Epidemiology and chronobiology of out-of-hospital cardiac arrest in a subpopulation of southern Poland: A two-year observation

Background: Although recent studies indicate temporal variations in the incidence of out-of-hospital cardiac arrest (OHCA), the Polish experience in this research is scarce to date. We evaluated the epidemiology of OHCA and circadian, weekly and seasonal variations of OHCA frequency among the adult population of the Opole district, Poland. Methods: The retrospective analysis of 815 OHCA cases with presumed cardiac etiology was made based on dispatch cards from the Emergency Medical Center in Opole registered during a 2 year period (2006–2007). Results: The incidence of OHCA in the studied population was 1.56/1000 inhabitants per year. Mean age of the group was 69.2 ± 14.2 years, with the majority of men (63%), younger than women (66.1 vs. 74 years, p = 0.0001). The OHCA occurrence increased with age reaching a peak between 71 and 75 years. The incidence of OHCA stayed at stable low levels between 22:00 and 4:59 and started to increase at 5:00, with trimodal peaks: 8:00–10:59, 14:00–15:59 and 18.00–21.59. The lowest number of OHCA occurred from 00:00 to 5:59, the highest from 6:00 to 11:59 (13% vs. 32.4%, p < 0.001). The day with the lowest occurrence of OHCA was Friday, the highest Saturday (10.9% vs. 16%, p = 0.01). Summer was the season of the lowest incidence of OHCA, while winter — the highest (22.6% vs. 26%, p = 0.04). These seasons were the warmest and the coldest one, respectively (average temperature 18.5°C vs. 0°C, p < 0.001). Conclusions: Circadian and less marked, weekly variability in OHCA occurrence were confirmed. Existing seasonal differences may be affected by temperature. This is the first Polish analysis of a large subpopulation, which also includes seasonal temperature data

Platelet-to-lymphocyte ratio as a prognostic biomarker for COVID-19 severity: a single center retrospective data analysis and systematic review with meta-analysis of 187 studies

INTRODUCTION: This study aims to evaluate the prognostic value of the platelet-to-lymphocyte ratio in determining the severity and mortality of adults hospitalized for COVID-19 using retrospective data and a meta-analysis of previous studies on the platelet-to-lymphocyte ratio worldwide. MATERIAL AND METHODS: A retrospective study was conducted at the Kırdar City Hospital (Istanbul, Turkey) and included 521 COVID-19 patients. A systematic literature search of EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases was performed for relevant trials relating to the PLR ratio in COVID-19 published before April 12, 2023. RESULTS: In the retrospective part of the study, PLR values were found to predict COVID-19 severity at admission with an AUC of 0.61 (SE = 0.03; 95% CI: 0.56 to 0.65; p = 0.0003) as well as survival status in a statistically significant fashion with an AUC of 0.59 (SE = 0.03; 95% CI: 0.55 to 0.64; p = 0.0004). Results of our meta-analysis showed a significant relationship between PLR and COVID-19 severity, with a pooled standardized mean difference (SMD) of 1.34 (95% CI: 1.13 to 1.55; p < 0 .001), and that PLR was significantly lower among patients who survived compared to deceased patients (SMD = –1.32; 95% CI: 1.57 to –1.07; p < 0.001). CONCLUSIONS: PLR is a valid, readily available marker that can distinguish COVID-19 individuals with distinct progression and survival outcomes

NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA

Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host–pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H(2)O(2)), but its consequences on extracellular pathogens are unknown. Here we show that H(2)O(2), released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches

Phagocytosis of Staphylococcus aureus by Macrophages Exerts Cytoprotective Effects Manifested by the Upregulation of Antiapoptotic Factors

It is becoming increasingly apparent that Staphylococcus aureus are able to survive engulfment by macrophages, and that the intracellular environment of these host cells, which is essential to innate host defenses against invading microorganisms, may in fact provide a refuge for staphylococcal survival and dissemination. Based on this, we postulated that S. aureus might induce cytoprotective mechanisms by changing gene expression profiles inside macrophages similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis. To validate our hypothesis we first ascertained whether S. aureus infection could affect programmed cell death in human (hMDMs) and mouse (RAW 264.7) macrophages and, specifically, protect these cells against apoptosis. Our findings indicate that S. aureus-infected macrophages are more resistant to staurosporine-induced cell death than control cells, an effect partly mediated via the inhibition of cytochrome c release from mitochondria. Furthermore, transcriptome analysis of human monocyte-derived macrophages during S. aureus infection revealed a significant increase in the expression of antiapoptotic genes. This was confirmed by quantitative RT-PCR analysis of selected genes involved in mitochondria-dependent cell death, clearly showing overexpression of BCL2 and MCL1. Cumulatively, the results of our experiments argue that S. aureus is able to induce a cytoprotective effect in macrophages derived from different mammal species, which can prevent host cell elimination, and thus allow intracellular bacterial survival. Ultimately, it is our contention that this process may contribute to the systemic dissemination of S. aureus infection

A Potential New Pathway for Staphylococcus aureus Dissemination: The Silent Survival of S. aureus Phagocytosed by Human Monocyte-Derived Macrophages

Although considered to be an extracellular pathogen, Staphylococcus aureus is able to invade a variety of mammalian, non-professional phagocytes and can also survive engulfment by professional phagocytes such as neutrophils and monocytes. In both of these cell types S. aureus promptly escapes from the endosomes/phagosomes and proliferates within the cytoplasm, which quickly leads to host cell death. In this report we show that S. aureus interacted with human monocyte-derived macrophages in a very different way to those of other mammalian cells. Upon phagocytosis by macrophages, S. aureus persisted intracellularly in vacuoles for 3–4 days before escaping into the cytoplasm and causing host cell lysis. Until the point of host cell lysis the infected macrophages showed no signs of apoptosis or necrosis and were functional. They were able to eliminate intracellular staphylococci if prestimulated with interferon-γ at concentrations equivalent to human therapeutic doses. S. aureus survival was dependent on the alternative sigma factor B as well as the global regulator agr, but not SarA. Furthermore, isogenic mutants deficient in α-toxin, the metalloprotease aureolysin, protein A, and sortase A were efficiently killed by macrophages upon phagocytosis, although with different kinetics. In particular α-toxin was a key effector molecule that was essential for S. aureus intracellular survival in macrophages. Together, our data indicate that the ability of S. aureus to survive phagocytosis by macrophages is determined by multiple virulence factors in a way that differs considerably from its interactions with other cell types. S. aureus persists inside macrophages for several days without affecting the viability of these mobile cells which may serve as vehicles for the dissemination of infection