Genomic Profiling Uncovers a Broader Spectrum of Dermatofibrosarcoma Protuberans: Implications for Diagnosis and Therapy.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous neoplasm driven by PDGFB or, rarely, PDGFD gene fusions. In some cases, DFSP progresses to a fibrosarcomatous form with metastatic potential, which may respond to tyrosine kinase inhibitors. This study explores whether comprehensive genomic profiling can reveal a broader clinical, anatomic, and pathologic spectrum for DFSP.

Reconceptualizing Intrauterine Resuscitation and Its Short-Term Impact.

: Intrauterine resuscitation (IR) may be employed during labor to reduce emergency deliveries with concerns for fetal wellbeing emanating mostly from increased uterine contraction frequency and/or intensity. However, there is no standard definition of what constitutes IR, and how its impact is assessed. Here, we have created two measures of relative IR effectiveness, determined over a two-hour time frame after Pitocin was first initiated, and asked how fetal risk severity at the time of its initiation impacted IR effectiveness and the clinical decisions made.

MAD::NUT Fusion Sarcoma: A Sarcoma Class With NUTM1, NUTM2A, and NUTM2G Fusions and Possibly Distinctive Subtypes.

NUT fusion-associated cancers are heterogeneous and include NUT carcinoma and an emerging group with non-BRD4/BRD3/NSD3 fusion partners. In this study, we characterized 11 tumors harboring MAD::NUT fusions (10/11 in female patients; median age: 48 years; range: 1-67 years), all histologically different from NUT carcinoma. Eight cases were identified via sequencing database review and 3 were diagnosed prospectively.

Clinical and genetic characteristics in two cases of Birt-Hogg-Dubé syndrome associated with papillary renal cell carcinoma and rare Folliculin (FLCN) variants.

Birt-Hogg-Dubé syndrome (BHDS) is characterized by autosomal dominant alterations in the Folliculin (FLCN) gene, resulting in cutaneous, pulmonary, and renal abnormalities. In particular, affected individuals are susceptible to the development of renal cell carcinoma (RCC), which most frequently present as chromophobe tumors or hybrid cancers with features of oncocytoma and chromophobe RCC. Type 1 and type 2 papillary neoplasms have rarely been described in the setting of BHDS, and we present two additional cases.

Expression Patterns of DLL3 across Neuroendocrine and Non-neuroendocrine Neoplasms Reveal Broad Opportunities for Therapeutic Targeting.

DLL3-targeted therapies have recently shown robust clinical efficacy in aggressive neuroendocrine cancers, positioning them to fulfill a great unmet need in these settings. Here, we examine the clinical and biological correlates of DLL3 expression in both neuroendocrine and non-neuroendocrine cancers. Our findings may stimulate the development and application of DLL3-targeted therapies, as well as other precision therapies, in neuroendocrine cancers and beyond.

Loss of O6-Methylguanine-DNA Methyltransferase Protein Expression by Immunohistochemistry Is Associated With Response to Capecitabine and Temozolomide in Neuroendocrine Neoplasms.

Background: A recent prospective phase II study (ECOG-ACRIN E2211) demonstrated that MGMT deficiency was associated with a significant response to capecitabine and temozolomide (CAPTEM) in pancreatic neuroendocrine neoplasms (NENs); however, routine MGMT analysis in NENs was not recommended. Our study sought to demonstrate whether loss of MGMT protein expression is associated with improved overall survival (OS) in patients receiving CAPTEM for NENs from various tumor sites.

Materials And Methods: Paraffin-embedded tumor samples were evaluated by immunohistochemistry (IHC) using an MGMT monoclonal antibody.

Acute Myeloid Leukemia (AML) With T-Cell Differentiation Arising From Chronic Myelomonocytic Leukemia (CMML).

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm characterized by peripheral blood monocytosis and bone marrow dysplasia. In approximately one-fourth of cases, CMML can demonstrate progression to acute myeloid leukemia (AML), referred to as AML ex CMML. We present a 58-year-old woman with a past medical history of idiopathic thrombocytopenic purpura (ITP) who demonstrated 24% bone marrow blasts on a repeat biopsy obtained two years after being diagnosed with CMML.

Characterization of Somatostatin Receptor 2 Gene Expression and Immune Landscape in Sinonasal Malignancies.

Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene (), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzed gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database.

Understanding inequities in access to diabetes technologies in children and young people with type 1 diabetes: Qualitative study of healthcare professionals' perspectives and views.

Aims: We explored healthcare professionals' perceptions and understandings of the factors and considerations underlying inequities in technology access in children and young people (CYP) with type 1 diabetes.

Methods: We interviewed (n = 29) healthcare professionals working in paediatric diabetes in England recruited from (n = 15) purposively selected sites. We analysed data thematically.

Case report: High grade serous fallopian tube carcinoma with rare gene fusion presenting as widespread peritoneal carcinomatosis.

The discovery of gene fusions involving Neuregulin-1 () within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed :: fusion.

Postexercise Dietary Leucine Retention for Whole-Body Anabolism Is Greater With Whey Protein Isolate and Fish-Derived Protein Hydrolysate Than Nonessential Amino Acids in Trained Young Men.

Marine-derived proteins, such as blue whiting-derived protein hydrolysates (BWPH), represent high-quality sources of dietary protein, but their ability to support postexercise anabolism is not established. The impact of BWPH on whole-body anabolism was compared with an isonitrogenous whey protein isolate (WPI) and nonessential amino acid (NEAA) control in 10 trained young males (31 ± 4 years) who, on three separate visits, performed a session of whole-body resistance exercise and then consumed, in randomized crossover fashion, BWPH, WPI, or NEAA (0.33 g/kg; 19, 33, and 0 mg/kg leucine, respectively) with L-[1-13C]leucine.

Evidence for Unified Assessment Criteria of HER2 Immunohistochemistry in Colorectal Carcinoma.

Human epidermal growth factor receptor-2 (HER2) expression is an important biomarker for the management of RAS wild-type metastatic colorectal carcinoma (CRC). Immunohistochemistry (IHC) with reflex in situ hybridization (ISH) is accepted as a standard method of assessment, yet there are currently the following 2 sets of criteria used to interpret results: the HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) criteria and the MyPathway criteria. The HER2 Amplification for Colorectal Cancer Enhanced Stratification criteria require ISH confirmation when IHC staining is 3+ in 10% to 49% of cells, whereas the MyPathway criteria mirror those for gastric HER2 assessment and do not recommend ISH confirmation in the previously referenced scenario.

Aggressive Pediatric Primitive Round Cell Tumors with MN1::ZNF341 Fusion: A Mimic of Neuroblastoma.

Neuroblastoma is one of the most common tumors in young children, arising from the adrenal medulla or paraspinal sympathetic ganglia. We describe primitive round cell tumors presenting in three patients less than 1.5 years old, with striking clinical and pathologic similarities to neuroblastoma.

Reframing antepartum and intrapartum surveillance.

The original goal of electronic fetal monitoring was to reduce stillbirths. It worked. Then the mission expanded to reducing neurologic impairment including cerebral palsy.

Multiomic Characterization and Molecular Profiling of Nuclear Protein in Testis Carcinoma.

Purpose: Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene on chromosome 15q14. Co-occurring alternations have not been fully characterized.

Methods: We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris).

Impact of Ultra-Rapid Insulin on Boost and Ease-Off in the Cambridge Hybrid Closed-Loop System for Individuals With Type 1 Diabetes.

Objective: The objective was to evaluate the safety and efficacy of ultra-rapid-acting insulin with the Boost and Ease-off features of the Cambridge hybrid closed-loop system.

Methods: A secondary analysis of Boost and Ease-off from two double-blind, randomized, crossover hybrid closed-loop studies comparing (1) Fiasp to insulin aspart (n = 25), and (2) Lyumjev to insulin lispro (n = 26) was carried out. Mean glucose on initialization of Boost and Ease-off, change in glucose 60 and 120 minutes after initialization, duration and frequency of use, mean glucose, and time in, above, and below target glucose range were calculated for periods of Boost use, Ease-off use, or neither.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation.

Background: Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks' gestation. However, dosing remains unoptimized and lung benefits are highly variable.

Exomic and epigenomic analysis of pulmonary blastoma.

Objective: Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them.

Methods: We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons.