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High Apolipoprotein E Levels Predict Adverse Limb Events in Patients with Peripheral Artery Disease Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment.
Fukase, T, Dohi, T, Kato, Y, Chikata, Y, Takahashi, N, Endo, H, Doi, S, Nishiyama, H, Okai, I, Iwata, H, et al
International heart journal. 2021;(4):872-878
Abstract
Little is known about the association between limb prognosis in peripheral artery disease and apolipoprotein E (apoE). We evaluated the long-term impact of apoE on adverse limb events in patients with intermittent claudication receiving statin treatment.A total of 218 consecutive patients (mean age, 73 ± 8 years; 81% men) with intermittent claudication who underwent their first intervention between 2009 and 2020 were included in this study. All patients had achieved LDL-C < 100 mg/dL on statin treatment and were divided into two groups based on the apoE value (≥ 4.7 or < 4.7 mg/dL). We evaluated the incidence of major adverse limb events (MALEs), including vessel revascularization and limb ischemia development.A total of 39 and 179 patients were allocated to the higher and lower apoE groups, respectively. Compared to the lower apoE group, the higher apoE group had a significantly higher total cholesterol level, triglyceride level, and non-high-density lipoprotein cholesterol level. During the median follow-up period of 3.6 years, 30 patients (13.8%) developed MALEs. Kaplan-Meier analysis revealed that the cumulative incidence of MALEs in the higher apoE group was significantly higher than that in the lower apoE group (44.0% versus 21.6%, log-rank test, P = 0.002). During multivariable Cox hazard analysis, higher apoE level (≥ 4.7 mg/dL) (hazard ratio, 2.61; 95% confidence interval, 1.18-5.70, P = 0.019) was the only strong independent predictor of MALEs.ApoE levels could be a strong predictor and residual risk for long-term limb prognosis in patients with intermittent claudication and achieving LDL-C < 100 mg/dL with statin treatment.
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Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58.
Bonaca, MP, Wiviott, SD, Zelniker, TA, Mosenzon, O, Bhatt, DL, Leiter, LA, McGuire, DK, Goodrich, EL, De Mendonca Furtado, RH, Wilding, JPH, et al
Circulation. 2020;(8):734-747
Abstract
BACKGROUND Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduces the risk for hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes mellitus. An increased risk of amputation has been observed with canagliflozin in 1 previous trial. We examined cardiovascular and kidney efficacy and the risk of limb-related events in patients with and without PAD in an exploratory analysis. METHODS A total of 17 160 patients with type 2 diabetes mellitus, including 1025 (6%) with PAD, were randomized. Key efficacy outcomes were MACE (cardiovascular [CV] death, myocardial infarction, stroke), CV death/HHF, and progression of kidney disease. Amputations, peripheral revascularization, and limb ischemic adverse events were site-reported and categorized by a blinded reviewer. RESULTS Patients in the placebo arm with PAD versus those without tended to have higher adjusted risk of CV death, myocardial infarction, or stroke (adjusted hazard ratio [HR], 1.23 [95% CI, 0.97-1.56], P=0.094) and significantly higher adjusted risk of CV death/HHF (adjusted HR, 1.60 [95% CI, 1.21-2.12], P=0.0010) and progression of kidney disease (adjusted HR, 1.51 [95% CI, 1.13 - 2.03], P=0.0058), and limb adverse events (adjusted HR, 8.37, P<0.001). The relative risk reductions with dapagliflozin for CV death/HHF (HR, 0.86, PAD; HR, 0.82, no-PAD; P-interaction=0.79) and progression of kidney disease (HR, 0.78, PAD; HR, 0.76, no-PAD; P-interaction=0.84) were consistent regardless of PAD. There were 560 patients who had at least 1 limb ischemic event, 454 patients with at least 1 peripheral revascularization, and 236 patients with at least 1 amputation, with a total of 407 amputations reported. Overall, there were no significant differences in any limb outcome with dapagliflozin versus placebo including limb ischemic adverse events (HR, 1.07 [95% CI, 0.90-1.26]) and amputation (HR, 1.09 [95% CI, 0.84-1.40]), with no significant interactions by a history of PAD versus not (P-interactions=0.30 and 0.093, respectively). CONCLUSIONS Patients with versus without PAD are at a higher risk of CV death of CV death, HHF, and kidney outcomes, and have a consistent benefits for CV death/HHF and progression of kidney disease with dapagliflozin. Patients with PAD had a higher risk of limb events, with no consistent pattern of incremental risk observed with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01730534.
