A unified strategy to focal brachytherapy incorporating transperineal biopsy, image fusion, and real-time implantation with and without rectal spacer simulated in prostate phantoms.

Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Material and methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials.

Fecal Bacteria Contamination of Floodwaters and a Coastal Waterway From Tidally-Driven Stormwater Network Inundation.

Inundation of coastal stormwater networks by tides is widespread due to sea-level rise (SLR). The water quality risks posed by tidal water rising up through stormwater infrastructure (pipes and catch basins), out onto roadways, and back out to receiving water bodies is poorly understood but may be substantial given that stormwater networks are a known source of fecal contamination. In this study, we (a) documented temporal variation in concentrations of Enterococcus spp. (ENT), the fecal indicator bacteria standard for marine waters, in a coastal waterway over a 2-month period and more intensively during two perigean spring tide periods, (b) measured ENT concentrations in roadway floodwaters during tidal floods, and (c) explained variation in ENT concentrations as a function of tidal inundation, antecedent rainfall, and stormwater infrastructure using a pipe network inundation model and robust linear mixed effect models. We find that ENT concentrations in the receiving waterway vary as a function of tidal stage and antecedent rainfall, but also site-specific characteristics of the stormwater network that drains to the waterway. Tidal variables significantly explain measured ENT variance in the waterway, however, runoff drove higher ENT concentrations in the receiving waterway. Samples of floodwaters on roadways during both perigean spring tide events were limited, but all samples exceeded the threshold for safe public use of recreational waters. These results indicate that inundation of stormwater networks by tides could pose public health hazards in receiving water bodies and on roadways, which will likely be exacerbated in the future due to continued SLR.

Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907).

PURPOSE: This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. METHODS AND MATERIALS: This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. RESULTS: Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P = .65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P = .62) and 1.2 versus 0.6% (P = .62), respectively. CONCLUSIONS: Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results.

A new species of Zoraptera, Zorotypuskomatsui sp. nov. from Cameroon and a redescription of Zorotypusvinsoni Paulian, 1951 (Polyneoptera, Zoraptera).

A new species of the order Zoraptera, Zorotypuskomatsui Matsumura, Maruyama, Ntonifor & Beutel, sp. nov., is described from Cameroon. The female and male morphology of another species, Z.vinsoni, is re-described, and its new distribution in Madagascar is recorded. A particular focus is on the male postabdominal morphology. This is apparently a crucial body region in the very small order with an extreme variation of the genital apparatus but otherwise a very uniform morphology. The male of the newly described species shares rudimentary male genitalia and well-developed postabdominal projections with the distantly related Spermozorosimpolitus, apparently a result of parallel evolution. Whether males of Z.komatsui also perform external sperm transfer like S.impolitus remains to be shown. The collecting of the material used for this study suggests that the present knowledge of zorapteran species diversity of the Afrotropical region is very fragmentary.

S-144 lack of association between glycated hemoglobin and adverse outcomes in diabetic patients undergoing ventral hernia repair: an ACHQC study.

INTRODUCTION: Elevated preoperative glycated hemoglobin (HbA1c) is believed to predict complications in diabetic patients undergoing ventral hernia repair (VHR). Our objective was to assess the association between HbA1c and outcomes of VHR in diabetic patients. METHODS: We conducted a retrospective cohort study using the Abdominal Core Health Quality Collaborative (ACHQC) database. We included adult diabetic patients who underwent elective VHR with an available HbA1c result. The patients were divided into two groups (HbA1c < 8% and HbA1c ≥ 8%). Patient demographics, comorbidities, hernia characteristics, operative details, and surgical outcomes were compared. Multivariable logistic regression analysis of complications was performed. Cox proportional hazard regression was used to assess probability of composite recurrence at different HbA1c levels. RESULTS: 2167 patients met the inclusion criteria (HbA1c < 8% = 1,776 and HbA1c ≥ 8% = 391). Median age was 61 years and median body mass index was 34 kg/m2. 75% had an American Society of Anesthesiology class of 3. The median HbA1c was 6.5% in the HbA1c < 8% group versus 8.7% in the HbA1c ≥ 8% group. 73% were incisional hernias, 34% were recurrent, and median hernia width was 6 cm. Open approach was used in 63% and myofascial release was performed in 46%. Median follow-up was 27 days. There were no clinically significant differences in the rates of overall 30-day complications, wound complications, reoperation, readmission, mortality, length of stay and quality of life and pain scores between the two groups. Regression analyses did not identify an association between HbA1c and the rates of complications, surgical site infection or composite recurrence across the spectrum of HbA1c values. CONCLUSION: Our study finds no evidence of an association between HbA1c and operative outcomes in diabetic patients undergoing elective VHR.

