Transition to Enteral Triazole Antifungal Therapy for Pediatric Invasive Candidiasis: Secondary Analysis of a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

Atypical B Cells Promote Cancer Progression and Poor Response to Bacillus Calmette-Guérin in Non-Muscle Invasive Bladder Cancer.

Poor response to Bacillus Calmette-Guérin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle invasive bladder cancer (NMIBC). Multiple factors are associated with poor outcomes, including biological aging and female sex. More recently, it has emerged that a B-cell-infiltrated pretreatment immune microenvironment of NMIBC tumors can influence the response to intravesically administered BCG.

Outbreak of Human Trichinellosis - Arizona, Minnesota, and South Dakota, 2022.

Trichinellosis is a parasitic zoonotic disease transmitted through the consumption of meat from animals infected with spp. nematodes. In North America, human trichinellosis is rare and is most commonly acquired through consumption of wild game meat.

Outbreak of Human Trichinellosis - Arizona, Minnesota, and South Dakota, 2022.

Trichinellosis is a parasitic zoonotic disease transmitted through the consumption of meat from animals infected with Trichinella spp. nematodes. In North America, human trichinellosis is rare and is most commonly acquired through consumption of wild game meat.

Feasibility and Impact of Immunohistochemistry-based Molecular Subtyping for Muscle-invasive Bladder Cancer in Patients Treated with Radiation-based Therapy.

Background: Distinct molecular subtypes of muscle-invasive bladder cancer (MIBC) have been identified via gene expression profiling.

Objective: We investigated the feasibility of a simple immunohistochemistry (IHC)-based Lund subtyping method and the association of MIBC subtypes with oncological outcomes for patients after bladder-preserving radiation-based therapy.

Design Setting And Participants: Transurethral resected tumor tissues from 104 patients treated with radiation-based therapy were sampled on tissue microarray blocks.

Canadian Multicentric Pan-TRK (CANTRK) Immunohistochemistry Harmonization Study.

Tumor-agnostic testing for NTRK1-3 gene rearrangements is required to identify patients who may benefit from TRK inhibitor therapies. The overarching objective of this study was to establish a high-quality pan-TRK immunohistochemistry (IHC) screening assay among 18 large regional pathology laboratories across Canada using pan-TRK monoclonal antibody clone EPR17341 in a ring study design. TRK-fusion positive and negative tumor samples were collected from participating sites, with fusion status confirmed by panel next-generation sequencing assays.

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

Background: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown.

Methods: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017.

International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members.

Background: Grade of non-muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1-3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used.

Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems.

International Society of Urological Pathology Consensus Conference on Current Issues in Bladder Cancer. Working Group 4: Molecular Subtypes of Bladder Cancer-Principles of Classification and Emerging Clinical Utility.

Molecular subtyping has been a major focus of bladder cancer research over the past decade. Despite many promising associations with clinical outcomes and treatment response, its clinical impact has yet to be defined. As part of the 2022 International Society of Urological Pathology Conference on Bladder Cancer, we reviewed the current state of the science for bladder cancer molecular subtyping.

Quantitative Nuclear Grading: An Objective, Artificial Intelligence-Facilitated Foundation for Grading Noninvasive Papillary Urothelial Carcinoma.

In nonmuscle invasive bladder cancer, grade drives important treatment and management decisions. However, grading is complex and qualitative, and it has considerable interobserver and intraobserver variability. Previous literature showed that nuclear features quantitatively differ between bladder cancer grades, but these studies were limited in size and scope.

A DNA copy number alteration classifier as a prognostic tool for prostate cancer patients.

Background: Distinguishing between true indolent and potentially life-threatening prostate cancer is challenging in tumours displaying clinicopathologic features associated with low or intermediate risk of relapse. Several somatic DNA copy number alterations (CNAs) have been identified as potential prognostic biomarkers, but the standard cytogenetic method to assess them has a limited multiplexing capability.

Methods: Multiplex ligation-dependent probe amplification (MLPA) targeting 14 genes was optimised to survey 448 tumours of patients with low or intermediate risk (Grade Group 1-3, Gleason score ≤7) who underwent radical prostatectomy.

Redirecting Polyclonal T Cells against Cancer with Soluble T-Cell Receptors.

Cancer cells accumulate genetic mutations in coding proteins that may be presented by HLA as neoantigenic peptides (peptide HLA, pHLA). T cells scan for neoantigenic pHLA by the T-cell receptor (TCR):CD3 complex. This complex has the dual function of binding pHLA, by the TCR, and triggering T-cell activation by CD3.

Prevalence of NTRK Fusions in Canadian Solid Tumour Cancer Patients.

Introduction: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions occur in ~ 0.3% of all solid tumours but are enriched in some rare tumour types. Tropomyosin receptor kinase (TRK) inhibitors larotrectinib and entrectinib are approved as tumour-agnostic therapies for solid tumours harbouring NTRK fusions.

Raman spectroscopy and supervised learning as a potential tool to identify high-dose-rate-brachytherapy induced biochemical profiles of prostate cancer.

High-dose-rate-brachytherapy (HDR-BT) is an increasingly attractive alternative to external beam radiation-therapy for patients with intermediate risk prostate cancer. Despite this, no bio-marker based method currently exists to monitor treatment response, and the changes which take place at the biochemical level in hypo-fractionated HDR-BT remain poorly understood. The aim of this pilot study is to assess the capability of Raman spectroscopy (RS) combined with principal component analysis (PCA) and random-forest classification (RF) to identify radiation response profiles after a single dose of 13.

Immunohistochemical Assays for Bladder Cancer Molecular Subtyping: Optimizing Parsimony and Performance of Lund Taxonomy Classifiers.

Transcriptomic and proteomic profiling classify bladder cancers into luminal and basal molecular subtypes, with controversial prognostic and predictive associations. The complexity of published subtyping algorithms is a major impediment to understanding their biology and validating or refuting their clinical use. Here, we optimize and validate compact algorithms based on the Lund taxonomy, which separates luminal subtypes into urothelial-like (Uro) and genomically unstable (GU).

Mutually exclusive mutation profiles define functionally related genes in muscle invasive bladder cancer.

Muscle Invasive bladder cancer is known to have an abundance of mutations, particularly in DNA damage response and chromatin modification genes. The role of these mutations in the development and progression of the disease is not well understood. However, a mutually exclusive mutation pattern between gene pairs could suggest gene mutations of significance.

Diagnostic and prognostic implications of a three-antibody molecular subtyping algorithm for non-muscle invasive bladder cancer.

Intrinsic molecular subtypes may explain marked variation between bladder cancer patients in prognosis and response to therapy. Complex testing algorithms and little attention to more prevalent, early-stage (non-muscle invasive) bladder cancers (NMIBCs) have hindered implementation of subtyping in clinical practice. Here, using a three-antibody immunohistochemistry (IHC) algorithm, we identify the diagnostic and prognostic associations of well-validated proteomic features of basal and luminal subtypes in NMIBC.

Analysis of Prostate Cancer Tumor Microenvironment Identifies Reduced Stromal CD4 Effector T-cell Infiltration in Tumors with Pelvic Nodal Metastasis.

Background: Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively.

Objective: To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis.

Design Setting And Participants: We applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN-) pelvic nodal metastases.

Lack of definitive presurgical pathological diagnosis is associated with inadequate surgical margins in breast-conserving surgery.

Purpose: To determine the impact of definitive presurgical diagnosis on surgical margins in breast-conserving surgery (BCS) for primary carcinomas; clinicopathological features were also analyzed.

Methods: This retrospective study included women who underwent BCS for primary carcinomas in 2016 and 2017. Definitive presurgical diagnosis was defined as having a presurgical core needle biopsy (CNB) and not being upstaged between biopsy and surgery.

Use of cidofovir with extracorporeal membrane oxygenation to treat adenovirus-associated acute respiratory distress syndrome in paediatric patients- a case series.

What Is Known And Objective: Reports of cidofovir dosing with extracorporeal membrane oxygenation (ECMO) support are limited. This case series describes our clinical experience and provides a literature review regarding cidofovir dosing in paediatric patients requiring ECMO support.

Case Summary: Three patients with adenovirus-associated acute respiratory distress syndrome (ARDS) were treated with cidofovir while requiring ECMO support.

High throughput assessment of biomarkers in tissue microarrays using artificial intelligence: PTEN loss as a proof-of-principle in multi-center prostate cancer cohorts.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and has clinical potential as a prognostic biomarker. The objective of this work was to develop an artificial intelligence (AI) system for automated detection and localization of PTEN loss on immunohistochemically (IHC) stained sections. PTEN loss was assessed using IHC in two prostate tissue microarrays (TMA) (internal cohort, n = 272 and external cohort, n = 129 patients).

Development and initial clinical correlation of a DNA methylation-based blood test for prostate cancer.

Background: One of the principle limitations for more precise management of advanced prostate cancer is the lack of accurate biomarkers allowing estimation of tumor burden, ongoing assessment of progression, and response to treatment. Although prostate-specific antigen (PSA) performs modestly, nonsecreting cancers including those with early castrate-resistance warrant investigation of other predictive biomarkers. The objectives of these studies were to develop and perform initial validation of a circulating tumor DNA (ctDNA) methylation assay.