Vessel Puncture Research Articles

Pseudoaneurysm in the Axillary Tail of the Breast After A Core Needle Biopsy.

We present the case of a forty-year-old asymptomatic female with no personal or family history of breast cancer, who underwent a core needle biopsy (CNB) following the identification of a focal asymmetry in the right breast on screening mammography. Eight months later, a prominent adjacent vascular structure with a round outpouching was detected on breast ultrasound, confirmed as a post-biopsy pseudoaneurysm. Breast pseudoaneurysms, although exceedingly rare, result from inadvertent vessel puncture during core needle biopsies, particularly when larger gauge needles are used. They present as palpable, throbbing lumps in the breast and are well-defined heterogeneous structures that exhibit turbulent flow with a feeding artery on color Doppler imaging. This swirling sign showing a to-and-fro waveform is also known as the "yin-yang" sign on Doppler ultrasound. Post-CNB pseudoaneurysms in the breast, while rare, should be considered as potential complications following core need biopsy. Understanding their characteristic imaging features, risk factors, and available management options is essential for early diagnosis and appropriate treatment. This case underscores the importance of vigilance in biopsy procedures and the need for prompt recognition and intervention in case of such complications.

Femoral Large Bore Sheath Management: How to Prevent Vascular Complications From Vessel Puncture to Sheath Removal.

Transfemoral access is nowadays required for an increasing number of percutaneous procedures, such as structural heart interventions, mechanical circulatory support, and interventional electrophysiology/pacing. Despite technological advancements and improved techniques, these devices necessitate large-bore (≥12 French) arterial/venous sheaths, posing a significant risk of bleeding and vascular complications, whose occurrence has been related to an increase in morbidity and mortality. Therefore, optimizing large-bore vascular access management is crucial in endovascular interventions. Technical options, including optimized preprocedural planning and proper selection and utilization of vascular closure devices, have been developed to increase safety. This review explores the comprehensive management of large-bore accesses, from optimal vascular puncture to sheath removal. It also discusses strategies for managing closure device failure, with the goal of minimizing vascular complications.

Ultrasound-Guided Sciatic Nerve Hydrodissection Can Improve the Clinical Outcomes of Patients with Deep Gluteal Syndrome: A Case-Series Study.

Deep gluteal syndrome (DGS) is caused by sciatic nerve entrapment. Because fascial entrapment neuropathies may occur in multiple locations, ultrasound-guided nerve hydrodissection is a key component of DGS treatment. In this study, we examined the clinical outcomes of patients with DGS undergoing ultrasound-guided sciatic nerve hydrodissection. A 10 mL mixture consisting of 5% dextrose, 0.2% lidocaine (Xylocaine), and 4 mg betamethasone (Rinderon) was used for nerve hydrodissection. Clinical outcomes were evaluated using Numeric Rating Scale (NRS) scores of pain, the proportion of patients with favorable outcomes (reduction of ≥50% in pain), the duration for which patients exhibited favorable outcomes (percentage of follow-up duration), and the occurrence of major complications and minor side effects. A total of 53 patients were consecutively included and followed up for 3 to 19 months. After the initial injection, the NRS scores significantly improved at 1 week, 1 month, 3 months, and the final follow-up. Specifically, 73.6%, 71.7%, 64.2%, and 62.3% of the patients exhibited favorable outcomes at 1 week, 1 month, 3 months, and the final follow-up, respectively. The median duration for which the patients exhibited favorable outcomes was 84.7% of the follow-up period. Three patients (5.7%) experienced transient dizziness and vomiting, which resolved without further treatment. No vessel or nerve puncture was observed. Overall, ultrasound-guided sciatic nerve hydrodissection is a safe procedure that mitigates the pain associated with DGS. To achieve favorable outcomes, three consecutive injections 3 weeks apart are required.

Hemorrhagic pericardial tamponade in a hemodialysis patient with catheter-related superior vena cava syndrome: a case report

