BACKGROUND: The pathophysiology of sepsis-induced acute kidney injury remains elusive. Although mitochondrial dysfunction is often perceived as the main culprit, data from preclinical models yielded conflicting results so far. The aim of this study was to assess the immune-metabolic background of sepsis-associated renal dysfunction using sequential biopsy approach with mitochondria function evaluation in a large clinically relevant porcine models mimicking two different paces and severity of sepsis and couple this approach with traditional parameters of renal physiology. METHODS: In this randomized, open-label study, 15 anaesthetized, mechanically ventilated and instrumented (renal artery flow probe and renal vein catheter) pigs were randomized in two disease severity groups-low severity (LS) sepsis (0.5 g/kg of autologous faeces intraperitoneally) and high severity (HS) sepsis (1 g/kg of autologous faeces intraperitoneally). Sequential cortical biopsies of the left kidney were performed and a pyramid-shaped kidney specimen with cortex, medulla and renal papilla was resected and processed at the end of the experiment. Oxygraphic data and western blot analysis of proteins involved in mitochondrial biogenesis and degradation were obtained. RESULTS: In contrast to increased mitochondrial activity observed in LS sepsis, a significant decrease in the oxidative phosphorylation capacity together with an increase in the respiratory system uncoupling was observed during the first 24 h after sepsis induction in the HS group. Those changes preceded alterations of renal haemodynamics. Furthermore, serum creatinine rose significantly during the first 24 h, indicating that renal dysfunction is not primarily driven by haemodynamic changes. Compared to cortex, renal medulla had significantly lower oxidative phosphorylation capacity and electron-transport system activity. PGC-1-alfa, a marker of mitochondrial biogenesis, was significantly decreased in HS group. CONCLUSIONS: In this experimental model, unique sequential tissue data show that the nature and dynamics of renal mitochondrial responses to sepsis are profoundly determined by the severity of infectious challenge and resulting magnitude of inflammatory insult. High disease severity is associated with early and stepwise progression of mitochondria dysfunction and acute kidney injury, both occurring independently from later renal macro-haemodynamic alterations. Our data may help explain the conflicting results of preclinical studies and suggest that sepsis encompasses a very broad spectrum of sepsis-induced acute kidney injury endotypes.
- Publikační typ
- časopisecké články MeSH
Zatímco syntetické koloidy ze současné medicíny založené na důkazech právem zcela vymizely, zůstává albumin součástí klinické praxe i nadále. Hlavní myšlenkou využití toho koloidního roztoku je expanze intravaskulárního objemu, mobilizace tekutiny z intersticia a terapie komplikací jaterní cirhózy. Fyziologickými principy zdánlivě jasně ospravedlnitelné klinické použití ale není podpořeno robustními daty. Nová doporučení ICTM (International Collaboration for Transfusion Medicine) z letošního roku tak schvalují podání albuminu v zásadě jen u velmi specifické podskupiny pacientů a překvapivě ani zde nemáme jednoznačné důkazy o jeho přínosu.
Although synthetic colloids have fallen out of favour in the current evidence-based medicine, the use of albumin remains a common clinical practice. The rationale behind the utilisation of this colloid solution is to increase intravascular volume, facilitate fluid removal, and to treat complications of liver cirrhosis. Nevertheless, the apparently uncontroversial clinical use based on physiological principles is in fact not supported by any robust evidence. Consequently, the 2024 ICTM (International Collaboration for Transfusion Medicine) guidelines recommends albumin administration solely in a very specific subset of patients and notably, even in this limited population, the evidence supporting its use remains inconclusive.
- MeSH
- albuminy * farmakologie terapeutické užití MeSH
- hypoalbuminemie terapie MeSH
- jaterní cirhóza terapie MeSH
- kritický stav MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- podvýživa terapie MeSH
- sepse terapie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- šok terapie MeSH
- tekutinová terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The monocyte distribution width (MDW) has emerged as a promising biomarker for accurate and early identification of patients with potentially life-threatening infections. Here we tested the diagnostic performance of MDW in adult patients requiring hospital admission for community-acquired infections and sepsis, evaluated sources of heterogeneity in the estimates of diagnostic accuracy, and assessed the meaning of MDW in a patient population presenting to the emergency department (ED) for acute non-infectious conditions. 1925 consecutive patients were categorized into three groups: non-infection (n = 1507), infection (n = 316), and sepsis/septic shock (n = 102). Diagnostic performance for infection or sepsis of MDW alone or in combination with components of SOFA was tested using AUC of ROC curves, sensitivity, and specificity. The relationship between MDW and different pathogens as well as the impact of non-infectious conditions on MDW values were explored. For the prediction of infection, the AUC/ROC of MDW (0.84) was nearly overlapping that of procalcitonin (0.83), and C-reactive protein (0.89). Statistical optimal cut-off value for MDW was 21 for predicting infection (sensitivity 73%, specificity 82%) and 22 for predicting sepsis (sensitivity 79%, specificity 83%). The best threshold to rule out infection was MDW ≤ 17 (NPV 96.9, 95% CI 88.3-100.0), and ≤ 18 (NPV 99.5, 95% CI 98.3-100.0) to rule out sepsis. The combination of MDW with markers of organ dysfunction (creatinine, bilirubin, platelets) substantially improved the AUC (0.96 (95% CI 0.94-0.97); specificity and sensitivity of 88% and 94%, respectively). In conclusion, MDW has a good diagnostic performance in diagnosing infection and sepsis in patients presenting in ED. Its use as an infection marker even increases when combined with other markers of organ dysfunction. Understanding the impact of interactions of non-infectious conditions and comorbidities on MDW and its diagnostic accuracy requires further elucidation.
