BACKGROUND: In patients resuscitated after cardiac arrest, a higher mean arterial pressure (MAP) may increase cerebral perfusion and attenuate hypoxic brain injury. Here we present the protocol of the mean arterial pressure after cardiac arrest and resuscitation (MAP-CARE) trial aiming to investigate the influence of MAP targets on patient outcomes. METHODS: MAP-CARE is one component of the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) 2 x 2 x 2 factorial randomized trial. The MAP-CARE trial is an international, multicenter, parallel-group, investigator-initiated, superiority trial designed to test the hypothesis that targeting a higher (>85 mmHg) (intervention) versus a lower (>65 mmHg) (comparator) MAP after resuscitation from cardiac arrest reduces 6-month mortality (primary outcome). Trial participants are adults with sustained return of spontaneous circulation who are comatose following resuscitation from out-of-hospital cardiac arrest. The two other components of the STEPCARE trial evaluate sedation and temperature control strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. Neurological prognostication will be performed according to European Resuscitation Council and European Society of Intensive Care Medicine guidelines by a physician blinded to allocation group. The sample size of 3500 participants provides 90% power with an alpha of 0.05 to detect a 5.6 absolute risk reduction in 6-month mortality, assuming a mortality of 60% in the control group. Secondary outcomes will be poor functional outcome 6 months after randomization, patient-reported overall health 6 months after randomization, and the proportion of participants with predefined severe adverse events. CONCLUSION: The MAP-CARE trial will investigate if targeting a higher MAP compared to a lower MAP during intensive care of adults who are comatose following resuscitation from out-of-hospital cardiac arrest reduces 6-month mortality.

• MeSH
• arteriální tlak * fyziologie   MeSH
• dospělí MeSH
• hodnocení ekvivalence jako téma MeSH
• kardiopulmonální resuscitace * metody   MeSH
• kóma etiologie   MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• resuscitace * MeSH
• srdeční zástava * terapie   patofyziologie   mortalita   MeSH
• výsledek terapie MeSH
• zástava srdce mimo nemocnici * terapie   patofyziologie   mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: Fever is associated with brain injury after cardiac arrest. It is unknown whether fever management with a feedback-controlled device impacts patient-centered outcomes in cardiac arrest patients. This trial aims to investigate fever management with or without a temperature control device after out-of-hospital cardiac arrest. METHODS: The TEMP-CARE trial is part of the 2 × 2 × 2 factorial Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, a randomized, international, multicenter, parallel-group, investigator-initiated, superiority trial that will evaluate sedation strategies, temperature management, and blood pressure targets simultaneously in nontraumatic/nonhemorrhagic out-of-hospital cardiac arrest patients following hospital admission. For the temperature management component of the trial described in this protocol, patients will be randomly allocated to fever management with or without a feedback-controlled temperature control device. For those managed with a device, if temperature ≥37.8°C occurs within 72 h post-randomization the device will be started targeting a temperature of ≤37.5°C. Standard fever treatment, as recommended by local guidelines, including pharmacological agents, will be provided to participants in both groups. The two other components of the STEPCARE trial evaluate sedation and blood pressure strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. A physician blinded to the intervention will determine the neurological prognosis following European Resuscitation Council and European Society of Intensive Care Medicine guidelines. The primary outcome is all-cause mortality at six months post-randomization. To detect a 5.6% absolute risk reduction (90% power, alpha .05), 3500 participants will be enrolled. Secondary outcomes include poor functional outcome at six months, intensive care-related serious adverse events, and overall health status at six months. CONCLUSION: The TEMP-CARE trial will investigate if post-cardiac arrest management of fever with or without a temperature control device affects patient-important outcomes after cardiac arrest.

