Predicted leukocyte telomere length and risk of myeloid neoplasms.

Maintenance of telomere length has long been established to play a role in the biology of cancer and several studies suggest that it may be especially important in myeloid malignancies. To overcome potential bias in confounding and reverse causation of observational studies, we use both a polygenic risk score (PRS) and inverse-variance weighted (IVW) Mendelian randomization (MR) analyses to estimate the relationship between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk in 498 cases and 2099 controls and myelodysplastic syndrome (MDS) risk in 610 cases and 1759 controls. Genetic instruments derived from four recent studies explaining 1.23-4.57% of telomere variability were considered. We used multivariable logistic regression to estimate odds ratios (OR, 95% confidence intervals [CI]) as the measure of association between individual single-nucleotide polymorphisms and myeloid malignancies. We observed a significant association between a PRS of longer predicted LTL and AML using three genetic instruments (OR = 4.03 per ~1200 base pair [bp] increase in LTL, 95% CI: 1.65, 9.85 using Codd et al. [Codd, V., Nelson, C.P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J.L., Hottenga, J.J., Fischer, K., Esko, T., Surakka, I. et al. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet., 45, 422-427 427e421-422.], OR = 3.48 per one-standard deviation increase in LTL, 95% CI: 1.74, 6.97 using Li et al. [Li, C., Stoma, S., Lotta, L.A., Warner, S., Albrecht, E., Allione, A., Arp, P.P., Broer, L., Buxton, J.L., Alves, A.D.S.C. et al. (2020) Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length. Am. J. Hum. Genet., 106, 389-404.] and OR = 2.59 per 1000 bp increase in LTL, 95% CI: 1.03, 6.52 using Taub et al. [Taub, M.A., Conomos, M.P., Keener, R., Iyer, K.R., Weinstock, J.S., Yanek, L.R., Lane, J., Miller-Fleming, T.W., Brody, J.A., Raffield, L.M. et al. (2022) Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom., 2.] genetic instruments). MR analyses further indicated an association between LTL and AML risk (PIVW ≤ 0.049) but not MDS (all PIVW ≥ 0.076). Findings suggest variation in genes relevant to telomere function and maintenance may be important in the etiology of AML but not MDS.

Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.

Investigation of the weekend effect on perioperative complications and mortality after carotid revascularization.

OBJECTIVE: Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications than weekday interventions. Although prior investigations have reported the "weekend effect" for carotid endarterectomy (CEA), this association remains unclear for transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS). We investigated the weekend effect for all three carotid revascularization methods. METHODS: We queried the Vascular Quality Initiative for patients who underwent CEA, TCAR, and TFCAS between 2016 and 2022. χ2 and logistic regression modeling analyzed outcomes including in-hospital stroke, death, myocardial infarction, and 30-day mortality by weekend vs weekday intervention. Backward stepwise regression was used to identify significant confounding variables and was ultimately included in each final logistic regression model. Logistic regression of outcomes was substratified by symptomatic status. Secondary multivariable analysis compared outcomes between the three revascularization methods by weekend vs weekday interventions. RESULTS: A total of 155,962 procedures were analyzed including 103,790 CEA, 31,666 TCAR, and 20,506 TFCAS. Of these, 1988 CEA, 246 TCAR, and 820 TFCAS received weekend interventions. Logistic regression demonstrated no significant differences for TCAR and increased odds of in-hospital stroke/death/myocardial infarction for CEA (odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.04-1.65) and TFCAS (OR: 1.46, 95% CI: 1.09-1.96) weekend procedures. Asymptomatic TCAR patients had nearly triple the odds of 30-day mortality (OR: 2.85, 95% CI: 1.06-7.68, P = .038). Similarly, odds of in-hospital death were nearly tripled for asymptomatic CEA (OR: 2.89, 95% CI: 1.30-6.43, P = .009) and asymptomatic TFCAS (OR: 2.78, 95% CI: 1.34-5.76, P = .006) patients. Secondary analysis demonstrated that CEA and TCAR had no significant differences for all outcomes. TFCAS was associated with increased odds of stroke and death compared with CEA and TCAR. CONCLUSIONS: In this observational cohort study, we found that weekend carotid revascularization is associated with increased odds of complications and mortality. Furthermore, asymptomatic weekend patients perform worse in the CEA and TFCAS procedural groups. Among the three revascularization methods, TFCAS is associated with the highest odds of perioperative stroke and mortality. As such, our findings suggest that TFCAS procedures should be avoided over the weekend in favor of CEA or TCAR. In patients who are poor candidates for CEA, TCAR offers the lowest morbidity and mortality for weekend procedures.

