Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model. Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis. Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups. Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART.

Although gut and lymph node (LN) memory CD4 T cells represent major HIV and simian immunodeficiency virus (SIV) tissue reservoirs, the study of the role of dendritic cells (DCs) in HIV persistence has long been limited to the blood due to difficulties to access lymphoid tissue samples. In this study, we show that LN migratory and resident DC subpopulations harbor distinct phenotypic and transcriptomic profiles. Interestingly, both LN DC subpopulations contain HIV intact provirus and inducible replication-competent HIV despite the expression of the antiviral restriction factor SAMHD1. Notably, LN DC subpopulations isolated from HIV-infected individuals treated for up to 14 years are transcriptionally silent but harbor replication-competent virus that can be induced upon TLR7/8 stimulation. Taken together, these results uncover a potential important contribution of LN DCs to HIV infection in the presence of ART.

Systematic hybrid laparoscopic and endovascular treatment of median arcuate ligament syndrome: A single-center experience.

Background: Median arcuate ligament syndrome (MALS) is caused by celiac trunk (CT) compression by the median arcuate ligament. Clinically, this pathology varies from postprandial pain (Dunbar syndrome) to a life-threatening hemorrhage because of a rupture of a gastroduodenal artery aneurysm (GAA). Due to the low prevalence of this disease, there is no standard management for MALS. Material and method: This was a single-center, retrospective study of 13 patients. Two groups were identified on the basis of the initial clinical presentation: those operated for a GAA rupture (bleeding group-BG) and those operated electively for Dunbar syndrome (Dunbar syndrome group-DG). The primary endpoint was 30-day postoperative complications of a systematic laparoscopic release of the median arcuate ligament and stenting during the same procedure. Results: Seven patients (54%) underwent elective surgery. Six patients (46%) underwent semiurgent repair under elective conditions post-embolization for GAA bleeding. The total operative time was longer in the BG (p = 0.06). Two patients in the BG suffered early major complications and needed reintervention, and those in the DG had a lower comprehensive complication index. No mortality was reported at 30 days. Overall median length of stay was 5 days (IQR: 3.5-15.3). Patients in the DG had a significantly shorter length of stay (p = 0.02). At 6 months, the primary and secondary CT stent patencies were 82% and 100%, respectively. There were no high-flow GAA recurrences. Conclusions: A combined approach of laparoscopic release of the median arcuate ligament and stenting during the same procedure is feasible and safe, and this approach must be systematically discussed in symptomatic patients.

The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection.

Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3- Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3- Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3+ Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3+ B cells showed lower rate of somatic hypermutation, as compared to CXCR3- B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.

Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging.

The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods: To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results: Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions: Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient's survival.

Predictors and Consequences of Sac Shrinkage after Endovascular Infrarenal Aortic Aneurysm Repair.

Background: Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). We evaluated the impact of sac shrinkage on secondary interventions, on survival and its association with endoleaks, and on compliance with instructions for use (IFU). Methods: This observational retrospective study was conducted on all consecutive patients receiving EVAR for an infrarenal abdominal aortic aneurysm (AAA) using exclusively Endurant II/IIs endograft from 2014 to 2018. Sixty patients were entered in the study. Aneurysm sac shrinkage was defined as decrease ≥5 mm of the maximum aortic diameter. Univariate methods and Kaplan-Meier plots assessed the potential impact of shrinkage. Results: Twenty-six patients (43.3%) experienced shrinkage at one year, and thirty-four (56.7%) had no shrinkage. Shrinkage was not significantly associated with any demographics or morbidity, except hypertension (p = 0.01). No aneurysm characteristics were associated with shrinkage. Non-compliance with instructions for use (IFU) in 13 patients (21.6%) was not associated with shrinkage. Three years after EVAR, freedom from secondary intervention was 85 ± 2% for the entire series, 92.3 ± 5.0% for the shrinkage group and 83.3 ± 9% for the no-shrinkage group (Logrank: p = 0.49). Survival at 3 years was not significantly different between the two groups (85.9 ± 7.0% vs. 79.0 ± 9.0%, Logrank; p = 0.59). Strict compliance with IFU was associated with less reinterventions at 3 years (92.1 ± 5.9% vs. 73.8 ± 15%, Logrank: p = 0.03). Similarly, survival at 3 years did not significantly differ between strict compliance with IFU and non-compliance (81.8 ± 7.0% vs. 78.6 ± 13.0%, Logrank; p = 0.32). Conclusion: This study suggests that shrinkage ≥5 mm at 1-year is not significantly associated with a better survival rate or a lower risk of secondary intervention than no-shrinkage. In this series, the risk of secondary intervention regardless of shrinkage seems to be linked more to non-compliance with IFU. Considering the small number of patients, these results must be confirmed by extensive prospective studies.

