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Background Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. Aim Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. Methods An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. Results The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime ( p  < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h ( p  = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p  = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime ( p  < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p  = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. Conclusions EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.

In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6–11] days in early extubated patients versus 11 [6–15] days in standard weaning group ( p  = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p  = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p  = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation.

Importance Approximately 70% of individuals critically buried in avalanche debris die within 35 minutes as a result of asphyxial cardiac arrest. An artificial air-pocket device (AAPD) that separates inhaled air from exhaled air may delay the onset of severe hypoxemia and eventual asphyxia during snow burial. Objective To investigate the efficacy of a new AAPD during snow burial in a supine position. Design, Setting, and Participants This comparative effectiveness trial was performed in winter 2016 with data analysis in November 2016 and November 2022. Each trial used a simulated critical avalanche burial scenario, in which a trough was dug in a snow pile and an additional air pocket of 0.5 L volume was punched into the lateral wall for each control trial. All participants were buried in a supine position. Trials could be voluntarily terminated at any time, with a maximum length of 60 minutes; trials were automatically terminated if the participant’s peripheral oxygen saturation (Spo2) dropped to less than 84%. Exposures Each participant conducted 2 trials, one in which they breathed into the AAPD (intervention trial) and the other in which they breathed into the prepared air pocket (control trial). Main Outcomes and Measures Measurements included Spo2, cerebral oxygenation, ventilatory parameters, respiratory gas concentrations, and visual-analogue scales. Kaplan-Meier survival curves and rank test for matched survival data were used to analyze the total burial time in each trial. Results A total of 13 volunteers (9 men; mean [SD] age, 33 [8] years) were exposed to the intervention and control trials. Intervention trials were terminated less often (2 of 13 trials) as a result of hypoxemia than control trials (11 of 12 trials). Similarly, survival curves showed a longer duration of burial in the intervention compared with the control trials for the time to reach an Spo2less than 84% (rank test for matched survival data:P = .003). The intervention trials, compared with the control trials, also had slower rates of decrease in fraction of inspired oxygen (mean [SD] rate, −0.8 [0.4] %/min vs −2.2 [1.2] %/min) and of increase in fraction of inspired carbon dioxide (mean [SD] rate, 0.5 [0.3] %/min vs 1.4 [0.6] %/min) and expired ventilation per minute (mean [SD] rate, 0.5 [1.0] L/min2vs 3.9 [2.6] L/min2). Conclusions and Relevance This comparative effectiveness trial found that the new AAPD was associated with delaying the development of hypoxemia and hypercapnia in supine participants in a critical burial scenario. Use of the AAPD may allow a longer burial time before asphyxial cardiac arrest, which might allow longer times for successful rescue by companions or by prehospital emergency medical services.

Background To characterize current clinical practices and outcomes associated with the use of the extracorporeal blood purification (EBP) device Oxiris® in critically ill patients. Methods This was a prospective clinical registry database that analyzed patients treated with Oxiris®. Three different clusters of critically ill patients were identified: Group A—patients with chronic kidney disease and systemic inflammation who required postoperative support of renal function; Group B—patients requiring immunomodulation without definitive indications for renal support; Group C—patients with abdominal septic shock necessitating both postoperative renal support and immunomodulation. The primary endpoint was the comparison between mortality rates predicted by the Simplified Acute Physiology Score II (SAPS II) and observed mortality rates 4 days after EBP initiation. Results Observed 4-day mortality rates were markedly lower than SAPS II-predicted rates: 16.7% vs. 41% in Group A, 30.8% vs. 77% in Group B, and 21.3% vs. 83% [66;89] in Group C. Early mortality was significantly associated with baseline hemodynamic instability (vasopressor requirement, OR = 3.62 [1.59–9.80], p  = 0.005) and a lower PaO₂/FiO₂ ratio (OR = 0.99 [0.98–0.99], p  = 0.001). Conclusions The removal of inflammatory mediators and microbial components is an emerging therapeutic target for Oxiris® use. Oxiris® may offer therapeutic benefit through the removal of inflammatory mediators in critically ill patients with severe systemic inflammation and renal failure. Although observed mortality was lower than historical estimates, these findings must be interpreted cautiously given the lack of a control group and the limitations of SAPS II. Controlled trials are needed to confirm its clinical impact. Trial registration The study was registered on ClinicalTrials.gov (Identifier: NCT03807414; Registration Date: June 28, 2019).

Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients’ cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes. In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.

Background: A survey conducted by the European Observatory on Cataract Surgery showed high heterogeneity in the use of antiseptics both preoperatively and in the operating room, highlighting the absence of a global consensus regarding ocular infection prophylaxis in cataract surgery. Methods: The antibacterial activity of seven antiseptic ophthalmic formulations (AOFs) registered as medical devices and the two most common disinfectants were evaluated in vitro against five bacterial species. The viability of bacterial strains after exposure to the antiseptic was evaluated with different techniques: the in vitro Minimum Inhibitory Concentration and the subsequent Minimum Bactericidal Concentration, performed on liquid and solid culture medium. Furthermore, a real-time assessment of bacterial viability was conducted using double staining for live/dead bacterial cells by fluorimetric assay. This evaluation was performed on both the time-killing curve and the tear dilution effect test. Results: We observed a high variability across the different AOFs in terms of inhibitory/bactericidal concentration and timing on Gram-positive and Gram-negative bacterial classes. The results indicated that among the tested AOFs, Visuprime, Iodim, and Oftasteril were the most rapid and effective for ocular surface disinfection against the tested bacterial species. Conclusions: The obtained results can support the clinician’s choice of the most suitable AOF for the prevention and treatment of ophthalmic infections associated with surgery.

The RAS is a hormonal system playing a pivotal role in the control of blood pressure and electrolyte homeostasis, the alteration of which is associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it is not surprising that a number of studies have attempted to elucidate the role and balance of the renin–angiotensin system (RAS) in COVID-19. In this review article, we will describe the evidence collected regarding the two main enzymes of the RAS (i.e., ACE and ACE2) and their principal molecular products (i.e., AngII and Ang1-7) in SARS-CoV-2 infection, with the overarching goal of drawing conclusions on their possible role as clinical markers in association with disease severity, progression, and outcome. Moreover, we will bring into the picture new experimental data regarding the systemic activity of ACE and ACE2 as well as the concentration of AngII and Ang1-7 in a cohort of 47 COVID-19 patients hospitalized at the IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy) between March and April 2020. Finally, we will discuss the possibility of considering this systemic pathway as a clinical marker for COVID-19.

Epilepsy is the most common comorbidity in patients with brain tumors. To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.