A Single-Institution Case Series of Total Endovascular Relining for Type 3 Endoleaks in Traditional Endovascular Aneurysm Repair (EVAR) Grafts with Raised Bifurcations.

BACKGROUND: The endovascular repair of infrarenal abdominal aortic aneurysms can be performed with a wide variety of devices. Many of these grafts elevate the aortic bifurcation which can limit future repairs if the graft material fails thereby creating a type III endoleak to aorto-uniliac grafts. Many manufacturers have grafts susceptible to this, but we have seen this in the Medtronic AneuRx graft. Our goal is to provide technical details and outcomes regarding a novel technique to reline these grafts while maintaining inline flow to the iliac arteries. METHODS: This was a single-institution review of patients who had endoleaks requiring intervention after a previously placed graft with an elevated aortic bifurcation. Primary outcomes included technical success defined as placement of all planned devices, resolution of type III endoleak, aneurysm size at follow-up, and requirement of reintervention. Secondary outcomes included 30-day complications, aneurysm-related mortality, and all-cause mortality. Technical details of the operation include back-table deployment of an Ovation device, modification of the deployment system tether and pre-emptive placement of an up and over 0.014″ wire. The wire is placed up and over and hung outside the contralateral gate. Once the main body is introduced above the old graft, the 0.014" is snared from the contralateral side and externalized. The main body is then able to be seated at the bifurcation as the limb is not fully deployed and then device deployment is completed per instructions for use. RESULTS: Our study consists of 4 individuals, 3 of which had an abdominal aortic aneurysm initially managed with an AneuRx endovascular aneurysm repair and 1 with a combination of Gore and Cook grafts. All 4 patients were male with an average age of 84.5 years at time of reline. All patients had at least 10 years between initial surgery and reline at our institution. Primary outcomes revealed no type 1 or 3 endoleaks at follow-up, technical success was 100% and 1 patient required reintervention for aneurysm growth and type 2 endoleak. In terms of our secondary outcomes, there was 1 postoperative complication which was cardiac dysfunction secondary to demand ischemia, aneurysm-related mortality was 0% and all-cause mortality was 25% at average follow-up of 2.44 years. CONCLUSIONS: As individuals continue to age, there are more patients who would benefit from less invasive reinterventions following endovascular aneurysm repair. Whether this is due to aortic degeneration, stent migration, or stent material damage is not always known. In this study, we present an endovascular approach to treating type III endoleak patients with a previous graft and elevated aortic bifurcation using Ovation stent grafts and found no evidence of type 1 or 3 endoleaks on follow-up imaging. This approach may allow patients with type III endoleak the option of a minimally invasive, percutaneous approach where they previously would not have had one.

Third window lesions of the inner ear: A pictorial review.

PURPOSE: Radiographic review of pathologies that associate with third window syndrome. METHODS: Case series and literature review. RESULTS: Eight unique third window conditions are described and illustrated, including superior, lateral, and posterior semicircular canal dehiscence; carotid-cochlear, facial-cochlear, and internal auditory canal-cochlear dehiscence, labyrinthine erosion from endolymphatic sac tumor, and enlarged vestibular aqueduct. CONCLUSION: The present study highlights the characteristic imaging features and symptoms to differentiate third window pathologies for expedient diagnosis and management planning.

Use of surgical augmented intelligence maps can reduce radiation and improve safety in the endovascular treatment of complex aortic aneurysms.

