MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients.

Introduction: Delayed cerebral ischemia (DCI) is a dreadful complication present in up to 30% of patients with spontaneous subarachnoid hemorrhage (SAH). Indeed, DCI is one of the main causes of long-term disability in SAH, yet its prediction and prevention are troublesome in poor-grade SAH cases. In this prospective study, we explored the potential role of micro ribonucleic acid (microRNA, abbreviated miRNAs)-small non-coding RNAs involved in clue gene regulation at the post-transcriptional level-as biomarkers of neurological outcomes in SAH patients. Methods: We analyzed the expression of several miRNAs present in the cerebrospinal fluid (CSF) of SAH patients during the early stage of the disease (third-day post-hemorrhage). NanoString Technologies were used for the characterization of the CSF samples. Results: We found an overexpression of miRNAs in the acute stage of 57 SAH in comparison with 10 non-SAH controls. Moreover, a differential expression of specific miRNAs was detected according to the severity of clinical onset, but also regarding the development of DCI and the midterm functional outcomes. Conclusion: These observations reinforce the potential utility of miRNAs as prognostic and diagnostic biomarkers in SAH patients. In addition, the identification of specific miRNAs related to SAH evolution might provide insights into their regulatory functions of pathophysiological pathways, such as the TGF-ß inflammatory pathway and blood-brain barrier disruption.

Minimally Invasive Surgery for Spontaneous Intracerebral Hematoma. Real-Life Implementation Model and Economic Estimation.

Objective: Spontaneous intracerebral hemorrhage is characterized by high fatality outcomes, even under best medical treatment. Recently, minimally invasive surgical (MIS) evacuation of the hematoma has shown promising results and may soon be implemented in the clinical practice. Hereby, we intended to foresee the logistic requirements for an early hematoma evacuation protocol, as well as to evaluate in a real-life implementation model the cost-utility of the two main MIS techniques for hemorrhagic stroke (catheter evacuation plus thrombolysis and neuroendoscopic aspiration). Methods: Data were obtained from the pool of hemorrhagic-stroke patients admitted to our institution during an annual period (2020-2021) and contrasted to the reported results in published trials of MIS techniques. Potential candidates for surgical treatment were identified according to the inclusion/exclusion criteria established in these trials. Then, a cost-utility analysis was performed, which explored the incremental cost per unit of health gained with a given treatment. The treatment effect was measured by differences in modified Rankin Score, and subsequently converted to quality-adjusted life years (QALY). Results: Of the 137 patients admitted to our center with supratentorial spontaneous intracerebral hemorrhage in a 1-year period, 17 (12.4%) were potential candidates for the catheter evacuation plus thrombolysis technique (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, MISTIE III criteria) and 59 (43.0%) for the neuroendoscopic aspiration technique (Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study, DIST criteria). The incremental cost-utility ratio was € 76,533.13 per QALY for the catheter-based evacuation and € 60,703.89 per QALY for the endoscopic-based technique. Conclusion: Around 12-43% of patients admitted to hospital with spontaneous hemorrhagic stroke could be potential candidates to MIS early evacuation of the cerebral hematoma. In our real-life implementation model, the cost-utility analysis favored the neuroendoscopic evacuation over the catheter aspiration technique. Further studies are advisable as new data from the ongoing randomized trials becomes available.

Characteristics and Outcomes in Patients with Ventilator-Associated Pneumonia Who Do or Do Not Develop Acute Respiratory Distress Syndrome. An Observational Study.

Ventilator-associated pneumonia (VAP) is a well-known complication of patients on invasive mechanical ventilation. The main cause of acute respiratory distress syndrome (ARDS) is pneumonia. ARDS can occur in patients with community-acquired or nosocomial pneumonia. Data regarding ARDS incidence, related pathogens, and specific outcomes in patients with VAP is limited. This is a cohort study in which patients with VAP were evaluated in an 800-bed tertiary teaching hospital between 2004 and 2016. Clinical outcomes, microbiological and epidemiological data were assessed among those who developed ARDS and those who did not. Forty-one (13.6%) out of 301 VAP patients developed ARDS. Patients who developed ARDS were younger and presented with higher prevalence of chronic liver disease. Pseudomonas aeruginosa was the most frequently isolated pathogen, but without any difference between groups. Appropriate empirical antibiotic treatment was prescribed to ARDS patients as frequently as to those without ARDS. Ninety-day mortality did not significantly vary among patients with or without ARDS. Additionally, patients with ARDS did not have significantly higher intensive care unit (ICU) and 28-day mortality, ICU, and hospital length of stay, ventilation-free days, and duration of mechanical ventilation. In summary, ARDS deriving from VAP occurs in 13.6% of patients. Although significant differences in clinical outcomes were not observed between both groups, further studies with a higher number of patients are needed due to the possibility of the study being underpowered.

Reliability of thromboelastometry for detecting the safe coagulation threshold in patients taking acenocoumarol after elective heart valve replacement.

BACKGROUND: Reversal of anticoagulation can be needed in patients undergoing heart valve surgery. ROTEM® has been correlated with international normalized ratio (INR) in patients on warfarin but not with patients on acenocoumarol. This study investigates the reliability of ROTEM® for detecting INR values below the 1.5 threshold in patients on acenocoumarol therapy. MATERIAL AND METHODS: Patients on oral anticoagulation with acenocoumarol after elective heart valve replacement were prospectively included in the study. INR and the ROTEM® were measured simultaneously. ROTEM® parameters included coagulation time, clot formation time, alpha angle, and maximal clot firmness after tissue factor activation (EXTEM). Concordance between INR and ROTEM® was analyzed by Lin's concordance coefficient (LCC) and the correlation with Spearman's rho. RESULTS: Fifty-four consecutive patients (40 female; median age 67years) were included. Clotting time (CT) was the parameter that best correlated with INR (r=0.81, p<0,001), and LCC was substantial (0.67). CT was able to predict INR values above or below 1.5: area under curve=0.998. CT≥84seconds, corresponding to a cut-off for likelihood ratio (LR+)=5, had a sensitivity and specificity of 100% and 80%, respectively, to detect an INR below 1.5. For the same INR threshold, CT≥84seconds had a predictive positive value of 92.9% and a predictive negative value of 100%. CONCLUSION: Our preliminary results suggest that CT≥84seconds in the EXTEM ROTEM® test is a feasible method for predicting an insufficient reversion of oral anticoagulant therapy in patients taking acenocoumarol after elective heart valve surgery.

Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.

BACKGROUND: The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope. METHODS: Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 µg•mL (PROP 2) or 3 µg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use. RESULTS: One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 µg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 µg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 µg•mL, respectively. CONCLUSIONS: We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.