CXCR2 inhibition in G-MDSCs enhances CD47 blockade for melanoma tumor cell clearance.

The use of colony-stimulating factor-1 receptor (CSF1R) inhibitors has been widely explored as a strategy for cancer immunotherapy due to their robust depletion of tumor-associated macrophages (TAMs). While CSF1R blockade effectively eliminates TAMs from the solid tumor microenvironment, its clinical efficacy is limited. Here, we use an inducible CSF1R knockout model to investigate the persistence of tumor progression in the absence of TAMs. We find increased frequencies of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the bone marrow, throughout circulation, and in the tumor following CSF1R deletion and loss of TAMs. We find that G-MDSCs are capable of suppressing macrophage phagocytosis, and the elimination of G-MDSCs through CXCR2 inhibition increases macrophage capacity for tumor cell clearance. Further, we find that combination therapy of CXCR2 inhibition and CD47 blockade synergize to elicit a significant anti-tumor response. These findings reveal G-MDSCs as key drivers of tumor immunosuppression and demonstrate their inhibition as a potent strategy to increase macrophage phagocytosis and enhance the anti-tumor efficacy of CD47 blockade in B16-F10 melanoma.

Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.

Impact of a multidimensional infection control approach on central line-associated bloodstream infections rates in adult intensive care units of 8 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Central line-associated bloodstream infections (CLABs) have long been associated with excess lengths of stay, increased hospital costs and mortality attributable to them. Different studies from developed countries have shown that practice bundles reduce the incidence of CLAB in intensive care units. However, the impact of the bundle strategy has not been systematically analyzed in the adult intensive care unit (ICU) setting in developing countries, such as Turkey. The aim of this study is to analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control approach to reduce the rates of CLAB in 13 ICUs of 13 INICC member hospitals from 8 cities of Turkey. METHODS: We conducted active, prospective surveillance before-after study to determine CLAB rates in a cohort of 4,017 adults hospitalized in ICUs. We applied the definitions of the CDC/NHSN and INICC surveillance methods. The study was divided into baseline and intervention periods. During baseline, active outcome surveillance of CLAB rates was performed. During intervention, the INICC multidimensional approach for CLAB reduction was implemented and included the following measures: 1- bundle of infection control interventions, 2- education, 3- outcome surveillance, 4- process surveillance, 5- feedback of CLAB rates, and 6- performance feedback on infection control practices. CLAB rates obtained in baseline were compared with CLAB rates obtained during intervention. RESULTS: During baseline, 3,129 central line (CL) days were recorded, and during intervention, we recorded 23,463 CL-days. We used random effects Poisson regression to account for clustering of CLAB rates within hospital across time periods. The baseline CLAB rate was 22.7 per 1000 CL days, which was decreased during the intervention period to 12.0 CLABs per 1000 CL days (IRR 0.613; 95% CI 0.43 - 0.87; P 0.007). This amounted to a 39% reduction in the incidence rate of CLAB. CONCLUSIONS: The implementation of multidimensional infection control approach was associated with a significant reduction in the CLAB rates in adult ICUs of Turkey, and thus should be widely implemented.

The effects of nurses' use of personal protective equipment on their vital signs during the COVID-19 pandemic.

BACKGROUND: In order for nurses to provide the desired/expected care during the COVID-19 pandemic, the personal protective equipment (PPE) they use should not cause additional damage. OBJECTIVE: The current study examined the effect of nurses' use of PPE on their vital signs during the COVID-19 pandemic. METHODS: The present study was executed in a public hospital located in Turkey between October 2020 and December 2020 with a total of 112 nurses, 54 of them were serving in COVID-19 clinics, and 58 of them were working in other clinics. The data of the study was collected by using the introductory information form, the vital signs measurement, and the Visual Analogue Scale. The numbers, percentages, means, standard deviation, Chi-square, ANOVA, Mann-Whitney U and Wilcoxon tests were used to analyze the data. RESULTS: The mean scores of SpO2, respiratory rate, body temperature, heart rate and blood pressure measurements of the nurses in the experimental group were compared before and after putting on the PPE. It was found that the difference between the two averages was statistically significant (p < 0.05). CONCLUSION: It was found that the use of PPE for a long time causes a decrease in SpO2, increase in respiratory rate, pulse and blood pressure, as well as the aches in face, ear, nose and head.

Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach, over 8 years, in 11 cities of Turkey.

AIMS: To evaluate the effectiveness of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach in Turkey and analyse predictors of poor hand hygiene compliance. DESIGN: An observational, prospective, interventional, before-and-after study was conducted from August 2003 to August 2011 in 12 intensive care units (ICU) of 12 hospitals in 11 cities. The study was divided into a baseline and a follow-up period and included random 30-minute observations for hand hygiene compliance in ICU. The hand hygiene approach included administrative support, supplies availability, education and training, reminders in the workplace, process surveillance, and performance feedback. RESULTS: We observed 21,145 opportunities for hand hygiene. Overall hand hygiene compliance increased from 28.8% to 91% (95% CI 87.6-93.0, p 0.0001). Multivariate and univariate analyses showed that several variables were significantly associated with poor hand hygiene compliance: males vs. females (39% vs. 48%; 95% CI 0.79-0.84, p 0.0001), ancillary staff vs. physicians (35% vs. 46%, 95% CI 0.73-0.78, p 0.0001), and adult vs. pediatric ICUs (42% vs. 74%, 95% CI 0.54-0.60, p 0.0001). CONCLUSIONS: Adherence to hand hygiene was significantly increased with the INICC Hand Hygiene Approach. Specific programmes should be directed to improve hand hygiene in variables found to be predictors of poor hand hygiene compliance.

Impact of a multidimensional infection control approach on catheter-associated urinary tract infection rates in adult intensive care units in 10 cities of Turkey: International Nosocomial Infection Control Consortium findings (INICC).

BACKGROUND: We evaluate the effectiveness of a multidimensional infection control approach for the reduction of catheter-associated urinary tract infections (CAUTIs) in 13 intensive care units (ICUs) in 10 hospital members of the International Nosocomial Infection Control Consortium (INICC) from 10 cities of Turkey. METHODS: A before-after prospective active surveillance study was used to determine rates of CAUTI. The study was divided into baseline (phase 1) and intervention (phase 2). In phase 1, surveillance was performed applying the definitions of the Centers for Disease Control and Prevention/National Healthcare Safety Network. In phase 2, we implemented a multidimensional approach that included bundle of infection control interventions, education, surveillance and feedback on CAUTI rates, process surveillance, and performance feedback. We used random effects Poisson regression to account for clustering of CAUTI rates across time periods. RESULTS: The study included 4,231 patients, hospitalized in 13 ICUs, in 10 hospitals, in 10 cities, during 49,644 patient-days. We recorded a total of 41,871 urinary catheter (UC)-days: 5,080 in phase 1 and 36,791 in phase 2. During phase 1, the rate of CAUTI was 10.63 per 1,000 UC-days and was significantly decreased by 47% in phase 2 to 5.65 per 1,000 UC-days (relative risk, 0.53; 95% confidence interval: 0.4-0.7; P value = .0001). CONCLUSION: Our multidimensional approach was associated with a significant reduction in the rates of CAUTI in Turkey.