High Rate of Mutations of Adhesion Molecules and Extracellular Matrix Glycoproteins in Patients with Adult-Onset Focal and Segmental Glomerulosclerosis.

(1) Background: Focal and segmental glomerulosclerosis (FSGS) is a pattern of injury that results from podocyte loss in the setting of a wide variety of injurious mechanisms. These include both acquired and genetic as well as primary and secondary causes, or a combination thereof, without optimal therapy, and a high rate of patients develop end-stage renal disease (ESRD). Genetic studies have helped improve the global understanding of FSGS syndrome; thus, we hypothesize that patients with primary FSGS may have underlying alterations in adhesion molecules or extracellular matrix glycoproteins related to previously unreported mutations that may be studied through next-generation sequencing (NGS). (2) Methods: We developed an NGS panel with 29 genes related to adhesion and extracellular matrix glycoproteins. DNA was extracted from twenty-three FSGS patients diagnosed by renal biopsy; (3) Results: The average number of accumulated variants in FSGS patients was high. We describe the missense variant ITGB3c.1199G>A, which is considered pathogenic; in addition, we discovered the nonsense variant CDH1c.499G>T, which lacks a Reference SNP (rs) Report and is considered likely pathogenic. (4) Conclusions: To the best of our knowledge, this is the first account of a high rate of change in extracellular matrix glycoproteins and adhesion molecules in individuals with adult-onset FSGS. The combined effect of all these variations may result in a genotype that is vulnerable to the pathogenesis of glomerulopathy.

Cardiac arrest as a manifestation of unknown Type V glycogenosis: a case report.

Few cases have been reported to date, in which a massive rhabdomyolysis causes a cardiac arrest in a male adult suffering from undiagnosed McArdle disease. Veno-arterial extracorporeal membrane oxygenation and cytokine adsorption filter (CytoSorb®) were required to reach a complete and successful recovery.

Histological Comparison of Buccal and Lingual Mucosa Grafts for Urethroplasty: Do They Share Tissue Structures and Vascular Supply?

Comparable outcomes were published using a buccal mucosa graft (BMG) from the cheek and a lingual mucosa graft (LMG) from the sublingual area, for urethral augmentation or substitution. To date, no histological comparison between both grafts has been conducted. We histologically assessed BMG and LMG harvested during urethral surgeries, aiming to compare graft properties and vascular support. We conducted a prospective single cohort study, including oral mucosa urethroplasty patients. During surgery, graft dimensions and donor sites were collected, and a 0.5 × 0.5 cm sample was obtained from the prepared graft. Formalin-fixed paraffin-embedded samples were sliced at 4 micrometres (µm) and hematoxylin-eosin stained. Using a telepathology tool, all slides were digitalized and measured from 10× to 40× magnification. In each graft, global and individual layers thicknesses were assessed, including vascular density and area. Descriptive and comparative (parametrical and non-parametrical) statistical analysis occurred. We collected 57 grafts during 33 urethroplasties, with 30 BMG and 22 LMG, finally, included. The mean age was 56.6 (SD 15.2) years, and the mean graft length was 5.8 (SD 1.7) cm and the width was 1.7 (SD 0.4) cm. The median graft thickness was 1598.9 (IQR 1200-2100) µm, the mean epithelium layer was 510.2 (SD 223.7) µm, the median submucosa was 654 (IQR 378-943) µm. the median muscular was 477.6 (IQR 286-772) µm, the median vascular area was 5% (IQR 5-10), and the median adipose tissue area was 5% (IQR 0-20). LMG were significantly longer and narrower than BMG. Total graft thickness was similar between LMG and BMG, but the epithelium and submucosa layers were significantly thinner in LMG. The muscular layer was significantly thicker in LMG. Vascular density and vascular areas were not significantly different between both types of grafts. LMG showed significantly less adipose tissue compared with BMG. Our findings show LMG and BMG for urethroplasty surgeries share the same thickness and blood supply, despite having significantly different graft sizes as well as mucosal and submucosal layers thickness.

Clonal Evolution in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.

Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive subtype of DLBCL with characteristic clinicopathologic features. Relapse outside the CNS involving extranodal locations has been found in a fraction of cases (16%). Here we describe a case of DLBCL arising in the CNS that relapsed 18 months after the initial diagnosis in the testis and bilateral adrenal glands. Both tumors showed equivalent morphology, phenotype, cytogenetic features, and clonal relationship. Somatic mutation analysis by next generation sequencing demonstrated MYD88L265P mutation in both tumors and de novo CD79B Y196S mutation exclusive to the relapse. The pattern of mutations suggest that the 2 tumors might have evolved from a common progenitor clone with MYD88L265P being the founder mutation. A meta-analysis of the literature shows a significantly high frequency of concurrent MYD88L265P and CD79B ITAM mutations in primary CNS lymphoma and testicular DLBCL, underscoring the role of B cell receptor and nuclear factor kB activation by somatic mutations in these lymphomas that colonize immune-privileged sites. In summary, here we illustrate that targeted next generation sequencing for the detection of hot spot somatic mutations in relapsed DLBCL is useful to confirm ABC phenotype and discovers relevant information that might influence therapeutic decision.