Predictors of Clinical Outcomes of Pharmacomechanical Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis: Analysis of a Multicenter Randomized Trial.

PURPOSE: To identify the baseline patient characteristics that predict who will benefit from pharmacomechanical catheter-directed thrombolysis (PCDT) of acute iliofemoral deep vein thrombosis (DVT). MATERIALS AND METHODS: In the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) multicenter randomized trial, 381 patients with acute iliofemoral DVT underwent PCDT and anticoagulation or anticoagulation alone. The correlations between baseline factors and venous clinical outcomes were evaluated over 24 months using post hoc regression analyses. Interaction terms were examined to evaluate for differential effects by treatment arm. RESULTS: Patients with clinically severe DVT (higher baseline Villalta score) experienced greater effects of PCDT in improving 24-month venous outcomes, including moderate or severe postthrombotic syndrome (PTS) (odds ratios [ORs] and 95% confidence intervals [CIs] per unit increase in the baseline Villalta scores were as follows: for PCDT, OR, 1.08 [95% CI, 1.01-1.15]; for control, OR, 1.20 [95% CI, 1.12-1.29]; Pinteraction = .03), PTS severity (between-arm differences in the Villalta [Pinteraction = .004] and Venous Clinical Severity Scale [VCSS] [Pinteraction = .002)] scores), and quality of life (between-arm difference in the Venous Insufficiency Epidemiological and Economic Study Quality of Life score; Pinteraction = .025). Patients with previous DVT had greater effects of PCDT on 24-month PTS severity than those in patients without previous DVT (mean [95% CI] between-arm difference in the Villalta score, 4.2 [1.56-6.84] vs 0.9 [-0.44 to 2.26], Pinteraction = .03; mean [95% CI] between-arm difference in the VCSS score, 2.6 [0.94-4.21] vs 0.3 [-0.58 to 1.14], Pinteraction = .02). The effects of PCDT on some but not all outcomes were greater in patients presenting with left-sided DVT (Villalta PTS severity, Pinteraction = .04; venous ulcer, Pinteraction = .0499) or a noncompressible popliteal vein (PTS, Pinteraction = .02). The effects of PCDT did not vary by sex, race, ethnicity, body mass index, symptom duration, hypertension, diabetes, or hypercholesterolemia. CONCLUSIONS: In patients with acute iliofemoral DVT, greater presenting clinical severity (higher baseline Villalta score) and a history of previous DVT predict enhanced benefits from PCDT.

Optimal Medical Therapy Following Deep Venous Interventions: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The optimal medical management of patients following endovascular deep venous interventions remains ill-defined. As such, the Society of Interventional Radiology Foundation (SIRF) convened a multidisciplinary group of experts in a virtual Research Consensus Panel (RCP) to develop a prioritized research agenda regarding antithrombotic therapy following deep venous interventions. The panelists presented the gaps in knowledge followed by discussion and ranking of research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were identified as high priority: 1) characterization of biological processes leading to in-stent stenosis/rethrombosis; 2) identification and validation of methods to assess venous flow dynamics and their effect on stent failure; 3) elucidation of the role of inflammation and anti-inflammatory therapies; and 4) clinical studies to compare antithrombotic strategies and improve venous outcome assessment. Collaborative, multicenter research is necessary to answer these questions and thereby enhance the care of patients with venous disease.

Clinical Outcomes of a Pharmacomechanical Catheter-Directed Venous Thrombolysis Strategy that Included Rheolytic Thrombectomy in a Multicenter Randomized Trial.

PURPOSE: To describe the clinical outcomes of a pharmacomechanical catheter-directed venous thrombolysis (PCDT) strategy that included AngioJet rheolytic thrombectomy. METHODS: In the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis multicenter randomized trial, physicians at 33 sites designated AngioJet as their preferred device for PCDT. In these sites, 364 patients with acute proximal lower-extremity deep vein thrombosis (DVT) were randomized to a strategy of PCDT that incorporated either AngioJet along with anticoagulation or anticoagulation alone. Relief from presenting DVT symptoms was evaluated over 30 days of follow-up. Postthrombotic syndrome (PTS), quality of life (QOL), recurrent venous thromboembolism (VTE), and safety were evaluated over 24 months of follow-up. RESULTS: Within 30 days, AngioJet-PCDT led to a greater improvement in leg swelling (mean difference calf circumference 0.55 cm, P = .009), venous QOL (mean difference 6.5 Venous Insufficiency Epidemiologic and Economic Study [VEINES]-QOL points, P = .0073), and venous symptoms (mean difference 5.6 VEINES-symptoms points, P = .0134) than control, with differences most apparent in iliofemoral DVT. AngioJet-PCDT reduced PTS at 6 months (24% with AngioJet-PCDT vs 40% with control, P = .003) but did not influence PTS or QOL between 12 and 24 months. Major bleeding, pulmonary embolism, renal failure, and bradycardia were infrequent with AngioJet-PCDT (<2% each), but 24-month VTE recurrence may have been more frequent (13.9% with AngioJet-PCDT vs 6.8% with control, P = .03) CONCLUSIONS: In patients with acute proximal DVT, a treatment strategy that included first-line AngioJet-PCDT was reasonably safe and led to an improved symptom status and venous QOL at 1 month and reduced PTS at 6 months compared with anticoagulation alone. However, AngioJet-PCDT did not influence PTS or the QOL beyond 6 months and may have increased recurrent VTE.

Opportunities for Excellence in Interventional Radiology Training: A Qualitative Study.

OBJECTIVE: The training experience in interventional radiology (IR) residency programs varies widely across the country. The introduction of an IR training pathway has provided the impetus for the specialty to better define outstanding IR education and for programs to rethink how their curricula prepare IR trainees for real-world practice. Although ACGME competencies define several training components that are necessary for independent practice, few quantitative or qualitative studies have explored current perceptions on what constitutes optimal IR training. Our goal was to qualitatively explore program training features deemed most important to adequately prepare IR physicians for practice and assess whether there were differences in perception between academic and nonacademic practices. METHODS: Semistructured interviews were conducted with 71 IR attending physicians, trainees, and support staff across the United States. All interviews were performed over the telephone by a single researcher for consistency and systematically coded by two independent coders for common themes. Frequency and prevalence of themes and facilitating features were analyzed. RESULTS: The most frequently perceived facilitating features included longitudinal patient care experience, practice-building education, interspecialty collaboration exposure, broad case mix, clinical decision-making exposure, diagnostic radiology training, procedural skills training, and graduated autonomy. Comparing nonacademic versus academic practice settings, significantly more nonacademic IR attending physicians expressed practice-building education (prevalence 72% versus 42%, frequency 2.2 versus 0.7, P < .01) as an important training experience. DISCUSSION: An understanding of perceived facilitating features for optimal IR trainee preparation, including potentially different needs between academic and nonacademic practices, can help programs prepare their trainees for a successful transition into practice.

Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention.

OBJECTIVE: Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH. METHODS: Twenty-five very preterm neonates (born at ≤ 32 weeks' gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention. RESULTS: The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson's r = -0.403, p = 0.046) and improved cognitive (r = -0.554, p = 0.047), motor (r = -0.487, p = 0.048), and language (r = -0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = -0.483, p = 0.014) and improved cognitive (r = -0.711, p = 0.001), motor (r = -0.675, p = 0.003), and language (r = -0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively). CONCLUSIONS: In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.

Catheter-Based Therapies and Other Management Strategies for Deep Vein Thrombosis and Post-Thrombotic Syndrome.