BackgroundIatrogenic complications of endovascular treatment for central venous stenosis have not yet been reported. Here we present a case of a patient on maintenance hemodialysis who developed catheter-related superior vena cava syndrome and subsequently suffered from hemorrhagic pericardial tamponade after undergoing percutaneous transluminal angioplasty and stenting.Case presentationA 72-year-old male patient presented with uremia, and had been receiving maintenance hemodialysis for the past five years. The patient initially presented with dysfunction of the dialysis catheter (a cuffed tunneled double-lumen catheter in the right internal jugular vein). Imaging examination revealed a segmental occlusion of the superior vena cava stretching from the distal end of the dialysis catheter up to right atrium entrance, apparent compensatory dilatation of the azygos vein, and abundant subcutaneous collaterals. The patient underwent percutaneous transluminal balloon dilatation and stenting (covered stent) of the superior vena cava in the Cath Lab. During the procedure, with forceful advancement of the guidewire, it was observed to progress for a distance before a “smoke” appeared, and an outward spillage of contrast agent was visible, which suggested a possible vessel puncture leading into the mediastinum. Unfortunately, postoperative hemorrhagic pericardial tamponade occurred and the patient developed cardiogenic shock. He experienced symptoms included chest tightness and breath shortness with a recorded blood pressure of 84/60mmHg. After draining 600 ml of bloody fluid through pericardiocentesis, the patient’s symptoms alleviated and his condition improved.ConclusionsThe case emphasizes the need for increased attention to iatrogenic endovascular injuries during catheter placement and endovascular treatment, such as causing pericardial hemorrhage leading to cardiac tamponade.

Catheterization of the internal jugular vein and subclavian/axillary vein under ultrasound control in the wounded with hemorrhagic shock due to combat trauma: a retrospective cohort study

INTRODUCTION: Catheterization of central veins using ultrasound navigation increases the rate of successful catheterizations and reduces the number of complications. The use of ultrasound navigation can improve the efficiency and safety of catheterization in conditions where central vein puncture is difficult. OBJECTIVE: Comparison of the readiness of the internal jugular vein and the subclavian vein/axillary vein for puncture, the effectiveness and safety of their catheterization using ultrasound navigation in patients with hemorrhagic shock. MATERIALS AND METHODS: A retrospective study of the medical data of 146 victims who required puncture and catheterization of vessels under the control of ultrasound navigation was performed. In all victims, using ultrasound, the readiness of the vessels for puncture was visually assessed by the compression and collapse of the vein at the moment of slight superficial pressure with the sensor. RESULTS: Assessment of the vessel's readiness for catheterization showed that, at all degrees of shock, the readiness of the subclavian vein/axillary vein for catheterization was higher than that of the internal jugular vein. Analysis of all central venous catheterizations performed showed that they were completed on the first attempt, but during the attempt it was necessary to redirect, sometimes tighten and advance the needle again. The data obtained showed statistical differences in patients with II and III degrees of shock (p = 0.001). CONCLUSIONS: Against the background of infusion therapy through a peripheral venous catheter for all degrees of shock, readiness for puncture and catheterization of the subclavian vein/axillary vein was higher compared to the internal jugular vein. Such tactics for shocks of degree II and III result in fewer needle passes.

High blood viscosity in acute ischemic stroke.

The changes in blood viscosity can influence the shear stress at the vessel wall, but there is limited evidence regarding the impact on thrombogenesis and acute stroke. We aimed to investigate the effect of blood viscosity on stroke and the clinical utility of blood viscosity measurements obtained immediately upon hospital arrival. Patients with suspected stroke visiting the hospital within 24 h of the last known well time were enrolled. Point-of-care testing was used to obtain blood viscosity measurements before intravenous fluid infusion. Blood viscosity was measured as the reactive torque generated at three oscillatory frequencies (1, 5, and 10 rad/sec). Blood viscosity results were compared among patients with ischemic stroke, hemorrhagic stroke, and stroke mimics diagnosed as other than stroke. Among 112 enrolled patients, blood viscosity measurements were accomplished within 2.4 ± 1.3 min of vessel puncture. At an oscillatory frequency of 10 rad/sec, blood viscosity differed significantly between the ischemic stroke (24.2 ± 4.9 centipoise, cP) and stroke mimic groups (17.8 ± 6.5 cP, p < 0.001). This finding was consistent at different oscillatory frequencies (134.2 ± 46.3 vs. 102.4 ± 47.2 at 1 rad/sec and 39.2 ± 11.5 vs. 30.4 ± 12.4 at 5 rad/sec, Ps < 0.001), suggesting a relationship between decreases in viscosity and shear rate. The area under the receiver operating curve for differentiating cases of stroke from stroke mimic was 0.79 (95% confidence interval, 0.69-0.88). Patients with ischemic stroke exhibit increases in whole blood viscosity, suggesting that blood viscosity measurements can aid in differentiating ischemic stroke from other diseases.

How I do it: Pedal access and pedal loop revascularization for patients with chronic limb-threatening ischemia.