Chronic reduction of store operated Ca2+ entry is viable therapeutically but is associated with cardiovascular complications.

Loss of function mutations in store-operated Ca2+ entry (SOCE) are associated with severe paediatric disorders in humans, including combined immunodeficiency, anaemia, thrombocytopenia, anhidrosis and muscle hypotonia. Given its central role in immune cell activation, SOCE has been a therapeutic target for autoimmune and inflammatory diseases. Treatment for such chronic diseases would require prolonged SOCE inhibition. It is, however, unclear whether chronic SOCE inhibition is viable therapeutically. Here we address this issue using a novel genetic mouse model (SOCE hypomorph) with deficient SOCE, nuclear factor of activated T cells activation, and T cell cytokine production. SOCE hypomorph mice develop and reproduce normally and do not display muscle weakness or overt anhidrosis. They do, however, develop cardiovascular complications, including hypertension and tachycardia, which we show are due to increased sympathetic autonomic nervous system activity and not cardiac or vascular smooth muscle autonomous defects. These results assert that chronic SOCE inhibition is viable therapeutically if the cardiovascular complications can be managed effectively clinically. They further establish the SOCE hypomorph line as a genetic model to define the therapeutic window of SOCE inhibition and dissect toxicities associated with chronic SOCE inhibition in a tissue-specific fashion. KEY POINTS: A floxed stromal interaction molecule 1 (STIM1) hypomorph mouse model was generated with significant reduction in Ca2+ influx through store-operated Ca2+ entry (SOCE), resulting in defective nuclear translocation of nuclear factor of activated T cells, cytokine production and inflammatory response. The hypomorph mice are viable and fertile, with no overt defects. Decreased SOCE in the hypomorph mice is due to poor translocation of the mutant STIM1 to endoplasmic reticulum-plasma membrane contact sites resulting in fewer STIM1 puncta. Hypomorph mice have similar susceptibility to controls to develop diabetes but exhibit tachycardia and hypertension. The hypertension is not due to increased vascular smooth muscle contractility or vascular remodelling. The tachycardia is not due to heart-specific defects but rather seems to be due to increased circulating catecholamines in the hypomorph. Therefore, long term SOCE inhibition is viable if the cardiovascular defects can be managed clinically.

Ionizing radiation protection and the linear No-threshold controversy: Extent of support or counter to the prevailing paradigm.

This study has developed a relationship that categorized radiation protection and allows for a proper, clear, and concise review of the different classifications in terms of principles of protection, dose criteria, categories, fundamental tools, exposure situations, applications and control measures. With the groundwork laid, advances of the linear no-threshold (LNT) model which has attracted attention in the field of radiobiology and epidemiology were examined in detail. Various plausible dose-response relationship scenarios were x-rayed under low-dose extrapolation. Intensive review of factors opposing the LNT model involving radiophobia (including misdiagnosis, alternative surgery/imaging, suppression of ionizing radiation (IR) research); radiobiology (including DNA damage repair, apoptosis/necrosis, senescence protection) and cost issues (including-high operating cost of LNT, incorrect prioritization, exaggeration of LNT impact, risk-to-benefit analysis) were performed. On the other hand, factors supporting the use of LNT were equally examined, they include regulatory bodies' endorsement, insufficient statistical significance, partial DNA repair, variability of irradiated bodies, different latency periods for cancer, dynamic nature of threshold and conflicting interests. After considering the gaps in the scientific investigations that either support or counter the scientific paradigm on the use of LNT model, further research and advocacy is recommended that will ultimately lead to the acceptance of an alternative paradigm by the international regulators.

Downregulation of CYP17A1 by 20-hydroxyecdysone: plasma progesterone and its vasodilatory properties.

