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3.
J Vet Intern Med ; 37(6): 2030-2038, 2023.
Article in English | MEDLINE | ID: mdl-37767953

ABSTRACT

BACKGROUND: Cardiovascular diseases with increased right ventricular (RV) afterload induce RV diastolic and systolic dysfunction, and myocardial fibrosis in humans. Studies in dogs with pulmonary stenosis (PS) evaluating RV diastolic function and markers of myocardial fibrosis are lacking. HYPOTHESIS/OBJECTIVES: Dogs with PS have echocardiographic evidence of RV diastolic and systolic dysfunction and increased serum concentrations of galectin-3 (Gal-3), a surrogate biomarker for myocardial fibrosis. ANIMALS: Forty client-owned dogs (10 controls, 30 with PS). METHODS: Prospective study. All dogs had systemic blood pressure measurement, serum biochemical analysis, echocardiography, and measurement of serum Gal-3 concentration performed. RESULTS: Variables of RV diastolic function were obtained in 39/40 dogs. Trans-tricuspid flow velocity in early diastole to trans-tricuspid flow velocity in late diastole ratios (RV E/A) were lower (P < .001) in dogs with PS (median, 0.94; range, 0.62-2.04) compared to controls (1.78; 1.17-2.35). Trans-tricuspid flow velocity in early diastole to tricuspid annular myocardial velocity in early diastole ratios (RV E/e') were higher (P < .001) in dogs with PS (11.55; 4.69-28) compared to control (6.21; 5.16-7.21). Variables of RV systolic function were lower in dogs with PS (P = <.001). Serum Gal-3 concentration was higher (P = .002) in dogs with PS (285.1 pg/mL; 94.71-406.97) compared to control dogs (162.83 pg/mL; 52.3-232.82). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with PS have RV diastolic and systolic dysfunction, and increased Gal-3 concentrations. These findings suggest the presence of RV myocardial fibrosis in dogs with PS, which could impact clinical management.


Subject(s)
Dog Diseases , Pulmonary Valve Stenosis , Humans , Dogs , Animals , Galectin 3 , Diastole , Prospective Studies , Pulmonary Valve Stenosis/veterinary , Fibrosis , Dog Diseases/diagnostic imaging
6.
J Vasc Surg Cases Innov Tech ; 9(1): 101080, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36747607

ABSTRACT

Background: Thoracic outlet syndrome (TOS) is a rare condition caused by compression of the neurovascular structures within the thoracic outlet. Different classifications of TOS exist depending on the neurovascular structure being compressed: neurogenic, venous, or arterial. Any of these forms can present independently or coexist with one other. TOS symptoms are sometimes precipitated by the presence of boney abnormalities that often require surgical intervention for ultimate resolution. This retrospective review will examine the presentations and outcomes of patients with TOS whose cause was a boney abnormality. Methods: A total of 73 patients who underwent thoracic outlet surgery between 2016 and 2021 were retrospectively reviewed via electronic medical records. Twelve (16%) patients demonstrated boney abnormalities on presentation causing their symptoms. The patients with boney abnormalities were analyzed based on venous, arterial, or neurogenic TOS diagnosis. Results: Of the 12 patients with boney abnormalities, 5 were classified as venous TOS, 6 patients as neurogenic TOS, and 1 as arterial TOS. The boney abnormalities were as follows: venous TOS: three clavicular fractures, one nonfused congenital clavicle, and one residual rib; neurogenic TOS: three fractured first ribs, one fractured clavicle, and two cervical ribs; and arterial TOS: fused first and second rib with bilateral cervical ribs and arterial compression. Postoperatively, there were no artery, vein, or nerve injuries. Five patients had a pneumothorax treated over night with a chest tube, and one patient had a superficial wound infection. The median hospital stay was 1 day. All patients completed physical therapy after surgery. All patients have symptom resolution at follow-up. Conclusions: Patients with boney abnormalities constitute about one-fifth of patients who can present with all three forms of TOS: neurogenic, arterial, and venous, and some will have more than one of these presentations. Results in patients undergoing surgery with boney abnormalities causing thoracic outlet syndrome are excellent with symptom resolution and without substantial complications.

7.
J Vasc Surg Venous Lymphat Disord ; 11(1): 156-160, 2023 01.
Article in English | MEDLINE | ID: mdl-36273741

ABSTRACT

BACKGROUND: Venous thoracic outlet syndrome (VTOS) is a debilitating condition with several well-documented treatment paradigms. We reviewed the outcomes from a large academic institution of patients who had undergone transaxillary first rib resection with delayed venography (TA) or infraclavicular first rib and subclavius muscle resection with concomitant venography (ICV) for VTOS with subclavian vein thrombosis. METHODS: We performed a retrospective review of the medical records of all patients who had undergone first rib resection and scalenectomy for VTOS with subclavian vein thrombosis at a single academic institution. The demographics, presentation, operative records, and outcomes were collected. Descriptive statistics were used to compare the two groups. RESULTS: A total of 73 patients had undergone first rib resection for VTOS during the study period. Of the 73 patients, 36 (49%) had presented with thrombosis of the subclavian vein and were included in the present review. Of the 36 patients, 26 (72%) had undergone TA and 10 (28%) had undergone ICV. No significant differences were seen between the two groups in female gender (54% vs 50%; P = 1.00) or age (28.7 years vs 29.5 years; P = .88). A higher percentage of the ICV group had undergone preoperative thrombolysis (70% vs 27%; P = .02). All the patients in the ICV group had undergone intraoperative balloon venoplasty at resection. The mean time from thrombosis to resection was 2.3 months. All of the TA group had undergone venography at 2 weeks postoperatively. Venography had revealed 15 stenotic veins requiring venoplasty, 8 widely patent veins, 1 acutely thrombosed vein, and 3 chronically occluded veins. The time from initial thrombosis to surgical intervention was 10 months for the patent group, 6 months for the stenotic group, and 4 months for the occluded group. In the TA group, 19% of the patients had required chest tube placement intraoperatively for pneumothorax. In the ICV group, complications included postoperative hematoma (n = 1), wound infection (n = 1), and hemothorax (n = 1). The mean length of stay was 1.04 days for the TA group and 2.00 days for the ICV group (P < .0001). The mean follow-up was 10.4 months and 15.8 months for the TA and ICV groups, respectively. No mortalities were reported. No differences in the vein patency rates were seen between the two groups at follow-up (TA, 93%; vs ICV, 100%; P = 1.00). All the patients were asymptomatic at follow-up. CONCLUSIONS: The outcomes for the patients who had undergone TA or ICV for subclavian vein thrombosis were excellent with no mortality and few complications. The subclavian vein patency rates were high, and all the patients were asymptomatic at follow-up.


Subject(s)
Thoracic Outlet Syndrome , Venous Thrombosis , Humans , Female , Adult , Subclavian Vein/diagnostic imaging , Subclavian Vein/surgery , Treatment Outcome , Thoracic Outlet Syndrome/diagnostic imaging , Thoracic Outlet Syndrome/surgery , Ribs/diagnostic imaging , Ribs/surgery , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/surgery , Retrospective Studies , Constriction, Pathologic
8.
Am J Vet Res ; 83(10)2022 08 02.
Article in English | MEDLINE | ID: mdl-35905145

