Correlation between post-procedure residual thrombus and clinical outcome in deep vein thrombosis patients receiving pharmacomechanical thrombolysis in a multicenter randomized trial

PURPOSE: To evaluate relationships between immediate venographic results and clinical outcomes of pharmacomechanical catheter-directed venous thrombolysis (PCDT). MATERIALS AND METHODS: Venograms from 317 acute proximal DVT patients who received PCDT in a multicenter randomized trial were reviewed. Quantitative thrombus resolution was assessed by independent readers using a modified Marder scale. The physician operators recorded their visual assessments of thrombus regression and venous flow. These immediate post-procedure results were correlated with patient outcomes at 1, 12, and 24 months. RESULTS: PCDT produced substantial thrombus removal (p < 0.001 for pre-PCDT versus post-PCDT thrombus scores in all segments). At procedure end, spontaneous venous flow was present in 99% of iliofemoral venous segments and in 89% of femoral-popliteal venous segments. For the overall proximal DVT population, and for the femoral-popliteal DVT subgroup, post-PCDT thrombus volume did not correlate with 1-month or 24-month outcomes. For the iliofemoral DVT subgroup, over 1 and 24 months, symptom severity scores were higher (worse) and venous disease-specific quality of life (QOL) scores were lower (worse) in patients with greater post-PCDT thrombus volume, with the difference reaching statistical significance for the 24-month Villalta PTS severity (p=0.0098). Post-PCDT thrombus volume did not correlate with 12-month valvular reflux. CONCLUSION: PCDT successfully removes thrombus in acute proximal DVT. However, the residual thrombus burden at procedure end does not correlate with the occurrence of PTS during the subsequent 24 months. In iliofemoral DVT, lower residual thrombus burden correlates with reduced PTS severity and possibly also with improved venous QOL and fewer early symptoms

State-Dependent Accessibility of the P-S6 Linker of Pacemaker (HCN) Channels Supports a Dynamic Pore-to-Gate Coupling Model

The hyperpolarization-activated cyclic nucleotide-modulated channel gene family (HCN1-4) encodes the membrane depolarizing current that underlies pacemaking. Although the topology of HCN resembles Kv channels, much less is known about their structure-function correlation. Previously, we identified several pore residues in the S5-P linker and P-loop that are externally accessible and/or influence HCN gating, and proposed an evolutionarily conserved pore-to-gate mechanism. Here we sought dynamic evidence by assessing the functional consequences of Cys-scanning substitutions in the unexplored P-S6 linker (residues 352–359), the HCN1-R background (that is, resistant to sulfhydryl-reactive agents). None of A352C, Q353C, A354C, P355C, V356C, S357C, M358C, or S359C produced functional currents; the loss-of-function of Q353C, A354C, S357C, and M358C could be rescued by the reducing agent dithiothreitol. Q353C, A354C, and S357C, but not M358C and HCN1-R, were sensitive to Cd2+ blockade (IC50 = 3–12 μM vs. >1 mM). External application of the positively charged covalent sulfhydryl modifier MTSET irreversibly reduced I−140mV of Q353C and A354C to 27.9 ± 3.4% and 58.2 ± 13.1% of the control, respectively, and caused significant steady-state activation shifts (∆V1/2 = –21.1 ± 1.6 for Q353C and −10.0 ± 2.9 mV for A354C). Interestingly, MTSET reactivity was also state dependent. MTSET, however, affected neither S357C nor M358C, indicating site specificity. Collectively, we have identified novel P-S6 residues whose extracellular accessibility was sterically and state dependent and have provided the first functional evidence consistent with a dynamic HCN pore-to-gate model

Molecular Basis of the Effect of Potassium on Heterologously Expressed Pacemaker (HCN) Channels