An increasing proportion of patients with chronic limb-threatening ischemia are older and have multiple comorbidities, including diabetes and renal failure. For those who are not candidates for a surgical bypass, this set of patients presents a challenge to vascular surgeons and interventionalists owing to the complex below-the-knee and increasingly below-the-ankle disease pattern that can fail traditional approaches for endovascular intervention. Two techniques, the retrograde pedal access and the pedal-plantar loop technique, can be useful in these settings and in skilled hands can be used safely, with a high technical success rate. In patients with chronic limb-threatening ischemia who are not candidates for a single-segment saphenous vein bypass, the retrograde pedal access technique can be used not only in the setting of failed antegrade treatment, but also primarily when faced with a difficult groin or as an adjunct during a planned antegrade-retrograde intervention. The pedal plantar loop technique allows for retrograde access to tibial vessels without retrograde vessel puncture and additionally offers the ability to treat the pedal-plantar arch, which may have added benefit in wound healing. We describe the tips and tricks for these two techniques used in our limb salvage practice.

Initial platelet aggregation in the complex shear environment of a punctured vessel model

To analyze flow conditions and cellular behavior at the onset of a hemostatic response in the injury of a microneedle-induced vessel puncture, a combined in silico and in vitro platform is created. A cell-resolved blood flow model is utilized for in-depth flow profile and cell distribution analyses, and a novel punctured vessel flow chamber is set up to complement the simulations with the evaluation of platelet aggregation around the wound neck of the puncture. The respective setups of the platform are explained, and the results of both experiments and simulations with various puncture diameters and pressure drops are combined, providing detailed insight into the basic processes of platelet transport and aggregation in the wound area. A special emphasis of the simulation evaluation is put on the cell distributions and the magnitude of shear rate and elongational flow in the wound neck area, as well as downstream from the puncture. Additionally, possible implications of wound size and pressure difference on the hemostatic response are discussed. The simulations display asymmetric cell distributions between the proximal and distal sides of the wound neck in regard to the flow direction. The flow chamber with the puncture diameter closest to the simulated domains confirms this asymmetry by displaying increased platelet aggregation at the wound neck's distal side. The presented punctured vessel in silico and in vitro experimental setups offer a platform to analyze the hemostatic environment of a vessel injured by a puncture and might assist in identifying differentiating factors between primary hemostasis and arterial thrombosis.

Vascular complications after peripheral veno-arterial extracorporeal life support cannulation in cardiogenic shock

BackgroundExtra Corporeal Life Support (ECLS) is an evolving therapy in therapy-resistant cardiogenic shock (CS). Vascular cannulation in emergency situations can be accomplished through puncture of the femoral vessels by specialised teams. Since lower limb ischemia constitutes one of the major complications following cannulation, a distal perfusion cannula (DPC) has emerged as standard of care. We here aimed to analyse the impact of the DPC on limb perfusion and 6-month survival rate. MethodsIn a retrospective study from January 2012 to December 2018, 98 patients with cardiogenic shock and peripheral (v-a) ECLS implantation with documented limb perfusion status were identified and analysed. Demographic data, laboratory parameters, cause of CS, comorbidities, limb perfusion complications and complication management were analysed. Results53 patients (54%) received ECLS therapy in referral centers by our mobile ECLS team, while in 45 patients (46%) the cannulation occured in our center. 71 patients (72%) received a DPC (group A) at the time of ECLS implantation, whereas 27 (28%) (group B) did not or received later (14 patients owing to limb ischemia). 44 patients (45%) developed limb ischemia as a complication of ECLS therapy (31% in group A and 81% in group B- p < 0.001). The 6-month survival rate was 28% in our study cohort (30% in group A and 22% in group B- p = 0.469). ConclusionLower limb ischemia remains a serious complication after peripheral ECLS cannulation in CS, especially when a DPC is absent. Standardised DPC implementation may reduce the rate of severe limb complications in peripheral ECLS.

Clinical, Electrophysiological, and Sonographic Findings in Patients With Nerve Injury After Vessel Puncture.

