Poor Prestroke Glycemic Control Increases the Rate of Symptomatic Intracranial Hemorrhage after Mechanical Thrombectomy.

(1) Background: Diabetes is a well-established risk factor for acute ischemic stroke (AIS). This study evaluated the impact of prestroke glycemic control in diabetic patients on their 3-month clinical outcome after mechanical thrombectomy (MT). (2) Methods: AIS patients with a premorbid modified Rankin scale (mRS) score of 0-2 who were admitted within 6 h after stroke onset and treated with MT between January 2020 and August 2023 were retrospectively analyzed. The study evaluated the effect of prestroke glycemic control on the stroke severity, reperfusion rate, symptomatic intracranial hemorrhage (sICH) and favorable clinical outcome (modified Rankin scale score 0-2) at 3 months after endovascular treatment. (3) Results: A total of 364 patients were analyzed, with 275 cases of non-diabetes (ND), 66 of well-controlled diabetes (WCD) and 23 of poorly controlled diabetes (PCD). There was no significant difference in the baseline neurological deficit expressed according to the National Institutes of Health Stroke Scale among the three groups. The time from stroke onset to groin puncture was similar in the ND, WCD and PCD groups (median 215 min, 194.5 min and 222.5 min, respectively). There was no significant difference in the favorable 3-month clinical outcomes among these three groups (35.2% of ND patients, 42.4% of WCD patients and 39.1% of PCD patients) or full recovery (12.4% of ND patients, 11.0% of WCD patients and 17.4% of PCD patients). The rate of sICH was significantly higher in the PCD group as compared to the ND and WDP groups (21.7% of PCD patients versus 7.6% of ND patients, p = 0.038, and 6.0% of WCD patients, p = 0.046), but the 3-month mortality did not differ between the three groups (21.8% of ND group, 19.7% of WCD group and 26.1% of PCD group). (4) Conclusions: This study shows that poor prestroke glycemic control in AIS diabetic patients does not change the chance of a good clinical functional outcome after endovascular treatment. However, the increased risk of hemorrhagic complications in this group of patients should be considered.

What happens to Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum in an experimental environment with eukaryotic cells?

BACKGROUND: The impact of probiotic strains on host health is widely known. The available studies on the interaction between bacteria and the host are focused on the changes induced by bacteria in the host mainly. The studies determining the changes that occurred in the bacteria cells are in the minority. Within this paper, we determined what happens to the selected Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum in an experimental environment with the intestinal epithelial layer. For this purpose, we tested the bacteria cells' viability, redox activity, membrane potential and enzymatic activity in different environments, including CaCo-2/HT-29 co-culture, cell culture medium, presence of inflammatory inductor (TNF-α) and oxygen. RESULTS: We indicated that the external milieu impacts the viability and vitality of bacteria. Bifidobacterium adolescentis decrease the size of the live population in the cell culture medium with and without TNF-α (p < 0.001 and p < 0.01 respectively). In contrast, Bifidobacterium longum ssp. longum significantly increased survivability in contact with the eukaryotic cells and cell culture medium (p < 0.001). Bifidobacterium adolescentis showed significant changes in membrane potential, which was decreased in the presence of eukaryotic cells (p < 0.01), eukaryotic cells in an inflammatory state (p < 0.01), cell culture medium (p < 0.01) and cell culture medium with TNF-α (p < 0.05). In contrast, Bifidobacterium longum ssp. longum did not modulate membrane potential. Instead, bacteria significantly decreased the redox activity in response to milieus such as eukaryotic cells presence, inflamed eukaryotic cells as well as the culture medium (p < 0.001). The redox activity was significantly different in the cells culture medium vs the presence of eukaryotic cells (p < 0.001). The ability to ß-galactosidase production was different for selected strains: Bifidobacterium longum ssp. longum indicated 91.5% of positive cells, whereas Bifidobacterium adolescentis 4.34% only. Both strains significantly reduced the enzyme production in contact with the eukaryotic milieu but not in the cell culture media. CONCLUSION: The environmental-induced changes may shape the probiotic properties of bacterial strains. It seems that the knowledge of the sensitivity of bacteria to the external environment may help to select the most promising probiotic strains, reduce research costs, and contribute to greater reproducibility of the obtained probiotic effects.

Is the Urinary and Gut Microbiome Associated With Bladder Cancer?

Background: Microbiome dysbiosis plays a role in the pathogenesis of many urological diseases, including bladder cancer (BC). The aim of the study was to compare the urinary and gut microbiota of patients with BC with a healthy control (HC) group. Methods: The study group included patients hospitalized in 2020 to 2021 with diagnosed BC and HC. Prior to the transurethral resection of bladder tumor, patients collected their urine and stool which was then subjected to 16S rRNA gene sequencing. Results: Overall, 25 patients were enrolled in the study: 18 in the BC group and 7 in the HC group. Analysis of the urine and stool microbiome showed no statistically significant differences between patients with BC and HC in alpha diversity, beta diversity, and difference in taxa relative abundance. Detailed analysis of urine and stool microbiome depending on patient- and tumor-related characteristics also showed no statistically significant differences in alpha diversity and beta diversity. Differences in abundance (ANCOM) were noted in both types of samples in patients with BC. In the urine test, genus Lactobacillus was more common in patients with a positive history of Bacillus Calmette-Guérin (BCG) therapy, while genus Howardella and the strain Streptococcus anginosus were more common in women. In stool samples, abundance of phylum Desulfobacterota was most abundant in Grade G1 and least in G2. Class Alphaproteobacteria, order Rhodospirillales, order Flavobacteriales, and family Flavobacteriaceae were more common in women. Conclusions: The microbiome of urine and stool of patients with BC does not differ significantly from that of HC; however, its composition in patients with BC varies according to the patient's sex.

Preoperative glycated hemoglobin concentration and early postoperative infections in patients undergoing spinal surgery: A systematic review.

Early postoperative infections can affect a significant number of spinal surgery patients. Many studies reported on the features that may associate with elevated risk of infectious complications in this group. Data on the impact of glucose metabolism disorders in this area are well known. At the same time information on the correlation of preoperative HbA1c level and postoperative infections in spinal surgery are still scarce. Furthermore there are no strict recommendations regarding routine HbA1c testing prior to elective surgery. In present SR we aimed to report available clinical evidence on association between preoperative HbA1c and early postoperative infections. We used PubMed and EMBASE database and a set of specific key words (spine surgery AND infections AND HbA1c) to identify eligible studies. The study was registered in PROSPERO database and reported according to PRISMA recommendations. 16 studies were selected for further assessment. Predominance of data indicated a significant correlation between preoperative HbA1c concentration and elevated risk of postoperative infections, as well as higher rate of non - infective complications and worse patients future outcome. Adequately designed future studies on purposely dimensioned sample size are needed to confirm the role of preoperative HbA1c testing in preoperative management of spinal surgery patients.

Studies of the Impact of the Bifidobacterium Species on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Murine Macrophages of the BMDM Cell Line.

Bifidobacterium species are one of the most important probiotic microorganisms which are present in both, infants and adults. Nowadays, growing data describing their healthy properties arise, indicating they could act at the cellular and molecular level. However, still little is known about the specific mechanisms promoting their beneficial effects. Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), is involved in the protective mechanisms in the gastrointestinal tract, where it can be provided by epithelial cells, macrophages, or bacteria. The present study explored whether induction of iNOS-dependent NO synthesis in macrophages stems from the cellular action of Bifidobacterium species. The ability of ten Bifidobacterium strains belonging to 3 different species (Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium animalis) to activate MAP kinases, NF-κB factor, and iNOS expression in a murine bone-marrow-derived macrophages cell line was determined by Western blotting. Changes in NO production were determined by the Griess reaction. It was performed that the Bifidobacterium strains were able to induce NF-қB-dependent iNOS expression and NO production; however, the efficacy depends on the strain. The highest stimulatory activity was observed for Bifidobacterium animalis subsp. animals CCDM 366, whereas the lowest was noted for strains Bifidobacterium adolescentis CCDM 371 and Bifidobacterium longum subsp. longum CCDM 372. Both TLR2 and TLR4 receptors are involved in Bifidobacterium-induced macrophage activation and NO production. We showed that the impact of Bifidobacterium on the regulation of iNOS expression is determined by MAPK kinase activity. Using pharmaceutical inhibitors of ERK 1/2 and JNK, we confirmed that Bifidobacterium strains can activate these kinases to control iNOS mRNA expression. Concluding, the induction of iNOS and NO production may be involved in the protective mechanism of action observed for Bifidobacterium in the intestine, and the efficacy is strain-dependent.

Polysaccharide BAP1 of Bifidobacterium adolescentis CCDM 368 is a biologically active molecule with immunomodulatory properties.

Bifidobacteria are among the most common bacteria used for their probiotic properties and their impact on the maturation and function of the immune system has been well-described. Recently, scientific interest is shifting from live bacteria to defined bacteria-derived biologically active molecules. Their greatest advantage over probiotics is the defined structure and the effect independent of the viability status of the bacteria. Here, we aim to characterize Bifidobacterium adolescentis CCDM 368 surface antigens that include polysaccharides (PSs), lipoteichoic acids (LTAs), and peptidoglycan (PG). Among them, Bad368.1 PS was observed to modulate OVA-induced cytokine production in cells isolated from OVA-sensitized mice by increasing the production of Th1-related IFN-γ and inhibition of Th2-related IL-5 and IL-13 cytokines (in vitro). Moreover, Bad368.1 PS (BAP1) is efficiently engulfed and transferred between epithelial and dendritic cells. Therefore, we propose that the Bad368.1 PS (BAP1) can be used for the modulation of allergic diseases in humans. Structural studies revealed that Bad368.1 PS has an average molecular mass of approximately 9,99 × 106 Da and it consists of glucose, galactose, and rhamnose residues that are creating the following repeating unit: →2)-ß-D-Glcp-1→3-ß-L-Rhap-1→4-ß-D-Glcp-1→3-α-L-Rhap-1→4-ß-D-Glcp-1→3-α-D-Galp-(1→n.