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels modulate the firing rates of neuronal and cardiac pacemaker cells. HCN channels resemble voltage-gated K+ channels structurally, but much less is known about their structure-function correlation. Although modulation of K+ channel gating by external K+ is a well-known phenomenon, such a link has not been established for HCN channels. Here we examined the effects of external permeant (K+, Na+ and Li+) and non-permeant (NMG+) ions on HCN1 and HCN2 gating. Substituting 64 of 96 mm external K+ with Na+, Li+ or NMG+ positively shifted steady-state activation (∼13 mV), and preferentially slowed activation of HCN1. Mutating the pore variant C-terminal to the GYG motif in HCN1, A352, to the analogous conserved Asp in K+ channels or Arg in HCN2 produced a significant hyperpolarizing activation shift (by 5–15 mV), slowed gating kinetics (up to 6-fold), and abolished or attenuated gating responses to external K+. Whereas Na+, Li+ and NMG+ substitutions produced depolarizing activation shifts of HCN2 similar to those of HCN1, deactivation but not activation of HCN2 was exclusively decelerated. We conclude that gating and permeation of HCN channels are coupled, and that modulation of this ‘pore-to-gate’ coupling by external K+ is isoform-specific

New routes toward chemical and photochemical vapor deposition of copper metal

Several types of volatile copper(I) and copper(II) complexes have been studied as precursors for chemical vapor deposition (CVD) of Cu metal films. Adducts of Cu(hfac)2 (hfacH = hexafluoroacetylacetone) with alcohols ROH (R = Me, Et, n-Pr, i-Pr, n-Bu, s-Bu, i-Bu) are self-reducing: CVD occurs by reduction of copper(II) to Cu metal, while the alcohols are oxidized to the corresponding carbonyl compounds. The best results have been obtained for Cu(hfac)2·i-PrOH (1.3 μm h-1 under N2 at 200°C, vs. 0.46 μm h-1 under H2). The adduct of CuII(hfac)2 with hydrazine is also self-reducing, leading to Cu metal formation under N2 at substrate temperatures of 140°C. Adducts with other nitrogen bases (e.g. piperidine) can be used for Cu CVD with H2 carrier gas. The copper(I) amide cluster [CuN(SiMe3)2]4 can be used for Cu CVD under H2. It is also phosphorescent, and it shows a slight lowering of the threshold substrate temperature for Cu deposition under UV irradiation; this suggests that the deposition can be photochemically induced

Results of an American College of Radiology-Society of Interventional Radiology Membership Survey on Exclusive Contracts and the Attitudes of Interventional Radiologists.

PURPOSE: To assess the attitudes of interventional radiologists (IRs) and diagnostic radiologists (DRs) toward exclusive contracts and independently practicing IRs who may request privileges at a hospital where an exclusive contract exists with a different group of radiologists. MATERIALS AND METHODS: A total of 22,400 survey instruments were distributed to 4,490 IRs and 17,910 DRs in the United States. Statistical evaluation included multivariate ordinal logistic regression analysis with calculation of the odds ratios and forest plots. RESULTS: Completed surveys were received from 525 (11.69%) IRs and 401 (2.23%) DRs. Given the low response rate of DRs, data analysis was focused on IRs. Early-career IRs and those in outpatient practices had a more positive attitude toward independent IRs who requested admitting and/or procedural privileges. A supermajority of both IRs and DRs who responded to the survey agreed that the importance of IR to hospital and health system contracts will increase. CONCLUSIONS: This survey identified many interrelated and complex variables that significantly affected the attitudes of IRs in various practice settings toward independent IRs requesting hospital admitting and/or procedural privileges. It will benefit independent IRs seeking admitting privileges to better understand some of the factors that impact the potential willingness of the radiology groups and other IRs with exclusive hospital contracts to work toward mutually beneficial practice paradigms, especially as more clinically oriented IRs complete their training in the new, integrated residency programs

ACR Appropriateness Criteria((R)) Suspected Lower Extremity Deep Vein Thrombosis

Suspected lower extremity deep venous thrombosis is a common clinical scenario which providers seek a reliable test to guide management. The importance of confidently making this diagnosis lies in the 50% to 60% risk of pulmonary embolism with untreated deep vein thrombosis and subsequent mortality of 25% to 30%, balanced with the risks of anticoagulation. The ACR Appropriateness Criteria Expert Panel on Vascular Imaging reviews the current literature regarding lower extremity deep venous thrombosis and compared various imaging modalities including ultrasound, MR venography, CT venography, and catheter venography. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment

ACR Appropriateness Criteria® Lower Extremity Arterial Claudication-Imaging Assessment for Revascularization: 2022 Update.

Arterial claudication is a common manifestation of peripheral artery disease. This document focuses on necessary imaging before revascularization for claudication. Appropriate use of ultrasound, invasive arteriography, MR angiography, and CT angiography are discussed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation