Microbial cell-free DNA for diagnosis of bacterial and fungal infection in the immunocompromised host - what do we know?

Purpose Of Review: Plasma metagenomic next-generation sequencing (mNGS) enables detection of microbial cell-free deoxyribonucleic acid (mcfDNA) in blood without the need for culture or organism-specific primers. Here, we review clinical performance, methodological variability, and real-world application of plasma mNGS for infectious disease diagnosis in immunocompromised hosts (ICHs).

Recent Findings: Plasma mNGS has rapidly gained attention as a novel diagnostic tool for infections in ICHs, offering broad-range pathogen detection from a noninvasive blood sample.

Preclinical evaluation of folate receptor-alpha chimeric antigen receptor T cells (FOLR1-CART) exhibit highly efficient anti-tumor activity against osteosarcoma.

Metastatic and relapsed osteosarcoma (OS) remains difficult to treat despite advanced surgical techniques, intensified chemotherapy, and targeted therapies. Adoptive immunotherapies such as chimeric antigen receptor (CAR) T cells, are in their nascent stage, but remain a viable therapeutic strategy for patients with aggressive solid tumors such as OS. Folate receptor- (FOLR1) has been functionally implicated in OS pathophysiology, providing rationale as a potential therapeutic target.

Tagraxofusp, a CD123-targeted therapy, for chronic myelomonocytic leukemia: final results of a phase 1/2 study.

Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic neoplasm characterized by an expansion of CD123 monocytes and plasmacytoid dendritic cells (pDCs). pDC bone marrow clusters in CMML have been associated with higher rates of acute myeloid leukemia transformation. We evaluated tagraxofusp, a CD123-targeted therapy, in a phase 1/2 trial for patients with CMML.

A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia.

IO-202 is a humanized immunoglobulin G1 monoclonal antibody with high affinity and specificity for leukocyte immunoglobulin-like receptor B4 (LILRB4; ILT3), which is predominantly expressed in monocytes and monocytic blasts. IO-202 induces antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vitro and in patients with leukemia. Herein, we present the phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and R/R chronic myelomonocytic leukemia (CMML), and the phase 1b dose expansion data of IO-202 combined with AZA for the treatment of hypomethylating agent (HMA)-naïve CMML.

Cystoscope assisted trans-conduit removal of fragmented percutaneous nephrostomy catheter.

Percutaneous nephrostomy catheter fragmentation is an uncommon complication that is managed through different approaches. In this report we describe an iatrogenicly fragmented nephrostomy catheter in a patient with an ileal conduit, that was removed by using combined cystoscope and fluoroscopy guidance through a retrograde trans conduit approach.

Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting.

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing , a common oncogene in brain tumors. GFP/c-MYC cells were isolated from tumor organoids and used in two different approaches: GFP/c-MYC cells co-cultured with cerebral organoid slices or fused as spheres to whole organoids.

Real-world management of blastic plasmacytoid dendritic cell neoplasm at an academic center with a broad regional referral base.

BPDCN is an aggressive myeloid malignancy characterized by unique expression of CD123, CD4, CD56, CD303, CD304, TCL1 and TCF4. The development of tagraxofusp, a CD123-directed cytotoxin, has revolutionized BPDCN treatment, especially for patients unfit for chemotherapy. While most patients respond to frontline tagraxofusp, there are challenges associated with treatment.

Metastasis-directed radiotherapy without systemic therapy for oligometastatic clear-cell renal-cell carcinoma: primary efficacy analysis of a single-arm, single-centre, phase 2 trial.

Background: Select patients with metastatic clear-cell renal-cell carcinoma can be treated without systemic therapy, yet few studies have explored this population. We investigated the efficacy of metastasis-directed therapy without systemic therapy in oligometastatic clear-cell renal-cell carincoma.

Methods: This investigator-initiated single-arm, phase 2 trial enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed clear-cell renal-cell carcinoma, and one to five metastases.

Phase I dose-escalation trial of AMXT 1501 dicaprate plus difluoromethylornithine: a dual-agent approach targeting immunosuppressive polyamine metabolism.

Background: Dysregulation of polyamine synthesis has been observed in various cancer cell types. A novel approach to depriving cancer cells of polyamines involves the use of difluoromethylornithine (DFMO) to block polyamine biosynthesis in combination with AMXT 1501, a potent inhibitor of polyamine transport. Preclinical mouse tumor models showed that the combination of AMXT 1501 plus DFMO had strong antitumor activity, together with evidence of a stimulated immune response against tumors.

From Wound Coverage to Functional Healing: A Narrative Review of Biomaterial Applications in Head and Neck Mucosal Defects.

