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Background: Nutcracker syndrome (NCS) describes the symptomatic compression of the left renal vein between the aorta and superior mesenteric artery. Whereas asymptomatic compression is a common radiological finding, patients with NCS can report a range of symptoms. There are no specific diagnostic criteria and interventions include a range of open surgical and endovascular procedures. Therefore, we wished to develop an international consensus document covering aspects of diagnosis, management, and follow-up for patients with NCS., Methods: A three-stage modified Delphi consensus was performed. A steering committee developed 37 statements covering 3 categories for patients with NCS: diagnosis, management, and follow-up. These statements were reported individually by 20 international experts in the management of venous disease, using a 5-point Likert scale. Consensus was defined if ≥70% of respondents rated the statement between 1 and 2 (agreement) and between 4 and 5 (disagreement). Those statements without consensus were recirculated in a second round of voting. A third round of the questionnaire was performed with 14 additional statements to clarify diagnostic values of NCS., Results: Responses were returned by 20 of 20 experts (100%) in round one and 17 of 20 (85%) in round two. Initial consensus was reached in 24 of 37 statements (65%) spread over all categories. Round two achieved a further consensus on 5 out of 10 statements (50%). No categories reported consensus on all statements. In round two consensus was reached in the category of follow-up (4/5 statements [80%]). The final round reached consensus on 5 out of 14 statements (36%). Experts agreed that imaging is obligated to confirm NCS. Experts did not agree on specific diagnostic cut-off values. There was a consensus that the first choice of operative treatment is left renal vein transposition and that the risk of stent migration outweighs the advantages of a percutaneous procedure., Conclusions: Consensus was achieved on most statements concerning the assessment and management of NCS. This Delphi consensus identified those areas in which further research is needed, such as antiplatelet therapy, endovascular treatment, and renal autotransplantation. A rare disease registry to improve data and reports of patient outcomes is warranted., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Overall inferior vena cava filter (IVCF) utilization has decreased in the United States since the 2010 US Food and Drug Administration (FDA) safety communication. The FDA renewed this safety warning in 2014 with additional mandates on reporting IVCF-related adverse events. We evaluated the impact of the FDA recommendations on IVCF placements for different indications from 2010 to 2019 and further assessed utilization trends by region and hospital teaching status., Methods: Inferior vena cava filter placements between 2010 and 2019 were identified in the Nationwide Inpatient Sample database using the associated International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision codes. Inferior vena cava filter placements were categorized by indication for venous thromboembolism (VTE) "treatment" in patients with VTE diagnosis and contraindication to anticoagulation and "prophylaxis" in patients without VTE. Generalized linear regression was used to analyze utilization trends., Results: A total of 823 717 IVCFs were placed over the study period, of which 644 663 (78.3%) were for VTE treatment and 179 054 (21.7%) were for prophylaxis indications. The median age for both categories of patients was 68 years. The total number of IVCFs placed for all indications decreased from 129 616 in 2010 to 58 465 in 2019, with an aggregate decline rate of -8.4%. The decline rate was higher between 2014 and 2019 than between 2010 and 2014 (-11.6% vs -7.2%). From 2010 to 2019, IVCF placement for VTE treatment and prophylaxis trended downward at rates of -7.9% and -10.2%, respectively. Urban nonteaching hospitals saw the highest decline for both VTE treatment (-17.2%) and prophylactic indications (-18.0%). Hospitals located in the Northeast region had the highest decline rates for VTE treatment (-10.3%) and prophylactic indications (-12.5%)., Conclusion: The higher decline rate in IVCF placements between 2014 and 2019 compared with 2010 and 2014 suggests an additional impact of the renewed 2014 FDA safety indications on national IVCF utilization. Variations in IVCF use for VTE treatment and prophylactic indications existed across hospital teaching types, locations, and regions., Clinical Impact: Inferior vena cava filters (IVCF) are associated with medical complications. The 2010 and 2014 FDA safety warnings appeared to have synergistically contributed to a significant decline in IVCF utilization rates from 2010 - 2019 in the US. IVC filter placements in patients without venous thromboembolism (VTE) declined at a higher rate than VTE. However, IVCF utilization varied across hospitals and geographical locations, likely due to the absence of universally accepted clinical guidelines on IVCF indications and use. Harmonization of IVCF placement guidelines is needed to standardize clinical practice, thereby reducing the observed regional and hospital variations and potential IVC filter overutilization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels., Methods: This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients' antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml., Results: Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %). Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders., Conclusion: Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect., Competing Interests: Declaration of competing interest Rahul Kashyap: Grant and contracts - Gordan and Betty Moore Foundation, Jenssen and Jenssen. LLC; all payments made to the institution. No conflict of interest related to this manuscript. Rest of the authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To explore the association of estimated plasma volume (ePV) and plasma volume status (PVS) as surrogates of volume status with new-onset AKI and in-hospital mortality among hospitalized COVID-19 patients., Materials and Methods: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and longitudinal analysis was performed to find the association of ePV and PVS with new-onset AKI during hospitalization as the primary outcome and in-hospital mortality as a secondary outcome., Results: Our analysis included 7616 COVID-19 patients with new-onset AKI occurring in 1365 (17.9%) and a mortality rate of 25.96% among them. A longitudinal multilevel multivariate analysis showed both ePV (OR 1.162; 95% CI 1.048-1.288, p=0.004) and PVS (OR 1.032; 95% CI 1.012-1.050, p=0.001) were independent predictors of new onset AKI. Higher PVS was independently associated with increased in-hospital mortality (OR 1.038, 95% CI 1.007-1.070, p=0.017), but not ePV (OR 0.868, 95% CI 0.740-1.018, p=0.082)., Conclusion: A higher PVS correlated with a higher incidence of new-onset AKI and worse outcomes in our cohort of hospitalized COVID-19 patients. Further large-scale and prospective studies are needed to understand its utility., Competing Interests: Declaration of competing interest Rahul Kashyap: Grant and contracts - Gordan and Betty Moore Foundation, Jenssen and Jenssen LLC; all payments made to the institution. No conflict of interest related to this manuscript. Rest other authors declare that they have no competing interests., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision-making for challenging presentations. This document will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta., Competing Interests: Potential conflicts of interest . L. M. B. reports royalty payments (authorship duties) from UpToDate, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision making for challenging presentations. This review will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta., Competing Interests: Potential conflicts of interest. L. M. B. reports royalty payments (authorship duties) from UpToDate, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Transvenous embolization is emerging as a promising treatment for cerebrospinal fluid-venous fistulas (CVF) associated with spontaneous intracranial hypotension (SIH)., Objective: To perform an independent validation of the efficacy and safety of the procedure and describe the procedural techniques used at our institution., Methods: A retrospective review was performed including consecutive patients with SIH who had undergone CVF embolization with 3-month clinical and imaging follow-up. Clinical evaluation included the Patient Global Impression of Change (PGIC) Scale and six-item Headache Impact Test (HIT-6). Bern SIH score was used for imaging evaluation on brain MRI. Post-treatment changes in scores were assessed by Wilcoxon signed rank test. Procedural technical details, including use of upper-extremity access and dual-microcatheter pressure cooker technique, were recorded., Results: 18 patients (13 female, median age 60 years) were included. 17 (94%) procedures were performed with upper-extremity access and 12 (67%) using dual-microcatheter pressure cooker technique. After embolization, 16 (89%) patients reported much or very much improved at follow-up PGIC; median (IQR) HIT-6 score improved from 68 (62-72) to 36 (36-38) and Bern SIH score improved from 8 (6-8) to 3 (1.5-3.5), p values <0.001. Side effects were transient embolization site back pain in 15 (83%) and rebound intracranial hypertension requiring medical management in 9 (50%) patients. HIT-6 and Bern SIH score changes were similar between conventional and pressure cooker techniques ( p values >0.05)., Conclusion: Transvenous embolization is independently validated as a highly effective and safe treatment for CVF and is feasible using upper-extremity venous access. Dual-microcatheter and balloon/coil pressure cooker techniques may be used to optimize distribution of embolic material and potentially, treatment efficacy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Carotid stenosis may cause silent cerebrovascular disease (CVD) through atheroembolism and hypoperfusion. If so, revascularization may slow progression of silent CVD. We aimed to compare the presence and severity of silent CVD to the degree of carotid bifurcation stenosis by cerebral hemisphere., Materials and Methods: Patients age ≥40 years with carotid stenosis >50% by carotid ultrasound who underwent MRI brain from 2011-2015 at Mayo Clinic were included. Severity of carotid stenosis was classified by carotid duplex ultrasound as 50-69% (moderate), 70-99% (severe), or occluded. White matter lesion (WML) volume was quantified using an automated deep-learning algorithm applied to axial T2 FLAIR images. Differences in WML volume and prevalent silent infarcts were compared across hemispheres and severity of carotid stenosis., Results: Of the 183 patients, mean age was 71±10 years, and 39.3% were female. Moderate stenosis was present in 35.5%, severe stenosis in 46.5% and occlusion in 18.0%. Patients with carotid stenosis had greater WML volume ipsilateral to the side of carotid stenosis than the contralateral side (mean difference, 0.42±0.21cc, p=0.046). Higher degrees of stenosis were associated with greater hemispheric difference in WML volume (moderate vs. severe; 0.16±0.27cc vs 0.74±0.31cc, p=0.009). Prevalence of silent infarct was 23.5% and was greater on the side of carotid stenosis than the contralateral side (hemispheric difference 8.8%±3.2%, p=0.006). Higher degrees of stenosis were associated with higher burden of silent infarcts (moderate vs severe, 10.8% vs 31.8%; p=0.002)., Conclusions: WML and silent infarcts were greater on the side of severe carotid stenosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the performance of a commercially available artificial intelligence (AI) algorithm for the detection of pulmonary embolism (PE) on contrast-enhanced computed tomography (CT) scans in patients hospitalized for coronavirus disease 2019 (COVID-19)., Patients and Methods: Retrospective analysis was performed of all contrast-enhanced chest CT scans of patients admitted for COVID-19 between March 1, 2020 and December 31, 2021. Based on the original radiology reports, all PE-positive examinations were included (n=527). Using a reversed-flow single-gate diagnostic accuracy case-control model, a randomly selected cohort of PE-negative examinations (n=977) was included. Pulmonary parenchymal disease severity was assessed for all the included studies using a semiquantitative system, the total severity score. All included CT scans were sent for interpretation by the commercially available AI algorithm, Aidoc. Discrepancies between AI and original radiology reports were resolved by 3 blinded radiologists, who rendered a final determination of indeterminate, positive, or negative., Results: A total of 78 studies were found to be discrepant, of which 13 (16.6%) were deemed indeterminate by readers and were excluded. The sensitivity and specificity of AI were 93.2% (95% CI, 90.6%-95.2%) and 99.6% (95% CI, 98.9%-99.9%), respectively. The accuracy of AI for all total severity score groups (mild, moderate, and severe) was high (98.4%, 96.7%, and 97.2%, respectively). Artificial intelligence was more accurate in PE detection on CT pulmonary angiography scans than on contrast-enhanced CT scans ( P <.001), with an optimal Hounsfield unit of 362 ( P =.048)., Conclusion: The AI algorithm demonstrated high sensitivity, specificity, and accuracy for PE on contrast-enhanced CT scans in patients with COVID-19 regardless of parenchymal disease. Accuracy was significantly affected by the mean attenuation of the pulmonary vasculature. How this affects the legitimacy of the binary outcomes reported by AI is not yet known., Competing Interests: The authors report no competing interests., (© 2023 The Authors.)

Background: Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach., Methods: To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log 2 fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state., Results: RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm)., Conclusions: MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia., (© 2023. The Author(s).)

Objective: Compression of the left renal vein by the superior mesenteric artery, known as nutcracker phenomenon (NCP), can cause retrograde flow and congestion in communicating venous systems. It has recently been speculated that NCP can result in retrograde flow and congestion of the lumbar veins and epidural venous plexus (EVP), thereby affecting the central nervous system. This study describes the novel use of time-resolved magnetic resonance angiography (trMRA) to evaluate for retrograde left second lumbar vein (L2LV) flow and early EVP enhancement in patients with chronic daily headache (CDH) with and without NCP., Methods: A retrospective analysis was performed of 31 patients with CDH (27 females and 4 males; median age, 38 years [range, 18-63 years]) who underwent trMRA centered over the L2LV to evaluate the direction of blood flow and presence of early EVP enhancement from May 2020 to March 2022. Descriptive statistics were performed, and anatomic associations were analyzed in patients with and without retrograde L2LV flow and early EVP enhancement. The accuracy of magnetic resonance imaging findings in detecting these flow patterns was also assessed., Results: Patients with NCP who demonstrated narrowing of the left renal vein, a positive beak sign ( P = 0.052), decreased aortomesenteric distance ( P = 0.038), and decreased SMA angle demonstrated increased rates of retrograde L2LV flow and early EVP enhancement. A positive beak sign was 83% specific, and an aortomesenteric distance of ≤6.5 mm was 61% sensitive and 83% specific for identifying retrograde L2LV flow with early regional EVP enhancement in patients with CDH., Conclusions: Retrograde L2LV flow with early EVP enhancement in CDH patients can be effectively evaluated using trMRA and was seen with greater propensity in those patients with NCP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Ruptured abdominal aortic aneurysm (AAA) carries high morbidity and mortality. Elective repair of AAA with endovascular stent-grafts requires lifetime imaging surveillance for potential complications, most commonly endoleaks. Because endoleaks result in antegrade or retrograde systemic arterialized flow into the excluded aneurysm sac, patients are at risk for recurrent aneurysm sac growth with the potential to rupture. Multiphasic CT has been the main imaging modality for surveillance and symptom evaluation, but contrast-enhanced US (CEUS) offers a useful alternative that avoids radiation and iodinated contrast material. CEUS is at least equivalent to CT for detecting endoleak and may be more sensitive. The authors provide a general protocol and technical considerations needed to perform CEUS of the abdominal aorta after endovascular stent repair. When there are no complications, the stent-graft lumen has homogeneous enhancement, and no contrast material is present in the aneurysm sac outside the stented lumen. In patients with an antegrade endoleak, contrast material is seen simultaneously in the aneurysm sac and stent-graft lumen, while delayed enhancement in the sac is due to retrograde leak. Recognition of artifacts and other potential pitfalls for CEUS studies is important for examination performance and interpretation. Online supplemental material is available for this article. © RSNA, 2022.