OBJECTIVE: The introduction of endovascular procedures has revolutionized the management of complex aortic aneurysms. Although repair has traditionally required longer operative times and increased radiation exposure compared with simple endovascular aneurysm repair, the recent introduction of three-dimensional technology has become an invaluable operative adjunct. Surgical augmented intelligence (AI) is a rapidly evolving tool initiated at our institution in June 2019. In our study, we sought to determine whether this technology improved patient and operator safety. METHODS: A retrospective review of patients who had undergone endovascular repair of complex aortic aneurysms (pararenal, juxtarenal, or thoracoabdominal), type B dissection, or infrarenal (endoleak, coil placement, or renal angiography with or without intervention) at a tertiary care center from August 2015 to November 2021 was performed. Patients were stratified according to the findings from intelligent maps, which are patient-specific AI tools used in the operating room in conjunction with real-time fluoroscopic images. The primary outcomes included operative time, radiation exposure, fluoroscopy time, and contrast use. The secondary outcomes included 30-day postoperative complications and long-term follow-up. Linear regression models were used to evaluate the association between AI use and the main outcomes. RESULTS: During the 6-year period, 116 patients were included in the present study, with no significant differences in the baseline characteristics. Of the 116 patients, 76 (65.5%) had undergone procedures using AI and 40 (34.5%) had undergone procedures without AI software. The intraoperative outcomes revealed a significant decrease in radiation exposure (AI group, 1955 mGy; vs non-AI group, 3755 mGy; P = .004), a significant decrease in the fluoroscopy time (AI group, 55.6 minutes; vs non-AI group, 86.9 minutes; P = .007), a decrease in the operative time (AI group, 255 minutes; vs non-AI group, 284 minutes; P = .294), and a significant decrease in contrast use (AI group, 123 mL; vs non-AI group, 199 mL; P < .0001). No differences were found in the 30-day and long-term outcomes. CONCLUSIONS: The results from the present study have demonstrated that the use of AI technology combined with intraoperative imaging can significantly facilitate complex endovascular aneurysm repair by decreasing the operative time, radiation exposure, fluoroscopy time, and contrast use. Overall, evolving technology such as AI has improved radiation safety for both the patient and the entire operating room team.

Impact of Flow Reversal Duration on Neurological Outcomes of Transcarotid Artery Revascularization (TCAR).

BACKGROUNDS: Flow reversal is a key component of transcarotid artery revascularization (TCAR). However, the impact of flow reversal duration on neurological outcomes and the duration of flow reversal which optimizes TCAR's outcomes is not known. We evaluated the association of flow reversal time with the intraoperative and postoperative neurological outcomes of TCAR. METHODS: We studied all patients undergoing TCAR from September 2016 to October 2021. The exposure of interest was the duration of flow reversal. Multivariable logistic and fractional polynomial models were used to study the impact of flow reversal duration on in-hospital stroke, intraoperative neurological change/intolerance and stroke/death following TCAR and to identify the flow reversal time above which significant perioperative neurological events occur. RESULTS: The study included 19,462 patients with mean age of 73.4 years who were mostly Caucasian (91%) and male (63%). The mean flow reversal time was 10.7 minutes, and the overall stroke rate was 1.4%. The odds of intraoperative neurological change increased by 3.6% per minute increase in flow reversal time (odds ratio (OR), 1.04; 95%, 1.01-1.06; P < 0.002). Flow reversal duration >10 minutes was associated with 78% increased odds of neurological changes compared to flow reversal duration <10 minutes. There was no significant association between flow reversal duration and stroke, and stroke/death in the first 5 minutes after initiation of flow reversal. The odds of stroke increased by 2.7% per minute increase in flow reversal time >5 minutes (OR, 1.03; 95%, 1.01-1.04; P < 0.001), with flow reversal duration >10 minutes associated with 38% increased odds of stroke compared to flow reversal duration ≤10 minutes (OR, 1.37, 95% confidence interval (CI), 1.09-1.73, P = 0.006). The odds of stroke/death increased by 2.5% per minute increase in flow reversal time >5 minutes (OR, 1.03; 95%, 1.01-1.04; P < 0.001). Flow reversal duration >10 minutes was associated with 25% increased odds of stroke/death compared to flow reversal duration <10 minutes (OR, 1.25, 95% CI, 1.01-1.53, P = 0.038). Symptomatic status did not modify outcomes. CONCLUSIONS: Our findings suggest that outcomes following TCAR are optimal if the duration of flow reversal is minimized. A clinical cutoff time of 10 minutes is suggested by this study and recommended as a guide. Further studies targeted at the flow reversal component of TCAR are needed to solidify the evidence regarding the clinical effects of temporarily induced retrograde cerebral blood flow during TCAR.

Upper Extremity Access Has Worse Outcomes in F/BEVAR Using the VQI Dataset.

BACKGROUND: Physician-modified endografts and custom-manufactured devices use branched and fenestrated techniques (F/BEVAR) to repair complex aneurysms. Traditionally, many of these are deployed through a combination of upper and lower extremity access. However, with newer steerable sheaths, you can now simulate upper extremity (UEM) access from a transfemoral approach. Single-institution studies have demonstrated increased risks of access site complications and stroke when UEM access is used. This study compares outcomes after F/BEVAR in a national database between total transfemoral (TTF) access and mixed UEM access. METHODS: This study is an analysis of the Vascular Quality Initiative for all patients who underwent F/BEVAR from 2014 to 2021. Patients were stratified based on a TTF delivery of all devices versus any UEM access for deployment of target vessel stents. Primary outcomes included stroke, myocardial infarction (MI), and perioperative death. Secondary outcomes included access site hematoma, occlusion or embolization, operative time, fluoroscopy time, and technical success. Multivariable linear and logistic regression analyses were performed. RESULTS: Three thousand one hundred forty six patients underwent an F/BEVAR: 2,309 (73.4%) TTF and 837 (26.6%) UEM. Logistic regression analysis indicated a two-fold increased risk of death and MI and a three-fold increased risk of stroke in the UEM group. Furthermore, there is decreased operative time (221 vs. 297 min, P < 0.001) and fluoroscopy time (62 vs. 80 min, P < 0.001) in the TTF group and no difference in technical success between groups (96% vs. 97%, P = 0.159). Finally, there was a decrease in access site hematoma 2.54% vs. 4.31% (P = 0.013), access site occlusion 0.61% vs. 1.91% (P = 0.001), and extremity embolization 2.17% vs. 3.58% (P = 0.026) in the TTF versus UEM group. CONCLUSIONS: This study using Vascular Quality Initiative data demonstrates that patients who undergo an F/BEVAR using UEM access have an increased risk of perioperative MI, death, and stroke compared to TTF access.

Natural history of facial paraganglioma with 2 decades of follow-up: A case report and literature review.

OBJECTIVE: To report 20 years of natural history data for a facial paraganglioma and provide a comprehensive review of the existing literature. PATIENT: 81-year-old female with a remote history of cardiac arrest while under anesthesia who elected to observe her facial paraganglioma for 20 years. INTERVENTIONS: Observation, clinical documentation, radiographic surveillance. MAIN OUTCOME MEASURES: Tumor progression, patient symptomatology, and review of management options. RESULTS: The initial presentation of the facial paraganglioma was facial spasm. Over the course of observation, symptoms progressed to include complete facial nerve paralysis, pulsatile tinnitus, and otalgia on the affected side. Radiologic surveillance demonstrated incremental growth and erosion of surrounding structures, including the posterior external auditory canal, stylomastoid foramen, and lateral semicircular canal with near-dehiscence. Twenty-four cases of facial paraganglioma were identified in the extended literature search and are summarized herein. CONCLUSIONS: This unique case contributes to the scarce literature surrounding facial paragangliomas by reporting the extended natural history of this disease.

Predicted leukocyte telomere length and risk of germ cell tumours.

