Inhibition of Dopamine Neurons Prevents Incentive Value Encoding of a Reward Cue: With Revelations from Deep Phenotyping.

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the NAc is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats, it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCutTM revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient toward and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.SIGNIFICANCE STATEMENT Activity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCutTM revealed that cue-directed behaviors do not emerge without dopamine neuron activity in the VTA. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of dopamine neuron activity in the VTA during cue presentation to encode the incentive value of reward cues.

Percent Thrombus Predicts Popliteal Artery Aneurysm Related Limb Threatening Events.

OBJECTIVE: The objective of this study was to identify clinical and anatomic characteristics of Popliteal artery aneurysms (PAAs) associated with acutely limb threatening events. SUMMARY BACKGROUND DATA: Popliteal artery aneurysms (PAAs) are associated with high morbidity and mortality. Current guidelines recommend operative repair for PAAs with a diameter greater than 20 mm based on very limited evidence. METHODS: This retrospective cross-sectional cohort was derived from a multi-institutional database queried for all patients with a PAA from 2008 to 2022. Duplex ultrasound (DUS) characteristics of PAAs were abstracted by registered physicians in vascular interpretation. Symptom status at the time of DUS was divided into three categories: asymptomatic PAA, symptomatic PAA with claudication or chronic limb ischemia, and acutely limb threatening PAAs with a thromboembolic event, acute limb ischemia, or rupture. RESULTS: There were 470 PAAs identified in 331 patients. The mean age was 74 years at diagnosis, 94% of patients were white, and 97% of patients were male. In a univariate analysis, patient comorbidities and medications were not associated with symptom status. In a multivariate analysis including age, higher percent thrombus was significantly associated with symptomatic PAAs (RRR 15.2; CI 2.69-72.3; P<0.01) and PAAs with an acutely limb threatening event (RRR 17.9; CI 3.76-85.0; P<0.01). All other anatomic characteristics were not associated with symptom status. CONCLUSION: Percent thrombus was significantly associated with symptomatic PAAs and acutely limb threatening events, whereas diameter was not significantly associated with any symptom group. This analysis supports the use of percent thrombus in identifying high risk PAAs that warrant repair.

The Impact of Sex on Antiplatelet and Anticoagulant Thromboprophylaxis in Patients With Peripheral Artery Disease Post-revascularization.

OBJECTIVE: The aim of this prospective study was to (1) objectively quantify the impact of sex on platelet function in patients with peripheral artery disease (PAD) taking antiplatelet and anticoagulant medications and (2) to develop and test a personalized, iterative algorithm that personalizes thromboprophylaxis that incorporates platelet function testing. BACKGROUND: Women with PAD have worse outcomes as compared with their male counterparts despite having lower risk factors. This health disparity may be mitigated by personalizing thromboprophylaxis regimens. METHODS: Patients undergoing revascularization were enrolled. Serial thromboelastography (TEG) and TEG with platelet mapping (TEG-PM) were performed up to 6 months postoperatively to determine objective coagulation profiles. In a subset of patients, the Antiplatelet Coagulation Exactness (ACE) algorithm was implemented, where patients were iteratively evaluated with TEG and given antiplatelet medications to maintain platelet inhibition at >29%. Statistical analysis was performed using unpaired t test, analysis of variance, and Fisher exact test. RESULTS: One hundred eighty-one patients met the study criteria. Fifty-eight (32%) patients were females and 123 (68%) were males. In the Aspirin cohort, females showed significantly greater clot strength as maximum amplitude - arachidonic acid (MA AA ) and significantly lower platelet inhibition than males: (37.26 vs 32.38, P <0.01) and (52.95% vs 61.65%, P <0.05), respectively. In the Clopidogrel cohort, females showed higher Maximum Amplitude - Adenosine Diphosphate (MA ADP ) (42.58 vs 40.35, P = not significant [NS]) compared with males. Females on dual antiplatelet therapy had higher MA ADP (39.74 vs 35.07, P =NS) and lower platelet inhibition (45.25% vs 54.99%, P= NS) than males. The incidence of thrombosis of the revascularized segment, defined as thrombotic event, was objectively identified on an arterial duplex. Women showed significantly higher thrombotic events than men (22.95% vs 10.57%, P< 0.05) on the same medication. In our pilot study, implementation of the ACE algorithm led to a significant decrease in the thrombosis rate (3%), including nonthrombotic events for females, versus the historic thrombotic rate (22%) from our institution. CONCLUSIONS: Women with PAD exhibited higher platelet reactivity, clot strength, and reduced platelet inhibition in response to antiplatelet therapy. The use of the ACE algorithm to tailor antiplatelet medication in patients with PAD post-revascularization, resulted in a significant decrease in thrombotic event rates. This may serve as an opportune way to mitigate outcome sex-specific disparities caused by inadequate thromboprophylaxis in women.

