for the ongoing STAND randomised trial comparing the microstent with standard PTA in BTK PAD (NCT). This trial aims to enrol participants with RC 4–5 BTK PAD across multiple centres in the US and to examine primary patency, defined as freedom from target vessel occlusion, CD-TLR or major amputation in the target limb, at 6 months. Primary safety endpoints are freedom from MALE at 6 months and POD at 30 days. Stenting has largely been reserved as a bailout strategy to treat recoil and flow-limiting dissections in BTK PAD. This is notably one of the first contemporary randomised trials in this population comparing primary stenting with standard of care PTA. If the primary patency rates seen in the feasibility study of the microstent carry over to the STAND trial, this may prove to be a paradigm shift for the field of BTK PAD, particularly if these patency rates are maintained in the long term.

Reflow Medical has developed the Spur device for use in the BTK distribution, specifically in combination with antiproliferative drug therapy. One of the principal issues with drug-eluting technology in BTK PAD is achieving adequate vessel preparation to facilitate maximum vessel surface contact with the drug-eluting device and adequate penetration of the antiproliferative drug into the vessel wall. The Spur device uses a temporary stent with radial spikes designed to penetrate atherosclerotic lesions to reach deeper layers of the arterial wall to facilitate acute luminal gain and delivery of the antiproliferative drug. The DEEPER LIMUS trial is an ongoing pilot study conducted on 30 patients in a single centre in Germany assessing the safety of this device in people with BTK PAD (NCT). The primary endpoint in that study is a 6-month composite endpoint of all-cause mortality, freedom from CD-TLR and major amputation. Secondary efficacy endpoints include 6-month late lumen loss, primary patency, change in RC and wound healing. The FDA has given the Spur device Breakthrough Device designation. This designation facilitates the speedy review of devices with the potential to offer more effective treatment of life-threatening or permanently debilitating diseases.

The final device we discuss is the LimFlow stent graft system (LimFlow), designed to achieve percutaneous deep vein arterialisation (DVA) in no-option BTK PAD patients, which is defined as RC 5–6 deemed by a team of vascular surgeons and interventionalists to have no percutaneous or surgical bypass options for their level of disease. The procedure uses simultaneous retrograde pedal access to the desired deep vein and antegrade arterial access to the diseased tibial vessel. A valvulotome is used to render the vein distal to the diseased artery incompetent, after which an iatrogenic atrioventricular (AV) fistula is created proximal to the level of disease in the target artery. This AV fistula is then lined with polytetrafluoroethylene-covered stents, creating an in-line flow to the pedal vessels with the goal of improving wound healing, limb salvage and symptom improvement. In , Mustapha et al. reported the interim results of the PROMISE I trial, a single-arm multicentre pilot study examining the safety and efficacy of the LimFlow stent graft system in 10 patients with no-option critical limb ischaemia.⁴⁰ The primary and secondary safety endpoints were AFS at 30 days and 6 months, respectively. Secondary efficacy endpoints included primary patency, wound healing and technical success. The authors reported % AFS at both 30 days and 6 months, with a % technical success rate and no reported procedural complications.⁴⁰ The 1- and 6-month primary patency rates were 90% and 40%, respectively with 30% of patients requiring reintervention. At 6 months, 80% of patients had >60% wound healing In early , Clair et al. reported month data from the full PROMISE I cohort, including 32 patients across seven sites in the US treated with the LimFlow stent graft system The authors reported a 97% technical success rate, and day, 6-month and month AFS rates of 91%, 74% and 70%, respectively. Seventy-five per cent of wounds were healed or healing at 12 months. Fifty-two per cent of patients required reintervention, predominantly driven by inflow disease proximal to the DVA circuit At 24 months, the AFS rate was 59%, driven by an overall increase in all-cause mortality with a stable rate of freedom from major amputation.⁴¹ Eighty-five per cent of patients had fully healed wounds The encouraging results of the PROMISE I trial have led to the initiation of a larger PROMISE II trial, which is being conducted at 22 sites across the US and Japan, enrolling patients with no-option BTK PAD.

It’s am on Thursday, May 12th, three weeks before the Festival of Miles. I am writing this now, in the middle of the night, because I can’t sleep anyway so I figure this is as good a time as any. And I can’t sleep because I woke up in a panic, courtesy of a nightmare. It’s the same nightmare I’ve had every year around this time for the last several years. The same nightmare I’ll probably have a few more times over these next three weeks. I dream that it’s FOM night but no one showed up. We somehow messed up the marketing and no one knew about the event. Or sometimes it takes a different form and the people are in the stands but I forgot to put the fields together and there are no athletes to compete. This all sounds completely messed up, I know. As confident as I am in a lucid state, my sub-conscious is a complete wreck.