• MeSH
• horečka * terapie   MeSH
• kardiopulmonální resuscitace * MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• tělesná teplota MeSH
• terapeutická hypotermie * přístrojové vybavení   MeSH
• zástava srdce mimo nemocnici * terapie   komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: Basic management for patients who have suffered a cardiac arrest and are admitted to an intensive care unit (ICU) after resuscitation includes setting targets for blood pressure and managing sedation and temperature. However, optimal targets and management are unknown. METHODS: The STEPCARE (Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation) trial is a multicenter, parallel-group, randomized, factorial, superiority trial in which sedation, temperature, and blood pressure strategies will be studied in three separate comparisons (SED-CARE, TEMP-CARE, and MAP-CARE). The trial population will be adults admitted to intensive care who are comatose after resuscitation from out-of-hospital cardiac arrest. The primary outcome will be all-cause mortality, and the secondary outcomes will be poor functional outcome (modified Rankin Scale 4-6), Health-Related Quality of Life using EQ-VAS, and specific serious adverse events in the intensive care unit predefined for each trial. All outcomes will be assessed at 6 months after randomization. The prognosticators, outcome assessors, statisticians, data managers, steering group, and manuscript writers will be blinded to treatment allocation. This statistical analysis plan includes a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Analyses will be conducted according to the intention-to-treat principle, that is, all randomized participants with available data will be included. The analyses will be performed independently by two statisticians following the present plan. CONCLUSION: This statistical analysis plan describes the statistical analyses for the STEPCARE trial in detail. The aim of this predefined statistical analysis plan is to minimize the risk of analysis bias.

• MeSH
• kardiopulmonální resuscitace * metody   MeSH
• krevní tlak * MeSH
• kvalita života MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• tělesná teplota MeSH
• zástava srdce mimo nemocnici * terapie   mortalita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• protokol klinické studie MeSH

BACKGROUND: Sedation is often provided to resuscitated out-of-hospital cardiac arrest (OHCA) patients to tolerate post-cardiac arrest care, including temperature management. However, the evidence of benefit or harm from routinely administered deep sedation after cardiac arrest is limited. The aim of this trial is to investigate the effects of continuous deep sedation compared to minimal sedation on patient-important outcomes in resuscitated OHCA patients in a large clinical trial. METHODS: The SED-CARE trial is part of the 2 × 2 × 2 factorial Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) trial, a randomized international, multicentre, parallel-group, investigator-initiated, superiority trial with three simultaneous intervention arms. In the SED-CARE trial, adults with sustained return of spontaneous circulation (ROSC) who are comatose following resuscitation from OHCA will be randomized within 4 hours to continuous deep sedation (Richmond agitation and sedation scale (RASS) -4/-5) (intervention) or minimal sedation (RASS 0 to -2) (comparator), for 36 h after ROSC. The primary outcome will be all-cause mortality at 6 months after randomization. The two other components of the STEPCARE trial evaluate sedation and temperature control strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. Neurological prognostication will be performed according to European Resuscitation Council and European Society of Intensive Care Medicine guidelines by a physician blinded to the allocation group. To detect an absolute risk reduction of 5.6% with an alpha of 0.05, 90% power, 3500 participants will be enrolled. The secondary outcomes will be the proportion of participants with poor functional outcomes 6 months after randomization, serious adverse events in the intensive care unit, and patient-reported overall health status 6 months after randomization. CONCLUSION: The SED-CARE trial will investigate if continuous deep sedation (RASS -4/-5) for 36 h confers a mortality benefit compared to minimal sedation (RASS 0 to -2) after cardiac arrest.

• MeSH
• analgosedace * metody   MeSH
• dospělí MeSH
• hluboká sedace * metody   MeSH
• kardiopulmonální resuscitace * metody   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• zástava srdce mimo nemocnici * terapie   mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• srovnávací studie MeSH

The circadian clock in choroid plexus (ChP) controls processes involved in its physiological functions, but the signals that synchronize the clock have been sparsely studied. We found that the ChP clock in the fourthventricle (4V) is more robust than that in the lateral ventricle (LV) and investigated whether both clocks use information about mealtime as a signal to synchronize with the current activity state. Exposure of mPer2Luc mice to a 10-day reverse restricted feeding (rRF) protocol, in which food was provided for 6 h during daytime, advanced the phase of the ChP clock in 4V and LV, as evidenced by shifted (1) PER2-driven bioluminescence rhythms of ChP explants ex vivo and (2) daily profiles in clock gene expression in both ChP tissues in vivo. In contrast, clocks in other brain regions (DMH, ARC, LHb) of the same mice did not shift. The 4V ChP responded more strongly than the LV ChP to rRF by modulating the expression of genes to ensure a decrease in resistance to cerebrospinal fluid drainage and increase the secretory capacity of ChP cells. Mechanistically, rRF affects the ChP clock through food-induced increases in insulin, glucose and temperature levels, as in vitro all three signals significantly shifted the clocks in both ChP tissues, similar to rRF. The effect of glucose was partially blocked by OSMI-1, suggesting involvement of O-linked N-acetylglucosamine posttranslational modification. We identified mechanisms that can signal to the brain the time of feeding and the associated activity state via resetting of the ChP clock.