Pharmacological prevention of intimal hyperplasia: A state-of-the-art review.

Intimal hyperplasia (IH) occurs in a considerable number of cases of blood vessel reconstruction by stenting or balloon angioplasty, venous bypass grafting, and arteriovenous dialysis accesses. It is triggered by endothelial injury during the vascular intervention and leads to vessel restenosis with life-threatening consequences for patients. To date, the drugs used for IH prevention in clinics-paclitaxel and rapalog drugs-have been focusing primarily on the vascular smooth muscle cell (VSMC) proliferation pathway of IH development. Limitations, such as endothelial toxicity and inappropriate drug administration timing, have spurred the search for new and efficient pharmacological approaches to control IH. In this state-of-the-art review, we present the pathways of IH development, focusing on the key events and actors involved in IH. Subsequently, we discuss different drugs and drug combinations interfering with these pathways based on their effect on peripheral circulation IH models in animal studies, or on clinical reports. The reports were obtained through an extensive search of peer-reviewed publications in Pubmed, Embase, and Google Scholar, with search equations composed based on five concepts around IH and their various combinations. To improve vascular intervention outcomes, rethinking of conventional therapeutic approaches to IH prevention is needed. Exploring local application of drugs and drug combinations acting on different pathophysiological pathways of IH development has the potential to provide effective and safe restenosis prevention.

Stapled Porcine Pericardium Displays Lower Infectivity In Vitro Than Native and Sutured Porcine Pericardium.

BACKGROUND: Biological xenografts using tubulized porcine pericardium are an alternative to replace infected prosthetic graft. We recently reported an innovative technique using a stapled porcine pericardial bioconduit for immediate vascular reconstruction in emergency. The objective of this study is to compare the growth and adherence to grafts of bacteria and yeast incubated with stapled porcine pericardium, sutured or naked pericardium. MATERIAL AND METHODS: One square centimeter of porcine pericardial patches, with or without staples or sutures, was incubated with 105 colony forming units of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans for 1, 6, and 24 h. The medium was collected to quantify planktonic microorganisms, while grafts were sonicated to quantify adherent microorganisms. Dacron and Dacron Silver were analyzed in parallel as synthetic reference prostheses. RESULTS: Stapled porcine pericardium reduced the growth and the adherence of E coli (2- to 30-fold; P < 0.0005), S aureus (11- to 1000-fold; P < 0.0006), S epidermidis (>500-fold; P < 0.0001), and C albicans (12- to 50-fold; P < 0.0001) when compared to medium alone (growth) and pericardium or Dacron (adherence). Native and sutured porcine pericardium interfered with the growth and the adherence of E coli and C albicans, and Dacron with that of S epidermidis. As expected, Dacron Silver was robustly bactericidal. CONCLUSIONS: Stapled porcine pericardium exhibited a lower susceptibility to infection by bacteria and yeasts in vitro when compared to the native and sutured porcine pericardium. Stapled porcine pericardium might be a good option for rapid vascular grafting without increasing infectivity.

Predictive Factors of Surgical Complications in the First Year Following Kidney Transplantation.

BACKGROUND: In the recent years, an increased use of marginal donors and grafts and a growing prevalence of peripheral arterial disease in the recipients have been observed. Meanwhile, the open surgical technique for kidney transplantation has not changed. The aim of this study is to analyze all surgical complications occurring in the first year after kidney transplant and to determine potential predictive risk factors. METHODS: Data of the 399 patients who underwent kidney transplant in our University Hospital between January 2006 and December 2015 were retrospectively reviewed. The primary endpoint was the overall rate of vascular, parietal and urological complications at 1 year following kidney transplantation. The secondary outcomes were graft and patient' survival rates, and the identification of predictive factors of the surgical complications. RESULTS: 24% of patients developed 134 complications. Vascular complication represented 39% of all complications and resulted in 9 graft losses. Parietal and urological complications represented 46-15% of all complications, respectively, No parietal or urological complications were associated with graft loss. 5 patients died during the 1st year, none of these cases was associated with graft loss. The graft survival rate reached 96% at 1 year, including patients still alive. The occurrence of surgical complication was associated with reduced graft survival at 1 year. Using a multivariate analysis, 4 predictive factors were identified: age, deceased donor, operative time and dyslipidemia. CONCLUSION: Surgical complications after kidney transplantation remained frequent and age, deceased kidney donors, and operative time were identified as risk factors. As vascular complications were a major cause of early graft loss, efforts should aim to reduce their occurrence to increase graft survival.