Acute deep vein thrombosis (DVT) causes substantial short-term and long-term patient morbidity. Medical, lifestyle, and compressive therapies have been investigated for the prevention of pulmonary embolism (PE) and recurrence of venous thromboembolism (VTE). However, patient-centered outcomes such as resolution of presenting DVT symptoms and late occurrence of post-thrombotic syndrome (PTS) have not been prioritized to the same degree. Imaging-guided, catheter-based endovascular therapy has been used in selected patients to alleviate these sequelae, but important questions remain about their optimal use. In this article, we review the available evidence and summarize the rationale for use of catheter-based therapy in specific patient groups.

Nanoparticles in thermosensitive gel based composite nanosystem for ocular diseases.

The pentablock (PB) copolymers based composite nanosystems were designed to provide a long-term delivery of macromolecules to the back of the eye. A unique arrangement of each block (polyethylene glycol, polylactic acid, and polycaprolactone) with various molecular weights (PB-A and PB-B) was selected for the synthesis of nanoparticles (NPs) and thermosensitive gel (PB-C) by sequential ring-opening bulk copolymerization reaction. PB copolymers were characterized for their molecular weight and purity by 1H-NMR spectroscopy and crystallinity by PXRD. The macromolecule model drugs [lysozyme (Lyz ~ 14.5 kDa), IgG-Fab (~ 50 kDa), and IgG (~ 150 kDa)] were selected to delineate the effect of molecular weights on in vitro release profile of nanoformulations. Lyz-, Fab-, and IgG-encapsulated NPs were prepared by double emulsion solvent evaporation method. The entrapment efficiency (EE%) and drug loading (DL%) of macromolecules was higher for PB-B copolymers due to its higher molecular weight and hydrophobicity compare to PB-A. The particle size range of NPs was ~ 200-270 nm. In vitro release profiles of Lyz-, Fab-, and IgG-encapsulated in NPs alone and NPs suspended in gel (composite nanosystem) demonstrated a minimal burst release and drug release over a long period. The effect of hydrodynamic diameter of macromolecules and hydrophobicity of PB copolymers was investigated on the release profile of nanosystems. In vitro biocompatibility study showed negligible cytokine (IL-1, IL-6, and TNF-α) release, which confirmed the safety of the PB copolymers. Based on the results, it is anticipated that long-term ocular delivery of macromolecules can be achieved through composite nanosystems.

Recent Patents and Emerging Therapeutics on Ocular Inflammation and Allergy.

BACKGROUND: Ocular inflammation and allergic eye diseases range from mild to severe may disturb visual function and affect` quality of life. Since these diseases require intensive therapies, the pathophysiology and treatments of these conditions are highlighted. OBJECTIVE: The ocular diseases caused by inflammation and allergy are extensively studied in this review to provide an overview of the newer compounds, novel delivery approaches, preclinical and clinical trials for the treatment of allergic conjunctivitis, dry eye syndrome, and uveitis. METHOD: The eye is divided into two segments; anterior and posterior. Both segments provide barriers to the drug delivery to the eye. Despite many efforts by scientists, several potential drug candidates are often dropped from the initial screening portfolio due to failure in overcoming these barriers. Thus to overcome unmet challenges, remarkable progresses have been made towards the design of novel ocular therapeutics with enhanced activity and minimal toxicity to the ocular tissue. A comprehensible understanding of the diseased conditions, physiological barriers and pharmacokinetics of the eye would significantly accelerate the development of new therapeutics. Moreover, identification of new targets drives the discovery of novel drug molecules for the ocular disease treatment. RESULTS: The advancement in the drug discovery and dosage from design showcases the increasing number of patent applications being filed and issued for allergic conjunctivitis, dry eye syndrome, and uveitis. In addition, preclinical and clinical trials are now becoming available showing the newer generation of ocular drugs. CONCLUSION: This review presented a brief background on the disease condition, types, treatment, advancement in the delivery approaches, focus on emerging therapeutics, related patents and clinical trials for the treatment of allergic conjunctivitis, dry eye syndrome, and uveitis.