• MeSH
• cirkadiánní hodiny * fyziologie   genetika   MeSH
• cirkadiánní proteiny Period metabolismus   genetika   MeSH
• cirkadiánní rytmus fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• plexus chorioideus * metabolismus   fyziologie   MeSH
• regulace genové exprese MeSH
• stravovací zvyklosti * fyziologie   MeSH
• ventriculi laterales metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Směrnice, které se zaměřují na proces sterilizace zdravotnických prostředků pomocí páry a tepla. Určeno odborné veřejnosti.

• MeSH
• pára MeSH
• reprodukovatelnost výsledků MeSH
• řízení kvality MeSH
• sektor zdravotní péče MeSH
• sterilizace MeSH
• vysoká teplota MeSH
• zdravotnické prostředky MeSH
• Publikační typ
• směrnice MeSH
• Geografické názvy
• Česká republika MeSH
• Evropa MeSH

• Konspekt
• Metrologie. Standardizace
• NLK Obory
• technika lékařská, zdravotnický materiál a protetika

Zoonózy se každoročně v České republice významně podílejí na počtu hlášených infekčních onemocnění. Stoupající tendence výskytu zoonotických virů, jako je virus zika virus, virus horečky dengue, virus chikungunyi a virus západonilské horečky, přenášených invazivními tropickými druhy komárů, je v první řadě důsledkem dlouhodobého, postupného a prakticky nezastavitelného šíření tohoto hmyzu po evropském kontinentu, včetně severských států. Evropa nyní již pravidelně zažívá opakované každoroční vlny veder, stejně jako časté záplavy. Navyšuje se nejen počet letních dnů s tropickými teplotami, ale období léta jako takového se významně prodlužuje. Stírají se jarní a podzimní období, rychlost nástupu letních teplot po období zim je často až drastická. Tento proces navozuje příznivé životní podmínky pro etablování tropických druhů komárů na našem území. Například ještě v roce 2013 se invazivní druh komára Aedes albopictus, původem z Asie, vyskytoval „pouze" v osmi evropských zemích a zasaženo bylo 114 regionů. O pouhých deset let později byl jeho výskyt potvrzen již ve třinácti zemích a 337 oblastech, včetně České republiky. Tento trend bude pokračovat, je proto nutné očekávat nárůsty autochtonních infekcí, včetně komplikovaných průběhů infekcí a úmrtí, obzvláště v rizikových skupinách rychle stárnoucí evropské populace. Kromě nutnosti hledat nové způsoby kontroly populací komárů, vývoje nových desinsekčních a larvicidních chemikálií je třeba zásadně posilovat programy surveillance napříč spolupracující Evropou, prosazovat používání osobních ochranných pomůcek a jednoznačně posílit výzkum a vývoj specifických antivirotik a nových očkovacích látek.

Zoonoses contribute significantly to the number of reported infectious diseases in the Czech Republic each year. The rising trend in zoonotic viruses such as Zika virus, dengue virus, Chikungunya virus, West Nile virus, transmitted by invasive tropical mosquito species, is primarily due to the long-term, gradual and virtually unstoppable spread of these insects across the European continent, including the Nordic countries. Europe now regularly experiences recurrent annual heat waves as well as frequent flooding. Not only are the number of summer days with tropical temperatures increasing, but the summer period itself is being significantly extended. The spring and autumn seasons are becoming shorter, and the speed of the onset of summer temperatures after winter is often drastic. This process creates favorable living conditions for the establishment of tropical mosquito species in our territory. For example, as recently as 2013, the invasive mosquito species Aedes albopictus, native to Asia, was present in "only" eight European countries and 114 regions were affected. In 2023, its presence has already been confirmed in thirteen countries and 337 regions, including the Czech Republic. This trend is set to continue, so increases in autochthonous infections, including complicated infection patterns and deaths, are to be expected, especially in at-risk groups of the rapidly ageing European population. In addition to the need to find new ways of controlling mosquito populations, the development of new disinsecticidal and larvicidal chemicals, surveillance programs across a cooperating Europe need to be substantially strengthened, the use of personal protective equipment needs to be promoted, and research and development of specific antivirals and new vaccines needs to be clearly stepped up.