Hydrogen Sulphide Release via the Angiotensin Converting Enzyme Inhibitor Zofenopril Prevents Intimal Hyperplasia in Human Vein Segments and in a Mouse Model of Carotid Artery Stenosis.

OBJECTIVE: Hypertension is a major risk factor for intimal hyperplasia (IH) and re-stenosis following vascular and endovascular interventions. Preclinical studies suggest that hydrogen sulphide (H2S), an endogenous gasotransmitter, limits re-stenosis. While there is no clinically available pure H2S releasing compound, the sulfhydryl containing angiotensin converting enzyme inhibitor zofenopril is a source of H2S. Here, it was hypothesised that zofenopril, due to H2S release, would be superior to other non-sulfhydryl containing angiotensin converting enzyme inhibitors (ACEi) in reducing intimal hyperplasia. METHODS: Spontaneously hypertensive male Cx40 deleted mice (Cx40-/-) or wild type (WT) littermates were randomly treated with enalapril 20 mg or zofenopril 30 mg. Discarded human vein segments and primary human smooth muscle cells (SMCs) were treated with the active compound enalaprilat or zofenoprilat. IH was evaluated in mice 28 days after focal carotid artery stenosis surgery and in human vein segments cultured for seven days ex vivo. Human primary smooth muscle cell (SMC) proliferation and migration were studied in vitro. RESULTS: Compared with control animals (intima/media thickness 2.3 ± 0.33 µm), enalapril reduced IH in Cx40-/- hypertensive mice by 30% (1.7 ± 0.35 µm; p = .037), while zofenopril abrogated IH (0.4 ± 0.16 µm; p < .002 vs. control and p > .99 vs. sham operated Cx40-/- mice). In WT normotensive mice, enalapril had no effect (0.9665 ± 0.2 µm in control vs. 1.140 ± 0.27 µm; p > .99), while zofenopril also abrogated IH (0.1623 ± 0.07 µm; p < .008 vs. control and p > .99 vs. sham operated WT mice). Zofenoprilat, but not enalaprilat, also prevented IH in human vein segments ex vivo. The effect of zofenopril on carotid and SMCs correlated with reduced SMC proliferation and migration. Zofenoprilat inhibited the mitogen activated protein kinase and mammalian target of rapamycin pathways in SMCs and human vein segments. CONCLUSION: Zofenopril provides extra beneficial effects compared with non-sulfhydryl ACEi in reducing SMC proliferation and re-stenosis, even in normotensive animals. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases and hypertension.

The effects of COVID-19 pandemic on patients with lower extremity peripheral arterial disease: A near miss disaster.

BACKGROUND: The COVID-19 pandemic has led to widespread postponement and cancelation of elective vascular surgeries in Switzerland. The consequences of these decisions are poorly understood. PATIENTS AND METHODS: In this observational, retrospective, single-center cohort study, we describe the impact of COVID-19 pandemic containment strategies on patients with lower extremity peripheral arterial disease (PAD) referred during the period March 11, to May 11, 2020, compared to the same time frames in 2018 to 2019. Patients admitted for acute limb ischemia (ALI) or chronic PAD and undergoing urgent or elective vascular surgery or primary amputation were included. Patients' characteristics, indications for admission, and surgical features were analyzed. The occurrence of 30 day outcomes was assessed, including length of stay, rates of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and procedural and hemodynamic success. RESULTS: Overall, 166 patients were included. Fewer subjects per 10 day period were operated in 2020 compared to, 2018 to 2019 (6.7 vs. 10.5, respectively; P < 0.001). The former had higher rates of chronic obstructive pulmonary disease (COPD) (25% vs. 11.1%; P = 0.029), and ASA score (3.13 vs. 2.90; P = 0.015). The percentage of patients with ALI in 2020 was about double that of the same period in 2018 to 2019 (47.5% vs. 24.6%; P = 0.006). Overall, the types of surgery were similar between 2020 and 2018 to 2019, while palliative care and primary amputations occurred only in 2020 (5 out 40 cases). The rate of post-operative MACE was significantly higher in 2020 (10% vs. 2.4%; P = 0.037). CONCLUSIONS: During the first state of emergency for COVID-19 pandemic in 2020, less regular medical follow-up and hindered hospital access could have resulted in more acute and advanced clinical presentations of patients with PAD undergoing surgery. Guidelines are needed to provide appropriate care to this vulnerable population and avoid a large-scale disaster.

