The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence of bacterial community- and hospital-acquired pneumonia (CAP and HAP) and its effect on mortality in critically ill COVID-19 patients admitted to the intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 and 31 December 2022. The secondary objectives of this study include identifying the bacterial etiology of CAP and HAP and exploring the capabilities of diagnostic tools, with a focus on inflammatory biomarkers. Data were collected from the electronic information hospital system, encompassing biomarkers, microbiological findings, and daily visit records, and subsequently evaluated by ICU physicians and clinical microbiologists. Out of 171 patients suffering from critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically ill COVID-19 patients who experienced bacterial CAP and HAP exhibited higher mortality compared to COVID-19 patients without any bacterial infection, with rates of 38% and 56% versus 11%, respectively. In CAP, the most frequent causative agents were chlamydophila and mycoplasma; Enterobacterales, which were multidrug-resistant in 71% of cases; Gram-negative non-fermenting rods; and Staphylococcus aureus. Notably, no strains of Streptococcus pneumoniae were detected, and only a single strain each of Haemophilus influenzae and Moraxella catarrhalis was isolated. The most frequent etiologic agents causing HAP were Enterobacterales and Gram-negative non-fermenting rods. Based on the presented results, commonly used biochemical markers demonstrated poor predictive and diagnostic accuracy. To confirm the diagnosis of bacterial CAP in our patient cohort, it was necessary to assess the initial values of inflammatory markers (particularly procalcitonin), consider clinical signs indicative of bacterial infection, and/or rely on positive microbiological findings. For HAP diagnostics, it was appropriate to conduct regular detailed clinical examinations (with a focus on evaluating respiratory functions) and closely monitor the dynamics of inflammatory markers (preferably Interleukin-6).
- Publikační typ
- časopisecké články MeSH
This observational retrospective study aimed to analyze whether/how the spectrum of bacterial pathogens and their resistance to antibiotics changed during the worst part of the COVID-19 pandemic (1 November 2020 to 30 April 2021) among intensive care patients in University Hospital Olomouc, Czech Republic, as compared with the pre-pandemic period (1 November 2018 to 30 April 2019). A total of 789 clinically important bacterial isolates from 189 patients were cultured during the pre-COVID-19 period. The most frequent etiologic agents causing nosocomial infections were strains of Klebsiella pneumoniae (17%), Pseudomonas aeruginosa (11%), Escherichia coli (10%), coagulase-negative staphylococci (9%), Burkholderia multivorans (8%), Enterococcus faecium (6%), Enterococcus faecalis (5%), Proteus mirabilis (5%) and Staphylococcus aureus (5%). Over the comparable COVID-19 period, a total of 1500 bacterial isolates from 372 SARS-CoV-2-positive patients were assessed. While the percentage of etiological agents causing nosocomial infections increased in Enterococcus faecium (from 6% to 19%, p < 0.0001), Klebsiella variicola (from 1% to 6%, p = 0.0004) and Serratia marcescens (from 1% to 8%, p < 0.0001), there were significant decreases in Escherichia coli (from 10% to 3%, p < 0.0001), Proteus mirabilis (from 5% to 2%, p = 0.004) and Staphylococcus aureus (from 5% to 2%, p = 0.004). The study demonstrated that the changes in bacterial resistance to antibiotics are ambiguous. An increase in the frequency of ESBL-positive strains of some species (Serratia marcescens and Enterobacter cloacae) was confirmed; on the other hand, resistance decreased (Escherichia coli, Acinetobacter baumannii) or the proportion of resistant strains remained unchanged over both periods (Klebsiella pneumoniae, Enterococcus faecium). Changes in pathogen distribution and resistance were caused partly due to antibiotic selection pressure (cefotaxime consumption increased significantly in the COVID-19 period), but mainly due to clonal spread of identical bacterial isolates from patient to patient, which was confirmed by the pulse field gel electrophoresis methodology. In addition to the above shown results, the importance of infection prevention and control in healthcare facilities is discussed, not only for dealing with SARS-CoV-2 but also for limiting the spread of bacteria.
- Publikační typ
- časopisecké články MeSH
Regulation of phosphatidylinositol phosphates plays a crucial role in signal transduction, membrane trafficking or autophagy. Members of the myotubularin family of lipid phosphatases contribute to phosphoinositide metabolism by counteracting the activity of phosphoinositide kinases. The mechanisms determining their subcellular localization and targeting to specific membrane compartments are still poorly understood. We show here that the inactive phosphatase MTMR9 localizes to the intermediate compartment and to the Golgi apparatus and is able to recruit its active phosphatase partners MTMR6 and MTMR8 to these locations. Furthermore, MTMR8 and MTMR9 co-localize with the small GTPase RAB1A and regulate its localization. Loss of MTMR9 expression compromises the integrity of the Golgi apparatus and results in altered distribution of RAB1A and actin nucleation-promoting factor WHAMM. Loss or overexpression of MTMR9 leads to decreased rate of protein secretion. We demonstrate that secretion of physiologically relevant cargo exemplified by the WNT3A protein is affected after perturbation of MTMR9 levels.
