Search

The effectiveness of natural killer (NK) cells transferred adoptively in combating solid tumours is limited by challenges such as their difficulty in penetrating tumours from the bloodstream and maintaining viability without the support of interleukin-2 (IL-2). Genetically modified NK-92MI cells, which can release IL-2 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL-2 administration. The role of PSD-95/discs large/ZO-1 (PDZ)-binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK-92MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small-molecule inhibitor HI-TOPK-032, which inhibits PBK, enhances the cytotoxicity of NK-92MI cells toward OV cells. It increases the production of interferon-γ and tumour necrosis factor-α, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI-TOPK-032 upregulates CD107a on NK-92 cells. In vivo studies demonstrated that HI-TOPK-032 improves the antitumour effects of NK-92MI cells in OVCAR3Luc xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI-TOPK-032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK-92MI cells with HI-TOPK-032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of the implementation of intervention packages for postpartum hemorrhage (PPH) management in pregnant women hospitalized in a High Obstetric Complexity Unit in a Latin American country. Methods: Retrospective cohort study including pregnant women with PPH attended between January 2011 to December 2019. Three periods of time were defined according to management strategies We performed univariate and multivariate robust Poisson regression logistic models for each of the outcomes derived from each period. Results: We included 602 patients. There was a reduction in period 3 of the incidence of massive PPH (16% versus 12% P < 0.001, relative risk [RR] 0.61, 95% confidence interval [CI] 0.44–0.85; P = 0.003), major surgery (24%, 13%, 11%, P = 0.002, RR 0.54, 95% CI 0.33–0.883; P = 0.014), and admission to the intensive care unit (ICU) (14%, 7%, 6.1%, P = 0.0, RR 0.40, 95% CI 0.17–0.96 P = 0.00). Conclusion: The implementation of PPH intervention packages in a hospital in a middle‐income country from Latin America, led to a significant decrease in the incidence of massive bleeding, the rate of major surgery, and the ICU stay of pregnant women affected by this condition. Synopsis: Intervention packages for PPH in LMICs enable integrated care for early detection of PPH risk, early recognition, and interventions to reduce its progression. [ABSTRACT FROM AUTHOR]

Objective To determine the spectrum of etiology and the incidence of healthcare-associated infections (HAIs) among gynecologic and obstetric patients. Methods In a descriptive survey, data were analyzed from in-patients at the Department of Gynecology and Obstetrics, University Hospital and Faculty of Medicine in Hradec Králové, Czech Republic, between January 2007 and December 2011. Results Among 21 937 patients treated during the study period, there were 189 (0.86%) cases of HAI. Gynecologic patients had a higher incidence of HAIs (1.31%) compared with pregnant women (0.60%). The incidence of HAI was 0.13% after laparoscopic surgery, 0.63% after a minor gynecologic intervention, and 3.73% after major surgery. Vaginal delivery (0.36%) represented a low risk of HAI. Compared with vaginal delivery, the incidence of HAI increased twofold for planned cesarean delivery (0.64%), and tenfold for emergency cesarean delivery (3.63%). The majority of causative microorganisms (72.7%) were susceptible to penicillin antibiotics. None of the patients died as a result of HAI. Conclusion The incidence of HAIs at a university hospital in the Czech Republic was very low. Antibiotic resistance was only a minor problem, and the incidence of multiresistant strains was rare. [ABSTRACT FROM AUTHOR]