Diagnosing acute kidney injury ahead of time in critically ill septic patients using kinetic estimated glomerular filtration rate.

INTRODUCTION: Accurate and actionable diagnosis of Acute Kidney Injury (AKI) ahead of time is important to prevent or mitigate renal insufficiency. The purpose of this study was to evaluate the performance of Kinetic estimated Glomerular Filtration Rate (KeGFR) in timely predicting AKI in critically ill septic patients. METHODS: We conducted a retrospective analysis on septic ICU patients who developed AKI in AmsterdamUMCdb, the first freely available European ICU database. The reference standard for AKI was the Kidney Disease: Improving Global Outcomes (KDIGO) classification based on serum creatinine and urine output (UO). Prediction of AKI was based on stages defined by KeGFR and UO. Classifications were compared by length of ICU stay (LOS), need for renal replacement therapy and 28-day mortality. Predictive performance and time between prediction and diagnosis were calculated. RESULTS: Of 2492 patients in the cohort, 1560 (62.0%) were diagnosed with AKI by KDIGO and 1706 (68.5%) by KeGFR criteria. Disease stages had agreement of kappa = 0.77, with KeGFR sensitivity 93.2%, specificity 73.0% and accuracy 85.7%. Median time to recognition of AKI Stage 1 was 13.2 h faster for KeGFR, and 7.5 h and 5.0 h for Stages 2 and 3. Outcomes revealed a slight difference in LOS and 28-day mortality for Stage 1. CONCLUSIONS: Predictive performance of KeGFR combined with UO criteria for diagnosing AKI is excellent. Compared to KDIGO, deterioration of renal function was identified earlier, most prominently for lower stages of AKI. This may shift the actionable window for preventing and mitigating renal insufficiency.

Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

Anesthetic (r)evolution from the conventional concept to the minimally invasive techniques in thoracic surgery-narrative review.

Background and Objective: Thanks to the growing experience with the non-intubated anesthetic and surgical techniques, most pulmonary resections can now be performed by using minimally invasive techniques. The conventional method, i.e., surgery on the intubated, ventilated patient under general anesthesia with one-lung ventilation (OLV) was considered necessary for the major thoracoscopic lung resections for all patients. An adequate analgesic approach (regional or epidural anesthesia) allows video-assisted thoracoscopy (VATS) to be performed in anesthetized patients and thus the potential adverse effects related to general anesthesia and mechanical OLV can be minimized. Methods: Multiple medical literature databases (PubMed, Google Scholar, Scopus) were searched, using the terms [(non-intubated) OR (nonintubated) OR (tubeless) OR (awake)] AND [(thoracoscopic surgery)] from 2004 to December 2021. Thirty hundred and six scientific papers were collected. The editorials, commentaries, letters, and papers were excluded, that focus on other than the non-intubated (aka awake or tubeless) VATS technique, as well as the full text scientific papers available in languages other than English. Key Content and Findings: After reviewing the literature, we identified "schools" with different techniques but with very similar results. Most of the differences were in the anesthetic technique, oxygenation and analgesia, however, the immunological results, and the qualitative parameters (inpatient hospital care days, complication rate, mortality) of the perioperative period showed great similarity, in addition, all three schools identified the same risk factors (hypoxia, hypercapnia, airway safety). The combination of spontaneous ventilation with double lumen tube intubation, called VATS-spontaneous ventilation with intubation (SVI) method seems to be suitable for reducing these risk factors, which may serve as an alternative for patients not suitable for the non-intubated technique in the near future. Conclusions: Based on the results, non-intubated thoracic surgery appears to be an increasingly widespread, safe procedure, that will be available to a wider range of patients as experience expands and by the implication of the constantly evolving new processes.

Differentiating Phenotypes of Coronavirus Disease-2019 Pneumonia by Electric Impedance Tomography.

Introduction: Coronavirus disease-2019 (COVID-19) pneumonia has different phenotypes. Selecting the patient individualized and optimal respirator settings for the ventilated patient is a challenging process. Electric impedance tomography (EIT) is a real-time, radiation-free functional imaging technique that can aid clinicians in differentiating the "low" (L-) and "high" (H-) phenotypes of COVID-19 pneumonia described previously. Methods: Two patients ("A" and "B") underwent a stepwise positive end-expiratory pressure (PEEP) recruitment by 3 cmH2O of steps from PEEP 10 to 25 and back to 10 cmH2O during a pressure control ventilation of 15 cmH2O. Recruitment maneuvers were performed under continuous EIT recording on a daily basis until patients required controlled ventilation mode. Results: Patients "A" and "B" had a 7- and 12-day long trial, respectively. At the daily baseline, patient "A" had significantly higher compliance: mean ± SD = 53 ± 7 vs. 38 ± 5 ml/cmH2O (p < 0.001) and a significantly higher physiological dead space according to the Bohr-Enghoff equation than patient "B": mean ± SD = 52 ± 4 vs. 45 ± 6% (p = 0.018). Following recruitment maneuvers, patient "A" had a significantly higher cumulative collapse ratio detected by EIT than patient "B": mean ± SD = 0.40 ± 0.08 vs. 0.29 ± 0.08 (p = 0.007). In patient "A," there was a significant linear regression between the cumulative collapse ratios at the end of the recruitment maneuvers (R 2 = 0.824, p = 0.005) by moving forward in days, while not for patient "B" (R 2 = 0.329, p = 0.5). Conclusion: Patient "B" was recognized as H-phenotype with high elastance, low compliance, higher recruitability, and low ventilation-to-perfusion ratio; meanwhile patient "A" was identified as the L-phenotype with low elastance, high compliance, and lower recruitability. Observation by EIT was not just able to differentiate the two phenotypes, but it also could follow the transition from L- to H-type within patient "A." Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04360837.

