Early comparison robotic bronchoscopy versus electromagnetic navigational bronchoscopy for biopsy of pulmonary nodules in a thoracic surgery practice.

Pulmonary nodules are frequently encountered in high-risk patients. Often these require biopsy which can be challenging. We relate our experience comparing use of electromagnetic navigational bronchoscopy (ENB) to a robotic bronchoscopy system (RB). A retrospective review of patients undergoing bronchoscopic biopsy from 2015 to 2021. The timeframe overlapped with transition from ENB using Veran SPiN system to RB using Ion system by Intuitive. Patient and nodule characteristics were collected. Primary end point was overall diagnostic yield which was defined by pathologic confirmation of malignancy or benign finding. Secondary outcomes included diagnostic yield based on overall size of nodules and need for further work up and testing. 116 patients underwent ENB or RB of 134 nodules. No perioperative complications occurred. Diagnostic yield of ENB was 49.5% (41/91 nodules) versus 86.1% (37/43 nodules) for RB. Average nodule size for ENB was 2.55 cm versus 1.96 cm for RB. When divided based on size, ENB had a 30% diagnostic yield for nodules 1-2 cm (11/37 nodules, mean size 1.46 cm) and 64% yield for nodules 2-3 cm (14/22 nodules, mean size 2.38 cm). RB had an 81% yield for nodules 1-2 cm (mean size 1.41 cm) and 100% yield for nodules 2-3 cm (mean 2.3 cm). RB showed superiority over ENB in early implementation trials for biopsy of suspicious pulmonary nodules. It is a safe technology allowing for increased access to all lung fields and utilization in the thoracic surgical practice will be paramount to advancing the field.

A pilot investigation of the tricuspid valve annulus in newborns with hypoplastic left heart syndrome.

Objective: Hypoplastic left heart syndrome (HLHS) is a congenital disease characterized by an underdevelopment of the anatomical components inside the left heart. Approximately 30% of HLHS newborns will develop tricuspid regurgitation (TR), and it is currently unknown how the valve annulus mechanics and geometry are associated with regurgitation. Thus, we present an engineering mechanics-based analysis approach to quantify the mechanics and geometry of the HLHS-afflicted tricuspid valve (TV), using 4-dimensional echocardiograms. Methods: Infants born with hypoplastic left heart syndrome (n=8) and healthy newborns (n=4) had their tricuspid valves imaged, and the data was imported to the 3D Slicer. The annular curves were defined at five points in the cardiac cycle. The geometry and deformation (strain) of the TV annulus were calculated to elucidate the mechanics of this critical structure, and compare them between HLHS and normal neonates. Results: For the annular geometry, HLHS-afflicted newborns had significantly larger annular circumferences (20-30%) and anterior-posterior diameters (35-45%) than the healthy patients. From a biomechanics perspective, the HLHS patients had significantly smaller strains in the anterior segments (-0.1±2.6%) during end diastolic and end isovolumetric relaxation (1.7±3.0%) compared to the healthy counterparts (-13.3±2.9% and 6.8±0.9%, respectively). Conclusions: The image-based analysis in this study may provide novel insights into the geometric and mechanistic differences in the TV annulus between healthy and HLHS newborns. Future longitudinal studies of the biomechanics of TV annulus and other subvalvular structures may inform our understanding of the initiation and development of TR and the design of optimal repairs in this challenging population.

Whole-exome sequencing for variant discovery in blepharospasm.

BACKGROUND: Blepharospasm (BSP) is a type of focal dystonia characterized by involuntary orbicularis oculi spasms that are usually bilateral, synchronous, and symmetrical. Despite strong evidence for genetic contributions to BSP, progress in the field has been constrained by small cohorts, incomplete penetrance, and late age of onset. Although several genetic etiologies for dystonia have been identified through whole-exome sequencing (WES), none of these are characteristically associated with BSP as a singular or predominant manifestation. METHODS: We performed WES on 31 subjects from 21 independent pedigrees with BSP. The strongest candidate sequence variants derived from in silico analyses were confirmed with bidirectional Sanger sequencing and subjected to cosegregation analysis. RESULTS: Cosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. Deleterious variants in HS1BP3 (NM_022460.3: c.94C>A, p.Gly32Cys) and GNA14 (NM_004297.3: c.989_990del, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio-cervical dystonia first manifest as BSP. Deleterious variants in DNAH17, TRPV4, CAPN11, VPS13C, UNC13B, SPTBN4, MYOD1, and MRPL15 were found in two or more independent pedigrees. To our knowledge, none of these genes have previously been associated with isolated BSP, although other CACNA1A mutations have been associated with both positive and negative motor disorders including ataxia, episodic ataxia, hemiplegic migraine, and dystonia. CONCLUSIONS: Our WES datasets provide a platform for future studies of BSP genetics which will demand careful consideration of incomplete penetrance, pleiotropy, population stratification, and oligogenic inheritance patterns.