- MeSH
- akutní nemoc MeSH
- biologické markery * krev MeSH
- dospělí MeSH
- infekce získané v komunitě diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- monocyty * metabolismus MeSH
- prospektivní studie MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- sepse * diagnóza krev MeSH
- urgentní služby nemocnice * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Infuzní léčba ve smyslu tekutinové resuscitace je bezesporu jednou z nejčastějších terapeutických intervencí u akutně nemocných pacientů. I přes hromadící se data ukazující potenciálně negativní dopad neindikovaného podání tekutin je i nadále tento „tekutinový reflex“ běžnou praxí v prostředí urgentního příjmu. Jedním z důvodů je často velmi obtížná klinická interpretace volemie a hydratace, pokud pacient nevykazuje krajní poruchy tekutinové rovnováhy. Implementace ultrasonografie dolní duté žíly do vyšetření prvního kontaktu umožňuje relativně rychle a jednoduše odpovědět na základní klinickou otázku: „Potřebuje můj pacient tekutinu nebo dekongesci?“ Zdánlivá přímočarost této informace je ale vykoupena řadou limitací, které je nutné při hodnocení hemodynamiky akutních stavů znát.
Infusion therapy, in terms of fluid resuscitation, is without a doubt one of the most common therapeutic intervention in the management of an acutely ill patient. Despite the growing body of evidence showing potentially harmful effects of non-indicated fluid administration, this "fluid-reflex" remains a common practice in the Emergency department. One of the reasons for this is that fluid status assessment, based just on the clinical findings, is generally difficult if the patient does not have extreme fluid balance disturbances. Inferior Vena Cava ultrasound provides a relatively quick and simple answer to the basic clinical question: "Does my patient need fluids or decongestion?" However, this seemingly straightforward information is redeemed by several limitations which must be considered assessing the hemodynamics of medical emergencies.
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
UNLABELLED: The most common cause of vasoplegic shock in critical care is sepsis. However, although rarely and only in specifically sensitised individuals previously bitten by a tick, red meat may provoke a delayed allergic reaction called an alpha-gal syndrome. We present a case of a protracted life-threatening manifestation of alpha-gal syndrome, which, due to an unusual absence of typical features of anaphylaxis can masquerade as septic shock and calls attention to the premature diagnostic closure as a contributor to diagnostic error. Alpha-gal syndrome is a relatively new, but increasingly recognised health issue. We propose that alpha-gal syndrome should be considered in the differential diagnosis of vasoplegic shock of unclear aetiology even in the absence of typical allergic symptomatology and typical allergen exposure since alpha-gal is present in a wide variety of carriers. LEARNING POINTS: Alpha-gal syndrome, otherwise known as "red meat allergy", is a potentially life-threatening allergic syndrome induced by the immunological properties of tick saliva.A typical case of alpha-gal syndrome is a patient bitten by a tick who develops an allergic reaction, anaphylaxis or anaphylactic shock even after an ingestion of a significant amount of alpha-gal, typically present in red mammalian meat or organs.As global warming continues, we may expect tick-borne diseases to spread wider around the globe and due to the possibility of complete absence of typical allergic symptomatology and the delayed onset of symptoms, this syndrome needs to be considered when encountering vasoplegic shock of uncertain origin.
- Publikační typ
- časopisecké články MeSH
3 nečíslované strany : ilustrace ; 21 cm
- MeSH
- dítě MeSH
- rodiče MeSH
- určení symptomu MeSH
- Check Tag
- dítě MeSH
- Publikační typ
- informační letáky pro pacienty MeSH
- populární práce MeSH
- příručky MeSH
- Konspekt
- Pediatrie
- NLK Obory
- pediatrie
- diagnostika
- zdravotní výchova