ABSTRACT

OBJECTIVE: To assess whether cardiac MRI or various biomarkers can be used to detect myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD). ANIMALS: 6 dogs with cardiomegaly secondary to naturally occurring stage B2 MMVD being treated only with pimobendan with or without enalapril and 6 control dogs with no cardiac disease. All dogs were ≥ 5 years old with no systemic illness. PROCEDURES: Serum cardiac troponin I and concentrations were measured, and dogs were anesthetized for cardiac MRI with ECG-triggered acquisition of native T1- and T2-weighted images. Gadolinium contrast was administered to evaluate myocardial perfusion and late gadolinium enhancement (LGE). Mean T1 and T2 values and regions of LGE were measured with dedicated software. Extracellular volume (ECV) was estimated on the basis of Hct and T1 values of myocardium and surrounding blood. Subjective analysis for myocardial perfusion deficits was performed. RESULTS: Dogs with MMVD had significantly (P = .013) higher cardiac troponin I concentrations than control dogs, but galectin-3 concentrations did not differ (P = .08) between groups. Myocardial fibrosis was detected in 4 dogs with MMVD and 3 control dogs; no dogs had obvious myocardial perfusion deficits. Native T1 and T2 values, postcontrast T1 values, and ECV values were not significantly different between groups (all P > .3). CLINICAL RELEVANCE: Results suggest that some dogs with cardiomegaly secondary to MMVD may not have clinically relevant myocardial fibrosis.


Subject(s)
Dog Diseases , Heart Valve Diseases , Myocardial Ischemia , Animals , Cardiomegaly/drug therapy , Cardiomegaly/veterinary , Contrast Media , Dog Diseases/diagnostic imaging , Dog Diseases/etiology , Dogs , Fibrosis , Gadolinium , Heart Valve Diseases/veterinary , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/veterinary , Mitral Valve , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/etiology , Myocardial Ischemia/veterinary , Troponin I
9.
J Phys Chem B ; 126(22): 4160-4167, 2022 06 09.
Article in English | MEDLINE | ID: mdl-35594491

ABSTRACT

Employing X-ray photon correlation spectroscopy, we measure the kinetics and dynamics of a pressure-induced liquid-liquid phase separation (LLPS) in a water-lysozyme solution. Scattering invariants and kinetic information provide evidence that the system reaches the phase boundary upon pressure-induced LLPS with no sign of arrest. The coarsening slows down with increasing quench depths. The g2 functions display a two-step decay with a gradually increasing nonergodicity parameter typical for gelation. We observe fast superdiffusive (γ ≥ 3/2) and slow subdiffusive (γ < 0.6) motion associated with fast viscoelastic fluctuations of the network and a slow viscous coarsening process, respectively. The dynamics age linearly with time τ ∝ tw, and we observe the onset of viscoelastic relaxation for deeper quenches. Our results suggest that the protein solution gels upon reaching the phase boundary.


Subject(s)
Muramidase , Water , Gels/chemistry , Kinetics , Viscosity , Water/chemistry
10.
Fed Pract ; 39(1): 32-36a, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35185318

ABSTRACT

OBJECTIVES: Spinal cord stimulation (SCS) has been shown to be an effective and safe option to treat patients with intractable pain in the general population. Our study examined the experience of US veterans with SCS. METHODS: We reviewed electronic health records and conducted phone interviews with 65 veterans who had SCS from 2008 to 2020 at the Southeastern Louisiana Veterans Health Care System (SLVHCS). Our primary outcome measure was veteran would recommend SCS to peers. Secondary outcomes were improvements in activities of daily living and ability to decrease opioid pain medications. RESULTS: A majority (77%) of veterans recommended SCS to their peers. Statistical difference was seen in 16 of 18 categories of activities of daily living based on the Pain Outcomes Questionnaire. No permanent neurologic deficits or deaths were associated with SCS use. There were no neurological sequelae. Three patients (5%) developed skin dehiscence postimplant and were treated with explant surgery but all were eager to get a new SCS implanted. CONCLUSION: Veterans at SLVHCS were satisfied with their experience using SCS and few experienced adverse effects.

11.
J Radiol Prot ; 41(3)2021 Aug 19.
Article in English | MEDLINE | ID: mdl-34107455

ABSTRACT

Yttrium-90 (Y-90) radioembolization for the treatment of hepatocellular carcinoma can present safety challenges when transplanting recently treated Y-90 patients. To reduce surgeons' contact with radioactive tissue and remain within occupational dose limits, current guidelines recommend delaying transplants at least 14 days, if possible. We wanted to determine the level of radiation exposure to the transplant surgeon when explanting an irradiated liver before the recommended decay period. Anex-vivoradiation exposure analysis was conducted on the explanted liver of a patient who received Y-90 therapy 46 h prior to orthotopic liver transplant. To estimate exposure to the surgeon's hands, radiation dosimeter rings were placed inside three different surgical glove configurations and exposed to the explanted liver. Estimated radiation doses corrected for Y-90 decay were calculated. Radiation safety gloves performed best, with an average radiation exposure rate of 5.36 mSV h-1in the static hand position, an 83% reduction in exposure over controls with no glove (31.31 mSv h-1). Interestingly, non-radiation safety gloves also demonstrated reduced exposure rates, well below occupational regulation limits. Handling of Y-90 radiated organs within the immediate post-treatment period can be done safely and does not exceed federal occupational dose limits if appropriate gloves and necessary precautions are exercised.


Subject(s)
Occupational Exposure , Radiation Exposure , Hepatectomy , Humans , Occupational Exposure/analysis , Radiation Dosage , Yttrium Radioisotopes/therapeutic use
12.
Kidney Med ; 3(2): 248-256.e1, 2021.
Article in English | MEDLINE | ID: mdl-33851120

ABSTRACT

BACKGROUND: It is unclear whether surgical placement of an arteriovenous (AV) fistula (AVF) confers substantial clinical benefits over an AV graft (AVG) in older adults with end-stage kidney disease (ESKD). We report vascular access outcomes of a pilot clinical trial. STUDY DESIGN: Pilot randomized parallel-group open-label trial. SETTING & PARTICIPANTS: Patients 65 years and older with ESKD and no prior AV access receiving maintenance hemodialysis through a tunneled central venous catheter referred for AV access placement by their treating nephrologist. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to surgical placement of an AVG or AVF. OUTCOMES: Index AV access primary failure, successful cannulation, adjuvant interventions and infections. RESULTS: Of 122 older adults receiving hemodialysis and no prior AV access surgery, 24% died before (n = 18) or were too sick for (n = 11) referral for a permanent AV access. Of 46 eligible patients, 36 (78%) consented and were randomly assigned to AVG (n = 18) and AVF (n = 18) placement, of whom 13 (72%) and 16 (89%) underwent index AV access surgical placement, respectively. At a median follow-up of 321.0 days, primary AV access failure was noted in 31% in each group. The proportion of patients with successful cannulation was 62% (8 of 13) in the AVG and 50% (8 of 16) in the AVF group; median times to successful cannulation were 75.0 and 113.5 days, respectively. Endovascular procedures were recorded in 38% and 44%, and surgical reinterventions, in 23% and 25%, respectively. AV access infection was seen in 3 (23%) and 2 (13%) patients, respectively. LIMITATIONS: Small sample size precludes statistical inference. CONCLUSIONS: Almost one-quarter of older adults with incident ESKD and a central venous catheter as primary access were not referred for AV access placement due to medical reasons. Based on these limited results, there is little reason to favor either an AVF or AVG in this population until results from a larger randomized clinical trial become available. FUNDING: Government funding to an author (Dr Murea is supported by National Institutes of Health∖National Institute on Aging grant 1R03 AG060178-01). TRIAL REGISTRATION: NCT03545113.