• Klíčová slova
• tropičtí komáři,
• MeSH
• Culicidae MeSH
• infekce virem zika epidemiologie   přenos   terapie   MeSH
• komáří přenašeči * MeSH
• lidé MeSH
• virus zika * izolace a purifikace   účinky léků   MeSH
• zoonózy * epidemiologie   přenos   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

Fibroblast growth factors (FGFs) control organ morphogenesis during development as well as tissue homeostasis and repair in the adult organism. Despite their importance, many mechanisms that regulate FGF function are still poorly understood. Interestingly, the thermodynamic stability of 22 mammalian FGFs varies widely, with some FGFs remaining stable at body temperature for more than 24 h, while others lose their activity within minutes. How thermodynamic stability contributes to the function of FGFs during development remains unknown. Here we show that FGF10, an important limb and lung morphogen, exists as an intrinsically unstable protein that is prone to unfolding and is rapidly inactivated at 37 °C. Using rationally driven directed mutagenesis, we have developed several highly stable (STAB) FGF10 variants with a melting temperature of over 19 °C more than that of wildtype FGF10. In cellular assays in vitro, the FGF10-STABs did not differ from wildtype FGF10 in terms of binding to FGF receptors, activation of downstream FGF receptor signaling in cells, and induction of gene expression. In mouse embryonal lung explants, FGF10-STABs, but not wildtype FGF10, suppressed branching, resulting in increased alveolarization and expansion of epithelial tissue. Similarly, FGF10-STAB1, but not FGF10 wildtype, inhibited the growth of mouse embryonic tibias and markedly altered limb morphogenesis when implanted into chicken limb buds, collectively demonstrating that thermal instability should be considered an important regulator of FGF function that prevents ectopic signaling. Furthermore, we show enhanced differentiation of human iPSC-derived lung organoids and improved regeneration in ex vivo lung injury models mediated by FGF10-STABs, suggesting an application in cell therapy.

• MeSH
• fibroblastový růstový faktor 10 * metabolismus   genetika   chemie   MeSH
• lidé MeSH
• myši MeSH
• plíce metabolismus   embryologie   MeSH
• receptory fibroblastových růstových faktorů metabolismus   MeSH
• signální transdukce * MeSH
• stabilita proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Airway management is a critical component of out-of-hospital cardiac arrest (OHCA) resuscitation. The primary aim of this study was to describe pre-hospital airway management in adult patients post-OHCA. Secondary aims were to investigate whether tracheal intubation (TI) versus use of supraglottic airway device (SGA) was associated with patients' outcomes, including ventilator-free days within 26 days of randomization, 6 months neurological outcome and mortality. METHODS: Secondary analysis of the Target Temperature Management-2 (TTM2) trial conducted in 13 countries, including adult patients with OHCA and return of spontaneous circulation, with data available on pre-hospital airway management. A multivariate logistic regression model with backward stepwise selection was employed to assess whether TI versus SGA was associated with outcomes. RESULTS: Of the 1900 TTM2 trial patients, 1702 patients (89.5%) were included, with a mean age of 64 years (Standard Deviation, SD = 13.53); 79.1% were males. Pre-hospital airway management was SGA in 484 (28.4%), and TI in 1218 (71.6%) patients. At hospital admission, 87.8% of patients with SGA and 98.5% with TI were mechanically ventilated (p < 0.001). In the multivariate analysis, TI in comparison with SGA was not independently associated with an increase in ventilator-free days within 26 days of randomization, improved neurological outcomes, or decreased mortality. The hazard ratio for mortality with TI vs. SGA was 1.06, 95%Confidence Interval (CI) 0.88-1.28, p = 0.54. CONCLUSIONS: In the multicentre randomized TTM2-trial including patients with OHCA, most patients received prehospital endotracheal intubation to manage their airway. The choice of pre-hospital airway device was not independently associated with patient clinical outcomes. TRIAL REGISTRATION NUMBER: NCT02908308.

• MeSH
• intratracheální intubace * metody   MeSH
• kardiopulmonální resuscitace * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• terapeutická hypotermie metody   MeSH
• urgentní zdravotnické služby * metody   MeSH
• zajištění dýchacích cest * metody   MeSH
• zástava srdce mimo nemocnici * terapie   mortalita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. METHODS: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure >60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. CONCLUSION: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest.Trial registration:Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.

• Publikační typ
• časopisecké články MeSH