Aim: To investigate the effect of 20-hydroxyecdysone on steroidogenic pathway genes and plasma progesterone, and its potential impact on vascular functions. Methods: Chimeric mice with humanized liver were treated with 20-hydroxyecdysone for 3 days, and hepatic steroidogenic pathway genes and plasma progesterone were measured by transcriptomics and GC-MS/MS, respectively. Direct effects on muscle and mesenteric arterioles were assessed by myography. Results: CYP17A1 was downregulated in 20-hydroxyecdysone-treated mice compared with untreated group (p = 0.04), with an insignificant increase in plasma progesterone. Progesterone caused vasorelaxation which was blocked by 60 mM KCl, but unaffected by nitric oxide synthase inhibition. Conclusion: In the short term, 20-hydroxyecdysone mediates CYP17A1 downregulation without a significant increase in plasma progesterone, which has a vasodilatory effect involving inhibition of voltage-dependent calcium channels, and the potential to enhance 20-hydroxyecdysone vasorelaxation.

Remote surgical education using synthetic models combined with an augmented reality headset.

Objective: The objective was to investigate the use of an augmented reality headset to remotely train clinicians on medical devices using anatomic models. Design: Disease-specific phantoms were developed to train physicians in mpMRI-guided fusion prostate biopsy, brachytherapy, and rectal spacer insertion. Training was remotely demonstrated using 1-way virtual video conferencing format. Participants responded to an educational content survey. A heads-up display with software and augmented reality was used for remote 2-way training with the proctor and student using on their own phantoms. Setting: The virtual video meeting took place during a prostate cancer conference in 2020, while the augmented reality training occurred in 2021. The proctor and student wore a heads-up display containing a projector and webcam where the ultrasound image was displayed onto a see-through optic along with the physician's hands. The heads-up display allowed the proctor to teach by line-of-sight while the student watched and repeated the steps. Participants: Faculty with expertise with the medical devices used in these procedures provided training to urologists unfamiliar with these techniques. Results: Participants responded that the 1-way training on the phantoms was realistic and mimicked human tissue. A total of 70.9% requested more training or training on the phantoms. The remote training platform was successfully beta tested at the 2 locations in transperineal prostate biopsy and rectal spacer insertion. Conclusion: Remote training using augmented reality eliminates the need for travel. For training programs and workshops, this technology may mitigate the risk of infectious exposures, reduce training cost, and increase proctor availability, allowing training from their own institution or clinic.This investigation qualifies for the Accreditation Council for Graduate Medical Education competency in medical knowledge.

Depot- and diabetes-specific differences in norepinephrine-mediated adipose tissue angiogenesis, vascular tone, collagen deposition and morphology in obesity.

AIMS: Norepinephrine (NE) is a known regulator of adipose tissue (AT) metabolism, angiogenesis, vasoconstriction and fibrosis. This may be through autocrine/paracrine effects on local resistance vessel function and morphology. The aims of this study were to investigate, in human subcutaneous and omental adipose tissue (SAT and OAT): NE synthesis, angiogenesis, NE-mediated arteriolar vasoconstriction, the induction of collagen gene expression and its deposition in non-diabetic versus diabetic obese subjects. MATERIALS AND METHODS: SAT and OAT from obese patients were used to investigate tissue NE content, tyrosine hydroxylase (TH) density, angiogenesis including capillary density, angiogenic capacity and angiogenic gene expression, NE-mediated arteriolar vasoconstriction and collagen deposition. KEY FINDINGS: In the non-diabetic group, NE concentration, TH immunoreactivity, angiogenesis and maximal vasoconstriction were significantly higher in OAT compared to SAT (p < 0.05). However, arterioles from OAT showed lower NE sensitivity compared to SAT (10-8 M to 10-7.5 M, p < 0.05). A depot-specific difference in collagen deposition was also observed, being greater in OAT than SAT. In the diabetic group, no significant depot-specific differences were seen in NE synthesis, angiogenesis, vasoconstriction or collagen deposition. SAT arterioles showed significantly lower sensitivity to NE (10-8 M to 10-7.5 M, p < 0.05) compared to the non-diabetic group. SIGNIFICANCE: SAT depot in non-diabetic obese patients exhibited relatively low NE synthesis, angiogenesis, tissue fibrosis and high vasoreactivity, due to preserved NE sensitivity. The local NE synthesis in OAT and diabetes desensitizes NE-induced vasoconstriction, and may also explain the greater tissue angiogenesis and fibrosis in these depots.