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock.

Hemodynamic instability due to dysregulated host response is a life-threatening condition requiring vasopressors and vital organ support. Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. We reviewed the PubMed database to assess evidence of the impact of Cytosorb on norepinephrine needs in the critically ill. We further analyzed those studies including data on control cohorts in a comparative pooled analysis, defining a treatment effect as the standardized mean differences in relative reductions in vasopressor dosage at 24 h. The literature search returned 33 eligible studies. We found evidence of a significant reduction in norepinephrine requirement after treatment: median before, 0.55 (IQR: 0.39-0.90); after, 0.09 (0.00-0.25) µg/kg/min, p < 0.001. The pooled effect size at 24 h was large, though characterized by high heterogeneity. In light of the importance of a quick resolution of hemodynamic instability in the critically ill, further research is encouraged to enrich knowledge on the potentials of the therapy.

Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study.

BACKGROUND: The aim of this proof of concept, prospective, randomized pilot trial was to investigate the effects of extracorporeal cytokine removal (CytoSorb®) applied as a standalone treatment in patients with septic shock. METHODS: 20 patients with early (<24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrine>10 µg/min, procalcitonin (PCT) > 3 ng/mL without the need for renal replacement therapy were randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24 h. Clinical and laboratory data were recorded at baseline (T0), T12, T24, and T48 hours. RESULTS: Overall SOFA scores did not differ between the groups. In the CytoSorb-group norepinephrine requirements and PCT concentration decreased significantly (norepinephrine: CytoSorb: T0 = 0.54[IQR:0.20-1.22], T48 = 0.16[IQR:0.07-0.48], p = .016; Controls: T0 = 0.43[IQR:0.19-0.64], T48 = 0.25[IQR:0.08-0.65] µg/kg/min; PCT: CytoSorb: T0 median = 20.6[IQR: 6.5-144.5], T48 = 5.6[1.9-54.4], p = .004; Control: T0 = 13.2[7.6-47.8], T48 = 9.2[3.8-44.2]ng/mL). Big-endothelin-1 concentrations were also significantly lower in the CytoSorb group (CytoSorb: T0 = 1.3 ±â€¯0.6, *T24 = 1.0 ±â€¯0.4, T48 = 1.4 ±â€¯0.8, *p = .003; Control: T0 = 1.1 ±â€¯0.7, T24 = 1.1 ±â€¯0.6, T48 = 1.2 ±â€¯0.6 pmol/L, p = .115). There were no CytoSorb therapy-related adverse events. CONCLUSIONS: This is the first trial to investigate the effects of early extracorporeal cytokine adsorption treatment in septic shock applied without renal replacement therapy. It was found to be safe with significant effects on norepinephrine requirements, PCT and Big-endothelin-1 concentrations compared to controls. TRIAL REGISTRATION: The study has been registered on ClinicalTrials.gov, under the registration number of NCT02288975, registered 13 November 2014.

The cytoprotective effect of biglycan core protein involves Toll-like receptor 4 signaling in cardiomyocytes.

AIMS: Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection. METHODS AND RESULTS: A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats. In separate experiments, we have shown that similarly to glycanated biglycan, recombinant human biglycan core protein (rhBGNc) protects cardiomyocytes against SI/R injury. In contrast, the glycosaminoglycan component dermatan sulfate had no significant effect on cell viability, while chondroitin sulfate further enhanced cell death induced by SI/R. Treatment of cardiomyocytes with rhBGNc reverses the effect of SI/R upon markers of necrosis, apoptosis, mitochondrial membrane potential, and autophagy. We have also shown that pharmacological blockade of Toll-like receptor 4 (TLR4) signaling or its downstream mediators (IRAK1/4, ERK, JNK and p38 MAP kinases) abolished the cytoprotective effect of rhBGNc against SI/R injury. Pretreatment of cardiomyocytes with rhBGNc for 20h resulted in increased Akt phosphorylation and NO production without having significant effect on phosphorylation of ERK1/2, STAT3, and on the production of superoxide. Treatment over 10min and 1h with rhBGNc increased ERK1 phosphorylation, while the SI/R-induced increase in superoxide production was attenuated by rhBGNc. Blockade of NO synthesis also prevented the cardiocytoprotective effect of rhBGNc. CONCLUSIONS: The core protein of exogenous biglycan protects myocardial cells from SI/R injury via TLR4-mediated mechanisms involving activation of ERK, JNK and p38 MAP kinases and increased NO production. The cytoprotective effect of rhBGNc is due to modulation of SI/R-induced changes in necrosis, apoptosis and autophagy.