A Gardening Session Turns Into a Life Threatening Aortic Transection.

INTRODUCTION: Penetrating injuries to the sub-diaphragmatic aorta are challenging, with high mortality rates. Most penetrating aortic trauma results from gunshots or stab wounds. This case reports a successful aortic bypass, following partial aortic transection caused by an accidental fall on a utility knife. REPORT: A healthy 82 year old woman was admitted to the emergency department following penetrating abdominal trauma following an accidental fall on an 18 cm long utility knife. On admission, the patient was haemodynamically stable, with no neurological deficit. Computed tomography angiography revealed multiple abdominal injuries to the stomach, duodenum, L4-L5 left vertebrae, and infrarenal abdominal aorta. The patient underwent urgent midline laparotomy, followed by successful aortic repair using a 14 mm polyester graft. The gastric and duodenal lesions were repaired with an omental patch. The post-operative course was uneventful. DISCUSSION: Penetrating abdominal trauma with visceral lesions and aortic transection are high risk injuries, albeit rarely described in the literature. A low threshold for imaging, and multidisciplinary management by vascular and visceral surgeons are essential for timely recognition and successful intervention.

Paclitaxel-Coated Balloon Angioplasty for the Treatment of Infrainguinal Arteries: 24-Month Outcomes in the Full Cohort of BIOLUX P-III Global Registry.

PURPOSE: After promising small randomized trials, the aim of BIOLUX P-III was to further investigate the safety and performance of the Passeo-18 lx drug-coated balloon in infrainguinal arteries under real-world conditions. METHODS: BIOLUX P-III is a global prospective single-arm study with follow-up at 6, 12 and 24 months. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months. The primary performance endpoint was freedom from clinically driven target lesion revascularization (TLR) within 12 months. RESULTS: 877 patients/1084 lesions were enrolled. Diabetes mellitus was present in 47.7%, and 42.1% had critical limb ischemia (CLI). The mean lesion length was 89.0 mm with 76.1% of calcified lesions, and 24.9% occluded. At 24 months, freedom from MAE was 83.1% in the full cohort; 84.9% in the femoropopliteal population (592 patients, 691 lesions); 77.7% for long lesions (187 subjects/192 lesions); and 72.5% in the in-stent restenosis (ISR) subgroup (103 subjects/116 lesions). Twenty-four-month freedom from clinically driven TLR was 88.1% in the full cohort; 88.9% in the femoropopliteal population; 80.3% for the long lesions; and 78.4% for ISR. Twenty-four-month all-cause mortality was 12.0% in the full cohort, 10.2% in the femoropopliteal population, 14.8% for the long lesions and 12.0% for ISR. There was no device- or procedure-related death up to 24-month follow-up. CONCLUSION: The BIOLUX P-III 24-month outcomes confirm the safety and performance of Passeo-18 lx in infrainguinal arteries in a large population treated under real-world conditions with low complication rates and good clinical outcomes (NCT02276313).

BIOLUX P-III Passeo-18 Lux All-Comers Registry: 24-Month Results in Below-the-Knee Arteries.

PURPOSE: The BIOLUX P-III registry was initiated to further assess the safety and efficacy of the Passeo-18 Lux drug-coated balloon (DCB) in infrainguinal lesions in a real-world environment and in prespecified risk groups. MATERIALS AND METHODS: BIOLUX P-III is a prospective, global, all-comers registry with patients treated under real-world conditions. We herein report 24-month results of the prespecified subgroup of 151 patients with 185 below-the-knee (BTK) lesions. The primary safety and efficacy endpoints were freedom from major adverse events (a composite of freedom from device and procedure mortality through 30 days, major target limb amputation and clinically driven target lesion revascularization) at 6 months and freedom from clinically driven target lesion revascularization (FfTLR) at 12 months. RESULTS: At baseline, 76.0% of patients had critical limb ischemia and 48.9% of lesions were TASC C or D lesions. Technical success was achieved in 97.8%, and bailout stenting was required in 1.1%. Freedom from major adverse events was 86.2% [95% CI 79.4; 90.8] at 6 months, and FfTLR was 90.9% [95% CI 85.2; 94.4] at 12 months. At 24 months, FfTLR was 90.9% [95% CI 85.2; 94.4], freedom from major amputation was 90.1% [95% CI 83.9, 94.0], and overall survival was 79.2% [70.7, 85.5]. There was a significant clinical improvement (mean Rutherford class improvement of - 2.9 ± 1.9, p < 0.0001) and an improvement in pain (mean improvement on Wong-Baker Faces Pain Scale of - 2.7 ± 2.9, p < 0.0001). CONCLUSIONS: In this real-world DCB registry, 24-month outcomes of Passeo-18 Lux demonstrated safety and efficacy in BTK lesions with high patency rates and sustained clinical improvements at 24 months. TRIAL REGISTRATION: NCT02276313.

