Bott, Matthew J.

Background The use of 3D imaging with navigation bronchoscopy has increased with the introduction of mobile cone-beam CT (mCBCT). Shape-sensing robotic-assisted bronchoscopy (ssRAB) integrated with mCBCT has been introduced to correct for CT to body divergence (CT-BD) during the biopsy of peripheral pulmonary nodules (PPNs). Methods Prospective observational multicentre study, enrolling patients with a PPN of ≤20 mm suspicious for malignancy, assessing tool-in-lesion (TIL), diagnostic yield, sensitivity for malignancy and incidence of pneumothorax or airway bleeding. Non-malignant index biopsies were followed for 12 months. Descriptive statistics are reported for all variables along with 95% CI for primary endpoints. Results 155 consecutive patients were enrolled at six centres. Median nodule size was 14.0 mm (IQR 11.0–17.0), with 54.8% of nodules (85/155) in the upper lobes, 25.8% (40/155) with CT bronchus sign present and median distance to the nearest pleural surface of 8.2 mm (IQR 1.8–20.0). TIL was achieved in 154/155 (99.4%, 95% CI 96.5 to 100.0) procedures. A median of two (IQR 1–3) mCBCT spins were performed, with median dose area product of 25.7 Gy · cm 2 (IQR 11.0–46.7). Diagnostic yield per the American Thoracic Society/American College of Chest Physicians (ATC/ACCP) definition was 89.0% (n=138/155; 95% CI 83.0 to 93.5) and sensitivity for malignancy was 91.5% (95% CI 86.4 to 96.5). No pneumothorax (0%, 95% CI 0.0 to 2.4) and two Nashville Grade three bleeding events were reported (1.3%, 95% CI 0.2 to 4.6). Interpretation The first prospective multicentre study of integrated ssRAB and mCBCT for small peripheral nodules resulted in diagnostic outcomes similar to those reported for transthoracic biopsy with a more favourable safety profile. Trial registration number ClinicalTrials.gov ID: NCT05562895 .

Abstract Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation). We used embryonic stem cells as a tool to study EXOSC2 function as the aging trait epigenetic memory determined in A-iPSC because these aging traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of EXOSC2 and this regulation is preserved in stem cells and cancer.