- MeSH
- endoplazmatické retikulum metabolismus MeSH
- exocytóza MeSH
- Golgiho aparát metabolismus MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- lidé MeSH
- nereceptorové tyrosinfosfatasy genetika metabolismus MeSH
- protein Wnt3A metabolismus MeSH
- rab1 proteiny vázající GTP metabolismus MeSH
- signální dráha Wnt MeSH
- transport proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antibakteriální látky aplikace a dávkování terapeutické užití MeSH
- infekce spojené se zdravotní péčí * diagnóza etiologie farmakoterapie komplikace MeSH
- lidé MeSH
- mnohočetná bakteriální léková rezistence MeSH
- nozokomiální pneumonie * epidemiologie etiologie komplikace mortalita prevence a kontrola MeSH
- pneumonie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- ventilátorová pneumonie * diagnóza etiologie farmakoterapie komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Úvod: Pro určení optimální metody získání vzorku biologického materiálu k určení etiologického agens nozokomiální pneumonie (HAP) stále neexistuje dostatek důkazů, přičemž snaha je zaměřena na určení nejsnáze proveditelného, levného a přitom dostatečně validního způsobu odběru, který je v klinické praxi snadno proveditelný. Metody: Primárním cílem prospektivní, observační studie bylo určení prediktivní hodnoty vzorků výtěru orofaryngu (OS) a žaludečního aspirátu (GA) pro určení původců HAP. Výtěžnost těchto odběrů byla porovnána se vzorky endotracheálního aspirátu (ETA) a krytého brushe (PSB), který je považován za zlatý standard metod průkazu původce HAP. Výsledky: Do studie bylo zařazeno 56 pacientů. U 48 z nich bylo určeno v 79 izolátech signifikantní množství bakteriálních patogenů ve dvou kolech odběrů s odstupem 72 hodin. U zbylých 8 pacientů nebylo zaznamenáno signifikantní množství patogenů v žádném izolátu. Senzitivita jednotlivých typů odběrů v prvním kole byla u ETA 98%, PSB 31%, OS 64% a GA 67%; ve druhém kole ETA 87%, PSB 32%, OS 74% a GA 42%. Ve vzorcích bylo identifikováno celkem dvanáct bakteriálních species. Nejčastěji zachycenými byli: Klebsiella pneumoniae (23,7%), Burkholderia multivorans (21,1%) a Pseudomonas aeruginosa (15,8%). Závěr: Necíleně odebraný vzorek ETA je u intubovaných pacientů optimální metoda pro získání biologického materiálu k identifikaci etiologického agens HAP. U vzorků ETA byl zaznamenán výrazně častější záchyt mikrobiálního etiologického agens HAP než u PSB. V případě negativního výsledků ETA/PSB lze přihlédnout k výsledku stěru z orofaryngu a/nebo vzorku aspirátu žaludečního obsahu, které v četnosti záchytu etiologických agens následovaly ETA.
Background: There is still a lack of evidence as to which method of biological sample collection is optimal for identifying bacterial pathogens causing hospital-acquired pneumonia (HAP). Much effort has been made to find an easy and valid approach to be used in clinical practice. Methods: The primary endpoint of this prospective, observational study was to determine the predictive value of oropharyngeal swab (OS) and gastric aspiration (GA) as simple and non-invasive methods for diagnosing HAP. Their efficacy was compared to endotracheal aspiration (ETA) and protected specimen brushing (PSB), the standard methods approved for HAP diagnosis. Results: Initially, 56 patients were enrolled. Significant amounts of bacterial pathogens were detected in 48 patients (79 isolates) in Round A and in 39 patients (45 isolates) in Round B (after 72 hours). The sensitivity rates were: ETA 98%, PSB 31%, OS 64% and GA 67% in Round A and ETA 87%, PSB 32%, OS 74% and GA 42% in Round B. Strains of 12 bacterial species were identified in the samples. The three most common etiological agents (both rounds together) were Klebsiella pneumoniae (23.7%), Burkholderia multivorans (21.1%) and Pseudomonas aeruginosa (15.8%). Conclusions: Blind ETA is an optimum method for obtaining biological samples for identification of etiological agents causing HAP in intubated patients. Microbial etiological agents were more frequently detected in ETA samples than in those collected by PSB. If ETA/PSB results are negative, samples may be collected by OS and/or GA as these techniques followed ETA in terms of the frequency of pathogen detection.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- bakteriální infekce * diagnóza etiologie MeSH
- Burkholderia patogenita MeSH
- infekce spojené se zdravotní péčí * diagnóza etiologie patofyziologie MeSH
- interpretace statistických dat MeSH
- Klebsiella pneumoniae patogenita MeSH
- lidé MeSH
- nozokomiální pneumonie MeSH
- orofarynx mikrobiologie patologie MeSH
- prospektivní studie MeSH
- Pseudomonas aeruginosa patogenita MeSH