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

The impact of sex on platelet responses to aspirin in patients with peripheral artery disease.

Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. Viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post-revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG-PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex-specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men (16.66 vs. 14.94, p < .03 and 37.26 vs. 32.38, p < .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p < .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p < .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.

Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease.

PURPOSE: To identify associations between computed tomography (CT)-based lower-extremity calcium score (LECS) across different anatomic segments and the presence, severity, and clinical outcomes of peripheral artery disease (PAD). MATERIALS AND METHODS: In a mixed retrospective and prospective cohort study, 139 patients without prior lower-extremity intervention who underwent CT angiography of the aorta and lower extremities were identified. Subjects were classified as asymptomatic, claudicants, or having chronic limb-threatening ischemia (CLTI). LECS was measured using the Agatston method. Univariate and multivariate analyses were performed across categories of PAD severity. Receiver operating characteristic (ROC) analysis was performed, and an optimal cutoff point for LECS was identified. Claudicants were followed prospectively for CLTI and mortality. RESULTS: Higher infrapopliteal calcium score (CS) was independently associated with CLTI versus claudication (odds ratio [OR], 3.24 per unit increase in log10-transformed CS; P < .001) in addition to hemodialysis dependence and poor functional status. One hundred eighty-eight Agatston units was identified as the optimal cutoff for infrapopliteal CS in assessing the risk of CLTI versus claudication (area under the ROC curve, 0.84 [SD ± 0.049]). This cutoff was validated in an independent cohort to be associated with progression to CLTI (OR, 12.8; P = .0039). In the claudicant group followed prospectively, infrapopliteal CS ≥188 predicted increased risk of CLTI or death after adjusting for functional status and hemodialysis dependence (Cox hazard ratio, 4.92; P = .0202). CONCLUSIONS: Higher infrapopliteal CS was associated with CLTI among those with symptomatic PAD. An infrapopliteal CS cutoff of 188 Agatston units may serve as a useful tool to identify patients with increased risk of CLTI and mortality.

Popliteal artery aneurysm ultrasound criteria for reporting characteristics.

INTRODUCTION: Duplex ultrasound (DUS) is the modality of choice for surveillance of popliteal artery aneurysms (PAAs). However, noninvasive vascular laboratories have no standard guidelines for reporting results. This study assessed reports of PAA DUS for inclusion of information pertinent to operative decision-making and timing of surveillance. METHODS: This study was a retrospective review of a multi-institutional repository that was queried for all patients with a PAA from 2008 to 2022 and confirmed via manual chart review. DUS reports were abstracted and images were individually annotated for features of interest including dimensions, flow abnormalities, and percent thrombus burden. RESULTS: A total of 166 PAAs in 130 patients had at least one DUS available for viewing. Postoperative surveillance of PAAs was performed at several intervals: the first at 30 months (IQR 3.7-113, n = 44), the second at 64 months (IQR 20-172, n = 31), and the third at 152 months (IQR 46-217, n = 16) after the operation. The largest diameter of operative PAAs (median 27.5 mm, IQR 21.8-38.0) was significantly greater than nonoperative PAAs (median 20.9 mm, IQR 16.7-27.3); p < 0.01. Fewer than 33 (21%) reports commented on patency of distal runoff. We calculated an average percent thrombus of 60% (IQR 19-81) in nonoperative PAAs, which is significantly smaller than 75% (IQR 58-89) in operative PAAs; p < 0.01. CONCLUSION: In this multi-institutional retrospective study, PAAs are often not followed at intervals recommended by the Society for Vascular Surgery guidelines and do not include all measurements necessary for clinical decision-making in the multi-institutional repository studied. There should be standardization of PAA DUS protocols performed by all noninvasive vascular laboratories to ensure completeness of PAA DUS images and inclusion of characteristics pertinent to clinical decision-making in radiology reports.

The Influence of Diabetes on Thrombotic Profiles and Outcomes on Patients with Peripheral Artery Disease.

BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis postrevascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. METHODS: Patients with peripheral artery disease undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, postoperative day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student's t-test for pairwise analysis and Mann-Whitney U tests. RESULTS: Among 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, P < 0.01), AA MA (36.6 vs. 29.65, P < 0.05), clot strength without platelets activator F MA (13.10 vs. 10.80, P < 0.01), and heparin-neutralized uninhibited clot strength from thrombin activation heparinized kaolin with heparinase MA (61.10 vs. 57.70, P < 0.01) values at baseline. Postoperatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen citrated functional fibrinogen levels (40.95 vs. 371.35, P < 0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor citrated functional fibrinogen MA values (22.90 vs. 20.40, P < 0.05) when measured within 36 hrs of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261-unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. CONCLUSIONS: Elevated HbA1c levels appear to be associated with prothrombotic tendencies in clot dynamics as measured by thromboelastography with platelet mapping, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.

The Use of Clot Strength as a Predictor of Thrombosis in Peripheral Artery Disease.

BACKGROUND: Graft/stent thrombosis is the leading cause of amputation in patients over 60, and while dual antiplatelet therapy is the standard of care, there is a significant variability in platelet response and limited guidance on measuring effectiveness. Thromboelastography with platelet mapping (TEG-PM) can objectively detail an individual's coagulation profile, namely the strength of the clot and its response to antiplatelet medication. Although TEG-PM has been used for predicting postoperative bleeding and assessing platelet dysfunction in traumatic brain injury, its application in thrombosis diseases such as peripheral artery disease remains unexplored. The aim of this observational study was to determine if objective measures of clot strength could predict a high clinical risk of thrombosis. METHODS: Patients >60 years with peripheral artery disease undergoing revascularization were prospectively evaluated from 2021 to 2023. They were clinically followed for 1 year to detect any thrombotic events. TEG-PM was used to objectively evaluate coagulation profiles in patients at 1, 3, 6, and 9 months. These follow-up periods were chosen based on studies showing that 1-3 month intervals in the first year after lower extremity revascularization optimize therapy and risk control. The TEG-PM data preceding a thrombotic/stenotic event in patients with thrombosis was compared to the last known well TEG-PM event in those without a thrombotic/stenotic event. We stratified the groups based on the occurrence of thrombosis/stenotic events. Descriptive statistics were applied to characterize each group and a chi-square test was conducted to assess the variance between both groups. An unpaired t-test was run to identify differences in platelet function. Receiver operating characteristic analysis was performed to determine the optimal TEG-PM cutoff for predicting a higher risk of thrombosis. RESULTS: One hundred and fifty-eight patients were analyzed, from whom 28 (17.7%) experienced a thrombotic event. The thrombosis cohort exhibited significantly greater MAADP, MAFibrin, and MAThrombin [50.2 vs. 40.0, P < 0.05], [18.19 vs. 14.64, P < 0.05], and [63.8 vs. 58.5, P < 0.05], respectively, indicative of greater clot strength. By receiver operating characteristic analysis, the optimal predictor cut-off for MAADP, indicating a higher risk of thrombosis, was >42 mm [P < 0.05] with 82% sensitivity and 50% specificity. CONCLUSIONS: An increase in clot strength was found to be predictive of thrombosis/stenosis within 30 days. Using a MAADP cut-off greater than 42 mm might serve as an alternative approach to tailor the use of antiplatelet medication, potentially reducing the risk of thrombosis.

Examining Outcomes and Complications for Operative Versus Nonoperative Treatment of Pediatric Type II Supracondylar Humerus Fractures: A Systematic Review of Comparative Studies.

OBJECTIVE: The optimal management of pediatric type II supracondylar humerus fractures (SCHFs) is debated. We conducted a systematic review comparing outcomes and complications of nonoperative versus operative management to aid decision-making and inform future research. METHODS: We searched PubMed, Web of Science, MEDLINE, and CINAHL from their inception until February 7, 2024, including studies on pediatric patients (<18 y) with any type II SCHF, provided they compared operative to nonoperative care and were in English. The quality of articles was evaluated using the Methodological Index for Non-Randomized Studies Scale. RESULTS: Out of 417 studies reviewed, 7 met the inclusion criteria. These studies involved 1446 patients (mean age: 4.9 y; mean follow-up: 5.0 mo), comparing operative (n = 427) and nonoperative (n = 1019) treatments. Functional outcomes such as carrying angle, Baumann angle, elbow range-of-motion, and patient satisfaction were similar across treatment groups. Nonoperative management showed a higher incidence of residual sagittal deformity (14.1% vs 0.0%; P < 0.0001) and a treatment failure rate of 8.9% to 20.6%, necessitating surgical intervention. Factors prompting operative care included rotational deformity, varus/valgus misalignment, and a shaft-condylar angle below 30 degrees. CONCLUSION: Nonoperative treatment of type II SCHF is linked with higher rates of residual sagittal deformity and a notable failure rate requiring subsequent surgery. Both treatment strategies showed similar functional outcomes and patient satisfaction. Further research should focus on identifying anatomic criteria predictive of nonoperative treatment failure. LEVEL OF EVIDENCE: Level III-systematic review.

Preoperative Anemia is Associated with Poorer Postoperative Outcomes in Patients Undergoing Infrainguinal Bypass Surgery.

BACKGROUND: Preoperative anemia is an important, modifiable risk factor among surgical patients. However, data are scarce on the impact of preoperative anemia on postoperative outcomes after infrainguinal bypass. METHODS: In this multi-institutional analysis, data were retrospectively collected on all infrainguinal bypass procedures performed between 2010 and 2020. Patients were grouped by preoperative hemoglobin as per the National Cancer Institute anemia scale (mild, 10 g/dL-lower limit of normal; moderate, 8.0-9.9 g/dL; severe, 6.5-7.9 g/dL). Multivariable comparisons were performed using logistic regression analysis. RESULTS: A total of 492 patients underwent bypass for peripheral artery disease over the 10-year study period. Median preoperative hemoglobin was 11.0 g/dL (interquartile range 9.5-12.7) and median follow-up was 1.7 years. Preoperative anemia was prevalent among bypass patients (mild 52.4% [n = 258], moderate 26.4% [n = 130], and severe 5.1% [n = 25]). Women were more likely to have moderate (49.2% [women] vs. 50.8% [men]) or severe anemia (52.0% [women] vs. 48.0% [men]) compared with normal hemoglobin (17.7% [women] vs. 82.3% [men]) (P < 0.001). Patients with preoperative anemia were more likely to present with tissue loss (22.8% [normal] vs. 47.7% [moderate] vs. 52.0% [severe], P = 0.01). Bypass target and conduit types were similar between groups. Anemic patients had longer median hospital length of stay compared with nonanemic patients (4 days [normal] vs. 5 days [mild] vs. 6 days [moderate] vs. 7 days [severe], P < 0.001). Postoperative mortality at 30 days was similar across anemia groups (2.5% [normal] vs. 4.6% [moderate] vs. 8.0% [severe], P = 0.23). On multivariable analysis, however, postoperative mortality was independently associated with severe anemia (odds ratio 7.5 [1.2-48.8], P = 0.04) and male gender (odds ratio 7.5 [1.2-26.4], P = 0.03). CONCLUSIONS: Preoperative anemia is common among patients undergoing infrainguinal bypass surgery and is an independent risk factor for postoperative mortality. Future investigation is needed to determine whether correction of anemia improves postoperative outcomes in these high-risk patients.

Wall shear rate and energy loss coefficient measures using conventional Doppler ultrasound do not predict carotid plaque progression.

Background: The rate of carotid plaque progression is believed to be related to blood flow hemodynamics and shear stress. Our objective was to determine if wall shear rate (WSR) and the energy loss coefficient (ELC) measured by Doppler ultrasound could predict atherosclerotic carotid disease progression. Patients and methods: Patients at a large tertiary center with an initial ultrasound between 2016 and 2018 with a significant carotid plaque were included if they had at least one 6 months follow-up comparative study. Stenosis progression was assessed according to the NASCET (The North American Symptomatic Carotid Endarterectomy Trial) percentage criterion. Results: The average annual progression rate for the 74 plaques included was 5.7% NASCET per year. We identified 18 plaques with ≥10% NASCET progression and 56 plaques without significant progression <10% NASCET. Among the plaques with progression, only four plaques had progression greater than 20% NASCET. Median WSR was 6266 s-1 [5813-8974] in plaques with progression and 6564 s-1 [5285-8766] in stable plaques (p=0.643). Median ELC was 3.86 m2 [2.78-5.53] in plaque with progression and 4.32 m2 [3.42-6.81] in stable plaques (p=0.296). Conclusions: Although it is a widely accepted hypothesis that shear stress and hemodynamics of the carotid bifurcation contribute to plaque progression, we found that WSR and ELC estimated by Doppler ultrasound do not reliably predict atherosclerotic plaque progression in the carotid artery. Other ultrasound modalities, such as 3D imaging, may be used to assess the influence of plaque geometry and hemodynamics in plaque progression.

Impact of anticoagulation/antiplatelet therapy on femoropopliteal bypass graft outcomes.

BACKGROUND: Anticoagulant and antiplatelet (AC/AP) medications have been reported to improve bypass graft patency, however, the optimal AC/AP strategy remains unclear in the heterogenous peripheral artery disease population. METHODS: A multi-institutional retrospective review utilizing the Research Patient Data Registry database from 1995 to 2020 was performed for all patients who underwent femoropopliteal bypass procedures. Electronic medical records were used to obtain demographic information, comorbidities, smoking status, operative details (bypass target), postoperative AC/AP medications, postoperative complications, and long-term outcomes and were reviewed for the cohort. Cox proportional hazards model was used to determine independent risk factors for major adverse limb events (MALE) after bypass. MALE was defined as reintervention for patency or major amputation of index limb (above- or below-knee amputation). RESULTS: A total of 1421 patients underwent femoropopliteal bypass between 1995 and 2020 throughout five institutions included in this study. Complete data were available for 1292 of the 1421 patients (90.9%). The indications for bypass included intermittent claudication (21.4%), rest pain (30.3%), tissue loss (33.5%), and nonatherosclerotic disease (14.8%). Distal bypass targets comprised above-knee (38.6%) and below-knee (61.4%) popliteal arteries. Patients were divided into six groups based on postoperative AC/AP use including none (n = 57 [4.4%]), monoantiplatelet therapy (n = 587 [45.4%]), dual AP therapy (n = 214 [16.6%]), AC alone (n = 73 [5.7%]), AC + monoantiplatelet therapy (n = 319 [24.7%]), and AC + dual AP therapy (n = 42 [3.3%]). Postoperative bleeding complications were low for both hematoma (3.7%) and pseudoaneurysm (0.7%). There was no difference in bleeding complications across AC/AP groups (hematoma, P = .61; pseudoaneurysm, P = .31). After adjusting for patient factors, below-knee bypass target (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.52; P = .019) and bypass for tissue loss (HR, 1.40; 95% CI, 1.04-1.88; P = .028) were independent predictors for MALE. Great saphenous vein conduit trended toward protection for MALE, compared with prosthetic grafts (HR, 0.84; 95% CI, 0.70-1.01; P = .06). No AC/AP regimen was associated with of MALE, even stratifying by above-knee and below-knee bypass cohorts. The median follow-up period was 2 years. CONCLUSIONS: Among patients undergoing femoropopliteal bypass grafting, no combination of AC or AP medications was associated with improved graft patency; however, a below-knee target and tissue loss were associated with adverse limb events. AC and AP regimen may be individualized after bypass with regard to other concomitant medical comorbidities.

Risk factors and consequences of graft infection after femoropopliteal bypass: A 25-year experience.

OBJECTIVE: In this multi-institutional series, we aimed to determine the incidence, risk factors, and long-term outcomes of graft infection in patients post-femoropopliteal bypass. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures from 1995 through 2020. Cumulative incidence function estimated the long-term rate of bypass graft infection (BGI), and the Fine-Gray model was used to determine independent risk factors for BGI to account for death as a competing risk. RESULTS: Over the 25-year period, 1315 femoral popliteal bypasses were identified with a median follow-up of 2.89 years (interquartile range, 0.75-6.55 years). BGI was diagnosed in 34 patients (2.6%). BGI occurred between 9 days and 11.2 years postoperatively, with a median of 109 days. Estimated 1- and 5-year incidence of BGI was 2.1% (95% confidence interval [CI], 1.4%-3.1%) and 2.8% (95% CI, 1.9%-3.9%), respectively. Medical comorbidities, indications for bypass, and popliteal bypass targets (above- vs below-knee) were similar between patients with BGI and all patients (P = not significant for each). Patients with BGI were more frequently complicated by postoperative hematoma (14.7% vs 3.7%), superficial wound infection (38.2% vs 19.2%), lymphocele/lymphorrhea (8.8% vs 2.1%), and 30-day readmission rates (47.1% vs 21.3%) (P < .05 for each). Most commonly isolated pathogens were Staphylococcus aureus (n = 19; 55.9%) and polymicrobial cultures (n = 5; 14.7%). Reoperation for BGI involved incision and drainage (n = 7; 20.6%), graft excision without reconstruction (n = 12; 35.3%), graft excision with in-line reconstruction (n = 11; 32.4%), and graft excision with extra-anatomic reconstruction (n = 2; 5.9%). Nine patients with BGI (26.5%) ultimately required major amputation. Prosthetic bypass (subdistribution hazard ratio [SHR], 3.73; 95% CI, 1.64-8.51; P = .002), postoperative hematoma (SHR, 3.44; 95% CI, 1.23-9.61; P = .018), and 30-day readmission (SHR, 2.75; 95% CI, 1.27-5.44; P = .010) were independently associated with BGI. One-year amputation-free survival was 50% (95% CI, 31.9%-65.7%) after BGI. CONCLUSIONS: BGI is a rare complication of femoral-popliteal bypass with significant morbidity. Graft infection is associated with the use of prosthetic grafts, postoperative hematoma, and unplanned hospital readmission. Mitigation of these risk factors may decrease the risk of this dreaded complication.

A systematic review of thromboelastography utilization in vascular and endovascular surgery.

OBJECTIVE: Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS: Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS: This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.

Outcomes of Femoropopliteal Bypass for Lifestyle-Limiting Claudication in the Endovascular Era.

INTRODUCTION: Outcomes after femoropopliteal bypass for intermittent claudication (IC) remain unclear in the endovascular era. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures performed between 1995 and 2020. Demographics, operative details, and outcomes were documented. A statistical analysis included Kaplan-Meier curves and Cox proportional hazards ratios (HR). RESULTS: A total of 282 patients underwent femoropopliteal bypass surgery for IC. Median age was 68 y (interquartile range, 61-73 y). Bypass conduits included great saphenous vein (GSV) (48.2%), prosthetic grafts (48.9%), and non-GSV autogenous grafts (2.8%). Distal bypass target was above-knee in 62.1% and below-knee in 37.9% of patients. The most common postoperative complications were wound infections (14.2%) followed by unplanned 30-d hospital readmissions (12.4%). Mortality rates were low at 0.4% (30 d) and 3.2% (1 y). Five-year primary patency rates trended highest for claudicants undergoing above-knee bypass with GSV conduit (log-rank P = 0.065). Five-year amputation-free survival rates were highest using GSV conduit regardless of distal bypass target (log-rank P = 0.017). On a multivariable analysis, age (HR 1.02 [1.00-1.04], P = 0.023) and active smoking (HR 1.48 [1.06-2.06], P = 0.021) were identified as risk factors for diminished primary graft patency. Risk factors for amputation-free survival included age (HR 1.03 [1.01-1.05], P < 0.001) and GSV conduit type (HR 0.65 [0.46-0.90], P = 0.011). CONCLUSIONS: Femoropopliteal bypass among claudicants is associated with high rates of wound infection and hospital readmission. Active smoking portends worse outcomes in this population. These data may inform clinical decision-making regarding surgical intervention for claudication in the endovascular era.

An Electromyography-Based Constitutive Law for Force Generation in Skeletal Muscle-Part II: Model Validation on the Ankle Joint Complex.

Part II of this study evaluates the predictive ability of the skeletal muscle force model derived in Part I within the ankle joint complex. The model is founded in dimensional analysis and uses electromyography and the muscle force-length, force-velocity, and force-frequency curves as inputs. Seventeen subjects (eight males, nine females) performed five different exercises geared toward activating the primary muscles crossing the ankle joint. Motion capture, force plate, and electromyography data were collected during these exercises for use in the analysis. A constant, Km, was calculated for each muscle of each subject using four of the five exercises. The fifth exercise was then used to validate the results by treating the moments due to muscle forces as known and all other components in Euler's second law as unknown. While muscle forces cannot be directly validated in vivo, methods can be developed to test these values with reasonable confidence. This study compared moments about the ankle joint due to the calculated muscle forces to the sum of the moments due to all other sources and the kinematic terms in the second Newton-Euler equation of rigid body motion. Average percent errors for each subject ranged from 4.2% to 15.5% with a total average percent error across all subjects of 8.2%, while maximum percent errors for each subject ranged from 33.3% to 78.0% with an overall average maximum of 52.4%. Future work will examine sensitivity analyses to identify any potential simplifications to the model and solution process, as well as validate the model on a more complex joint system to ensure it still performs at a satisfactory level.

Efficacy, Safety, and Applications of Skin Protectants.

The skin barrier is essential for protection against allergens, irritants, and pathogens and is intimately involved in a variety of inflammatory conditions. As such, approaches to treating these inflammatory skin conditions could involve the repair and protection of the skin barrier. This form of treatment can be delivered in the form of skin protectants, though their protective value remains questionable. Evidence suggests that skin protectants could form an additional layer of protection against harmful substances that could penetrate the skin barrier. However, although several studies support the efficacy of skin protectants, others suggest potentially aggravating effects instead. The range of active ingredients included in skin protectant formulas varies widely, which could account for these observed differences. While the use of skin protectants could prove beneficial in populations at higher risk of exposure to irritants, their effectiveness may be hindered by a lack of proper adherence. The findings gathered from the existing literature on skin protectants appear promising, though further investigation must be conducted to better understand their protective effects against conventional barrier repair approaches. J Drugs Dermatol. 2022;21(9):977-982. doi:10.36849/JDD.6705.

Effects of faecal inorganic content variability on quantifying glucocorticoid and thyroid hormone metabolites in large felines: Implications for physiological assessments in free-ranging animals.

Faecal glucocorticoid (GC) and triiodothyronine (T3) metabolites and their interactions are increasingly used to monitor perceived stress and nutritional challenges in free-ranging animals. However, a number of extrinsic and intrinsic factors including hormone-inert dietary materials, inorganic matters etc. are known to affect reliable hormone metabolite quantifications. In this study, the impacts of inorganic matter (IOM) on faecal GC (fGCMs) and T3 (fT3Ms) metabolite measure were addressed in wild tiger (n = 193 from Terai Arc landscape, India) and captive lion (n = 120 from Sakkarbaug Zoological Garden, Gujarat, India) and possible corrective measures were evaluated. The wild tiger samples contained highly variable IOM content (9-98%, mostly with > 40% IOM) compared to captive Asiatic lion (17-57%, majority with < 40% IOM). Significant correlations were observed between IOM content and tiger fGCM (r = -0.46, p = 0.000), fT3M (r = -0.58, p = 0.000) and lion fT3M measures (r = -0.43, p = 0.003). Two corrective measures viz. removing samples with ≥ 80% IOM and subsequently expressing concentrations as per gram of organic dry matter (instead of total dry matter) reduced IOM influence on tiger fGCM, fT3M and lion fT3M, without affecting lion fGCM measures. The corrective measures changed the interpretations of fT3M data of field-collected tiger samples with no significant changes in fGCM (both tiger and lion) and fT3M (lion) data. As faecal IOM content is common in many wild species, the results emphasize the need to reduce IOM-driven hormone data variation for ecologically relevant interpretations towards species conservation.

Advancements in spontaneous microbial desalination technology for sustainable water purification and simultaneous power generation: A review.

Population growth and rapid urbanization have put a lot of pressure on the already scarce freshwater around the globe. The availability of freshwater is not only limited but it is non-uniform also. Available desalination technologies help mitigate water shortage; however, these techniques are energy-intensive and unsustainable. Desalination technologies utilizing renewable energy and bio-electrochemical systems have been developed to achieve limited sustainability. With technological advancements, microbial desalination cell (MDC) has been developed which is capable of desalination, wastewater treatment, and power generation simultaneously. This review critically examined the performance of various MDC techniques concerning their stimulus parameters including COD removal, total desalination rate, total dissolved solids reduction rate, Coulombic efficiency, and power density. Limitations of MDCs have also been incorporated in the review. Work on MDC coupled with other robust desalination techniques offering advantages such as better desalination and more water recovery e.g. osmotic-MDC etc. has been included. Researchers have tremendously worked on MDCs with different electro-catalysts. Few of these are not sustainable and costly. Authors have reviewed critically with belief that it will pave a way for the commercialization of this eco-friendly technology.