Innovative Technique for Below the Knee Arterial Revascularisation Using Porcine Self Made Stapled Pericardial Tube Grafts.

INTRODUCTION: When no autologous vein is available for distal bypass in the setting of chronic limb threatening ischaemia (CLTI), new alternatives are required to solve the problems of availability, patency, and resistance to infection. An innovative technique of below the knee bypass for CLTI using a porcine self made stapled pericardial tube graft is reported. REPORT: An 84 year old man, admitted with right CLTI with foot infection due to long occlusion of the femoropopliteal segment, required urgent revascularisation. In the absence of autologous vein and cryopreserved vessels, a 4 mm self made stapled porcine pericardial tube graft 56 cm long was created from two 14 × 8 cm patches, to perform a femorotibioperoneal trunk bypass. On day 10, bypass thrombectomy and balloon angioplasty of the distal anastomosis were needed to treat early occlusion. Oral anticoagulation was then started. Right toe pressure increased from 0 to 70 mmHg, and no infection was reported. Complete wound healing was achieved. At six months, the bypass was still patent. DISCUSSION: The use of porcine self made stapled pericardial tube grafts could offer new options for revascularisation in CLTI. Larger cohort studies with longer follow up are needed to confirm this successful preliminary experience.

Real-World Experience With a Paclitaxel-Coated Balloon in Critical Limb Ischemia: 24-Month Subgroup Outcomes of BIOLUX P-III.

OBJECTIVES: The aim of the BIOLUX P-III (A Prospective, International, Multi-Centre, Post-Market All-Comers Registry to Assess the Clinical Performance of the Passeo-18 Lux Paclitaxel Releasing Balloon Catheter in Infrainguinal Arteries - III) registry was to collect real-world data on the Passeo-18 Lux paclitaxel-coated balloon. BACKGROUND: Critical limb ischemia (CLI) is a severe condition associated with high morbidity and mortality. Prospective data are needed to provide further insights on drug-eluting devices. METHODS: BIOLUX P-III is a prospective, post-market, all-comers registry assessing the safety and performance of the Passeo-18 Lux. Clinical information was collected at 6, 12, and 24 months. The authors report 24-month outcomes of the CLI subgroup with patients in Rutherford classes 4 to 6. RESULTS: The CLI subgroup included 328 patients with 422 lesions. Patients were 71.1 ± 10.5 years of age, and 61.0% had diabetes. Femoropopliteal lesions were present in 53.8% (n = 227), below-the-knee lesions were present in 27.0% (n = 114), and lesions were moderate or heavily calcified in 45.0% (n = 190). Major adverse events, defined as 30-day device- or procedure-related mortality, major target limb amputation, and clinically driven target lesion revascularization, occurred in 9.8% of patients through 6 months, in 14.9% through 12 months, and in 19.4% through 24 months. Clinically driven target lesion revascularization occurred in 4.4%, 8.5%, and 12.1%, major amputation in 4.9%, 5.2%, and 6.1%, and mortality in 8.1%, 11.1%, and 20.1%, respectively. Predictors of mortality were age ≥75 years and higher Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease class, and higher Rutherford class was associated with increased mortality and amputation rates. CONCLUSIONS: In a large, multimorbid patient population with complex lesions and CLI, the safety and performance of the Passeo-18 Lux paclitaxel-coated balloon has been confirmed, with low rates of major amputation and target lesion revascularization.

Ex Vivo Analysis of Kidney Graft Viability Using 31P Magnetic Resonance Imaging Spectroscopy.

BACKGROUND: The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. METHODS: To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. RESULTS: Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. CONCLUSIONS: ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.