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Objectives: Exploiting the complete blood count (CBC) with differential (CBC-diff) for early sepsis detection has practical value for emergency department (ED) care, especially for those without obvious presentations. The objective of this study was to develop the CBC Sepsis Index (CBC-SI) that incorporates monocyte distribution width (MDW) to enhance rapid sepsis screening., Design: A retrospective observational study., Setting: The ED of the University of Kansas Medical Center, United States., Patients: All adult patients (age 18 or over) presenting to the ED between August 8, 2020, and April 1, 2022, that received a CBC-diff as part of routine clinical care., Interventions: MDW, WBC count, and neutrophil-to-lymphocyte ratio were used to develop a CBC-SI (0 low to 5 high risk) for early sepsis detection. The diagnostic performance of CBC-SI was evaluated for patients with and without obvious early signs of sepsis., Measurements and Main Results: In a cohort of 51,407 ED visits, 1,683 (3.3%) met sepsis criteria; 1,343 (79.8%) septic patients presented with obvious signs and 340 (20.2%) without. The overall area under the curve of the CBC-SI was 0.83 (95% CI, 0.81-0.85). A CBC-SI of greater than or equal to 1 point exhibited a sensitivity of 83.1% (95% CI, 79.9-86.2%) and specificity of 64.8% (95% CI, 64.0-65.5%). Superior performance was observed in the patient subgroup presenting without obvious signs; greater than or equal to 1 point, 81.1% (95% CI, 73.2-88.9%) sensitivity and 69.1% (95% CI, 68.3-69.9%) specificity. Septic patients without obvious signs exhibited delays in antibiotic administration from arrival (median 4.7 vs. 3.4 hr; p < 0.001) and higher rates of ICU admission (43.8% vs. 27.9%; p < 0.001) and in-hospital mortality (14.7% vs. 9.8%; p = 0.011) compared with the septic subgroup presenting with obvious signs., Conclusions: The CBC-SI demonstrated strong performance for early sepsis detection. Its performance was best for nonobvious presentations, suggesting highest utility in a subgroup that is most susceptible to delayed interventions and poorer outcomes., Competing Interests: Dr. Levin, Dr. Hinson, Dr. Naiman, Ms. Smith, Mr. Steinhart, and Mr. DeBraine are employed by Beckman Coulter. Drs. Sarani, Taribichi, and Badaki-Makun have performed other research or consulting for Beckman Coulter. Dr. Kehoe is an employee of Danaher Diagnostics, an indirectly wholly owned subsidiary of Danaher Corporation (NYSE: DHR). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Ovarian cancer (OC) is the sixth most common malignancy in women and the poor 5-year survival emphasises the need for novel therapies. NK cells play an important role in the control of malignant disease but the nature of tumour-infiltrating and peripheral NK cells in OC remains unclear., Methods: Using flow cytometric analysis, we studied the phenotype and function of NK cells in blood, primary tumour and metastatic tissue in 80 women with OC. The cell type contexture of metastatic OC tissue was explored utilising scRNAseq analysis, with a focus on portraying an immunogenic tumour microenvironment and determining the characteristics of a dysfunctional NK cell population., Results: The proportion of peripheral NK cells was markedly elevated with a highly activated profile and increased cytotoxicity. In contrast, NK cell numbers in primary tumour and metastasis were substantially reduced, with downregulation of activatory receptors together with elevated PD-1 expression. scRNA-Seq identified 5 NK cell subpopulations along with increased exhausted and immature NK cells within tumour tissue compared to normal tissue. These features were attenuated following chemotherapy where higher levels of activated and cytotoxic NK cells associated with improved disease-free survival. Correlation of NK cell phenotype with clinical outcomes revealed high levels of DNAM-1 expression on tissue-localised and peripheral NK cells to be associated with reduced survival. Expression of PVR, the DNAM-1 ligand, was significantly increased on tumours and DNAM-1 mediated NK cell lysis of primary tumour tissue was observed in vitro ., Discussion: These findings reveal profound modulation of the tumour tissue and systemic profile of NK cells which likely contributes to the high rates of local progression and metastasis seen with OC. Immunotherapeutic approaches that overcome local immune suppression and enhance DNAM-1-targeted lysis of OC offer the potential to improve disease control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Pounds, Croft, Pearce, Hossain, Singh, Balega, Jeevan, Sundar, Kehoe, Yap, Moss and Zuo.)

Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate the outcomes, prognostic factors and recurrence patterns of G2 EEC and whether the differentiation between G1 and G2 EEC is clinically useful. Methods: we retrospectively reviewed 523 patients with EEC treated with primary surgery over a decade (March 2010-January 2020) at Oxford University Hospitals NHS Trust, focusing on those with G2 disease. Results: Patients with G2 EEC had worse 5-year cancer-specific survival (93.3% vs. 98.5%, p < 0.01) compared to patients with G1 EEC, but a favourable prognosis compared to G3 EEG, both in terms of disease-free survival (91.6 vs. 83.8%, p = 0.04) and cancer-specific survival (93.3% vs. 78.5%, p < 0.01). Both stage and grade are independent risk factors for cancer-specific mortality in EEC. Cervical stromal involvement, parametrial involvement and distant metastatic disease are all independent risk factors for cancer-related mortality in G2 ECC. Only 12.5% of recurrences of G2 EEC were diagnosed with examination in routine follow up in asymptomatic patients. Conclusions: our results suggest that the grading system should continue to differentiate G1 EEC and G2 EEC for better prognosis interpretation.