Citations

Introduction: Percutaneous nephrolithotomy (PCNL) has been a mainstay treatment for large stone burdens since the 1980s, historically offering improved stone-free rates over retrograde intrarenal surgery (RIRS). Gaining optimal access into the renal collecting system can be challenging, requiring advanced skills or interventional radiology assistance. The learning curve for fluoroscopic and ultrasonography access can be steep, with only a minority of PCNL access performed by urologists in the United States. This study compares robotic-assisted electromagnetic (EM) guidance to traditional fluoroscopy for obtaining percutaneous renal access between cohorts of novice and expert urologists. Methods: Ten novices and five expert urologists used robotic-assisted EM guidance to obtain access in a modified supine position compared with using fluoroscopy in a traditional prone position in human cadavers. Primary success was defined as papillary access. Performance metrics, including number of puncture attempts, time to access, radiation exposure, and participant confidence, were compared between novices and experts. Results: Robotic-assisted EM guidance improved success rates for both novices (100% vs 70%) and experts (93% vs 87%) compared with fluoroscopy. Novices showed greater accuracy using robotic assistance (97% vs 37%). The number of insertion attempts decreased with robotic guidance for both groups (novices: 3.42 ± 0.44 vs 1.47 ± 0.19; experts: 2.13 ± 0.36 vs 1.40 ± 0.24; p < 0.002). EM guidance ( p < 0.05) and experience ( p < 0.05) significantly reduced the time from needle insertion to access (novices: 12.86 ± 2.41 minutes vs 4.49 ± 0.96 minutes; experts: 4.90 ± 1.40 minutes vs 4.09 ± 1.12 minutes). Radiation exposure was notably lower with EM guidance (novices, 1.12 ± 0.17 mGy vs 4.86 ± 0.70 mGy; experts, 0.69 ± 0.12 mGy vs 4.11 ± 1.21 mGy; p < 0.001). Novices felt more confident (5[3–5] vs 2[1–4], p < 0.001) and at ease (5[3–5] vs 2.75[1–3], p < 0.001) with EM guidance. Conclusion: Robotic-assisted EM guidance improves percutaneous access success, reduces attempts and radiation exposure, and enhances novice confidence and accuracy. This technology could enable urologists to more effectively and safely perform PCNL, especially for less experienced practitioners.

ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P &amp;lt; .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P &amp;lt; .001]; ADNI: t = 9.1 [P &amp;lt; .001]; HABS: t = 5.4 [P &amp;lt; .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P &amp;lt; .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism ( MACROD2 ), development ( NEDD4 ), and mental retardation ( UBE2A ) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.