Comparison of AUA and phoenix definitions of biochemical failure following permanent brachytherapy for prostate cancer.

PURPOSE: To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions. METHODS AND MATERIALS: 2634 men with T1-T4N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant hormonal therapy or external beam radiation therapy. Five, 10, and 15- year BCRFS and CSS were estimated with Kaplan-Meier estimates with log rank. Multivariate analysis of survival was performed with Cox regression analysis. RESULTS: Median age was 66, follow-up was 8.6 years, and prostate specific antigen was 6.9. Overall, 11.1% (n = 293) of patients experienced Phoenix BCR and 17.48% (n = 457) experienced AUA BCR. The rates of AUA BCR and Phoenix BCR were significantly different at 5 and 10-years but not at 15 years. Patients treated with BED ≤ 200 Gy were more likely to experience AUA BCR (22.5% vs. 12.4%, OR 1.44, p < 0.001) and Phoenix BCR (14.3% and 8.3%, OR 1.37, p < 0.001) than patients treated with a BED > 200 Gy. CONCLUSIONS: Compared to the Phoenix definition, the AUA definition of BCR after brachytherapy is associated with significantly worse BCRFS for the first 15 years after treatment. Receiving a BED > 200, which cannot be achieved without the addition of brachytherapy, is associated with better BCRFS and CSS. Our findings reaffirm the importance of dose in the management of prostate cancer.

Oxidant-induced disruption of vascular K+ channel function: Implications for diabetic vasculopathy.

Diabetes in humans a chronic metabolic disorder characterised by hyperglycaemia, it is associated with an increased risk of cardiovascular disease, disruptions to metabolism and vascular functions. It is also linked to oxidative stress and its complications. Its role in vascular dysfunctions is generally reported without detailed impact on the molecular mechanisms. Potassium ion channel (K+ channels) are key regulators of vascular tone, and as membrane proteins, are modifiable by oxidant stress associated with diabetes. This review manuscript examined the impact of oxidant stress on vascular K+ channel functions in diabetes, its implication in vascular complications and metabolic and cardiovascular diseases.

Untargeted Metabolomics Identifies a Novel Panel of Markers for Autologous Blood Transfusion.

Untargeted metabolomics was used to analyze serum and urine samples for biomarkers of autologous blood transfusion (ABT). Red blood cell concentrates from donated blood were stored for 35−36 days prior to reinfusion into the donors. Participants were sampled at different time points post-donation and up to 7 days post-transfusion. Metabolomic profiling was performed using ACQUITY ultra performance liquid chromatography (UPLC), Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The markers of ABT were determined by principal component analysis and metabolites that had p < 0.05 and met ≥ 2-fold change from baseline were selected. A total of 11 serum and eight urinary metabolites, including two urinary plasticizer metabolites, were altered during the study. By the seventh day post-transfusion, the plasticizers had returned to baseline, while changes in nine other metabolites (seven serum and two urinary) remained. Five of these metabolites (serum inosine, guanosine and sphinganine and urinary isocitrate and erythronate) were upregulated, while serum glycourdeoxycholate, S-allylcysteine, 17-alphahydroxypregnenalone 3 and Glutamine conjugate of C6H10O2 (2)* were downregulated. This is the first study to identify a panel of metabolites, from serum and urine, as markers of ABT. Once independently validated, it could be universally adopted to detect ABT.

P-FLUX: A phosphorus budget dataset spanning diverse agricultural production systems in the United States and Canada.

Quantifying spatial and temporal fluxes of phosphorus (P) within and among agricultural production systems is critical for sustaining agricultural production while minimizing environmental impacts. To better understand P fluxes in agricultural landscapes, P-FLUX, a detailed and harmonized dataset of P inputs, outputs, and budgets, as well as estimated uncertainties for each P flux and budget, was developed. Data were collected from 24 research sites and 61 production systems through the Long-term Agroecosystem Research (LTAR) network and partner organizations spanning 22 U.S. states and 2 Canadian provinces. The objectives of this paper are to (a) present and provide a description of the P-FLUX dataset, (b) provide summary analyses of the agricultural production systems included in the dataset and the variability in P inputs and outputs across systems, and (c) provide details for accessing the dataset, dataset limitations, and an example of future use. P-FLUX includes information on select site characteristics (area, soil series), crop rotation, P inputs (P application rate, source, timing, placement, P in irrigation water, atmospheric deposition), P outputs (crop removal, hydrologic losses), P budgets (agronomic budget, overall budget), uncertainties associated with each flux and budget, and data sources. Phosphorus fluxes and budgets vary across agricultural production systems and are useful resources to improve P use efficiency and develop management strategies to mitigate environmental impacts of agricultural systems. P-FLUX is available for download through the USDA Ag Data Commons (https://doi.org/10.15482/USDA.ADC/1523365).

