MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis.

BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). RESULTS: T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-ß. The individual extent of immunosuppression differed markedly. MicroRNA-143, - 150 and - 223 independently indicated T-cell immunoparalysis and significantly correlated with patient's IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 - both predominantly expressed in T-cells - retained strong power of discrimination also in whole blood samples. CONCLUSIONS: These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis.

[Quality of postoperative pain therapy: evaluation of an established anesthesiology acute pain service]. / Qualität der postoperativen Schmerztherapie : Evaluation eines etablierten anästhesiologischen Akutschmerzdiensts.

BACKGROUND: Despite well-designed concepts of perioperative pain management, recent studies have revealed that a large number of patients still suffer from unacceptable pain after surgery. The purpose of this prospective evaluation was to critically analyze postoperative pain treatment provided by a routinely established, DIN certified acute pain service (APS) at the University Hospital Großhadern in Munich. MATERIALS AND METHODS: A total of 1,000 consecutive patients received one of the following analgesic procedures: continuous epidural analgesia (EA, n = 401), continuous and patient-controlled epidural analgesia (PCEA, n = 305), intravenous patient-controlled analgesia with opioids (PCA, n = 169) or continuous peripheral nerve block (CPNB, n = 125). For EA and PCEA, ropivacaine 0.2 % and sufentanil 0.24 µg/ml were administered while peripheral regional analgesia was performed with infusion of ropivacaine 0.2 % only. Patients with PCEA were allowed a 3 mg bolus once per hour on demand. Standardized intravenous PCA was performed with piritramide 2.5 mg/ml, a bolus of 2.5 mg, a lock-out time of 15 min, a maximum of 25 mg/4 h and no background infusion. During the daily visits the APS assessed pain intensity at rest and during movement on a numerical rating scale from 0 (no pain) to 10 (maximum pain), acceptance of pain, satisfaction with the analgesic procedure, demand of additional non-opioid analgesics, the need for optimization including bolus applications and changes of the infusion rate or retraction of the epidural catheter. The duration of the procedures, side effects and complications were documented. The catheter insertion sites were inspected daily for redness and tenderness on palpation. RESULTS: In general, epidural and peripheral regional analgesic techniques were superior in terms of postoperative analgesia to intravenous opioid PCA and were associated with fewer side effects, such as sedation, nausea, vomiting, obstipation and sensorimotor deficits. A subgroup analysis revealed that in major upper abdominal surgery, EA provided significantly better analgesia at rest and during movement than PCA. In lower abdominal surgery PCEA induced significantly better analgesia than both PCA and EA, especially during movement. Patient satisfaction was generally high and was best with PCEA (95 %) followed by CPNB (94 %), EA (91 %) and PCA (88 %). On the first postoperative day analgesic procedures had to be optimized (e.g. by bolus administration, retraction of catheters or changes to standardized PCA) in 23 % of EA patients, 10 % of PCEA patients, 6 % of PCA patients and 12 % of CPNB patients. Major complications, such as neuraxial hematoma, infections or respiratory depression were not observed. CONCLUSIONS: As described in many prospective studies, this evaluation revealed that for postoperative pain control, regional anesthesia is superior to intravenous patient-controlled analgesia with strong opioids in terms of analgesia and side effects. In the setting of a well-organized acute pain service with frequent education and training of all members involved, postoperative pain management is safe and effective. However, regular re-evaluation of the defined and certified procedures is necessary.

Higher procoagulatory potential but lower DIC score in COVID-19 ARDS patients compared to non-COVID-19 ARDS patients.

BACKGROUND: COVID-19 is a novel viral disease. Severe courses may present as ARDS. Several publications report a high incidence of coagulation abnormalities in these patients. We aimed to compare coagulation and inflammation parameters in patients with ARDS due to SARS-CoV-2 infection versus patients with ARDS due to other causes. METHODS: This retrospective study included intubated patients admitted with the diagnosis of ARDS to the ICU at Munich university hospital. 22 patients had confirmed SARS-CoV2-infection (COVID-19 group), 14 patients had bacterial or other viral pneumonia (control group). Demographic, clinical parameters and laboratory tests including coagulation parameters and thromboelastometry were analysed. RESULTS: No differences were found in gender ratios, BMI, Horovitz quotients and haemoglobin values. The median SOFA score, serum lactate levels, renal function parameters (creatinine, urea) and all inflammation markers (IL-6, PCT, CRP) were lower in the COVID-19 group (all: p < 0.05). INR (p < 0.001) and antithrombin (p < 0.001) were higher in COVID-19 patients. D-dimer levels (p = 0.004) and consecutively the DIC score (p = 0.003) were lower in this group. In ExTEM®, Time-to-Twenty (TT20) was shorter in the COVID-19 group (p = 0.047), these patients also had higher FibTEM® MCF (p = 0.005). Further, these patients presented with elevated antigen and activity levels of von-Willebrand-Factor (VWF). CONCLUSION: COVID-19 patients presented with higher coagulatory potential (shortened global clotting tests, increased viscoelastic and VWF parameters), while DIC scores were lower. An intensified anticoagulation regimen based on an individual risk assessment is advisable to avoid thromboembolic complications.