This study aimed to describe the clinical, electrophysiological, and ultrasonographic findings of patients with nerve injury after vessel puncture. Data on ten patients (three males and seven females) with nerve injury after vessel puncture were reviewed. Demographic and clinical data were analyzed retrospectively. Bilateral electrophysiological studies were performed based on clinical findings. Ultrasonographic examinations were performed on both the affected and unaffected sides of the injured nerve. The nerves of nine patients were injured following vein puncture, and injury occurred following arterial sampling in one patient. Seven patients had superficial radial sensory nerve injury: five medial, one lateral, and one at both branches. One patient had injury to the dorsal ulnar cutaneous nerve, one to the lateral antebrachial cutaneous nerve, and one to the median nerve. Nerve conduction studies produced abnormal findings in 80% of patients, whereas ultrasonographic examinations produced abnormal findings in all of the patients. Spearman's coefficient for the correlation between the amplitude ratio and nerve cross-sectional area ratio was not significant, at -0.127 (95% confidence interval=-0.701 to 0.546, p=0.721). Ultrasonography supported by electrodiagnosis was found to be a useful method for identifying the lesion location and structural abnormalities of vessel-puncture-related neuropathy.

Unilateral exophthalmos in a dog following bilateral maxillary nerve block for rhinoscopy

AbstractLocal anaesthetic techniques are utilised to provide analgesia and anaesthesia during rhinoscopy (and biopsy) in small animals. This report describes the incidence and management of exophthalmos in a 1‐year‐old, male, neutered whippet as a consequence of a retrobulbar haematoma, following inadvertent vessel puncture while performing a maxillary nerve block. The patient recovered fully without further complications following conservative management.

Traumatic vessel injuries initiating hemostasis generate high shear conditions

AbstractBlood flow is a major regulator of hemostasis and arterial thrombosis. The current view is that low and intermediate flows occur in intact healthy vessels, whereas high shear levels (>2000 s−1) are reached in stenosed arteries, notably during thrombosis. To date, the shear rates occurring at the edge of a lesion in an otherwise healthy vessel are nevertheless unknown. The aim of this work was to measure the shear rates prevailing in wounds in a context relevant to hemostasis. Three models of vessel puncture and transection were developed and characterized for a study that was implemented in mice and humans. Doppler probe measurements supplemented by a computational model revealed that shear rates at the edge of a wound reached high values, with medians of 22 000 s−1, 25 000 s−1, and 7000 s−1 after puncture of the murine carotid artery, aorta, or saphenous vein, respectively. Similar shear levels were observed after transection of the mouse spermatic artery. These results were confirmed in a human venous puncture model, where shear rates in a catheter implanted in the cubital vein reached 2000 to 27 000 s−1. In all models, the high shear conditions were accompanied by elevated levels of elongational flow exceeding 1000 s−1. In the puncture model, the shear rates decreased steeply with increasing injury size. This phenomenon could be explained by the low hydrodynamic resistance of the injuries as compared with that of the downstream vessel network. These findings show that high shear rates (>3000 s−1) are relevant to hemostasis and not exclusive to arterial thrombosis.

Use of cangrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Study design and interim analysis of the ARCANGELO study.

BackgroundThe itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice.HypothesisThe safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines.MethodsAdults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two‐thirds of the enrollment period are presented.ResultsA total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor.ConclusionsThe interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

Exsanguination from ruptured femoral artery pseudoaneurysm - A fatal complication of groin heroin injection.

Intravenous drug users (IDUs) eventually encounter a common problem- a need to turn to a new vessel to inject drugs. Whether it is because no other spot is available due to scarring or convenience, the groin is the preferred spot for some. Chronic puncture of femoral vessels can lead to a rare but significant complication- femoral artery pseudoaneurysm (FAP). Its fatal consequence- rupture and bleeding is well recognized, but the forensic literature on this subject is limited. We present eight cases of exsanguination due to the ruptured FAP in IDUs who share most or all the following characteristics: long-term heroin use and/or pronounced drug use stigmata, chronic groin injection-related lesions, absence of significant precipitating pseudoaneurysm trauma, and no or minimal concentrations of heroin metabolites in blood. The FAP presentation varied greatly, from palpable fist-sized mass or slight elevation under the skin defect to infundibular arterio-cutaneous fistula that ruptured through the skin induration. In some, surrounding skin or soft tissue showed signs of inflammation but without suppuration. The most prominent FAP characteristic was smooth-surface cavitation on cross-sections. We performed microscopic evaluation in two cases and verified disruption of the artery wall (i.e., pseudoaneurysm) with elements of acute and chronic inflammation and fibrosis; foci of fibrinoid necrosis were noticed on the arterial wall. All subjects were pale, with faint hypostasis and organ anemia, consistent with reported massive hemorrhage. Because such sudden, unwitnessed, and suspicious deaths may raise the question of injury infliction, proper autopsy evaluation is crucial, for which we propose guidelines.

Post-Marketing Safety Concerns With Secukinumab: A Disproportionality Analysis of the FDA Adverse Event Reporting System.