- ventilátorová pneumonie etiologie patofyziologie MeSH
- žaludek mikrobiologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- pozorovací studie MeSH
The Wnt family of proteins is a group of extracellular signalling molecules that regulate cell-fate decisions in developing and adult tissues. It is presumed that all 19 mammalian Wnt family members contain two types of post-translational modification: the covalent attachment of fatty acids at two distinct positions, and the N-glycosylation of multiple asparagines. We examined how these modifications contribute to the secretion, extracellular movement and signalling activity of mouse Wnt1 and Wnt3a ligands. We revealed that O-linked acylation of serine is required for the subsequent S-palmitoylation of cysteine. As such, mutant proteins that lack the crucial serine residue are not lipidated. Interestingly, although double-acylation of Wnt1 was indispensable for signalling in mammalian cells, in Xenopus embryos the S-palmitoyl-deficient form retained the signalling activity. In the case of Wnt3a, the functional duality of the attached acyls was less prominent, since the ligand lacking S-linked palmitate was still capable of signalling in various cellular contexts. Finally, we show that the signalling competency of both Wnt1 and Wnt3a is related to their ability to associate with the extracellular matrix.
- MeSH
- buněčné linie MeSH
- cystein metabolismus MeSH
- embryonální vývoj MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lipoylace MeSH
- molekulární sekvence - údaje MeSH
- mutace MeSH
- myši MeSH
- protein Wnt1 genetika metabolismus MeSH
- protein Wnt3 MeSH
- protein Wnt3A MeSH
- proteiny Wnt genetika metabolismus MeSH
- proteiny Xenopus MeSH
- sekvence aminokyselin MeSH
- serin metabolismus MeSH
- substituce aminokyselin MeSH
- Xenopus embryologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: To determine the incidence of postoperative nausea and vomiting (PONV), identify risk factors, assess treatment and its effectiveness. DESIGN: A prospective, observational, questionnaire- and interview-based study. SETTING: Standard and intensive care units of the following university hospital departments: abdominal, thoracic and vascular surgery; gynecology; plastic and esthetic surgery; urology; and traumatology. MATERIAL AND METHODS: Adult patients scheduled for elective surgery who gave informed consent were enrolled. A questionnaire-based study was performed on the first postoperative day. The collected data relevant to PONV were statistically analyzed. CONCLUSION: The incidence of PONV was significantly lower than generally presumed and was related to the patient gender, type of surgery and overall health status. PONV was more frequent in obese patients and when drugs antagonizing opioids or muscle relaxants were used. Early administration of antiemetic agents led to considerably less discomfort.
- MeSH
- dospělí MeSH
- financování organizované MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemocnice univerzitní MeSH
- pooperační nevolnost a zvracení MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
Wnt signaling enhances cell proliferation and the maintenance of hematopoietic cells. In contrast, cytotoxic ligand Apo2L/TRAIL induces the apoptosis of various transformed cells. We observed that co-culture of human pre-B leukemia cells KM3 and REH with Wnt1- or Wnt3a-producing rat embryonic fibroblasts efficiently suppressed Apo2L/TRAIL-induced apoptosis of the lymphoid cells. This suppression occurs at the early stages of the Apo2L/TRAIL apoptotic cascade and, interestingly, the activation of the Wnt pathway alone in human leukemia cells is not sufficient for their full anti-apoptotic protection. We hypothesize that a stimulus emanating specifically from Wnt1- or Wnt3a-expressing rat fibroblasts is responsible for the observed resistance to Apo2L/TRAIL. This anti-apoptotic signaling was significantly hampered by the inhibition of the MEK1/ERK1/2 or NFkappaB pathways in KM3 and REH cells. Our results imply that paracrine Wnt-related signals could be important for the survival of pre-B cell-derived malignancies.
- MeSH
- apoptóza fyziologie MeSH
- beta-katenin fyziologie MeSH
- cykloheximid farmakologie MeSH
- daktinomycin farmakologie MeSH
- financování organizované MeSH
- kokultivační techniky MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- pre-B-buněčná leukemie MeSH
- protein TRAIL antagonisté a inhibitory MeSH
- protein Wnt1 biosyntéza MeSH
- proteiny regulující apoptózu fyziologie MeSH
- proteiny Wnt biosyntéza MeSH
- signální transdukce fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
