Feasibility of MALDI-MSI-Based Proteomics Using Bouin-Fixed Pathology Samples: Untapping the Goldmine of Nephropathology Archives

The application of innovative spatial proteomics techniques, such as those based upon matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology, has the potential to impact research in the field of nephropathology. Notwithstanding, the possibility to apply this technology in more routine diagnostic contexts remains limited by the alternative fixatives employed by this ultraspecialized diagnostic field, where most nephropathology laboratories worldwide use bouin-fixed paraffin-embedded (BFPE) samples. Here, the feasibility of performing MALDI-MSI on BFPE renal tissue is explored, evaluating variability within the trypsin-digested proteome as a result of different preanalytical conditions and comparing them with the more standardized formalin-fixed paraffin-embedded (FFPE) counterparts. A large proportion of the features (270, 68.9%) was detected in both BFPE and FFPE renal samples, demonstrating only limited variability in signal intensity (10.22-10.06%). Samples processed with either fixative were able to discriminate the principal parenchyma regions along with diverse renal substructures, such as glomeruli, tubules, and vessels. This was observed when performing an additional "stress test", showing comparable results in both BFPE and FFPE samples when the distribution of several amyloid fingerprint proteins was mapped. These results suggest the utility of BFPE tissue specimens in MSI-based nephropathology research, further widening their application in this field

Long-term morphofunctional remodeling of internal thoracic artery grafts: a frequency-domain optical coherence tomography study

BACKGROUND: Internal thoracic arteries (ITAs) are frequently anastomosed to the coronary circulation for bypass grafting. The purpose of this research was to investigate in vivo the long-term morphofunctional changes of ITAs after their use as coronary artery bypass conduits, by comparing the morphological features and vasoreactivity of the grafted left ITA (LITA) with the native, nonharvested right ITA (RITA) in the same patient. METHODS AND RESULTS: At least 10 years after surgery, in 10 patients, LITA graft and nonharvested RITA were assessed by quantitative angiography and frequency-domain optical tomography. Endothelium-dependent and independent vasodilation was tested by selective infusion of acetylcholine and isosorbide dinitrate. Quantitative angiography showed that baseline mean diameter of LITA graft was significantly smaller than that of RITA (2.59 mm [2.29-3.04] versus 3.05 mm [2.75-3.32]; P=0.01). LITA showed a significant intimal thickening (P=0.05) and a nonsignificant medial thinning (P=0.22) compared with RITA, leading to an increased intima-media ratio (intima-media ratio, 0.72 [0.53-0.91] versus 0.23 [0.12-0.38]; P=0.02). The intima-media ratio correlated inversely with the vasodilatatory response in RITA (r=-0.68, P=0.03 for acetylcholine and r=-0.62, P=0.05 for isosorbide dinitrate) but not in LITA (r=-0.18, P=0.63 for acetylcholine and r=-0.11, P=0.75 for isosorbide dinitrate). CONCLUSIONS: Ten years after implantation to the coronary circulation, LITA grafts show intimal thickening, increased intima/media ratio, and maintained endothelium-derived vasodilation. These changes are likely to be an adaptive answer to the different flow dynamics typical of coronary circulatio

Transplant results in adults with Fanconi anaemia

The outcomes of adult patients transplanted for Fanconi anaemia (FA) have not been well described. We retrospectively analysed 199 adult patients with FA transplanted between 1991 and 2014. Patients were a median of 16 years of age when diagnosed with FA, and underwent transplantation at a median age of 23 years. Time between diagnosis and transplant was shortest (median 2 years) in those patients who had a human leucocyte antigen identical sibling donor. Fifty four percent of patients had bone marrow (BM) failure at transplantation and 46% had clonal disease (34% myelodysplasia, 12% acute leukaemia). BM was the main stem cell source, the conditioning regimen included cyclophosphamide in 96% of cases and fludarabine in 64%. Engraftment occurred in 82% (95% confidence interval [CI] 76-87%), acute graft-versus-host disease (GvHD) grade II-IV in 22% (95% CI 16-28%) and the incidence of chronic GvHD at 96 months was 26% (95% CI 20-33). Non-relapse mortality at 96 months was 56% with an overall survival of 34%, which improved with more recent transplants. Median follow-up was 58 months. Patients transplanted after 2000 had improved survival (84% at 36 months), using BM from an identical sibling and fludarabine in the conditioning regimen. Factors associated with improved outcome in multivariate analysis were use of fludarabine and an identical sibling or matched non-sibling donor. Main causes of death were infection (37%), GvHD (24%) and organ failure (12%). The presence of clonal disease at transplant did not significant impact on survival. Secondary malignancies were reported in 15 of 131 evaluable patients

Clinical characteristics, management and in-hospital mortality of patients with COVID-19 In Genoa, Italy

To describe clinical characteristics, management and outcome of COVID-19 patients; and to evaluate risk factors for all-cause in-hospital mortality