But of course, thankfully, none of these nightmares will come true three weeks from now. In fact, my awake self can tell you with all the confidence in the world, that FOM will once again be spectacular. Everyone who comes out will be absolutely amazed, the athletes will make themselves a host of memories that will last a lifetime and our sport will be displayed in a super cool way, the way it should be. Then afterwards I’ll be exhausted. Our whole team who puts this thing on will be exhausted. But it will have all been worth it.

And speaking of it all being worth it, I have wanted to write this post for a while now. I’ve been searching for a way to say what I’m about to say and at the same time honor FOM for what I think it’s been and what I hope it will continue to be. So here goes: After nine years of this one day being my absolute favorite day of the year I have reached the decision, for a variety of reasons, that the Festival of Miles will be my last year helping to organize the event. But of course, I want to go out with a bang! The fields for this year’s pro races are as deep as we’ve ever had. High school entries are once again rolling in from all over the country and I can feel the excitement starting to build in Saint Louis, even from afar.

I could go into more detail about how awesome June 2nd is going to be but you’ll see, hear and read all about that on social media over these next three weeks. We are marketing machines after all! What I’d rather do here though, for those who are interested, is just tell you some stories and share some of the pictures and videos that made me pretty darn emotional earlier this week when I pored through the history of the event.

Brigette Schutzman addressing the crowd at FOM 2 in

That’s Brigette Shutzman. She’s the reason there is a Festival of Miles. I remember standing around in the kitchen at the tiny house in Shrewsbury that Jen and I rented with Tim Bradley and Jon Bell, Brigette’s coaches at Saint Louis University, and trying to come up with a way to raise money for her. Brigette had been in a horrible car accident on New Year’s Eve / and things didn’t look good. Tragedy is never easy to handle but for some reason it always seems even a little tougher when the person is young, in-shape, vibrant. When they have such a bright future. Because Brigette was a middle-distance runner we thought a track meet would be a more fitting way to celebrate her than a typical 5k road race.

The start of the Saint Louis Track Club Men&#;s Mile

We held the first Festival of Miles in late April of , just four months after the accident. We weren’t sure about how many people would turn out so we held it after a JV track meet at Saint Louis University High School on a Monday night. We wanted a built-in crowd just in case. But we hyped it up as much as we possibly could. The schedule was pretty light- a couple of youth races, a masters men’s race, a local women’s race and finally an elite men’s mile where we were hoping for that magical sub 4. Well, to our surprise the bleachers started filling up and by the time the men’s mile came around we had more than 1, people in the stands. Unfortunately, as it turns out, late April in Saint Louis is not a great time for a high level track meet. The guys did the best job they could and it was a super fun race but Neville Miller (a local guy from Vianney HS and Mizzou) could only muster a for the win. But everyone there had a blast, we raised $8, for Brigette and more importantly we gave her a really fun experience. She even took a few steps in front of the crowd and thanked everyone for coming, this from a girl who had been given only a slim chance of making it through the night four months earlier.

And that would have been the one and only Festival of Miles if it weren’t for another accident that summer. Mike Rathmann, an all-state high jumper at Saint Louis U High, was paralyzed from the chest down just a few weeks after his high school graduation. Jim Linhares, Joe Porter and Tom Flanagan, Mike’s coaches at SLUH, had been a huge part of the planning committee for the meet back in April and I don’t think it took us all very long at all to realize we wanted to put on another edition of the Festival of Miles, but this time we’d do it for Mike.

The one and only Mike Rathmann

With almost a full year to plan the event, things really exploded in Of course, Big River Running Company was also exploding. We had opened our second store and our database was growing by leaps and bounds. That helped immensely with the promotion of the event. We were able to talk some sponsors into coming on board, which gave us a bigger budget so we could put together a better prize purse and a better travel budget for the pro race. I have appreciated all the different sponsors we’ve worked with over the years but I am especially grateful to the Saint Louis Track Club, GO! St. Louis, Saint Louis Injury and Rehab, Drury Hotels and TRXC Timing. They are our longest-running partners and we couldn’t have done all of this without them.

But as much as their money and our promotion helped to set us up for success that year we really have one person to thank more than anyone. And not only for what he did for us in but really for how big the event has become since. It was about a week before the race and the fields were set. The budget was spent. We were bringing in a handful of really solid milers from around the Midwest and felt pretty good about our chances of seeing a sub 4. Then I get an email from Ryan Ponsonby, one of the coaches of Olympian Leo Manzano. Leo was coming off a sub-par race and was looking for some redemption. They wanted to know if we could get Leo into our race. Let’s see…can we add an Olympian to our little track meet in Saint Louis at a local high school? Yeah…I think we can make that happen! It’s funny in retrospect but I remember talking to Matt Helbig, my friend and Big River Running Company business partner, about the $ dollars it was going to cost to bring him in. Turned out to be the best $ we ever spent.

