Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective.

Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx®) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx®. Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69-0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx® was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx®, and histology has aided in early diagnosis and timely individualized intervention.

Salivary gland fine-needle aspiration cytology with the application of the Milan system for risk stratification and histological correlation: A retrospective 6-year study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is based on risk stratification. We presented our experience with fine-needle aspiration cytology (FNAC) for the diagnosis of salivary glands lesions by applying the MSRSGC categorization to the cytological diagnoses, and determined risk of malignancy (ROM) for each category. METHODS: Fine-needle aspiration cytology of salivary gland lesions performed over a 6-year period was retrieved. FNAC results were retrospectively categorized according to the MSRSGC criteria, and correlated with corresponding histologic follow-up. ROM for each diagnostic category was calculated. RESULTS: A total of 208 FNAC of salivary gland lesions were reviewed and retrospectively categorized as: non-diagnostic (ND) 23 (11%), non-neoplastic (NN) 54 (26%), atypia of undetermined significance (AUS) 10 (4.8%), benign neoplasms (BN) 77 (37%), salivary gland of uncertain malignant potential (SUMP) 13 (6.3%), suspicious for malignancy (SM) 7 (3.4%), and malignant (M) 24 (11.5%). Histopathological follow-up was available for 84 of 208 cases (40.4%). Overall concordance rate between FNAC and histology was 78.8%. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 93.3%, 94.6%, 82.4%, and 98.2%, respectively. Diagnostic accuracy to distinguish benign from malignant disease was 94.4%. ROM for each category was ND 0%, NN 0%, AUS 75%, BN 2.2%, SUMP 28.6%, SM 50%, and M 100%. CONCLUSION: Fine-needle aspiration cytology continues to be an accurate diagnostic tool for most salivary gland neoplasms showing classical morphologic features. However, difficult cases with unusual or overlapping features will occur. In these situations, the use of MSRSGC risk-stratification could be helpful to define appropriate management.

Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p < 0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.