Pulmonary and renal protection: targeting PARP to ventilator-induced lung and kidney injury?

Both acute lung injury and acute kidney injury (AKI) are frequent and serious problems in intensive care medicine. Therefore, the avoiding of any iatrogenic insult to these organs is of great importance. While an increasing body of evidence suggests that mechanical ventilation is capable of inducing lung and distant organ injury, the complex underlying molecular mechanisms remain insufficiently understood. In the previous issue of Critical Care, Vaschetto and colleagues reported the results of an experimental study designed to further explore pathways linking injurious ventilation with AKI. The authors demonstrated that scavenging of peroxynitrite or inhibiting poly(ADP-ribose) polymerase (PARP) afforded protection against AKI induced by double-hit lung injury. Although PARP inhibition or peroxynitrite detoxification or both may become viable candidates for a protective strategy in this setting, the implementation of a lung-protective ventilatory strategy remains the only clinical tool to mitigate the lung biotrauma and its systemic consequences

Early urinary biomarkers of diabetic nephropathy in type 1 diabetes mellitus show involvement of kallikrein-kinin system

Abstract Background Additional urinary biomarkers for diabetic nephropathy (DN) are needed, providing early and reliable diagnosis and new insights into its mechanisms. Rigorous selection criteria and homogeneous study population may improve reproducibility of the proteomic approach. Methods Long-term type 1 diabetes patients without metabolic comorbidities were included, 11 with sustained microalbuminuria (MA) and 14 without MA (nMA). Morning urine proteins were precipitated and resolved by 2D electrophoresis. Principal component analysis (PCA) and Projection to latent structures discriminatory analysis (PLS-DA) were adopted to assess general data validity, to pick protein fractions for identification with mass spectrometry (MS), and to test predictive value of the resulting model. Results Proteins (n = 113) detected in more than 90% patients were considered representative. Unsupervised PCA showed excellent natural data clustering without outliers. Protein spots reaching Variable Importance in Projection score above 1 in PLS (n = 42) were subjected to MS, yielding 33 positive identifications. The PLS model rebuilt with these proteins achieved accurate classification of all patients (R2X = 0.553, R2Y = 0.953, Q2 = 0.947). Thus, multiple earlier recognized biomarkers of DN were confirmed and several putative new biomarkers suggested. Among them, the highest significance was met in kininogen-1. Its activation products detected in nMA patients exceeded by an order of magnitude the amount found in MA patients. Conclusions Reducing metabolic complexity of the diseased and control groups by meticulous patients’ selection allows to focus the biomarker search in DN. Suggested new biomarkers, particularly kininogen fragments, exhibit the highest degree of correlation with MA and substantiate validation in larger and more varied cohorts

Effects of climate factors and vegetation on the CO 2

The relationship between stable carbon isotope composition (δ13C -CO2) of soil CO2 flux, vegetation cover and weather conditions was investigated in a short-term campaign at a temperate re-established grassland in Germany. During August-September 2016, we measured surface CO2 flux with a closed-chamber method at high and low soil moisture content (‘wet’, ‘dry’), with and without above ground vegetation (‘planted’, ‘clear-cut’) and estimated the effects of treatments on respective δ13C -CO2 values. The concentration and stable carbon isotope composition of CO2 were determined using the gas chromatography and mass spectrometry analyses. The δ13C -CO2 of the soil fluxes decreased over sampling time for the ‘dry-warm’ conditions and canopy manipulation. The ecosystem-derived δ13C -CO2 values (corrected for the atmospheric δ13C -CO2) which included predominately soil-and rhizosphere respiration were –26.2 ± 0.8‰ for the ‘dry-warm’ conditions and decreased down to –28.1 ± 1.4‰ over a period of 28 days from late August to the end of September. The decrease coincided with the lowering of CO2 flux and could be attributed to changes in plant physiological processes at the end of the vegetation season. Though the removal of shoots did not significantly affect the δ13C -CO2 values as compared with the control, the pattern of further δ13C -CO2 decrease (down to –28.8 ± 0.8‰) supported the role of living vegetation in a contribution of 13C-enriched CO2 to the ecosystem respiration

Alpha-gal syndrome – A case report of tick-borne anaphylactic shock

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

Defining the characteristics and expectations of fluid bolus therapy : A worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes.Facultad de Ciencias Médica

Blood transcriptome responses in patients correlate with severity of COVID-19 disease

BackgroundCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state.AimOur current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants.ResultsAll WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways.ConclusionsOur data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery

COMMENTARY Pulmonary and renal protection: targeting PARP to ventilator-induced lung and kidney injury?

Both acute lung injury and acute kidney injury (AKI) are frequent and serious problems in intensive care medicine. Therefore, the avoiding of any iatrogenic insult to these organs is of great importance. While an increasing body of evidence suggests that mechanical ventilation is capable of inducing lung and distant organ injury, the complex underlying molecular mechanisms remain insufficiently understood. In the previous issue of Critical Care, Vaschetto and colleagues reported the results of an experimental study designed to further explore pathways linking injurious ventilation with AKI. The authors demonstrated that scavenging of peroxynitrite or inhibiting poly(ADP-ribose) polymerase (PARP) afforded protection against AKI induced by double-hit lung injury. Although PARP inhibition or peroxynitrite detoxification or both may become viable candidates for a protective strategy in this setting, the implementation of a lung-protective ventilatory strategy remains the only clinical tool to mitigate the lung biotrauma and its systemic consequences. In the previous issue of Critical Care, Vaschetto and colleagues [1] sought to determine whether and by which mechanism(s) the activation of poly(ADP-ribose) polymerase (PARP) contributes to the acute kidney injury (AKI) induced by injurious mechanical ventilation (MV). The authors used a double-hit rat model of acute lung injury comprising lipopolysaccharide-induced lung inflammation and MV with either very high tidal volume (19 mL/ kg, zero positive end-expiratory pressure [PEEP]) or low tidal volume (6 mL/kg, PEEP 5 cm H 2 O). To address th

Sepsis, Kidney, and Tissue Oxygenation: New Methods, New Insights, New Perspectives?

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