Weaning Failure in Critically Ill Patients Is Related to the Persistence of Sepsis Inflammation

Introduction: Septic patients undergoing mechanical ventilation (MV) often experience difficulty in weaning. Th aim of this study was to determine whether inflammatory biomarkers of sepsis could be indicative of the failure or success of spontaneous breathing trial (SBT) in these patients. Methods: Sixty-five patients on MV (42 septic and 23 intubated for other reasons) fulfilling the criteria for SBT were included in the study. Blood samples were collected right before, at the end of (30 min) and 24 h after the SBT. Serum inflammatory mediators associated with sepsis (IL-18, IL-18BP, TNF) were determined and correlated with the outcome of SBT. Results: A successful SBT was achieved in 45 patients (69.2%). Septic patients had a higher percentage of SBT failure as compared to non-septic patients (85% vs. 15%, p = 0.026), with an odds ratio for failing 4.5 times (OR = 4.5 95%CI: 1.16–17.68, p 0.022). IL-18 levels and the relative mRNA expression in serum were significantly higher in septic as compared to non-septic patients (p < 0.05). Sepsis was independently associated with higher serum IL-18 and TNF levels in two time-point GEE models (53–723, p = 0.023 and 0.3–64, p = 0.048, respectively). IL-18BP displayed independent negative association with rapid shallow breathing index (RSBI) (95% CI: −17.6 to −4, p = 0.002). Conclusion: Sustained increased levels of IL-18 and IL-18BP, acknowledged markers of sepsis, were found to be indicative of SBT failure in patients recovering from sepsis. Our results show that, although subclinical, remaining septic inflammation that sustaines for a long time complicates the weaning procedure. Biomarkers for the estimation of the septic burden and the right time for weaning are needed.

Comparison of Protein Carbonyl (PCO), Paraoxonase-1 (PON1) and C-Reactive Protein (CRP) as Diagnostic and Prognostic Markers of Septic Inflammation in Dogs

Reliable diagnostic and prognostic markers of sepsis are lacking, but essential in veterinary medicine. We aimed to assess the accuracy of C-Reactive Protein (CRP), protein carbonyls (PCO) and paraoxonase-1 (PON1) in differentiating dogs with sepsis from those with sterile inflammation and healthy ones, and predict the outcome in septic dogs. These analytes were retrospectively evaluated at admission in 92 dogs classified into healthy, septic and polytraumatized. Groups were compared using the Kruskal–Wallis test, followed by a Mann–Whitney U test to assess differences between survivors and non-survivors. Correlation between analytes was assessed using the Spearman’s test, and their discriminating power was assessed through a Receiver Operating Characteristic (ROC) curve. PON1 and CRP were, respectively, significantly lower and higher in dogs with sepsis compared with polytraumatized and clinically healthy dogs (p < 0.001 for both the analytes), and also in dogs with trauma compared with healthy dogs (p = 0.011 and p = 0.017, respectively). PCO were significantly increased in septic (p < 0.001) and polytraumatized (p < 0.005) as compared with healthy dogs. PON1 and CRP were, respectively, significantly lower and higher in dogs that died compared with survivors (p < 0.001 for both analytes). Ultimately, evaluation of CRP and PON1 at admission seems a reliable support to diagnose sepsis and predict outcomes.

Targeting Gα13-integrin interaction ameliorates systemic inflammation

Systemic inflammation as manifested in sepsis is an excessive, life-threatening inflammatory response to severe bacterial or viral infection or extensive injury. It is also a thrombo-inflammatory condition associated with vascular leakage/hemorrhage and thrombosis that is not effectively treated by current anti-inflammatory or anti-thrombotic drugs. Here, we show that MB2mP6 peptide nanoparticles, targeting the Gα13-mediated integrin “outside-in” signaling in leukocytes and platelets, inhibited both inflammation and thrombosis without causing hemorrhage/vascular leakage. MB2mP6 improved mouse survival when infused immediately or hours after onset of severe sepsis. Furthermore, platelet Gα13 knockout inhibited septic thrombosis whereas leukocyte Gα13 knockout diminished septic inflammation, each moderately improving survival. Dual platelet/leukocyte Gα13 knockout inhibited septic thrombosis and inflammation, further improving survival similar to MB2mP6. These results demonstrate that inflammation and thrombosis independently contribute to poor outcomes and exacerbate each other in systemic inflammation, and reveal a concept of dual anti-inflammatory/anti-thrombotic therapy without exacerbating vascular leakage.

Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia

Background Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, previously included in another study, before and at multiple time points between 12 and 240 h after intravenous infusion of Escherichia coli O55:B5 lipopolysaccharide (LPS). Results Compared with baseline values, a progressive transient decrease of PON-1 activity was observed starting from 24 h post-infusion, with lowest values observed between 3 to 7 days post-infusion, followed by a normalisation to pre-infusion levels the tenth day. Conclusions The results of this study suggest that measurement and monitoring of PON-1 activity might be useful to evaluate progression and recovery from endotoxemia in horses. Further studies in horses with naturally occurring sepsis are warranted.

Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia

Background: Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, previously included in another study, before and at multiple time points between 12 and 240 hours after intravenous infusion of Escherichia coli O55:B5 lipopolysaccharide (LPS). Results: compared with baseline values, a progressive transient decrease of PON-1 activity was observed starting from 24 hours post-infusion, with lowest values observed between 3 to 7 days post-infusion, followed by a normalisation to pre-infusion levels the tenth day. Conclusions: the results of this study suggest that measurement and monitoring of PON-1 activity might be useful to evaluate progression and recovery from endotoxemia in horses. Further studies in horses with naturally occurring sepsis are warranted.

Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia

Background: Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, previously included in another study, before and at multiple time points between 12 and 240 hours after intravenous infusion of Escherichia coli O55:B5 lipopolysaccharide (LPS). Results: compared with baseline values, a progressive transient decrease of PON-1 activity was observed starting from 24 hours post-infusion, with lowest values observed between 3 to 7 days post-infusion, followed by a normalisation to pre-infusion levels the tenth day.Conclusions: the results of this study suggest that measurement and monitoring of PON-1 activity might be useful to evaluate progression and recovery from endotoxemia in horses. Further studies in horses with naturally occurring sepsis are warranted.

Serial Measurements of Paraoxonase-1 (PON-1) Activity in Horses with Experimentally Induced Endotoxemia

Background: Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, previously included in another study, before and at multiple time points between 12 and 240 hours after intravenous infusion of Escherichia coli O55:B5 lipopolysaccharide (LPS). Results: compared with baseline values, a progressive transient decrease of PON-1 activity was observed starting from 24 hours post-infusion, with lowest values observed between 3 to 7 days post-infusion, followed by a normalisation to pre-infusion levels the tenth day. Conclusions: the results of this study suggest that measurement and monitoring of PON-1 activity might be useful to evaluate progression and recovery from endotoxemia in horses. Further studies in horses with naturally occurring sepsis are warranted.

Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

ABSTRACT We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing “trained” nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a “low-risk–high-reward” preventive measure in saving lives during this unprecedented COVID-19 pandemic.

Traumatic fragmentation and concurrent infection of a palmar sesamoid in a cat

Case summary A 9-year-old neutered male domestic shorthair cat was referred for assessment of a chronic non-weightbearing left forelimb lameness that had an acute onset following a suspected cat bite to the distal limb 4 weeks previously. There was minimal improvement following conservative management. On examination there was discomfort on palpation of the left palmar metacarpal region. An orthopaedic examination performed under sedation identified a moderate effusion of the left fourth metacarpophalangeal joint. A CT scan was performed, which identified fragmentation of the medial palmar sesamoid of the fourth digit (sesamoid V). Arthrocentesis of the fourth metacarpophalangeal joint identified septic inflammation. Surgical removal of the fragmented palmar sesamoid was performed and was submitted for histopathology and bacteriology analysis. Postoperative CT confirmed the removal of all fragments. Pasteurella species were isolated from the sesamoid fragments. Histopathology revealed osteomyelitis, neutrophilic inflammation and multifocal necrosis, with evidence of fibrosis present. The cat was re-examined 3 months postoperatively, at which point there was no evidence of lameness and orthopaedic examination of the limb was unremarkable. Relevance and novel information To our knowledge, this is the first reported case of fragmentation of a palmar sesamoid in a cat. This case study describes the diagnosis and the successful management of a cat with fragmentation of a palmar sesamoid, following an altercation with another cat.

The laboratory diagnostic approach to thoracic and abdominal effusions in the dog, cat, and horse

Cases involving pleural and peritoneal effusions occur relatively frequently in clinical practice. Determining the underlying etiology in these cases relies mainly on fluid analysis. The technique used for obtaining the pleural or peritoneal fluid can impact greatly the results of the analysis. Most often used diagnostic tools include evaluation of gross appearance, Total Nucleated Cell Count / Total Protein (TNCC/TP) measurement, chemical/biochemical analysis (Lactate dehydrogenase and lactate, cholesterol, triglycerides, glucose, creatinine, pH, pO2, pCO2, and K measurements), cytology (identification of septic and non-septic inflammation and neoplasia), microbiology (Gram stain, culture, molecular techniques), and specific tests for certain clinical conditions and diseases. Classifying an effusion as transudate, modified transudate and exudate is traditionally based on the TNCC and TP values. New diagnostic methods encourage the clinician to approach the effusion etiologically instead of strictly following this traditional classification. Many of the diagnostic tests described in this review are simple and can be performed in-house, providing the clinician quickly with information about the cause of the effusion, essential for an effective treatment plan without wasting valuable time.