13.
Am J Vet Res ; 82(4): 318-325, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33764832

ABSTRACT

OBJECTIVE: To investigate the effects of recombinant equine IL-1ß on function of equine endothelial colony-forming cells (ECFCs) in vitro. SAMPLE: ECFCs derived from peripheral blood samples of 3 healthy adult geldings. PROCEDURES: Function testing was performed to assess in vitro wound healing, tubule formation, cell adhesion, and uptake of 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) by cultured ECFCs. Cell proliferation was determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Effects on function test results of different concentrations and exposure times of recombinant equine IL-1ß were assessed. RESULTS: Challenge of cultured ECFCs with IL-1ß for 48 hours inhibited tubule formation. Continuous challenge (54 hours) with IL-1ß in the wound healing assay reduced gap closure. The IL-1ß exposure did not significantly affect ECFC adhesion, DiI-Ac-LDL uptake, or ECFC proliferation. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggested a role for IL-1ß in the inhibition of ECFC function in vitro. Functional changes in ECFCs following challenge with IL-1ß did not appear to be due to changes in cell proliferative capacity. These findings have implications for designing microenvironments for and optimizing therapeutic effects of ECFCs used to treat ischemic diseases in horses.


Subject(s)
Endothelial Cells , Wound Healing , Animals , Cell Proliferation , Cells, Cultured , Horses , Interleukin-1beta , Male
14.
J Vet Intern Med ; 35(1): 10-21, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33241877

ABSTRACT

BACKGROUND: Arterial thromboembolism is a sequela of hypertrophic cardiomyopathy (HCM) in cats related to left atrial (LA) enlargement and dysfunction. HYPOTHESIS: Pimobendan improves LA transport function in cats. ANIMALS: Twenty-two client-owned cats with HCM and 11 healthy cats. METHODS: Prospective, double-blind, randomized, placebo-controlled clinical cohort study. Cats were randomized to receive either pimobendan (0.25 mg/kg PO q12h) or placebo for 4 to 7 days. Nineteen echocardiographic variables of LA size and function were evaluated. Statistical comparisons included t tests, analysis of variance, and multivariable analyses. RESULTS: Peak velocity of left auricular appendage flow (LAapp peak; mean ± SD, 0.85 ± 0.20 vs 0.71 ± 0.22 m/s; P = .01), maximum LA volume (P = .03), LA total emptying volume (P = .03), peak velocity of late diastolic transmitral flow (A peak velocity; 0.77 ± 0.12 vs 0.62 ± 0.17 m/s; P = .05), and A velocity time integral (A VTI; 3.05 ± 0.69 vs 3.37 ± 0.49; P = .05) were increased after pimobendan. Mean change after pimobendan was larger in cats with HCM compared to healthy cats for LA fractional shortening (2.1% vs -2.1%; P = .05), A VTI (0.58 vs 0.01 cm; P = .01), LAapp peak (0.20 vs 0.02 m/s; P = .02), LA kinetic energy (3.51 vs -0.10 kdynes-cm; P = .05), and LA ejection force (1.93 vs -0.07 kdynes; P = .01) in the multivariable model. The stronger effect of pimobendan in cats with HCM was independent of LA size. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified positive, albeit minor, effects of pimobendan on LA function in cats with HCM. Whether or not treatment with pimobendan decreases the risk of cardiogenic embolism deserves further study.


Subject(s)
Cardiomyopathy, Hypertrophic , Cat Diseases , Pyridazines , Animals , Atrial Function, Left , Cardiomyopathy, Hypertrophic/veterinary , Cat Diseases/drug therapy , Cats , Cohort Studies , Heart Atria , Prospective Studies , Pyridazines/pharmacology
15.
JFMS Open Rep ; 6(2): 2055116920959607, 2020.
Article in English | MEDLINE | ID: mdl-33062291

ABSTRACT

CASE SUMMARY: An 8-year-old spayed female domestic shorthair cat was presented for a recheck evaluation of hypertrophic cardiomyopathy and chronic kidney disease. Three years prior to presentation, the patient was diagnosed with obstructive hypertrophic cardiomyopathy and started on atenolol. The left ventricular outflow tract obstruction subsequently resolved. Biochemical analysis a week prior to presentation demonstrated severe azotemia. Transthoracic echocardiograph revealed pericardial effusion, pleural effusion, severe left ventricular concentric hypertrophy, severe left atrial enlargement and continuous left-to-right flow through the interatrial septum near the fossa ovalis. The patient was euthanized owing to poor prognosis, and gross examination at necropsy revealed a valve-incompetent patent foramen ovale secondary to severe left atrial dilation. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of an acquired left-to-right shunt through a valve-incompetent foramen ovale in a cat with hypertrophic cardiomyopathy. Severe left atrial dilation was suspected to cause interatrial shunting through the valve-incompetent foramen ovale, and this finding may be relevant to echocardiographic evaluations in other cats.

17.
Front Vet Sci ; 7: 423, 2020.
Article in English | MEDLINE | ID: mdl-32851013

ABSTRACT

Objective: This study describes the pharmacokinetics of parent pimobendan (PIM) and its active metabolite, o-desmethyl-pimobendan (ODMP), after oral and rectal administration of pimobendan to healthy dogs. Animals: A total of eight healthy privately owned dogs were used in this study. Procedures: The dogs received a single dose (0.5 mg/kg) of a commercially available pimobendan tablet per os (PO). Twelve blood samples were collected over a 12-h period for pharmacokinetic analysis. After a 24-h washout period, the dogs received the same dose of pimobendan solution per rectum (PR), and samples were obtained at the same time for analysis. Results: For PIM, PO vs. PR, respectively, the mean maximum plasma concentration (C max, ng/ml) was 49.1 ± 28.7 vs. 10.1 ± 2, the time to reach a maximum concentration (T max, h) was 2.1 ± 0.9 vs. 1 ± 0.4, the disappearance half-life (t 1/2, h) was 1.8 ± 0.8 vs. 2.2 ± 0.6, and the area under the concentration-time curve (AUC, ng*h/ml) was 148.4 ± 71.6 vs. 31.1 ± 11.9, with relative bioavailability (F, %) of 25 ± 8. For ODMP, PO vs. PR, respectively, C max was 30.9 ± 10.4 vs. 8.8 ± 4.8, T max was 3.2 ± 1.6 vs. 1.7 ± 1.1, and t 1/2 was 5.0 ± 2.7 vs. 8.3 ± 4.8, with AUC of 167.8 ± 36.2 vs. 50.1 ± 19.2 and F of 28 ± 6. The differences between PO and PR were significant (P < 0.03) for AUC and C max for both PIM and ODMP. Conclusions and Clinical Relevance: The pharmacokinetics of PIM and ODMP were described following PO and PR administration. The findings suggest that pimobendan PR might achieve effective concentrations and, as such, warrant future studies of clinical effectiveness in treating dogs with congestive heart failure and which are unable to receive medication PO.

18.
Front Hum Neurosci ; 14: 229, 2020.
Article in English | MEDLINE | ID: mdl-32670040

ABSTRACT

Nearly half of all mild brain injury sufferers experience long-term cognitive impairment, so an important goal in rehabilitation is to address their multiple cognitive deficits to help them return to prior levels of functioning. Cognitive training, or the use of repeated mental exercises to enhance cognition, is one remediation method for brain injury. The primary purpose of this hypothesis-generating pilot study was to explore the statistical and clinical significance of cognitive changes and transfer of training to real-life functioning following 60 h of Brain Booster, a clinician-delivered cognitive training program, for six patients with mild traumatic brain injury (TBI) or non-traumatic acquired brain injury (ABI). The secondary purpose was to explore changes in functional connectivity and neural correlates of cognitive test gains following the training. We used a multiple case study design to document significant changes in cognitive test scores, overall IQ score, and symptom ratings; and we used magnetic resonance imaging (MRI) to explore trends in functional network connectivity and neural correlates of cognitive change. All cognitive test scores showed improvement with statistically significant changes on five of the seven measures (long-term memory, processing speed, reasoning, auditory processing, and overall IQ score). The mean change in IQ score was 20 points, from a mean of 108 to a mean of 128. Five themes emerged from the qualitative data analysis including improvements in cognition, mood, social identity, performance, and Instrumental Activities of Daily Living (IADLs). With MRI, we documented significant region-to-region changes in connectivity following cognitive training including those involving the cerebellum and cerebellar networks. We also found significant correlations between changes in IQ score and change in white matter integrity of bilateral corticospinal tracts (CST) and the left uncinate fasciculus. This study adds to the growing body of literature examining the effects of cognitive training for mild TBI and ABI, and to the collection of research on the benefits of cognitive training in general. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918994.

