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Expert Strategies: Skull Base Reconstruction-Global Perspectives, Insights, and Algorithms through a Mixed Methods Approach
No full textOBJECTIVE: There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence.
METHODS: Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted.
RESULTS: A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low-flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized.
CONCLUSION: Skull base reconstruction and post-ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences
Optimizing Dose Reduction to the Left Anterior Descending Artery in Patients With Locally Advanced Lung Cancer Treated With Definitive Radiation Therapy: A Feasibility Study of Coplanar Treatments Using Double-Stacked Multileaf Collimator
No full textPURPOSE: Recent studies have shown that cardiac substructures and particularly left anterior descending artery (LAD) dose strongly correlates with the incidence of late adverse cardiac events. We evaluated whether greater cardiac and, importantly, LAD dose sparing could be achieved using a newly introduced closed bore (O-ring gantry) linac with a double-stacked multileaf collimator (Varian Ethos) relative to conventional linacs.
METHODS AND MATERIALS: Twenty patients with locally advanced non-small cell lung cancer previously treated with definitive chemoradiotherapy were retrospectively evaluated. Volumetric modulated arc therapy plans were retrospectively generated for the Ethos system using optimization criteria focused on reducing overall heart and LAD doses (Heart_Ethos). Plans were also reoptimized using the same optimization criteria on a conventional C-arm linac (Heart_TB). Investigational plans were compared with the original plans and with each other using standard dose-volume histogram metrics such as percentage (V) volume receiving a specific dose (x) in Gy (Vx) or mean dose (Dmean) in Gy.
RESULTS: Statistically significant decreases existed between the Heart_Ethos and original plans for mean heart dose (11.3 vs 14.8 Gy; P \u3c .001) and V5, V30, and V50 (63.6% vs 75.2%; P \u3c .001, 7.1% vs 12.3%; P \u3c .001, 2.1% vs 2.9%; P = .03, respectively) and also for LAD mean dose (4.8 Gy vs 12.0 Gy [P \u3c .001]) and V15 (4.9% vs 21.5%; P \u3c .001). Compared with Heart_TB, Heart_Ethos plans had significantly less mean heart dose (11.6 vs 12.2 Gy; P = .006), and less heart V5 (64.4% vs 67.2%; P = .049) and V30 (7.7% vs 8.8%; P = .03), whereas other parameters were not significant. Optimal target coverage and other organs at risk constraints were maintained for all generated plans.
CONCLUSIONS: Heart_Ethos plans showed significant reduction in cardiac and LAD doses in comparison to the original plans while maintaining target and organ at risk goals. Our findings suggest that Ethos technology has the potential for better cardiac toxicity safety because Heart_Ethos plans were still able to reduce cardiac dose compared with Heart_TB plans
A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes
No full textBACKGROUND: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in failed repair states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.
METHODS: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.
RESULTS: In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. Both PC1 and PC3 correlated with reduced survival, with PC1 effects strongly increasing over time whereas PC3 effects were independent of time. In this model, we studied the expression of 12 new gene sets annotated in single-nucleus RNA-sequencing studies of epithelial cells with failed repair in native kidneys. The new gene sets reflecting epithelial-mesenchymal transition correlated with injury PC1 and PC3, lower estimated glomerular filtration rate, higher donor age, and future failure as strongly as any gene sets previously derived in transplants and were independent of nephron segment of origin and graft rejection.
CONCLUSION: These results suggest 2 dimensions in the kidney transplant response to injury: PC1, AKI-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and PC3.
TRIAL REGISTRATION: INTERCOMEX (ClinicalTrials.gov NCT01299168); Trifecta-Kidney (ClinicalTrials.gov NCT04239703).
FUNDING: Genome Canada; Natera, Inc.; and Thermo Fisher Scientific
Limited-Access Zero-Contrast BASILICA Transcatheter Aortic Valve Replacement
No full textOBJECTIVE: Severe anaphylactic reactions to intra-arterial contrast agents, access site limitations, and high-risk coronary artery occlusion may all possibly prohibit the success of a transcatheter aortic valve replacement (TAVR). We describe a case including all 3 of these components and demonstrate the importance of multimodality imaging, including computed tomography (CT), fluoroscopy, and trans-esophageal echocardiography (TEE).
KEY STEPS: 1) Obtain orthogonal BASILICA angle from CT. 2) Set up a single femoral access for BASILICA and subsequent TAVR. 3) Place a coronary wire with the radial opaque part at the noncoronary cusp (NCC) from an ulnar artery. 4) Perform TEE with fluoroscopic guidance on BASILICA without intra-arterial contrast agent. 5) Use coronary wire as a marker at the NCC to facilitate TAVR deployment.
POTENTIAL PITFALLS: A single wire at cusp level minimizes the need to use a multiple pigtail technique. In general, cerebral protection devices are commonly used in leaflet modification procedures such as BASILICA to reduce stroke risk. In view of limited access, it was not feasible in this case to use them. Despite no intra-arterial contrast being used, pre-TAVR CT still requires an intravenous contrast agent for CT planning.
TAKE-HOME MESSAGE: In a case of limited access, high coronary occlusive risk, and anaphylactic reaction to contrast agents, a limited-access zero-contrast agent BASILICA TAVR is a feasible approach with the use of multimodality imaging
An Evolving Frontier: Left Transjugular Access for Transcatheter Tricuspid Valve Replacement With EVOQUE
No full textPredicting memory decline from left temporal lobe epilepsy surgery using preoperative fMRI: a multicenter study
No full textOBJECTIVE: While fMRI language laterality has been used to predict verbal memory after epilepsy surgery, supporting evidence is not yet definitive. The FMRI in Anterior Temporal Epilepsy Surgery (FATES) project was a prospective observational cohort study at 10 US epilepsy centers, performed to determine whether a multivariable model including fMRI language laterality can predict verbal memory outcome 6 months after left temporal lobe epilepsy surgery.
METHODS: This analysis includes 70 adults who underwent left temporal lobe epilepsy surgeries including hippocampal resection for treatment of epilepsy. Patients completed standard protocols, including preoperative fMRI language mapping with a semantic decision versus tone decision (SDTD) task contrast and preoperative and postoperative verbal memory assessment. Five memory measures, obtained from the Selective Reminding Test, Rey Auditory Verbal Learning Test, and Wechsler Memory Scale, were selected to cover a range of episodic memory tasks including word list learning, delayed list recall, and story recall. Multiple linear regression was performed using the preoperative memory score, duration of epilepsy, age at epilepsy onset, age at surgery, hippocampal sclerosis status, and fMRI SDTD laterality index (LI) as predictor variables for 6-month postoperative verbal memory change.
RESULTS: Across different memory measures, decline (defined using Reliable Change Index) was seen in 8%-28% of patients. Changes on all five memory measures were significantly correlated with preoperative score, epilepsy duration, and fMRI SDTD LI. Variance explained by linear regression models for each test ranged from 34%-41%, with fMRI LI independently accounting for 7%-25% of the total variance (all p \u3c 0.05). Cross-validation accuracy for predicting change scores in independent held-back samples ranged from 0.54-0.75 standard deviations of the preoperative sample.
SIGNIFICANCE: We demonstrate that models incorporating fMRI language LIs from a semantic decision task trained to predict verbal memory decline after left temporal lobe surgery provide meaningful information to help inform patients of the risk associated with left temporal lobe surgery and are practical to implement in different hospital settings. This confirms previous limited evidence that fMRI-based preoperative language protocols can be used to predict verbal episodic memory outcome after left temporal lobe epilepsy surgery
In vivo measurement of vertebral deformation using digital tomosynthesis based digital volume correlation
No full textVertebral fractures are the most common type of osteoporotic fracture and associated with significant complications. Timely intervention is important to prevent vertebral fractures, however the current standard for assessing osteoporosis (bone mineral density) is not fully accurate for identifying at-risk individuals. Inspired by a laboratory technique combining microcomputed tomography with mechanical loading for mechanical assessment of extracted bone structures, digital tomosynthesis-based digital volume correlation (DTS-DVC) uses supine and standing DTS images of patients in combination with DVC. The current study evaluated in vivo precision errors, and the utility of DTS-DVC in identifying mechanically compromised vertebrae. Seven patients with vertebral fracture (Fx) and twelve without (NFx) were DTS-imaged, and endplate-to-endplate displacement, stiffness, compliance, and endplate distribution statistics were calculated using supine reference images and images acquired in supine, standing, standing while holding added weight. The in vivo measurement error of DTS-DVC metrics and the extent to which DTS-DVC can measure differences in vertebrae due to loading and presence of vertebral deformity (vertebral fracture) were examined. Total measurement error was low (0.017-0.019 mm), and all measured parameters changed with loading (p \u3c 0.0001 to p \u3c 0.05). Endplate-to-endplate displacement and displacement heterogeneity were significantly higher in fractured vs adjacent intact vertebrae. There were large differences in DVC variables between intact L1 vertebrae of Fx and NFx groups; however, these were not statistically demonstrable. Collectively, results support the in vivo feasibility of DTS-DVC and warrant further investigation. A biomechanics-based assessment of vertebral bone quality is expected to improve our understanding and clinical assessment of vertebral fracture risk
Urothelial carcinoma with osteoclast-like giant cells: An expanded immunohistochemical and molecular profile
No full textOBJECTIVE: Osteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is a rare tumor currently classified under the poorly differentiated urothelial carcinoma subtype. This study aimed to evaluate the clinicopathologic, immunophenotypic, and molecular features of UCOGC to better characterize its origin and support its classification as a unique subtype.
METHODS: There were 14 UCOGCs studied with immunohistochemistry/in situ hybridization and compared to urothelial carcinomas with trophoblastic differentiation (n = 6) and giant cell urothelial carcinomas (n = 5). Markers were assessed in mononuclear (MN) and giant cell (GC) components. Next-generation sequencing was performed on 4 UCOGCs.
RESULTS: The MN cells of UCOGC demonstrated high expression of CD68, CD163, SATB2, cathepsin K, and CSF1 in situ hybridization (ISH), with moderate staining for GATA3, p63, and PU.1 and low staining for pankeratin. The GCs showed high CD68, PU.1, and cathepsin K expression but low CD163, SATB2, and CSF1 ISH, with no staining for urothelial markers or pankeratin. Both MN and GC were negative for H3.G34W and HCG. Next-generation sequencing revealed mutations consistent with conventional urothelial carcinomas.
CONCLUSIONS: The distinct biphasic morphology, characteristic immunophenotype, and molecular findings of UCOGC suggest it is of urothelial origin, and we believe it justifies its classification as a unique subtype rather than under poorly differentiated urothelial carcinoma
Fenestrated/branched endovascular aortic repair after failed endovascular aortic repair has similar perioperative outcomes to primary repairs
No full textOBJECTIVE: To evaluate the outcomes of fenestrated-branched endovascular aneurysm repair (FB-EVAR) in patients undergoing reintervention for failed EVAR compared with those undergoing primary FB-EVAR.
METHODS: Patients undergoing FB-EVAR between 2014 and 2024 were identified in the Vascular Quality Initiative database. Patients were then divided into two groups, those undergoing FB-EVAR after failed EVAR and those undergoing primary FB-EVAR. Baseline characteristics, operative details, and outcomes were compared between groups. Primary outcomes included mortality, reintervention, and endoleak (EL) (type I/III) rates. Secondary outcomes included perioperative complications. Kaplan-Meier survival analysis and Cox regression were used to evaluate 1-year outcomes.
RESULTS: A total of 2067 patients were included in this study; 386 (18.6%) underwent FB-EVAR after failed EVAR, and 1681 (81.4%) underwent primary FB-EVAR. In the failed EVAR group, perioperative mortality (3.1% vs 4%; P = .934) and rates of type I/III endoleaks (6.5% vs 8.6%; P = .164) were comparable with that of no prior EVAR. At the 12-month follow-up, mortality rates remained similar (17.2% vs 15.8%; P = .265), However, patients with prior EVAR had a significantly higher reintervention rates (hazard ratio, 1.60; 95% confidence interval, 1.10-2.35; P = .015), despite similar mortality and EL rates.
CONCLUSIONS: FB-EVAR is a safe and effective reintervention strategy after failed EVAR, achieving similar mortality and EL outcomes compared with primary FB-EVAR. However, the significantly higher reintervention rates in patients with prior EVAR may be related to the increased complexity this population
