OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.
- Publikační typ
- časopisecké články MeSH
AIMS: In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. METHODS AND RESULTS: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m2. LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P < 0.05 for all). CONCLUSIONS: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.
Almost a quarter of a millennium after the discovery of an acidic substance in sour milk by Swedish chemist Carl Wilhelm Scheele and more than 100 years after the demonstration of a tight connection between this lactic acid and tissue hypoxia in shock, we are still surrounded by false beliefs and misunderstandings regarding this fascinating molecule. Common perceptions of lactate, the conjugate base of lactic acid, as a plain waste product of anaerobic metabolism and a marker of cellular distress could not be further from the truth. Lactate is formed and utilized continuously by our cells, even under fully aerobic conditions, in large quantities, and although marked hyperlactatemia is always a red flag in our patients, not all these conditions are life-threatening and vice versa-not all critically ill patients have hyperlactatemia. Lactate also does not promote acidosis by itself; it is not toxic, nor is it a metabolic renegade. On the contrary, it has many beneficial properties, and an interpretation of hyperlactatemia might be trickier than we tend to think. The aim of this article is to debunk some of the deeply rooted myths regarding this fascinating molecule.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Komunitní pneumonie je akutní zánětlivé onemocnění plicního parenchymu vzniklé mimo zdravotnické zařízení nebo do 48 hodin od přijetí do nemocnice. I přes dostupnost kauzální antibiotické léčby se dle dat Světové zdravotnické organizace jedná o celosvětově nejčastější příčinu úmrtí z infekčních příčin. Přestože by se mohlo zdát, že léčba infekčních onemocnění dolních cest dýchacích je uzavřenou kapitolou, opak je pravdou. Diagnostický rámec pneumonie zahrnuje heterogenní skupinu pacientů, kteří svým individuálním fenotypem onemocnění vyžadují specifický terapeutický přístup. Kontroverzní otázkou posledních dvaceti let je především adjuvantní použití kortikosteroidů s cílem modulace imunitně ‐inflamatorního poškození plicního parenchymu u těžké komunitní pneumonie. Výsledky klinických studií a jejich metaanalýz jsou bohužel protichůdné. Poslední konsensus čtyř významných evropských odborných společností doporučuje podání kortikoidů pouze u pacientů se současně přítomným septickým šokem. Stanovisko však bylo vydáno před uveřejněním dosud největší studie (CAPE COD), která svými závěry kontrastuje s uvedeným doporučením a velmi pravděpodobně v dohledné době změní přísné vymezení kortikoidů u pacientů se závažnou komunitní pneumonií. Cílem tohoto sdělení je poskytnout krátký klinicky orientovaný přehled ve stále kontroverzním problému a nabídnout k další odborné diskuzi pohled našeho pracoviště do doby, než budou k dispozici nová data a doporučení relevantních odborných grémií.
Community-acquired pneumonia (CAP) is an acute inflammatory disease of the lung parenchyma acquired outside the healthcare facilities or within 48 hours after admission to the hospital. Despite the availability of antibiotics, pneumonia remains the leading cause of death from infectious causes, according to World Health Organization data. Although it might seem that the treatment of lower respiratory tract infections is a closed chapter in a medical textbooks, it is quite the opposite. Our perception of pneumonia as a unifying diagnosis comes with a burden of heterogeneity and we need to approach each patient individually, based on their disease-specific phenotype. The adjuvant use of corticosteroids to modulate and dampen inflammation-induced lung injury in severe community-acquired pneumonia has been a matter of debate for the last twenty years. Up until recently, clinical trials and meta-analyses yielded conflicting results. Therefore, the last consensus of four respected European societies, recommends using corticosteroids in patients with severe community-acquired pneumonia only if septic shock is present. Unfortunately, those guidelines had been released shortly before the largest trial ever conducted on this group of patients (CAPE COD), which indicated different conclusions. This will probably lead to a reevaluation of the current strict recommendations for the use of corticosteroids. The following text aims to provide a brief clinically-oriented review of this controversial topic and present a perspective of our intensive care unit for further discussion until we have new relevant data and subsequent guidelines.