Click to watch Leo&#;s sub 4.

As you can see Leo did not disappoint. He unleashed his patented crazy fast last meters in front of a crowd that was going absolutely ballistic. The result was a mile, the fastest ever run in the State of Missouri. Derek Scott and Tommy Schmitz also broke four that night. After that, there was no turning back. FOM was here to stay.

Since , we have continued on and always with one goal in mind—to make the event even bigger and better the following year. And thus far we’ve nailed it every time. The youth races have grown in numbers with every single edition of the meet. The crowd has gotten bigger and bigger. People are now arriving an hour early just so they can get a spot in the parking lot and a good seat. We had 2, fans last year and I wouldn’t be at all surprised if we got to 3, on June 2nd. I’m biased but I believe we’ve paved the way for a lot of the similar grassroots events you see going on around the country. Our event is short: two-and-a-half hours start to finish. We jam the music during the races. We have super cool athlete intros before our pro races. We have an excited meet announcer (sometimes me!). We do interviews in front of the crowd with our winners. And the races themselves are crazy fast. I’ll just give you a few quick stats before I get to some of my favorite pictures and moments from these last nine years.

FOM junior high invitational boys mile record

FOM junior high invitational girls mile record

Big River Running Company Boys Mile Record (HS Only Race)

Big River Running Company HS Girls Mile Record

FOM Women&#;s Meter Record

Saint Louis Track Club Men&#;s Mile Record

Hannah Long&#;s meter time (#2 US HS time that year)

Grant Fisher&#;s time to become the 7th US HS athlete under 4 minutes

$50,+- Money raised for local athletes in need from FOM since

All told, the four-minute-mile has been broken nineteen times at FOM between and Not too shabby for a high school track! But more important than any fast time or any one moment, what struck me the most as I took my little trip down nostalgia lane earlier this week was just how many people have been a part of this event. And I mean in every way. As l looked through the pics I saw so many of our best Big River customers and supporters cheering in the stands. I saw so many kids in the youth race pics from the early years that later went on to run in the high school all-star races. I saw distance running superstars like Emily Sisson and Colleen Quigley, two women who could very well be Olympians this summer, running at FOM as high school athletes. I saw professional athletes (and of course one high schooler) who broke four minutes for the first time at our meet. As an athlete you don’t forget that…ever.

And for me personally I just saw all of my friends. Essentially, my wife and I and our best friends put on this event and so many other great friends are in the stands or volunteering or even running around the track. I don’t know what else to say except that I love this event. I love the people who have given so much to it over the years. I love that we’ve shown that track can be a spectator sport. I love that my brother’s drinking buddies who’ve never run a step in their life come to FOM every single year because they have such a good time. I love that we’ve been able to help local families in need in a really tangible way. And I guess I just love the fact that after all these years it’s still so special to me that it wakes me up in the middle of the night three weeks beforehand in a cold sweat. If I can continue to find things that I’m this passionate about as I move forward I think I’ll live a pretty darn good life.

So thanks for reading. I hope to see many of you on June 2nd and I hope you enjoy the pictures (and captions) below:

Hometown favorite Neville Miller won the inaugural Saint Louis Track Club Men&#;s Mile. Eight years later and Neville is now our unofficial FOM weatherman (follow him on KMBC in Kansas City)

Oh my gosh I love this pic. It&#;s right before the start of the Men&#;s Mile in You can see how packed the stands are and in the foreground is the first family of FOM- The Longs! Zack, Hannah, Nate, Cindy and Dave&#;thanks for being such huge FOM supporters (and friends)!!

What a great pic. Love Leo throwing up the &#;Hook-Em Horns&#; but my favorite thing is the crowd in the background, especially longtime friend Tom Flanagan.

This is my brother Franklin! He&#;s now a freshman in college but this was him way back in grade school. I love that my family was able to be a part of FOM.

Maybe my favorite all-time FOM pic. Carter Snow (who is taking over FOM director duties) high-fiving Hannah Long after her US #1 meter. Pure joy!

What a powerful shot. Teammates embracing after a hard fought battle. So cool.

No one has done more to professionalize our meet than Rich Schilling and his TRXC Timing Crew. THANK YOU GUYS!

Love this black and white of JMac- our 3-time FOM Champ and meet record holder. I cannot speak highly enough about this guy.

Native Saint Louisan Shannon Leinert has run every FOM since we added it in She&#;s come so close to winning but never quite done it. I&#;d be lying if I said I wasn&#;t rooting for her on June 2nd.