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Extra-abdominal dual-energy CT applications: a comprehensive overview.
Cicero, G, Ascenti, G, Albrecht, MH, Blandino, A, Cavallaro, M, D'Angelo, T, Carerj, ML, Vogl, TJ, Mazziotti, S
La Radiologia medica. 2020;(4):384-397
Abstract
Unlike conventional computed tomography, dual-energy computed tomography is a relatively novel technique that exploits ionizing radiations at different energy levels. The separate radiation sets can be achieved through different technologies, such as dual source, dual layers or rapid switching voltage. Body tissue molecules vary for their specific atomic numbers and electron density, and the interaction with different sets of radiations results in different attenuations, allowing to their final distinction. In particular, iodine recognition and quantification have led to important information about intravenous contrast medium delivery within the body. Over the years, useful post-processing algorithms have also been validated for improving tissue characterization. For instance, contrast resolution improvement and metal artifact reduction can be obtained through virtual monoenergetic images, dose reduction by virtual non-contrast reconstructions and iodine distribution highlighting through iodine overlay maps. Beyond the evaluation of the abdominal organs, dual-energy computed tomography has also been successfully employed in other anatomical districts. Although lung perfusion is one of the most investigated, this evaluation has been extended to narrowly fields of application, such as musculoskeletal, head and neck, vascular and cardiac. The potential pool of information provided by dual-energy technology is already wide and not completely explored, yet. Therefore, its performance continues to raise increasing interest from both radiologists and clinicians.
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Crohn's Disease Complicated With Extensive Thrombosis of Limbs and Mesenteric Arteries: A Case Report and Literature Review.
Qu, C, Cao, J, Liu, K, Tan, B, Zhu, C, Li, K, Qu, L
Annals of vascular surgery. 2019;:382.e15-382.e19
Abstract
BACKGROUND Crohn's disease (CD) is a lifelong disease characterized by purulent inflammation in the gastrointestinal tract from any part of the mouth to the anus. Various studies have reported complications of the CD. However, arterial thrombosis is an extremely rare complication of CD. We report a patient with CD with extensive thrombosis of the extremities and mesenteric arteries. METHODS A 41-year-old man came to our hospital for 2 months of discomfort in the right upper abdomen and had previous left lower extremity arterial occlusive disease and left upper limb ischemic contraction for more than 2 months. The patient developed fever and abdominal pain repeatedly after admission; because of the increased abdominal pain, we urgently performed a laparotomy for him. And according to the findings in the surgery, we decided to perform partial small intestine resection, cholecystectomy, common bile duct exploration, and T-tube drainage. RESULTS Pathological findings of postoperative specimens showed Crohn's disease and mesenteric atherosclerosis with mesenteric artery thrombosis. We performed a series of treatments such as 5-aminosalicylic acid, intravenous infusion, broad-spectrum antibiotic infection treatment, nutritional support, and low molecular weight heparin. The patient was successfully discharged from the hospital. CONCLUSIONS The occurrence of IBD with arterial thromboembolism is extremely rare but can lead to serious consequences. During IBD treatment, we should be aware of the possibility of TEs (especially arterial TEs) and should be alert to the possibility of arterial TEs in young patients with IBD with active and extensive disease.
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CORP: Measurement of upper and lower limb muscle strength and voluntary activation.