BACKGROUND: Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults. METHODS: Paediatric GCT samples were obtained from a Children's Oncology Group study and state biobank programs in California and Michigan (N = 1413 cases, 1220 biological parents and 1022 unrelated controls). Replication analysis included 396 adult testicular GCTs (TGCT) and 1589 matched controls from the UK Biobank. Mendelian randomisation was used to look at the association between genetically predicted LTL and GCTs and TERT variants were evaluated within GCT subgroups. RESULTS: We identified significant associations between TERT variants reported in previous adult TGCT GWAS in paediatric GCT: TERT/rs2736100-C (OR = 0.82; P = 0.0003), TERT/rs2853677-G (OR = 0.80; P = 0.001), and TERT/rs7705526-A (OR = 0.81; P = 0.003). We also extended these findings to females and tumours outside the testes. In contrast, we did not observe strong evidence for an association between genetically predicted LTL by other variants and GCT risk in children or adults. CONCLUSION: While TERT is a known susceptibility locus for GCT, our results suggest that LTL predicted by other variants is not strongly associated with risk in either children or adults.

Genetic drivers of Cushing's disease: Frequency and associated phenotypes.

PURPOSE: Cushing's disease (CD) is often explained by a single somatic sequence change. Germline defects, however, often go unrecognized. We aimed to determine the frequency and associated phenotypes of genetic drivers of CD in a large cohort. METHODS: We studied 245 unrelated patients with CD (139 female, 56.7%), including 230 (93.9%) pediatric and 15 (6.1%) adult patients. Germline exome sequencing was performed in 184 patients; tumor exome sequencing was also done in 27 of them. A total of 43 germline samples and 92 tumor samples underwent Sanger sequencing of specific genes. Rare variants of uncertain significance, likely pathogenic (LP), or pathogenic variants in CD-associated genes, were identified. RESULTS: Germline variants (13 variants of uncertain significance, 8 LP, and 11 pathogenic) were found in 8 of 19 patients (42.1%) with positive family history and in 23 of 226 sporadic patients (10.2%). Somatic variants (1 LP and 7 pathogenic) were found in 20 of 119 tested individuals (16.8%); one of them had a coexistent germline defect. Altogether, variants of interest were identified at the germline level in 12.2% of patients, at the somatic level in 7.8%, and coexisting germline and somatic variants in 0.4%, accounting for one-fifth of the cohort. CONCLUSION: We report an estimate of the contribution of multiple germline and somatic genetic defects underlying CD in a single cohort.

A Single Center Review of a Total Transfemoral Approach to Upper Extremity Access in Branched and Fenestrated Physician Modified Endografts.

BACKGROUND: Aortic aneurysms are normally treated by an endovascular approach. Due to the lack of devices and increasing experience, there is a growing number of complex aneurysms undergoing repair by physician modified endografts (PMEGs). Previously, our practice was to target visceral vessels exclusively through upper extremity access. We have since then shifted to an all transfemoral approach when possible. This study aims to show the operative benefits of transfemoral only approaches. METHODS: Patients who underwent a PMEG at a tertiary center between 2015 and 2020 were included. Patients were stratified into 2 groups based on branched vessel approach-transfemoral only versus axillary or composite (axillary and femoral). Forty-one patients had a pararenal or type IV thoracoabdominal aortic aneurysm (TAAA) and 15 patients had more complex TAAA. Primary outcomes were operative time, radiation exposure, fluoroscopy time, contrast, and blood loss. Secondary outcomes were 30-day mortality and major adverse events. Linear regression models were used to evaluate the association between approach type and the main outcomes. RESULTS: Fifty-six patients were included with 48% (n = 27) in the transfemoral group and 52% (n = 29) in the axillary/composite group. Baseline characteristics were similar between the groups. Intraoperative outcomes revealed significant increase in the average operative time (418 vs. 246 min, P < 0.001), in radiation exposure (2,755 vs. 1,740 mGy, P = 0.03), in fluoroscopy time (108 vs. 74 min, P = 0.01) and in blood loss (579 vs. 202 cc, P = 0.002) in the axillary/composite group compared to the transfemoral group. There was no significant difference in 30-day mortality or major adverse events including stroke. CONCLUSIONS: This study shows a transfemoral approach to complex endovascular aortic aneurysm repair as opposed to axillary/composite approach has decreased operative time, radiation exposure, and fluoroscopy time and no significant differences in 30-day mortality or major adverse events. When treating complex aneurysms, improving efficiency is important to minimize morbidity to patients and operators.

Evaluation of hearing loss in young adults after exposure to 3.0T MRI with standard hearing protection.