Background: Reconstruction of head and neck mucosal defects presents unique challenges due to the anatomical complexity and functional demands of the region. Artificial biomaterials such as collagen and polyglycolic acid (PGA) sheets have gained clinical traction owing to their ease of use and reduced surgical burden. However, limitations such as local inflammation, degradation-related complications, and mechanical instability-particularly in highly mobile areas like the tongue-continue to hinder their broader application.

EXPRESS: Exacerbation of paclitaxel-induced neuropathic pain behaviors in breast tumor-bearing mice.

Background: Chronic pain and cancer interact bidirectionally, with pain enhancing sensory peptides and potentially promoting tumor growth. Despite this, most chemotherapy-induced neuropathic pain (CIPN) studies overlook the contribution of cancer itself to neuropathy, focusing instead on chemotherapy-induced mechanisms. Animal models of chemotherapy-induced neuropathic pain (CINP) have been developed by injecting chemotherapeutic drugs such as paclitaxel into normal animals without cancer.

Upper gastrointestinal symptoms and Gulf War Illness in a clinical cohort of US veterans: a retrospective, cross-sectional study.

Objective: Approximately 30% of the 700 000 US Gulf War Veterans (GWVs) report symptoms collectively termed Gulf War Illness (GWI), a multisymptom illness of uncertain pathophysiology. Prior studies in GWI focus on overlap with irritable bowel syndrome. This study examines the associations between upper gastrointestinal (UGI) symptoms, GWI and specialty GI care.

Phenotyping and Clinical Utility of Phagocytic Polyploid Giant Cancer Macrophages in Blood.

Historically, polyploid giant cancer cells (PGCCs) within tumors have been ignored as superfluous inflammatory refuse with no intrinsic clinical or biological relevance. However recently, multiple studies have described the existence PGCCs in solid tumor masses that appear to correlate with tumor progression, and can also appear in blood circulation as cancer associated macrophage like cells (CAMLs). In an effort to understand the clinical and biological role of CAMLs (i.

Coalescing single-cell genomes and transcriptomes to decode breast cancer progression.

Understanding epithelial lineages of breast cancer and genotype-phenotype relationships requires direct measurements of the genome and transcriptome of the same single cells at scale. To achieve this, we developed wellDR-seq, a high-genomic-resolution, high-throughput method to simultaneously profile the genome and transcriptome of thousands of single cells. We profiled 33,646 single cells from 12 estrogen-receptor-positive breast cancers and identified ancestral subclones in multiple patients that showed a luminal hormone-responsive lineage, indicating a potential cell of origin.

Mastectomy and breast augmentation outcomes among nonbinary, transgender, and cisgender adults.

The purpose of this study was to evaluate epidemiologic characteristics and postoperative complications among nonbinary, transgender, and cisgender adults undergoing mastectomy or breast augmentation. Comparable postoperative complication rates were observed between gender modality cohorts undergoing breast augmentation, but higher complication rates were observed among cisgender patients following mastectomy, likely due to variations in clinical indications and technique. These results underscore the safety of chest surgery for gender-diverse patients.

Sentinel node detection and imaging concordance in Early-Stage ovarian cancer: A MELISA trial analysis of tracer, timing, and intraoperative gamma camera.

Purpose: To evaluate the detection rate of sentinel lymph node (SLN) mapping in early-stage ovarian cancer using [Tc]Tc-nanocolloid and indocyanine green (ICG), and the added value of an intraoperative gamma camera.

Methods: This was a prospective single-center trial of 63 patients with suspected early-stage epithelial ovarian cancer who underwent SLN mapping with combined tracers. [Tc]Tc-nanocolloid was injected into the ovarian ligaments before adnexectomy, and if malignancy was confirmed on intraoperative frozen section, ICG was administered after adnexectomy in immediate staging cases.

Epidemiology of Early-onset Colorectal Cancer in a Safety-net Hospital System in Texas.

Goals: We aimed to characterize risk factors for early versus advanced-stage early-onset colorectal cancer (eoCRC) at our safety-net hospital system.

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Rates of CRC diagnosis in young adults (age below 50) have been rising despite an overall decrease in CRC.

The efficacy of a filtered handheld far-ultraviolet disinfection device for decontamination of high-touch surfaces in healthcare settings: a genomic bacterial analysis.

Background And Objectives: Enhanced environmental disinfection is linked to reduced hospital-acquired infection rates. In this study, we aimed to evaluate the efficacy of an emerging disinfection technology, a filtered far-UV-C handheld (FFUHH) device, for reducing bacterial loads on high-touch surfaces in shared clinical workrooms, and to isolate, identify and characterize clinically significant environmental pathogens.

Methods: We compared samples from high-touch items (dictation device, mouse, armchair, desk, and keyboard) before and after FFUHH treatment.