Nuzzo, JL, Taylor, JL, Gandevia, SC
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(3):513-543
Abstract
Muscle strength, the maximal force-generating capacity of a muscle or group of muscles, is regularly assessed in physiological experiments and clinical trials. An understanding of the expected variation in strength and the factors that contribute to this variation is important when designing experiments, describing methodologies, interpreting results, and attempting to replicate methods of others and reproduce their findings. In this review (Cores of Reproducibility in Physiology), we report on the intra- and inter-rater reliability of tests of upper and lower limb muscle strength and voluntary activation in humans. Isometric, isokinetic, and isoinertial strength exhibit good intra-rater reliability in most samples (correlation coefficients ≥0.90). However, some tests of isoinertial strength exhibit systematic bias that is not resolved by familiarization. With the exception of grip strength, few attempts have been made to examine inter-rater reliability of tests of muscle strength. The acute factors most likely to affect muscle strength and serve as a source of its variation from trial-to-trial or day-to-day include attentional focus, breathing technique, remote muscle contractions, rest periods, temperature (core, muscle), time of day, visual feedback, body and limb posture, body stabilization, acute caffeine consumption, dehydration, pain, fatigue from preceding exercise, and static stretching >60 s. Voluntary activation, the nervous system's ability to drive a muscle to create its maximal force, exhibits good intra-rater reliability when examined with twitch interpolation (correlation coefficients >0.80). However, inter-rater reliability has not been formally examined. The methodological factors most likely to influence voluntary activation are myograph compliance and sensitivity; stimulation location, intensity, and inadvertent stimulation of antagonists; joint angle (muscle length); and the resting twitch.
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Efficacy and safety of loxoprofen sodium topical patch for the treatment of pain in patients with minor acute traumatic limb injuries in Brazil: a randomized, double-blind, noninferiority trial.
Fujiki, EN, Netto, NA, Kraychete, DC, Daher, MT, Tardini, R, Nakamoto, A, Lopes, DG
Pain. 2019;(7):1606-1613
Abstract
Posttraumatic injury pain is commonly treated with oral nonsteroidal anti-inflammatory drugs. However, oral nonsteroidal anti-inflammatory drugs cause several adverse events, with topical formulations arising as an important alternative. Therefore, we aimed at evaluating the efficacy and safety of loxoprofen patch (LX-P) in the treatment of patients with posttraumatic pain. This phase III, randomized, double-blind, noninferiority study enrolled Brazilian patients aged 18 to 65 years diagnosed with lower and upper limb posttraumatic injury who were experiencing moderate or severe pain. Patients were assigned to active LX-P or to loxoprofen tablet (LX-T), and pain intensity was measured based on a visual analog scale score variation after 7 days of treatment. Data on clinical symptoms, rescue medication use, and adverse events were also collected. Visual analog scale score variation was compared using a 10% noninferiority margin. Two hundred forty-two patients were randomly assigned to LX-P (n = 123) or to LX-T (n = 119). The results showed a reduction in pain after 7 days of treatment: -49.96 (n = 118; SE 1.7) in the LX-P and -47.71 (n = 117; SE 1.6) in the LX-T groups (difference of -2.25; 95% CI: -5.97 to 1.47; P = 0.23). On the safety analysis, the LX-T group presented twice as many patients with treatment-emergent adverse events as the LX-P group (30.8% and 14.2%, respectively). A sensitivity analysis demonstrated that rescue medication use has not affected the primary end point. This study showed that LX-P has a comparable efficacy to LX-T, but with a better safety profile, being a therapeutic option for the treatment of posttraumatic injury pain.
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Modeling and evaluation of a high-resolution CMOS detector for cone-beam CT of the extremities.
Cao, Q, Sisniega, A, Brehler, M, Stayman, JW, Yorkston, J, Siewerdsen, JH, Zbijewski, W
Medical physics. 2018;(1):114-130
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Abstract
PURPOSE Quantitative assessment of trabecular bone microarchitecture in extremity cone-beam CT (CBCT) would benefit from the high spatial resolution, low electronic noise, and fast scan time provided by complementary metal-oxide semiconductor (CMOS) x-ray detectors. We investigate the performance of CMOS sensors in extremity CBCT, in particular with respect to potential advantages of thin (<0.7 mm) scintillators offering higher spatial resolution. METHODS A cascaded systems model of a CMOS x-ray detector incorporating the effects of CsI:Tl scintillator thickness was developed. Simulation studies were performed using nominal extremity CBCT acquisition protocols (90 kVp, 0.126 mAs/projection). A range of scintillator thickness (0.35-0.75 mm), pixel size (0.05-0.4 mm), focal spot size (0.05-0.7 mm), magnification (1.1-2.1), and dose (15-40 mGy) was considered. The detectability index was evaluated for both CMOS and a-Si:H flat-panel detector (FPD) configurations for a range of imaging tasks emphasizing spatial frequencies associated with feature size aobj. Experimental validation was performed on a CBCT test bench in the geometry of a compact orthopedic CBCT system (SAD = 43.1 cm, SDD = 56.0 cm, matching that of the Carestream OnSight 3D system). The test-bench studies involved a 0.3 mm focal spot x-ray source and two CMOS detectors (Dalsa Xineos-3030HR, 0.099 mm pixel pitch) - one with the standard CsI:Tl thickness of 0.7 mm (C700) and one with a custom 0.4 mm thick scintillator (C400). Measurements of modulation transfer function (MTF), detective quantum efficiency (DQE), and CBCT scans of a cadaveric knee (15 mGy) were obtained for each detector. RESULTS Optimal detectability for high-frequency tasks (feature size of ~0.06 mm, consistent with the size of trabeculae) was ~4× for the C700 CMOS detector compared to the a-Si:H FPD at nominal system geometry of extremity CBCT. This is due to ~5× lower electronic noise of a CMOS sensor, which enables input quantum-limited imaging at smaller pixel size. Optimal pixel size for high-frequency tasks was <0.1 mm for a CMOS, compared to ~0.14 mm for an a-Si:H FPD. For this fine pixel pitch, detectability of fine features could be improved by using a thinner scintillator to reduce light spread blur. A 22% increase in detectability of 0.06 mm features was found for the C400 configuration compared to C700. An improvement in the frequency at 50% modulation (f50 ) of MTF was measured, increasing from 1.8 lp/mm for C700 to 2.5 lp/mm for C400. The C400 configuration also achieved equivalent or better DQE as C700 for frequencies above ~2 mm-1 . Images of cadaver specimens confirmed improved visualization of trabeculae with the C400 sensor. CONCLUSIONS The small pixel size of CMOS detectors yields improved performance in high-resolution extremity CBCT compared to a-Si:H FPDs, particularly when coupled with a custom 0.4 mm thick scintillator. The results indicate that adoption of a CMOS detector in extremity CBCT can benefit applications in quantitative imaging of trabecular microstructure in humans.
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Effects of Limb Revascularization Procedures on Oxidative Stress.
Ismaeel, A, Lavado, R, Smith, RS, Eidson, JL, Sawicki, I, Kirk, JS, Bohannon, WT, Koutakis, P
The Journal of surgical research. 2018;:503-509
Abstract
Revascularization procedures to treat patients with peripheral artery disease are among the most common operations performed by vascular surgeons. However, there are major limitations to revascularizations, readmission rates due to procedural complications are high, and greater risks of cardiovascular and limb adverse outcomes have been reported for patients with peripheral artery disease undergoing limb revascularization. Specifically, surgical revascularization may be associated with increased generation of reactive oxygen species based on the ischemia reperfusion injury theory, as restored blood flow and reoxygenation of ischemic areas may be accompanied by increased oxidative stress. In this review, we present the current evidence regarding the effects of revascularization procedures on oxidative stress. We also discuss potential therapeutic interventions to prevent ischemia reperfusion injury-mediated tissue damage.
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Heparin-induced thrombocytopenia-associated thrombosis: from arterial to venous to venous limb gangrene.
Warkentin, TE
Journal of thrombosis and haemostasis : JTH. 2018;(11):2128-2132
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Abstract
Heparin-induced thrombocytopenia (HIT) is an acquired immune-mediated hypercoagulability state that is strongly associated with thrombosis. During the 1970s and 1980s, the prevailing concept was that HIT was associated only with arterial thrombosis, through its unique pathogenesis via heparin-dependent, platelet-activating IgG antibodies. However, in 1990, when I began to encounter HIT in my clinical practice, I found that most such patients developed symptomatic venous thrombosis. This historical sketch summarizes some of the research that challenged the dogma of HIT being a mainly arterial prothrombotic disorder. Two studies - one a substudy of a randomized trial of post-orthopedic surgery thromboprophylaxis, and the second a retrospective five-hospital analysis of consecutive patients with positive test results for HIT antibodies - showed a marked predominance of venous over arterial thrombosis complicating HIT (~ 4 : 1). By the end of the 1990s, an even more dramatic manifestation of HIT-associated venous thrombosis was recognized: venous limb gangrene. Here, ischemic limb necrosis occurs despite palpable arterial pulses, as a result of both macrovascular and microvascular venous thrombosis. The surprising explanation was natural anticoagulant impairment (severe depletion of protein C, a vitamin K-dependent anticoagulant) resulting from treatment of HIT-associated deep vein thrombosis with warfarin (vitamin K antagonist). These insights from HIT research helped to elucidate the pathogenesis of ischemic limb losses in other intense non-HIT hypercoagulability states, including warfarin-associated venous limb gangrene complicating cancer-associated hypercoagulability, and symmetrical peripheral gangrene complicating disseminated intravascular coagulation of critical illness, in which proximate 'shock liver' helps to explain the profound failure of natural anticoagulant systems (protein C; antithrombin) in predisposing to peripheral limb microthrombosis in circulatory shock.
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Dexmedetomidine for prevention of skeletal muscle ischaemia-reperfusion injury in patients with chronic limb ischaemia undergoing aortobifemoral bypass surgery: A prospective double-blind randomized controlled study.
Kundra, TS, Thimmarayappa, A, Dhananjaya, M, Manjunatha, N
Annals of cardiac anaesthesia. 2018;(1):22-25
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Abstract
BACKGROUND Dexmedetomidine is a selective α-2 agonist used for sedation. It has also been shown to have myocardial protective effect and prevent ischemia-reperfusion injury in off-pump coronary artery bypass patients. The aim of our study was to assess the effect of dexmedetomidine for prevention of skeletal muscle ischemia-reperfusion injury in patients undergoing aortobifemoral bypass surgery. METHODOLOGY Sixty adult patients (Group dexmedetomidine n = 30, Group normal saline n = 30) undergoing aortobifemoral bypass surgery were recruited over 3 months. Randomization was done using a computer-generated random table. The attending anesthesiologist would be blinded to whether the drug/normal saline was being administered. He would consider each unlabeled syringe as containing dexmedetomidine and calculate the volume to be infused via a syringe pump accordingly. Dexmedetomidine infusion (1 mcg/kg) over 15 minutes was given as a loading dose, followed by maintenance infusion of 0.5 mcg/kg/h till 2 h postprocedure in Group dexmedetomidine (D) while the same volume of normal saline was given in the control Group C till 2 h postprocedure. Creatine phosphokinase (CPK) values were noted at baseline (T0), 6 h (T1), 12 h (T2), and 24 h (T3) after the procedure. Hemodynamic variables (heart rate [HR] and mean blood pressure [MAP]) were recorded at T0, T1, T2, and T3. Results were analyzed using unpaired Student's t-test, P < 0.05 was considered statistically significant. RESULTS MAP and HR significantly decreased in Group D as compared to control group (P < 0.05). However, the decrease was never <20% of the baseline. The CPK values at 6, 12, and 24 h were statistically significant between the two groups. CONCLUSION Dexmedetomidine prevents skeletal muscle ischemia-reperfusion injury in patients undergoing aortobifemoral bypass surgery.