The Mayo Clinic Hospital — Rochester is a 2,059-bed hospital located in Rochester, Minnesota. It comprises the Saint Marys Campus, and Mayo Eugenio Litta Children's Hospital, forming an integral part of the Mayo Clinic academic medical center. Mayo Clinic Hospital — Rochester is ranked first on the 2019-20 U.S. News & World Report Best Hospitals Honor Roll and is ranked #1 in more specialties than any other hospital in the United States.
The recent inclusion of the Merlin clinicopathologic-gene expression profile (CP-GEP) assay in the National Comprehensive Cancer Network (NCCN) Melanoma Guidelines represents an important milestone in the clinical integration of molecular testing for cutaneous melanoma. Unlike earlier melanoma gene expression profile (GEP) assays, which focused primarily on prognostic risk stratification, CP-GEP was specifically developed to predict sentinel lymph node (SLN) metastasis risk by identifying early metastatic competence within primary melanomas, with additional prognostic utility. This review discusses the biological evidence supporting CP-GEP and examines how unbiased transcriptomic discovery converged with established insights from cancer cell biology, integrin signaling, focal adhesions, and extracellular matrix (ECM) remodeling to shape its conceptual framework. We further discuss how CP-GEP captures a transformation-associated biological state centered on an integrin- and TGF-β-dependent signaling axis (ITGB3, TGFBR1) that promotes pericellular proteolysis and ECM remodeling (PLAT, SERPINE2, LOXL4), inflammatory and angiogenic signaling (CXCL8, GDF15), and melanocytic lineage identity (MLANA). Collectively, these genes identify a dissemination-competent phenotype that is detectable within primary tumors before clinically apparent metastasis. Overall, the biological framework supporting CP-GEP reinforces the concept that altered adhesion signaling and ECM remodeling are central drivers of early melanoma metastasis and represent clinically actionable biomarkers for individualized melanoma management.
Part I of our three-part series outlines the essential technical and operational components required for successful digital pathology implementation including hardware, software, and IT infrastructure. It reviews the rationale for digitization, highlighting improvements in workflow efficiency, diagnostic collaboration, and preparedness for computational applications. Key components of Whole Slide Imaging (WSI) systems are discussed, including practical considerations for scanner selection, scanning modalities, and performance trade-offs relevant to dermatopathology. The article also examines image compression strategies and pyramid image representation, with attention to balancing image quality and storage efficiency. Finally, we review DICOM standards and storage infrastructure options, including cloud, on-premises, and hybrid models, and associated network bandwidth requirements.
BACKGROUND/OBJECTIVES:Bacterial infections are major precipitants of decompensation and death in cirrhosis. Multidrug-resistant (MDR) bacteria are increasingly recognized in this population, but their burden across infection sites and healthcare settings remains uncertain. We aimed to estimate the prevalence and distribution of MDR bacterial infections among hospitalized patients with cirrhosis and culture-proven infections. METHODS:PubMed, Embase, and Scopus were searched through November 2025 for observational studies reporting patient-level MDR prevalence among hospitalized patients with cirrhosis and culture-positive infections. A proportional meta-analysis was conducted using 95% confidence intervals (CI), and heterogeneity was assessed with the I² statistic. Stratified analyses were performed based on epidemiological and clinical factors. RESULTS:Twenty-nine studies including 13,361 patients were analyzed. Across heterogeneous hospitalized cirrhosis cohorts, the prevalence of patients with MDR bacterial infections was 36.73% (95% CI: 32.23-41.35%; I² = 92.9%). Asia had the highest estimate, at 41.95% (95% CI: 34.36-49.74%; I² = 90.6%). Europe had a prevalence of 31.75% (95% CI: 27.37-36.29%; I² = 66.3%), Latin America of 31.10% (95% CI: 23.77-38.94%; I² = 74.9%), and North America of 23.33% (95% CI: 13.07-35.50%; I² = 82.9%). Data from Oceania and Africa were limited. Acinetobacter spp. showed the strongest association with MDR, at 85.06% (95% CI: 54.39-99.73%; I² = 77.2%), whereas Escherichia coli was the most common MDR bacteria, at 42.39% (95% CI: 31.57-53.59%; I² = 90.7%). CONCLUSION:MDR bacteria are common among hospitalized patients with cirrhosis and culture-proven infections. Gram-negative organisms predominate, with E. coli accounting for the largest absolute MDR burden, while Acinetobacter spp. showed the highest pathogen-specific probability of MDR.