Purpose: Secukinumab was approved for the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. However, the long-term safety of secukinumab in large sample population was unknown. The current study was to evaluate the secukinumab-assocaited adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports in the FAERS from the first quarter of 2015 (FDA approval of secukinumab) to the third quarter of 2021 were collected and analyzed. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of secukinumab-related AEs. Results: A total of 89,228 reports of secukinumab as the “primary suspected (PS)” and 254,886 AEs induced by secukinumab were identified. Secukinumab-induced AE occurrence targeted 27 system organ classes (SOCs). A total of 257 signals of secukinumab-induced AEs in 19 SOCs were detected after conforming to the four algorithms simultaneously. Common significant signals of infections, respiratory disorders, skin and subcutaneous tissue disorders, immune system disorders, and ear and labyrinth disorders have emerged. Unexpected significant AEs such as injection site pain, vessel puncture site haemorrhage, arthralgia, hypokinesia, Bell’s palsy, parotid gland enlargement, and stress might also occur. The median onset time of secukinumab-associated AEs was 56 days (interquartile range [IQR] 5–214 days), and most of the onsets occurred within the first 1, 2, 3, and 4 months after initiation of secukinumab. Conclusion: Our study found potential new AE signals and provided a broader understanding of secukinumab’s safety profiles, supporting its rational use in chronic systemic inflammatory diseases.

Access Site Complications by Intracardiac Interventions

In recent decades, the number of intracardiac procedures using percutaneous puncture access has increased manifold. Despite the acquisition by operators of expertise and standardization of methods, the problem of complications remains relevant.&#x0D; AIM: to analyze the frequency and nature of complications of percutaneous access in intracardiac interventions. Suggest recommendations to reduce the incidence of complications.&#x0D; MATERIALS AND METHODS: analysis of data published in international peer-reviewed journals on the topic, as well as the experience of the vascular surgery clinic of St. Katarina's Hospital.&#x0D; CONCLUSIONS: the frequency and severity of complications depend on the experience of the operator, the size and frequency of changing the instrument, as well as compliance with the rules of preoperative diagnosis and postoperative management of the patient.&#x0D; RECOMMENDATIONS: standardized preoperative preparation, careful planning of the intervention, analysis of the state of the access vessels, compliance with the rules of vessel puncture and competent performance of postoperative compression in combination with the use of suturing devices according to indications can reduce the frequency and severity of complications.

Indocyanine green fluorescence staining based on the "hepatic pedicle first" approach during laparoscopic anatomic liver resection.

Indocyanine green (ICG) fluorescence staining is one of the most challenging procedures for laparoscopic anatomic liver resection (LALR). Here, we introduce a novel method based on the "hepatic pedicle first" approach that can improve the success rate of positive staining. The target hepatic pedicle (even for the subsegment) was dissected through the first porta until it became visible. Five milliliters of 0.025mg/ml ICG was injected after the target hepatic pedicle (extra-Glissonian approach) or portal vein/hepatic artery (intra-Glissonian approach) was punctured successfully using scalp acupuncture under direct vision. Then, the Glissonian pedicle or vessel was clamped immediately to prevent the intrahepatic diffusion of ICG. During the operation, a fluorescence imaging model was used repeatedly to confirm the segmental boundary. Finally, 24 patients underwent LALR with the "hepatic pedicle first" approach for ICG fluorescence-positive staining. In 5 patients, ICG-positive staining failed, representing a 79.17% success rate. The average staining time was 25.92min ± 14.64min. There were no complications associated with vessel puncture (bile leakage,hemorrhage,and thrombosis). The "hepatic pedicle first" approach is a feasible, convenient, and safe method for ICG-positive staining, with a high success rate.

Spectrum of Interventional Procedures During Hybrid Central Line Placement in Pediatric Intestinal Rehabilitation Patients With End-Stage Vascular Access.

BackgroundLoss of available central vein access sites for parenteral nutrition delivery represents one of the main indications for intestinal transplantation in children with intestinal failure. Placement of central venous catheters can be challenging in advanced loss of patent venous pathways. We recently described the hybrid technique (interventional plus surgical approach) of central line placement in children. The aim of this study was to describe and analyze the interventions used during the hybrid procedures regarding feasibility, safety and outcome.MethodsWe retrospectively analyzed the course of all children in our intestinal rehabilitation program undergoing hybrid central line placement. We evaluated patients' conditions, interventional techniques and surgical peculiarities as well as outcome.Results203 children were treated in our intestinal rehabilitation program between 2010 and 2021. Due to loss of venous access, hybrid technique was performed in 53 children during 76 interventions. In 40 cases the same vessel was reused via Seldinger technique. Among the 30 ultrasound-guided new vessel punctures, 12 were performed by puncture of collateral vessels. Extended interventions due to thoracic central venous obstruction and/or thrombosis requiring additional access via a femoral vein for rehabilitation of the vascular system was performed during 29 procedures including catheter extraction (1), angioplasties (18), stent placement (1), revascularization (5) and thrombectomy (4). Placement of a central line was not possible in 6 children which eventually underwent extended thoracic/vascular surgery: in three children the previously placed catheter could not be removed, in one child, placement of a thrombectomy-catheter was not possible because of inferior vena cava occlusion, and in two children, revascularization failed. Intestinal transplantation was considered in one patient because of impending loss of vascular access. Two self-limiting minor extravasations and one intervention-associated pericardial effusion occurred.ConclusionsHybrid interventions for central venous catheter placement and vascular rehabilitation enable a high success rate in children with intestinal failure and end-stage vascular access, circumventing the need for intestinal transplantation or advanced surgery. The relevant procedures are complex and require a foresighted and individualized approach with a wide range of interventional techniques. If performed with expertise, this combined interventional/surgical approach is feasible and safe.

Balloon-Assisted Retrograde Puncture of Distal Vessels in Patients Unsuitable for a Conventional Transpedal Approach

Purpose: To describe a novel bailout technique to approach below-the-knee chronic total occlusions after a failed bidirectional recanalization attempt using the plantar loop maneuver in patients who are poor candidates for a retrograde puncture. Technique: After a failure of recanalization of the opposite tibial artery using the plantar loop maneuver, an assisted direct retrograde transpedal approach can be performed regardless of poor vessel caliber or even arterial occlusion. After crossing the plantar arch, a low profile angioplasty balloon is used as a landmark for the pedal puncture and to give guidance for the wire advancement from the new access. Conclusion: A balloon-assisted retrograde transpedal approach may be considered for below-the-knee recanalization after standard plantar loop technique failure in patients who are not candidates for conventional retrograde puncture.

Single and multiple ascending dose studies in healthy volunteers to assess the safety and PK of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme

AbstractBackgroundLY3372689, an OGA enzyme inhibitor, is being developed as a potential treatment for tauopathies, including Alzheimer’s disease. OGA inhibition is proposed to delay the progression of tau‐related diseases by slowing the accumulation of hyper‐phosphorylated, insoluble tau filaments. We report the safety and pharmacokinetics (PK) of LY3372689 after single and multiple oral doses in healthy volunteers (HV).MethodThe single ascending dose (SAD) and multiple ascending dose (MAD) studies were single center, subject‐ and investigator‐blind, placebo‐controlled and randomized. In the SAD study [NCT03819270], 6 LY3372689 dose levels up to 16 mg and placebo were evaluated. In the MAD study [NCT04106206], LY3372689 (1, 3 and 7 mg) or placebo was given once daily (QD) for 14 days. Safety was assessed by adverse events (AE), safety laboratories, electrocardiograms, vital signs, physical exams, and neurological exams. Plasma pharmacokinetics (PK) was assessed in the SAD and MAD studies.ResultIn the SAD, 23 HV (15 males, 8 females; 22 – 63 years) participated, of which 18 HV completed. In the MAD, 40 HV (5 males, 35 females; 29 – 65 years) participated in the study, of which 39 HV completed. LY3372689 was generally well tolerated up to the highest dose in each study, and no serious AE were reported. In the SAD, 40 treatment‐emergent AEs (TEAEs) were reported, which were mostly mild in severity. The most common TEAEs were headache, nausea, pain in extremity, pain of skin, vessel puncture site pain, and limb discomfort. In the MAD, 42 TEAEs were reported, all of which were mild in severity. The most reported TEAE was headache. In both studies, there were no clinically significant changes in safety laboratories, including markers of inflammation, muscle injury, hormones and hepatoxicity. Following QD dosing of LY3372689, the tmax and t1/2 was about 1 hour and 6 hours, respectively, and LY3372689 exposure accumulation was minimal. Renal clearance was not a major contributor of LY3372689 elimination.ConclusionLY3372689 demonstrated an acceptable safety and PK profile following single and multiple doses of LY3372689 in HV. These results support investigation of LY3372689 in efficacy trials for tauopathies and help support dose selection for those trials.