- MeSH
- hormony kůry nadledvin * terapeutické užití MeSH
- infekce získané v komunitě farmakoterapie prevence a kontrola MeSH
- klinická studie jako téma MeSH
- klinické rozhodování MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- pneumonie * farmakoterapie prevence a kontrola MeSH
- riziko MeSH
- zánět farmakoterapie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Sepsis is a common worldwide health condition with high mortality. It is caused by a dysregulated immune response to the pathogen. Severe infections resulting in sepsis can be also determined by monitoring several bloodstream biomarkers, one of them being pro-hormone procalcitonin (PCT). PCT concentration in the bloodstream correlates well with sepsis and in severe cases increases up to a thousand times from the healthy physiological values in a short time. In this study, we developed a rapid technique for PCT detection by MALDI-TOF mass spectrometry, that uses in-situ enrichment directly on the specialized immuno MALDI chips that are utilized as MALDI plates. The method's ability to detect PCT was confirmed by comparing the results with LC-MS bottom-up workflow. The new method detects intact PCT by its m/z and uncovers its alternations in septic serum. METHODS: The MALDI chips used for the detection of PCT were prepared by ambient ion soft landing of anti-PCT antibody on an ITO glass slide. The chips were used for the development of the rapid MALDI-TOF MS method. A parallel method based on affinity enrichment on magnetic beads followed by LC-MS/MS data-dependent peptide microsequencing was used to prove PCT presence in the sample. All samples were also tested by ELISA to determine PCT concentration prior to analyzing them by mass spectrometry methods. RESULTS: The MALDI chip method was optimized using recombinant PCT spiked into the human serum. The PCT detection limit was 10 ng/mL. The optimized method was used to analyze 13 sera from patients suffering sepsis. The PCT results were confirmed by LC-MS/MS. The measurement of the intact PCT by the MALDI chip method revealed that sera of patients with severe sepsis have other forms of PCT present, which show post-processing of the primary sequence by cleavage of PCT, resulting in the formation of N and C termini fragments. CONCLUSIONS: Procalcitonin from human serum was successfully enriched and detected using immunoaffinity MALDI chips. The intact PCT was characterized in 13 septic patients. The method is more specific compared to non-MS-based immunoaffinity techniques and allows observation of different variants of PCT in septic patients.
- Publikační typ
- časopisecké články MeSH
Infectious diseases, which often result in deadly sepsis or septic shock, represent a major global health problem. For understanding the pathophysiology of sepsis and developing new treatment strategies, reliable and clinically relevant animal models of the disease are necessary. In this review, two large animal (porcine) models of sepsis induced by either peritonitis or bacteremia are introduced and their strong and weak points are discussed in the context of clinical relevance and other animal models of sepsis, with a special focus on cardiovascular and immune systems, experimental design, and monitoring. Especially for testing new therapeutic strategies, the large animal (porcine) models represent a more clinically relevant alternative to small animal models, and the findings obtained in small animal (transgenic) models should be verified in these clinically relevant large animal models before translation to the clinical level.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Animal models are essential in understanding of the mechanisms of sepsis moreover the development and the assessment of emerging therapies. In clinically relevant porcine model, however, a significant variability in the host response has been observed among animals. Thus, there is a strong demand to better understand the potential sources of this heterogeneity. In this study, we compared faecal microbiome composition of 12 animals. Three samples were collected at different time points from each animal. Bacteriome was subjected to 16S rDNA profiling. A significant difference in bacterial composition was associated with the season (p < 0.001) but not with the sex of the pig (p = 0.28), the timing of sample collection (p = 0.59), or interactions thereof (all p > 0.3). The season batch explained 55% of the total variance in the bacteriome diversity. The season term was highly significant from the high-resolution level of the bacterial amplicon sequencing variants up to the level of phylum. The diversity of the microbiome composition could significantly influence experimental model of sepsis, and studies are warranted to demonstrate the effects of gut microbiome diversity on the host-response. If confirmed, control of the gut microbiome should become a standard part of the pre-clinical sepsis experiments.
Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.
- MeSH
- čas zasáhnout při rozvinutí nemoci MeSH
- kardiopulmonální resuscitace metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mimotělní membránová oxygenace MeSH
- senioři MeSH
- transport pacientů * MeSH
- zástava srdce mimo nemocnici diagnóza mortalita terapie MeSH
- zbytečná diagnóza a terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.
- Publikační typ
- časopisecké články MeSH