Standard clinical protocols require hearing protection during magnetic resonance imaging (MRI) for patient safety. This investigation prospectively evaluated the auditory function impact of acoustic noise exposure during a 3.0T MRI in healthy adults. Twenty-nine participants with normal hearing underwent a comprehensive audiologic assessment before and immediately following a clinically indicated head MRI. Appropriate hearing protection with earplugs (and pads) was used per standard of practice. To characterize noise hazards, current sound monitoring tools were used to measure levels of pulse sequences measured. A third audiologic test was performed if a significant threshold shift (STS) was identified at the second test, within 30 days post MRI. Some sequences produced high levels (up to 114.5 dBA; 129 dB peak SPL) that required hearing protection but did not exceed 100% daily noise dose. One participant exhibited an STS in the frequency region most highly associated with noise-induced hearing loss. No participants experienced OSHA-defined STS in either ear. Overall, OAE measures did not show evidence of changes in cochlear function after MRI. In conclusion, hearing threshold shifts associated with hearing loss or OAE level shifts reflecting underlying cochlear damage were not detected in any of the 3.0T MRI study participants who used the current recommended hearing protection.

Outcomes of transcarotid artery revascularization with dynamic flow reversal in patients with contralateral carotid artery occlusion.

BACKGROUND: The outcomes of carotid revascularization in patients with contralateral carotid artery occlusion (CCO) are controversial. CCO has been defined by the Centers for Medicare and Medicaid Services as a high-risk criterion and is used as an indication for transfemoral carotid artery stenting. With the promising outcomes associated with transcarotid artery revascularization (TCAR), we aimed to study the perioperative outcomes of TCAR in patients with CCO and to assess the feasibility of TCAR in these high-risk patients. METHODS: All patients in the Vascular Quality Initiative database who underwent TCAR with flow reversal between September 2016 and May 2019 were included. Patients with trauma, dissection, or more than two treated lesions were excluded. Univariable and multivariable logistic analyses were used to compare the primary outcome of in-hospital stroke or death after TCAR in patients with CCO and those without CCO (patent and <99% stenosis). Secondary outcomes included intraoperative neurologic changes and the individual outcomes of in-hospital stroke, death, and myocardial infarction as well as 30-day mortality. RESULTS: A total of 5485 TCAR cases were included, of which 593 (10.8%) had CCO. In patients with CCO, mean flow reversal time was shorter (10.1 ± 6.7 minutes vs 11.1 ± 7.8 minutes; P < .01); intraoperative neurologic changes occurred in 1% of these patients compared with 0.7% of those with patent contralateral carotid arteries (P = .43). On univariable analysis, no significant difference in in-hospital stroke or death was shown between patients with and patients without CCO (1.7% vs 1.5%; P = .65). Similarly, no significant differences were noted between the groups in terms of in-hospital death (0.7% vs 0.4%; P = .27), stroke (1.7% vs 1.2%; P = .32), and stroke/death/myocardial infarction (2.2% vs 1.8%; P = .53) as well as 30-day mortality (0.8% vs 0.6%; P = .55). The results remained statistically nonsignificant after adjustment for baseline differences between the groups; the adjusted odds ratio (OR) of in-hospital stroke/death in patients with CCO compared with those with patent contralateral carotid arteries was not significant (OR, 1.39; 95% confidence interval, 0.65-3.0; P = .40). In symptomatic patients presenting with prior stroke, CCO was associated with significantly higher odds of stroke or death (OR, 4.63; 95% confidence interval, 1.39-15.4; P = .01) compared with no CCO. On the other hand, in asymptomatic patients, no significant difference in outcomes was observed between the groups. CONCLUSIONS: In this analysis, TCAR seems to be safe in patients with CCO. Caution should be taken in symptomatic patients with CCO and a history of prior stroke as they might have worse outcomes compared with patients with patent contralateral carotid arteries. Studies with larger sample size and longer follow-up are needed to assess the perioperative and long-term outcomes of TCAR in patients with CCO in comparison to other procedures.

Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.

Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired-end exome sequencing in 26 child/mother/father trios. Three children had rare (allele frequency ≤ 0.0001 in several public databases) inherited variants in TSPAN4, one with a loss-of-function variant and two with missense variants. Two children had loss-of-function variants in TUBE1. Four children had rare missense or nonsense variants (one per child) in WNT3, CRKL, MYH9, or LZTR1, genes previously associated with BE. We detected 17 de novo missense variants in 13 children and three de novo loss-of-function variants (AKR1C2, PRRX1, PPM1D) in three children (one per child). We also detected rare compound heterozygous loss-of-function variants in PLCH2 and CLEC4M and rare inherited missense or loss-of-function variants in additional genes applying autosomal recessive (three genes) and X-linked recessive inheritance models (13 genes). Variants in two genes identified may implicate disruption in cell migration (TUBE1) and adhesion (TSPAN4) processes, mechanisms proposed for BE, and provide additional evidence for rare variants in the development of this defect.

Clinical 7-T MRI for neuroradiology: strengths, weaknesses, and ongoing challenges.

Since the relatively recent regulatory approval for clinical use in both Europe and North America, 7-Tesla (T) MRI has been adopted for clinical practice at our institution. Based on this experience, this article reviews the unique features of 7-T MRI neuroimaging and addresses the challenges of establishing a 7-T MRI clinical practice. The underlying fundamental physics principals of high-field strength MRI are briefly reviewed. Scanner installation, safety considerations, and artifact mitigation techniques are discussed. Seven-tesla MRI case examples of neurologic diseases including epilepsy, vascular abnormalities, and tumor imaging are presented to illustrate specific applications of 7-T MRI. The advantages of 7-T MRI in conjunction with advanced neuroimaging techniques such as functional MRI are presented. Seven-tesla MRI produces more detailed information and, in some cases, results in specific diagnoses where previous 3-T studies were insufficient. Still, persistent technical issues for 7-T scanning present ongoing challenges for radiologists.

Resurrection of Chronically Occluded Prosthetic Bypass Grafts in a Single Stage with Suction Thrombectomy and Intervention.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) continues to be a vexing problem despite the advent of endovascular techniques augmenting traditional open repair. At our institution, we have found there is a growing number of patients with PAOD who are vein-challenged and have undergone prosthetic bypass previously for infrainguinal arterial reconstruction. When occluded, these grafts have been abandoned for a new bypass strategy or amputation. We present a novel technique of reestablishing flow through chronically occluded prosthetic bypass grafts. METHODS: A retrospective review of a prospectively maintained database compiled at 2 institutions between 2016 and 2019 was performed. Six patients had previous prosthetic bypass grafts with 4 patients having femoral to popliteal grafts, 1 patient with a femoral to femoral graft, and 1 with a femoral to posterior tibial bypass graft. All patients had an attempted single-stage intervention to clear chronically occluded grafts. RESULTS: A total of 6 patients were included in the study. Indications for intervention were chronic, critical limb ischemia with tissue loss (3), severe claudication (2), and acute on chronic limb ischemia (1). Average time from bypass to suction thrombectomy was 29 months (6-60 months). Mean patency duration is 13 months (1-28 months). Adjunctive procedures include overnight lysis to improve outflow in 1 patient (16.6%), drug-coated balloon angioplasty (83.3%), or stents (83.3%). There were no embolic complications during these procedures. All (2) wounds healed and all are maintained on full-dose anticoagulation and/or antiplatelet therapy. CONCLUSIONS: Often, the timing of bypass graft occlusion is unknown, and the risk of embolism with lysis for chronically occluded bypass grafts is concerning with traditional peripheral intervention techniques. We report a new and unique minimally invasive approach to resurrect chronically occluded prosthetic bypass grafts often successful in just one stage. This tool offers an alternative technique for limb salvage in complex patients and as use increases, requires further interrogation.

Common Iliac Artery Aneurysm Repair with Hypogastric Preservation via Balloon-Expandable Covered Stents Using the Eyelet Technique-Iliac Branched Devices Still Inappropriate in Many Patients.

BACKGROUND: Common iliac artery aneurysms (CIAAs) are seen in 20-40% of patients with abdominal aortic aneurysms. Historically treated with sacrifice of the hypogastric artery, which can result in significant morbidity related to pelvic ischemia, new devices have made hypogastric artery preservation more feasible but are only applicable to a small subset of aneurysm anatomy. We sought to assess the safety and efficacy or a novel technique for hypogastric artery preservation applicable to a wider variety of patients with CIAAs. METHODS: We conducted a retrospective review of a prospectively maintained database of all patients with CIAAs treated with a novel endovascular technique at the UC San Diego Sulpizio Cardiovascular Center or the San Diego Veterans Affairs Hospital between March 2016 and December 2017. The endovascular technique involved stent placement in both the internal and external iliac arteries, with balloon expansion to minimize gutters between the endografts. Primary end points included technical success, limb patency, and presence of endoleaks (ELs). RESULTS: A total of 14 limbs (12 patients) were treated for CIAAs with 100% technical success and limb patency at an average of 6.8 months of follow-up. No patients experienced type I or type III ELs or evidence of pelvic ischemia. Two patients required reintervention, and one patient died of causes unrelated to the procedure. CONCLUSIONS: This technique was performed with excellent short- and mid-term safety in patients with varying aneurysm anatomy. The high rates of technical success and low rate pelvic ischemia represent improvement over conventional techniques that sacrifice the hypogastric artery and warrant further testing in a larger patient series with longer term follow-up.

The importance of imaging in diagnosis of infected otogenic pneumatoceles.

OBJECTIVE: Spontaneous otogenic pneumatocele is a rare entity resulting from a pressure gradient between a dehiscent temporal bone and the intracranial space. Secondary infection can ensue in patients with concurrent otomastoiditis. The current study discusses the clinical presentation and imaging characteristics of two cases of secondarily infected otogenic pneumatoceles. STUDY DESIGN: Case series. RESULTS: Two patients were diagnosed with a temporal lobe abscess in the setting of otogenic pneumatocele. Diagnosis was aided by both CT and MRI demonstrating a diffusion restricting lesion within brain parenchyma in association with free air in close proximity to an underlying tegmen defect. CONCLUSION: Prompt diagnosis of a secondarily infected otogenic pneumatocele with CT and MRI allows for surgical drainage with closure of the tegmen defect to prevent further complications and recurrence.

Absent pyramidal eminence and stapedial tendon associated with congenital stapes footplate fixation: Intraoperative and radiographic findings.

OBJECTIVE: Report an association between congenital stapes footplate fixation (CSFF) and radiological absence of the pyramidal eminence and stapedial tendon. PATIENTS: Children and adults with intraoperatively confirmed CSFF and an absent stapedial tendon. INTERVENTIONS: Computed tomography (CT); exploratory tympanotomy with stapedotomy. MAIN OUTCOME MEASURES: Absence of a pyramidal eminence and stapedial tendon aperture identified on preoperative CT that was confirmed intraoperatively. RESULTS: Eight patients with intraoperative confirmation of CSFF and absent stapedial tendon were retrospectively identified. The average preoperative bone conduction and air conduction pure tone averages were 19.6 dB (SD 15.6 dB) and 55.9 dB (SD 23.6 dB), respectively. The average air-bone gap was 36.3 dB (SD 17.9 dB) preoperatively. In the seven patients who underwent preoperative CT, all were consistently identified to have an absent or hypoplastic pyramidal eminence and absent stapedial tendon aperture at the pyramidal eminence. In six cases, the stapedial footplate appeared normal, while in one case the footplate appeared abnormal which correlated with severe facial nerve prolapse observed intraoperatively. All eight cases underwent exploratory tympanotomy and demonstrated intraoperative stapes footplate fixation, absent stapedial tendon and either absent or hypoplastic pyramidal eminence, which correlated with preoperative CT findings. CONCLUSIONS: This study identifies a clinically pragmatic association between an absent pyramidal eminence identified on high-resolution CT and the diagnosis of CSFF. In a condition that otherwise generally lacks distinctive radiological features, the absence of a pyramidal eminence on CT in a patient with nonprogressive, congenital conductive hearing loss may strengthen clinical suspicion for CSFF.