Citations

Abstract Embolic protection devices (EPDs) have become a standard of care during internal carotid artery revascularization. 1,2 This video is about a 57-yr-old-male who presented with a wake-up stroke with a left hemispheric syndrome. Head computed tomography angiography (CTA) revealed tandem occlusions of the proximal left internal carotid artery (ICA) and of the distal left middle cerebral artery (MCA) with an ASPECT (Alberta Stroke Program Early CT Score) score of 6. The patient underwent a cerebral angiogram and was treated with balloon angioplasty with a distal EPD and mechanical thrombectomy. The EPD became occluded with thrombus from the ICA and was retrieved through a 6-Fr Sofia (MicroVention) under continuous aspiration. Successful revascularization of the proximal ICA and distal MCA was achieved. No procedure-related complications occurred, and the patient's neurological exam improved. Tandem occlusions can occur in up to 15% of strokes. The optimal treatment can be controversial, but mechanical thrombectomy and ICA revascularization with a distal EPD appear to be safe and effective in selected patients. 3 Consent was obtained for the procedure and for the video production.

Abstract Key Points The healthy kidney prominently expresses angiotensin-converting enzyme 2 (ACE2) mRNA, protein, and activity, with ACE2 protein abundantly displayed in proximal tubules. Renal ACE2 expression decreases after ischemic AKI but is induced by LPS in a heme oxygenase-1-dependent manner. ACE2 induction/angiotensin (1–7) and angiotensin (1–7) may offer therapeutic approaches for AKI without or with coronavirus disease 2019, respectively. Background The actions of angiotensin-converting enzyme 2 (ACE2) oppose those of the renin-angiotensin-aldosterone system. ACE2 may be a cytoprotectant in some tissues. This study examined ACE2 expression in models of AKI. Methods ACE2 mRNA and protein expression and ACE2 activity were assessed in murine ischemic AKI. Renal ACE2 mRNA expression was evaluated in LPS-induced AKI in wild-type (C57BL/6J) mice, in heme oxygenase-1 +/+ and heme oxygenase-1 −/− mice, and after unilateral ureteral obstruction (UUO) in wild-type mice. The effect of sex and age on renal ACE2 protein expression was also assessed. Results In ischemic AKI, ACE2 mRNA and protein expression and ACE2 activity were reduced as compared with such indices in the intact kidney. In ischemic AKI, ACE2, which, in health, is prominently expressed in the tubular epithelium, especially proximal tubules, is decreased in expression in these segments. Decreased ACE2 expression in AKI did not reflect reduced GFR, because ACE2 mRNA expression was unaltered after UUO. LPS induced renal ACE2 mRNA expression in wild-type mice, but this effect did not occur in heme oxygenase-1–deficient mice. In ischemic and LPS-induced AKI, renal expression of the Mas receptor was increased. In the intact kidney, renal ACE2 protein expression decreased in female mice as compared with male mice, but was unaltered with age. Conclusion We conclude that renal ACE2 expression is decreased in ischemic AKI, characterized by decreased GFR and abundant cell death, but is upregulated in LPS-induced AKI, an effect requiring heme oxygenase-1. Determining the significance of ACE2 expression in experimental AKI merits further study. We suggest that understanding the mechanism underlying ACE2 downregulation in AKI may offer insights relevant to COVID-19: ACE2 expression is downregulated after ACE2 mediates SARS-CoV-2 cellular entry; such downregulation is proinflammatory; and AKI commonly occurs and determines outcomes in COVID-19.

Abstract Background: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. Methods: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. Results: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. Conclusion: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Abstract Intracranial atherosclerotic disease (ICAD) is a common cause of stroke. Antiplatelet therapy is the mainstay for symptomatic ICAD treatment. Endovascular management with submaximal angioplasty and/or intracranial stenting is reserved for patients with repeated ischemic events despite optimal medical therapy. We demonstrate intracranial angioplasty and stenting technique, technique indications, and sizing of stent and target vessel diameter. Stenting and angioplasty have been described in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis and Wingspan Stent System Post Market Surveillance trials. 1,2 Submaximal angioplasty has also been described. 3 This patient, who had been on dual antiplatelet therapy for several months, initially presented with occlusion of the left middle cerebral artery M2 inferior division and underwent mechanical thrombectomy with successful reperfusion. Postoperatively, the patient's symptoms did not improve. Medical management was optimized with heparin infusion. However, repeat stroke study demonstrated M2 inferior division reocclusion. A decision was made to proceed with intracranial angioplasty and stenting. P2Y12 levels were therapeutic. Under moderate conscious sedation, submaximal angioplasty of up to 80% of the normal M2 caliber was attempted. However, we observed persistent high-grade stenosis of the M2 inferior division. The major risk of crossing the lesion for angioplasty is vessel perforation. To safely perform this maneuver, we used a J-configured Synchro-2 microwire (Stryker). Because of the patient's recent thrombectomy, we also had prior tactile feedback about how much resistance was encountered while crossing the occlusion. We then deployed a balloon-mounted intracranial stent for optimal radial force across the stenotic area to restore perfusion. Postoperative computed tomography perfusion showed resolution of the previously noticed perfusion deficit. The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary. Video. ©University at Buffalo Neurosurgery, September 2020. With permission.

Abstract Background Across complex traits, common variants explain only a modest amount of variance, with SNP-heritability consistently below heritability estimates from close relatives. Here, we examined the contribution of rare variant to tobacco use risk in up to 26,000 individuals of European ancestry in the Trans-Omics for Precision Medicine (TOPMed) program with whole genome sequence (WGS;~30X coverage).Method We grouped about 35 million genetic variants by their minor allele frequencies (MAF) and linkage disequilibrium (LD) and estimated SNP-heritability for age of smoking initiation (N = 14,747), cigarettes smoked per day (N = 15,425), smoking cessation (N = 17,871) and initiation (N = 26,340) using linear mixed model. Rare variant population structure is detected and adjusted for by permutation procedure. We estimated an upper bound for narrow-sense heritability for tobacco use using available pedigrees consisting of close relatives in TOPMed.Results Rare variants with MAF 0.1–0.01%, mostly from non-protein altering region, accounted for 26% of variation in age of initiation and 15% for cessation. Follow-up analysis indicated that about one-third of these rare variants contribtion is potentially confounded with rare variants structure even after adjusting for principal components. After further conservative adjustment of population structure, we estimated SNP-based heritability to be 0.21 (SE = 0.08) for age of initiation, 0.15 (0.06) for cigarettes per day, 0.21 (0.09) for cessation, and 0.24 (0.07) for initiation, 1.8–4.5 times higher than previous SNP-based estimates. Our pedigree-based upper-bound for SNP-based heritability ranged from 0.18–0.35.Conclusion The substantial contribution of rare variants for several smoking phenotypes sheds light on the missing heritability and genetic etiology of tobacco use. It also informs fine-mapping strategies since the majority of the rare variant contribution was located in non-coding regulatory regions.

Abstract Vascular access for cerebral angiography has traditionally been performed via the common femoral artery. It is crucial to obtain safe access to prevent complications that could lead to limb ischemia, groin hematoma, or retroperitoneal hematoma. This is especially true in neurointervention as many patients are anticoagulated or have received intravenous thrombolytics prior to their intervention. Special attention to anatomic landmarks, both grossly and radiographically, can help to assure safe access. The patient consented for this procedure. This video details rapid but safe femoral artery access in a patient undergoing emergent thrombectomy.

Significance RBM28 is a human protein essential for proper assembly of the large ribosomal subunit, crucially enabling synthesis of all cellular proteins. Defects in RBM28 cause rare ribosomopathies: alopecia, neurological defects, and endocrinopathy (ANE) syndrome. We investigated an ANE syndrome patient with a clinical presentation consistent with the definition of ANE syndrome but possessing differing genetic variants and molecular pathology. We find one inherited allele is null, clarifying that ANE syndrome is not caused by RBM28 haploinsufficiency, while the other inherited allele retains enough function to enable survival but preclude proper development. Our results define an underlying pathology of ANE syndrome, further delineating an emerging class of assembly factor ribosomopathies and underscoring the importance of nucleolar processes in human health.

Abstract Background: The ESE-ENSAT guidelines on the management of adrenocortical carcinoma (ACC) suggest adjuvant mitotane for patients at high risk of recurrence following radical surgery. This indication has a limited evidence base, lacking results from randomized controlled trials. No suggestion for or against adjuvant mitotane in low-risk patients was given, since studies did not stratify patients for prognosis. The randomized controlled study ADIUVO compared the efficacy of adjuvant mitotane treatment vs. observation in prolonging recurrence-free survival (RFS) in ACC patients at low-intermediate risk of recurrence. Methods: The main inclusion criteria were: stage I-III ACC, R0 surgery, and Ki-67 ≤10%. Patients were randomly assigned 1:1 to adjuvant mitotane (MIT) or observation (OBS). The primary endpoint of the study was RFS. Patients who refused randomization were offered inclusion in the ADIUVO OBSERVATIONAL study. In this prospective, observational study, patients were managed as in the ADIUVO study. A total of 91 patients were enrolled in ADIUVO, 45 in the MIT and 46 in the OBS arm. Baseline characteristics of patients were perfectly matched between the 2 arms: median age, 51 vs. 50.5 years; female, 73% vs. 67%; stage I, 20% vs. 26%; stage II, 67% vs. 63%, stage III, 13% vs. 11%; ACC secretion 44% vs. 36%; Weiss 5 vs. 5; respectively. In ADIUVO OBSERVATIONAL, 42 patients were treated with mitotane and 53 were untreated. Baseline characteristics of patients were matched between the 2 groups and with MIT and OBS groups in ADIUVO. Thus, the ADIUVO OBSERVATIONAL cohorts could be analyzed in parallel to those of ADIUVO. Results: In the ADIUVO study, recurrences were 8 in the MIT and 11 in the OBS arm, while deaths were 2 and 5, respectively. RFS and overall survival (OS) did not significantly differ between the 2 arms. Tumor size was a predictor of RFS in multivariable analysis. In the OBS arm, the HR for recurrence was 1.321 (95%CI, 0.55–3.32, p=0.54) and HR for death 2.171 (95%CI, 0.52–12.12, p=0.29). The survival analysis in the ADIUVO OBSERVATIONAL study confirmed the findings of ADIUVO. Given the outcome of both studies, the NNT is 55. Conclusions: ACC patients at low-intermediate risk of recurrence after surgery are a minority; however, they show a far better prognosis than expected (5-year RFS is about 75%) and do not benefit significantly from adjuvant mitotane. The results of the ADIUVO study do not support routine use of adjuvant mitotane in this subset of patients, who may thus avoid a potentially toxic treatment. This is an important step toward personalization of ACC care.

BackgroundPhysicians use fixed C‐arm fluoroscopy equipment with many interventional radiological and cardiological procedures. The associated effective dose to a patient is generally considered low risk, as the benefit‐risk ratio is almost certainly highly favorable. However, X‐ray‐induced skin injuries may occur due to high absorbed patient skin doses from complex fluoroscopically guided interventions (FGI). Suitable action levels for patient‐specific follow‐up could improve the clinical practice.There is a need for a refined metric regarding follow‐up of X‐ray‐induced patient injuries and the knowledge gap regarding skin dose‐related patient information from fluoroscopy devices must be filled. The most useful metric to indicate a risk of erythema, epilation or greater skin injury that also includes actionable information is the peak skin dose, that is, the largest dose to a region of skin.Materials and MethodsThe report is based on a comprehensive review of best practices and methods to estimate peak skin dose found in the scientific literature and situates the importance of the Digital Imaging and Communication in Medicine (DICOM) standard detailing pertinent information contained in the Radiation Dose Structured Report (RDSR) and DICOM image headers for FGI devices. Furthermore, the expertise of the task group members and consultants have been used to bridge and discuss different methods and associated available DICOM information for peak skin dose estimation.ResultsThe report contributes an extensive summary and discussion of the current state of the art in estimating peak skin dose with FGI procedures with regard to methodology and DICOM information. Improvements in skin dose estimation efforts with more refined DICOM information are suggested and discussed.ConclusionsThe endeavor of skin dose estimation is greatly aided by the continuing efforts of the scientific medical physics community, the numerous technology enhancements, the dose‐controlling features provided by the FGI device manufacturers, and the emergence and greater availability of the DICOM RDSR. Refined and new dosimetry systems continue to evolve and form the infrastructure for further improvements in accuracy. Dose‐related content and information systems capable of handling big data are emerging for patient dose monitoring and quality assurance tools for large‐scale multihospital enterprises.