For years I pulled double duty at FOM, coaching the Blazers and putting on the meet. Bella and Sophia Racette and Hadley Karandjeff were three of my favorites!!

And here are three more Blazer goofballs and I mean that in a good way- Aaron Hoyt, Dan Powell and Ben Reagan

We are very proud of the media coverage FOM receives every year in STL. Here is local broadcast legend Frank Cusumano interviewing FOM Mile champ Jack Bolas.

How cool is this? Twins Daniel and David Everett being interviewed by the great Toni Reavis after running and !!

Rich Anderson has supported FOM in so many ways. I had to include this pic. Lookin&#; good Rich!

One of the best FOM pics ever taken. Our boys race got a little tactical and four runners finished within a second of one another led by Spencer Haik.

If we had an FOM Hall of Fame (which we should!) this young lady would be in it. Stephanie Jenks of Iowa has won 3 FOM HS Miles in a row and will go for the 4-peat on June 2nd.

I think the timing board says it all!

Thanks to Katie Sutton and Ty Kanoya for all the pics I used in this post. I wanted to include so many more! If you want to take an even deeper trip down memory lane check out all of Ty&#;s pics from here:

Thanks so much everyone. You guys are the best and I&#;m excited to see so many of you on June 2nd!!

&#; BEN

Par Anne HOUESSIN

Arise Ports & Logistics devient officiellement nouveau et neuvième membre de l’Association de Gestion Portuaire de l’Afrique de l’Ouest et du Centre (AGPAOC) dont la mission principale est de renforcer l’efficacité des ports membres et de promouvoir le développement socio-économique des pays membres tout en veillant au respect de l’environnement.

L’intégration d’Arise Ports & Logistics réhausse encore plus l’image de l’AGPAOC tout en lui offrant plusieurs opportunités de networking, de partenariat et de partage d’expériences et d’expertise avec les leaders du secteur maritime. Ces opportunités contribuent à la synergie du développement tout en posant des bases pour des dialogues constructives de multiples initiatives. Ce qui servira de cadre pour évoquer les enjeux auxquels est confronté le secteur portuaire des différents pays représentés : le développement durable, le transport, l’économie maritime.

Arise Ports and Logistics demeure résolu quant à sa collaboration avec l’AGPAOC qui constitue un allié de confiance qui partage les mêmes ambitions avec l’intention de créer de la valeur et de l’impact sur le continent.

Le président de l’AGPAOC et directeur général de l’OPRAG (Autorité Portuaire du Gabon) Godwin Alini Yandjangoye exprime son enthousiasme face à l’intégration de son nouveau membre. « Nous sommes ravis d’accueillir Arise P&L au sein de l’AGPAOC, c’est une excellente occasion pour nous de collaborer et de partager nos connaissances et notre expérience dans le domaine de la gestion portuaire. Nous sommes impatients de travailler ensemble pour assurer le succès continu de l’industrie portuaire africaine ».

Ebrima Sawaneh directeur des Opérations d’Arise P&L  déclare: « Cette adhésion est une marque de confiance que nous estimons, et nous remercions les membres de nous accueillir au sein d’une équipe résolue à élaborer des solutions et des initiatives qui façonnent un avenir meilleur et durable pour le continent. Elle confirme notre engagement en faveur du développement, reposant sur une volonté de croissance et le respect collectif de l’environnement. Nous sommes déterminés à collaborer avec les leaders du secteur portuaire et de partager nos connaissances sur les meilleures pratiques en gestion et d’opérations portuaires afin de garantir l’efficacité des ports africains tout en sauvegardant l’environnement».

Il est important de rappeler qu’Arise Ports & Logistics est un développeur d’écosystèmes industriels qui conçoit, créé, finance et développe des infrastructures interconnectées. Son objectif principal est de créer un impact grâce à une stratégie d’expansion.

L’association de Gestion des Ports de l’Afrique de l’Ouest et Centre ou Port Management Association of West and Central Africa en anglais (PMAWCA) a été créé sous les auspices de la Commission Economique pour l’Afrique en et opère depuis 50 ans. Son objectif est de faire coopérer et de partager les connaissances sur les meilleures pratiques en matière de gestion et d’exploitation portuaires afin de fournir les services portuaires efficaces et efficients à ses clients tout en maintenant la meilleure culture d’exploitation portuaire : sûre, sécurisée et respectueuse de l’environnement. Elle est composée de vingt-quatre (24) ports membres permanents, 9 membres associés y compris les pays enclavés et les organisations maritimes. Des Assemblées Générales sont organisées annuellement, des formations, séminaires et des conférences des directeurs généraux de l’AGPAOC.

Source d’image : Pôle Logistique 

Journaliste Rédactrice Web

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