A Novel Mechanism of Macrophage Activation by the Natural Yolkin Polypeptide Complex from Egg Yolk.

Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-ß and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine.

Hypoxia may be a determinative factor in COVID-19 progression.

The disease which develops following SARS-CoV-2 virus infection, known as COVID-19, in most affected countries displays mortality from 1.5% to 9.8%. When leukocytosis due to granulocytosis, thrombocytopenia, and increased level of D-dimers are detected early during the disease course, they are accurate predictors of mortality. Based on the published observations that each of the aforementioned disturbances by itself may appear as a consequence of hypoxia, a hypothesis is presented that early hypoxia consequential to sleep apnea and/or blunted respiratory response to chemical stimuli is an early determinant of COVID-19 progression to the severe and critical stage. Further, it is noted that host-directed therapies which may counteract hypoxia and its early downstream effects are initiated only upon hospitalization of COVID-19 patients, which is too late to be fully effective. An example is anticoagulation treatment with low molecular weight heparin. Repurposing drugs which could counteract some early posthypoxic events, such as fluvoxamine, amantadine and N-acetylcysteine, for post-exposure prophylaxis of SARS-CoV-2 infection and early prehospital treatment of COVID-19, is indicated.

Direct admission vs. secondary transfer for mechanical thrombectomy: long-term clinical outcomes from a single Polish Comprehensive Stroke Centre.

INTRODUCTION: We aimed to compare 3-month clinical outcomes after mechanical thrombectomy (MT) in patients transferred directly to a comprehensive stroke centre ('mothership', MS) to the outcomes of patients transferred secondarily from primary stroke centres ('drip-and-ship', DAS) in Lubelskie province, the third largest province in Poland. MATERIAL AND METHODS: In a prospective stroke registry, all patients with large vessel occlusion in anterior circulation admitted within six hours of onset and treated with MT between 2017 and 2020 were retrospectively analysed. RESULTS: A total of 400 patients was evaluated: 267 treated with the MS approach and 133 with the DAS approach. Time from stroke onset to groin puncture was shorter in the MS group. There was a significant difference in 3-month excellent clinical outcomes (mRS 0-1) between these two groups (32.9% of MS patients vs. 22.5% of DAS patients, p < 0.05), but there was no difference if the 3-month endpoint was expressed as mRS ≤ 2 (42.3% of MS vs. 34.5% of DAS patients, p = 0.13). The rate of symptomatic intracranial haemorrhage and mortality was comparable in both groups. CONCLUSIONS: Our study shows that direct admission to a comprehensive stroke centre resulted in more patients achieving excellent treatment outcomes (mRS 0-1). At the same time, the superiority of the MT model over the DAS model in obtaining mRS 0-2 was not unequivocally demonstrated. Further studies are needed to determine the best stroke model for patients potentially eligible for MT.

Stroke patients from rural areas have lower chances for long-term good clinical outcome after mechanical thrombectomy.

BACKGROUND: This study evaluated 3-months clinical outcome after mechanical thrombectomy (MT) in stroke patients transferred to a comprehensive stroke center (CSC) from a rural and urban areas in a Lubelskie province, the third largest province in Poland. MATERIALS AND METHODS: Acute stroke patients with a premorbid modified Rankin scale (mRS) score 0-2 who were admitted within 6 h after stroke onset and treated with MT between 2016 and 2020 were retrospectively analyzed. Patients from rural and urban areas transported directly to CSC were compared regarding the onset-to-groin time, reperfusion rate, symptomatic intracranial hemorrhage (sICH) and favourable clinical outcome (modified Rankin Scale score 0-2) 3-months after MT. RESULTS: A total of 398 patients were analyzed: 179 from rural areas (RA) and 219 from urban areas (UA). There was no significant difference in baseline neurological deficit expressed in The National Institutes of Health Stroke Scale (median 18.4 for RA patients versus 18.1 for UA patients, p = 0.70). Time from stroke onset to groin puncture was significantly shorter in the UA patients (median 197.3 min versus 219.6 min, p = 0.004). There was a significant difference in 3 months favourable clinical outcome between these two groups (31.3% of RA patients versus 42.5% of UA patients, p = 0.021) and full recovery rates (5.6% of RA patients versus 15.0% of UA patients, p = 0.002). The rate of sICH and 3-months mortality was similar in both groups (7.3% of RA patients versus 8.7% of UA patients, p = 0.61% and 21.8% of RA group vs. 22.4% of UA group, p = 0.88, respectively). CONCLUSION: Stroke patients from RA undergoing thrombectomy had worse functional outcome compared to UA patients. Since the benefit of MT is time dependent, urban-rural differences in stroke outcome probably result from the longer time from stroke onset to reperfusion treatment in RA patients.