19.
Article in English | MEDLINE | ID: mdl-32551134

ABSTRACT

BACKGROUND: Although older adults encompass almost half of patients with advanced chronic kidney disease, it remains unclear which long-term hemodialysis vascular access type, arteriovenous fistula or arteriovenous graft, is optimal with respect to effectiveness and patient satisfaction. Clinical outcomes based on the initial AV access type have not been evaluated in randomized controlled trials. This pilot study tested the feasibility of randomizing older adults with advanced kidney disease to initial arteriovenous fistula versus graft vascular access surgery. METHODS: Patients 65 years or older with pre-dialysis chronic kidney disease or incident end-stage kidney disease and no prior arteriovenous vascular access intervention were randomized in a 1:1 ratio to undergo surgical placement of a fistula or a graft after providing informed consent. Trial feasibility was evaluated as (i) recruitment of ≥ 70% of eligible participants, (ii) ≥ 50 to 70% of participants undergo placement of index arteriovenous access within 90 to 180 days of enrollment, respectively, (iii) ≥ 80% adherence to study-related assessments, and (iv) ≥ 70% of participants who underwent index arteriovenous access placement will have a follow-up duration of ≥ 12 months after index surgery date. RESULTS: Between September 2018 and October 2019, 81% (44/54) of eligible participants consented and were enrolled in the study; 11 had pre-dialysis chronic kidney disease, and 33 had incident or prevalent end-stage kidney disease. After randomization, 100% (21/21) assigned to arteriovenous fistula surgery and 78% (18/23) assigned to arteriovenous graft surgery underwent index arteriovenous access placement within a median (1st, 3rd quartile) of 5.0 (1.0, 14.0) days and 13.0 (5.0, 44.3) days, respectively, after referral to vascular surgery. The completion rates for study-specific assessments ranged between 40.0 and 88.6%. At median follow-up of 215.0 days, 5 participants expired, 7 completed 12 months of follow-up, and 29 are actively being followed. Assessments of grip strength, functional independence, and vascular access satisfaction were completed by > 85% of patients who reached pre-specified post-operative assessment time point. CONCLUSIONS: Results from this study reveal it is feasible to enroll and randomize older adults with advanced kidney disease to one of two different arteriovenous vascular access placement surgeries. The study can progress with minor protocol adjustments to a multisite clinical trial. TRIAL REGISTRATION: Clinical Trials ID, NCT03545113.

20.
Molecules ; 25(7)2020 Mar 31.
Article in English | MEDLINE | ID: mdl-32244375

ABSTRACT

BACKGROUND: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. METHODS: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. RESULTS: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS-paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. CONCLUSIONS: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.


Subject(s)
Antineoplastic Agents/administration & dosage , Coated Materials, Biocompatible , Drug Carriers/chemistry , Drug Delivery Systems , Keratosis , Angioplasty, Balloon , Animals , Cardiovascular Agents/administration & dosage , Drug Evaluation, Preclinical , Immunohistochemistry , Paclitaxel/administration & dosage , Peripheral Arterial Disease/drug therapy , Peripheral Arterial Disease/etiology , Peripheral Arterial Disease/metabolism , Peripheral Arterial Disease/pathology
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