Objective: To describe the clinical characteristics and outcomes of CVT in patients with history of recent COVID-19 infection or vaccination., Methods: We reviewed demographic, clinical, and radiographic characteristics of non-pyrogenic, non-traumatic CVT cases at our multi-center institution between March 2020 and December 2021. Patients were grouped according to their history of recent COVID-19 infection or vaccination into group-I (+COVID-19 association) and group-II (-COVID-19 association)., Results: Fifty-one patients with CVT were included, of which 14 (27.4%) had a positive COVID-19 association: 10 with infection and 4 with mRNA-COVID-vaccine. Nine patients in group-I had COVID-19 infection or vaccine within 30 days of CVT diagnosis, including 3 patients with active infection at the time of CVT diagnosis. Half of the patients in group-I (n = 7,50.0%) and 32.4% (n = 12) of group-II were male, and mean age was 52.6 years in group-I and 51.4 years in group-II. Fever at presentation was noted in one patient who had active COVID infection (I=1 (7.1%), II= 0 (0%)). Higher rates of comorbidities were observed in group-II: hypertension (I= 2 (14.3%), II= 13 (35.1%)), deep venous thrombosis(I=1(7.1%), II= 10 (27.0%)), pulmonary emboli (I=1(7.1%), II= 8(21.6%)), or stroke(I=0(0%), II= 6(16.4%)). Three patients had thrombocytopenia at the time of CVT diagnosis (5.4%) and most patients (n = 37, 72.5%) were treated medically with anticoagulation. Complication rate during hospitalization was 17.6% (n = 6), and no mortality was noted., Conclusion: Twenty-seven percent of CVT patients were associated with COVID-19 infection or vaccination, and the majority presented within 30 days of infection/vaccination., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Patient Safety Indicator (PSI)-12, a hospital quality measure designed by Agency for Healthcare Research and Quality (AHRQ) to capture potentially preventable adverse events, captures perioperative venous thromboembolism (VTE). It is unclear how COVID-19 has affected PSI-12 performance., Objective: We sought to compare the cumulative incidence of PSI-12 in patients with and without acute COVID-19 infection., Design, Setting, and Participants: This was a retrospective cohort study including PSI-12-eligible events at three Mayo Clinic medical centers (4/1/2020-10/5/2021)., Exposure, Main Outcomes, and Measures: We compared the unadjusted rate and adjusted risk ratio (aRR) for PSI-12 events among patients with and without COVID-19 infection using Fisher's exact χ 2  test and the AHRQ risk-adjustment software, respectively. We summarized the clinical outcomes of COVID-19 patients with a PSI-12 event., Results: Our cohort included 50,400 consecutive hospitalizations. Rates of PSI-12 events were significantly higher among patients with acute COVID-19 infection (8/257 [3.11%; 95% confidence interval {CI}, 1.35%-6.04%]) compared to patients without COVID-19 (210/50,143 [0.42%; 95% CI, 0.36%-0.48%]) with a PSI-12 event during the encounter (p < .001). The risk-adjusted rate of PSI-12 was significantly higher in patients with acute COVID-19 infection (1.50% vs. 0.38%; aRR, 3.90; 95% CI, 2.12-7.17; p < .001). All COVID-19 patients with PSI-12 events had severe disease and 4 died. The most common procedure was tracheostomy (75%); the mean (SD) days from surgical procedure to VTE were 0.12 (7.32) days., Conclusion: Patients with acute COVID-19 infection are at higher risk for PSI-12. The present definition of PSI-12 does not account for COVID-19. This may impact hospitals' quality performance if COVID-19 infection is not accounted for by exclusion or risk adjustment., (© 2022 Society of Hospital Medicine.)

Background: COVID-19-associated coagulopathy is incompletely understood., Objectives: To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED)., Patients/methods: Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant., Results: COVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922)., Conclusions: Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EpiCypher is a commercial developer and supplier of platforms like those used in this study: recombinant semi-synthetic nucleosomes (dNucs), antibody validation platforms, and nucleosome based H3Cit assays (e.g. EpiCypher Catalog No. R&D143001). ALJ is an inventor on patents covering use of recombinant nucleosomes carrying histone or DNA modifications for antibody validation and assay quantification. All other authors declare no conflict of interest., (© 2021 The Authors.)

Objective: We sought to identify risk factors for intracranial aneurysms (IAs) in Marfan syndrome (MFS) patients and to describe their characteristics., Methods: Patients with confirmed MFS and vessel-dedicated brain imaging from January 1, 1980-December 1, 2020 were categorized according to the presence (IA) or absence (NIA) of IAs. Unmatched logistic regression analysis and propensity score matching were used for comparison., Results: We included 159 patients, of whom 18 (11.3%) patients had radiographic diagnosis of IAs. Three patients (16.7%) had multiple lesions for a total of 24 IAs. One patient (5.5%) had de novo IA formation. Four patients (22.2%) underwent treatment: Two (11.1%) had open surgical clipping for ruptured aneurysms, and two (11.1%) patients had endovascular embolization for growth. In the unmatched analysis, current tobacco smoker status (odds ratio [OR]: 4.20; confidence interval [CI]: 1.11-15.6; P = 0.027) and history of coronary artery disease (CAD) (OR: 5.79; CI 1.76-20.2; P = 0.004) increased the odds for IA. Propensity score matching yielded 18 IA and 18 NIA patients matched for age, gender, race, prior stroke, and family history of aneurysms. History of CAD (IA = 11 [61.1%] vs. NIA = 4 (22.2%), P = 0.043) and current smoker status (IA = 6 [33.3%] vs. NIA = 0 (0%), P < 0.01) were significantly higher in the IA cohort. Body mass index (P = 0.622), diabetes (P = 0.180), hypertension (P = 0.732), prior stroke (P = 1.00), family history (P = 0.732), alcohol (P = 0.314), recreational drugs (P = 1.00), and other aneurysms (P = 0.585) were not statistically significant., Conclusions: Prevalence of IAs in our series of MFS patients was 11.3%, and de novo formation was 5.5%. MFS patients with a history of CAD and current smoker status had an increased risk of IA. Neurovascular radiographic screening should be considered in all patients with MFS, particularly in patients who smoke or have a history of heart disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aortic dissection remains a highly morbid diagnosis. The treatment of aortic dissection has undergone several paradigm shifts since it was first understood. However, despite the robust research in treatment, the epidemiology of aortic dissection is limited. In this review, we discuss the historical perspectives of aortic dissection with a review of risk factors and presentation. We review the trends in incidence during the past 40 years, with consideration for sex, race, and ethnicity in admission. We further focus our discussion of the classically described Type B aortic dissection treatment. Lastly, we review the impact of long-term events, readmissions, cost assessments, and quality of life studies of patients with aortic dissection. Care for those with aortic dissection remains a long-term challenge for providers and a multispecialty approach is needed for complete patient management., (Copyright © 2021. Published by Elsevier Inc.)

Background: Short-term follow-up of pediatric inguinal herniorrhaphies has yielded low morbidity and recurrence rates. Nonetheless, the impact of childhood inguinal herniorrhaphy on the adulthood risk for repeat groin operation, chronic groin pain, and infertility has not been established., Study Design: A survey was mailed to all patients who underwent a primary inguinal hernia repair as a child at our institution from 1956 to 1960. The survey inquired about repeat groin operation, chronic groin pain, and fertility status. Demographic and operative information from respondents was obtained from medical record review., Results: Of 332 eligible patients, 213 (66%) responded to the survey, accounting for 252 inguinal herniorrhaphies (174 unilateral, 33 bilateral, and 6 sequential contralateral). All hernias were indirect, more common on the right (right, 49%; left, 25%; bilateral, 26%), with males predominating (91%). History of premature birth was present in 5 (2%) patients. High ligation of the hernia sac was performed in 90% of the repairs. Hydrocelectomy was performed in 25 (13%) and orchidopexy in 37 (19%) patients. With a median follow-up of 49 years (range 47.2 to 52.1 years), a total of 21 (8.4%) repeat and 13 (6%) contralateral groin operations were observed. Chronic groin pain and a medical diagnosis of infertility were reported by 7 (3%) and 10 (5%) patients, respectively., Conclusions: Childhood inguinal hernia repairs do not appear to decrease or increase the risk of inguinal hernia development in adulthood. Parents and children undergoing a childhood inguinal hernia repair should be informed that although the risk for a true indirect hernia recurrence is low, the risk of repeat groin operation (8.4%) and chronic groin pain (3%) remain present in adulthood., (Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)