Factors associated with late local failure and its influence on survival in men undergoing prostate brachytherapy.

BACKGROUND AND PURPOSE: To determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy. METHODS AND MATERIALS: Of 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards. RESULTS: After a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150-200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy. CONCLUSIONS: Higher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality.

HepCCATT: a multilevel intervention for hepatitis C among vulnerable populations in Chicago.

BACKGROUND: Hepatitis C infection could be eliminated. Underdiagnosis and lack of treatment are the barriers to cure, especially for vulnerable populations (i.e. unable to pay for health care). METHODS: A multilevel intervention from September 2014 to September 2019 focused on the providers and organizations in 'the safety net' (providing health care to populations unable to pay), including: (i) public education, (ii) training for primary care providers (PCPs) and case managers, (iii) case management for high-risk populations, (iv) policy advice and (v) a registry (Registry) for 13 health centers contributing data. The project tracked the number of PCPs trained and, among Registry sites, the number of people screened, engaged in care (i.e. clinical follow-up after diagnosis), treated and/or cured. RESULTS: In Chicago, 215 prescribing PCPs and 56 other health professionals, 86% of whom work in the safety net, were trained to manage hepatitis C. Among Registry sites, there was a 137% increase in antibody screening and a 32% increase in current hepatitis C diagnoses. Engagement in care rose by 18%. CONCLUSIONS: Hepatitis C Community Alliance to Test and Treat (HepCCATT) successfully targeted safety net providers and organizations with a comprehensive care approach. While there were challenges, HepCCATT observed increased hepatitis C screening, diagnosis and engagement in care in the Chicago community.

PROMISE I: Early feasibility study of the LimFlow System for percutaneous deep vein arterialization in no-option chronic limb-threatening ischemia: 12-month results.

OBJECTIVE: We report the 6- and 12-month outcomes of the PROMISE I early feasibility study after treatment of no-option chronic limb-threatening ischemia (CLTI) with percutaneous deep vein arterialization (pDVA) using the LimFlow System. METHODS: Thirty-two patients with no-option CLTI, previously offered major amputation, were enrolled in this single-arm early feasibility study of the LimFlow pDVA System. No-option CLTI was defined as being ineligible for surgical or endovascular arterial revascularization. Patients were assessed for clinical status, pain, wound healing, and duplex ultrasound at 30 days, 6 months, and 12 months post-treatment. Primary endpoint analysis was amputation-free survival (AFS) at 30 days and 6 and 12 months. AFS was defined as freedom from above-ankle amputation of the index limb and freedom from all-cause mortality. Secondary endpoints evaluated included technical success of the procedure, and wound healing at 6 and 12 months. RESULTS: Of 32 enrolled patients, 31 (97%) were successfully treated with the LimFlow System at the time of the procedure, and two (6.3%) were lost to follow-up. The 30-day, 6-month, and 12-month AFS rates were 91%, 74%, and 70% respectively. The wound healing status of fully healed or healing was 67% at 6 months, and 75% at 12 months. Reintervention was performed in 16 patients (52%) with 14 (88%) of the maintenance reinterventions occurring within the first 3 months. The majority of reinterventions (n = 12; 75%), involved the arterial inflow tract proximal to the stented LimFlow circuit, and no in-stent stenoses were determined to have been the cause of reintervention. CONCLUSIONS: The LimFlow pDVA System was utilized in treating patients with no-option CLTI. A high technical success rate was observed, with a significant percentage of patients surviving free of major amputation at 12 months. These results suggest early safety and provide an initial assessment of the efficacy of the LimFlow pDVA System that supports the expansion of carefully executed studies to determine whether this is a viable option that can be used in this critically disadvantaged and growing patient population.