Abstract Circumscribed meningeal melanocytic neoplasms (CMMNs) represent a spectrum of rare central nervous system (CNS) tumors. Knowledge of their clinical behavior and molecular correlates remains limited. In this single‐institution retrospective study, we analyzed 31 patients (14 male, 17 female; median age, 59 years) diagnosed with CMMN between 2004 and 2025. In this patient cohort, based on the current World Health Organization Central Nervous System Tumor Classification (WHO CNS5) criteria, the majority of cases (18, 58.1%) fell into the intermediate‐grade melanocytic tumor (IMT) category based on histology, with either increased mitotic activity, CNS invasion, or both; 7 (22.6%) were melanocytomas, 5 (16.1%) melanomas, and 1 (3.2%) indeterminate case because of limited tissue. By next‐generation sequencing, mutations were identified in GNAQ/GNA11 in 21/24 cases, BAP1 in 5/23 (2 IMT, 3 melanoma), EIF1AX in 9/21 (1 melanocytoma, 8 IMT), and SF3B1 in 3/23 (2 IMT, 1 melanoma). Primary sites were spinal (20), posterior fossa (6), and supratentorial (5). During follow‐up, progression was observed in 5/6 melanocytomas, 9/13 IMTs, and 4/5 melanomas, suggesting a high frequency of progression across all groups. Two‐year progression‐free survival was 83.3% (95% confidence interval [CI], 53.5%–100.0%) for melanocytoma, 55.9% (95% CI, 26.7%–85.2%) for IMT, and 25.0% (95% CI, 0.0%–67.4%) for melanoma. Five‐year overall survival (OS) was 80.0% (95% CI, 44.9%–100.0%) for melanocytoma, 65.3% (95% CI, 37.0%–93.6%) for IMT, and 0.0% for melanoma. OS was significantly worse in melanoma compared with melanocytoma ( p = 0.002). BAP1 mutation correlated with worse OS (hazard ratio 8.73, p = 0.006). Upfront maximal safe resection appeared to be associated with improved outcomes in selected patients, whereas radiotherapy and systemic therapy did not demonstrate clear additional benefit in this cohort. In summary, our study shows that all CMMNs, irrespective of grade, have a high propensity to recur and melanoma histology and BAP1 mutation are associated with significantly worse OS.
We examined the prognostic value of routine NGS data in newly diagnosed acute myeloid leukemia (AML) treated with intensive (7 + 3 backbone) induction, specified by AML subtype. A contemporary (2015-2025) series of 545 Mayo Clinic patients (median age 56 years, females 44%) was considered. Median follow-up was 49 months with 341 (63%) allogeneic hematopoietic stem cell transplantations (AHSCT) recorded. AML subtypes included core-binding factor (CBF; N = 72; 13%), primary non-CBF (N = 403; 74%), post-myelodysplastic syndromes (MDS) or post-myelodysplastic/myeloproliferative neoplasms (post-MDS-MDS/MPN; N = 28; 5%), post-MPN (N = 15; 3%), and therapy-related (t-AML; N = 27; 5%). Corresponding complete remission rates, with/without count recovery (CR/CRi), were 89%, 76%, 64%, 27%, and 78% (p < 0.01) and 5-year transplant-censored survival rates 68%, 57%, 21%, 0%, and 55% (p < 0.01). In multivariable analyses, the prognostic value of specific mutations was mostly limited to primary non-CBF AML where adverse karyotype (OR 1.9; p = 0.04) predicted inferior and FLT3-ITD (OR 0.4; p < 0.01) or NPM1 MUT/FLT3 WT (OR 0.1; p < 0.01) superior CR/CRi while KRAS MUT (HR 8.8; p < 0.01), TP53 MUT (HR 5.4; p < 0.01), and TET2 MUT (HR 2.3; p = 0.01) predicted inferior and NPM1 MUT/FLT3 WT (HR 0.3; p = 0.01) superior survival. Prognostication in intensively-treated AML should start with subtype specification and recognition of the limited value of NGS in non-primary AML. Post-MPN AML is particularly associated with dismal outcomes and should be prognostically distinguished from post-MDS-MDS/MPN AML. In primary non-CBF AML, in addition to previously established risk factors, the favorable impact of FLT3-ITD on achieving CR/CRi and the unfavorable impact of KRAS MUT and TET2 MUT on transplant-censored survival were noted and require confirmation from additional studies.
