Near-infrared spectroscopy StO monitoring to assess the therapeutic effect of drotrecogin alfa (activated) on microcirculation in patients with severe sepsis or septic shock

Sepsis is a leading cause of death despite appropriate management. There is increasing evidence that microcirculatory alterations might persist independently from macrohemodynamic improvement and are related to clinical evolution. Future efforts need to be directed towards microperfusion monitoring and treatment. This study explored the utility of thenar muscle oxygen saturation (StO) and its changes during a transient vascular occlusion test (VOT) to measure the microcirculatory response to drotrecogin alfa (activated) (DrotAA) in septic patients. A prospective, observational study was performed in three general intensive care units at three university hospitals. We studied 58 patients with recent onset of severe sepsis or septic shock and at least two organ dysfunctions. Thirty-two patients were treated with DrotAA and 26 were not treated because of formal contraindication. StO was monitored using near-infrared spectroscopy (NIRS), and VOT was performed to obtain deoxygenation (DeOx) and reoxygenation (ReOx) slopes. Measurements were obtained before DrotAA was started and were repeated daily for a 96-hour period. Patients' characteristics, outcome, severity, and baseline values of StO, DeOx, and ReOx did not differ between groups. Treated patients significantly improved DeOx and ReOx values over time, whereas control patients did not. In treated patients, ReOx improvements were correlated to norepinephrine dose reductions. Early clinical response (SOFA improvement after 48 hours of treatment) was not associated to changes in VOT-derived slopes. In the treated group, the relative improvement of DeOx within 48 hours was able to predict mortality (AUC 0.91, p < 0.01). In patients with severe sepsis or septic shock, DrotAA infusion was associated with improvement in regional tissue oxygenation. The degree of DeOx amelioration after 2 days in treated patients predicted mortality with high sensitivity and specificity. Thus, StO derived variables might be useful to evaluate the microcirculatory response to treatment of septic shock

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Earlobe arterialized capillary blood gas analysis in the intensive care unit:a pilot study

BACKGROUND: Earlobe arterialized capillary blood gas analysis can be used to estimate arterial gas content and may be suitable for diagnosis and management of critically ill patients. However, its utility and applicability in the ICU setting remains unexplored. METHODS: A prospective observational validation study was designed to evaluate this technique in a cohort of mechanically ventilated adult critically ill patients admitted to a polyvalent ICU. Precision and agreement between capillary gas measures and arterial references was examined. Acute Respiratory Distress Syndrome (ARDS) diagnosis capabilities with the proposed technique were also evaluated. Finally, factors associated with sampling failure were explored. RESULTS: Fifty-five patients were included into this study. Precision of capillary samples was high (Coefficient of Variation PO(2) = 9.8%, PCO(2) = 7.7%, pH = 0.3%). PO(2) measures showed insufficient agreement levels (Concordance Correlation Coefficient = 0.45; bias = 12 mmHg; percentage of error = 19.3%), whereas better agreement was observed for PCO(2) and pH (Concordance Correlation Coefficient = 0.94 and 0.93 respectively; depreciable bias; percentage of error 11.4% and 0.5% respectively). The sensitivity and specificity for diagnosing ARDS were 100% and 92.3% using capillary gasometric measures. Sampling was unsuccessful in 43.6% of cases due to insufficient blood flow. Age > 65 years was independently associated with failure (odds ratio = 1.6), however hemodynamic failure and norepinephrine treatment were also influencing factors. CONCLUSIONS: Earlobe capillary blood gas analysis is precise and can be useful for detecting extreme gasometrical values. Diagnosis of ARDS can be done accurately using capillary measurements. Although this technique may be insufficient for precise management of patients in the ICU, it has the potential for important benefits in the acute phase of various critical conditions and in other critical care arenas, such as in emergency medicine, advanced medical transport and pre-hospital critical care

Impact of hemoperfusion with polymyxin B added to hemofiltration in patients with endotoxic shock: a case–control study

Abstract Background Septic shock is a leading cause of death in critical patients. In patients with gram-negative septic shock, hemoperfusion with polymyxin B aims to remove endotoxins from plasma. We analyzed the clinical and biological response to hemoperfusion in patients with septic shock and acute kidney injury. Methods This prospective case–control study in the medical–surgical intensive care unit of a university hospital included consecutive adults patients with septic shock and suspected gram-negative bacteria infection with elevated plasma endotoxin activity (EAA > 0.6 EU/ml) and acute kidney injury requiring continuous renal replacement therapy (CRRT). At onset of septic shock, half underwent CRRT plus hemoperfusion with polymyxin B for two hours a day during two consecutive days (hemoperfusion group) and half received only CRRT (control group). We measured clinical, physiological, and biological parameters (EAA, C-reactive protein, procalcitonin, and cytokines) daily during the first 5 days. Results We included 18 patients (male, 33%; mean age, 67.5; mean SOFA score, 11.3). Abdominal infections predominated (50% had peritonitis). At the beginning of CRRT, RIFLE classification was “failure” for 72% and “injury” for 28%. Baseline characteristics did not differ between groups. Patients in the hemoperfusion group required longer mechanical ventilation (12.4 vs. 9.4 days, p = 0.03) and CRRT (8.5 vs. 6 days, p = 0.01) than in the control group. Noradrenaline doses, lactate, procalcitonin, and C-reactive protein decreased in both groups. At day 5, EAA was significantly lower in the hemoperfusion group (0.58 EU/ml vs. 0.73 EU/ml in controls, p = 0.03). There were no significant differences between groups in other biomarkers or ICU mortality (33.3% in the treatment group vs. 44.4% in the control group, p = 0.5). No adverse effects of hemoperfusion were observed. Conclusions Hemoperfusion with polymyxin B added to CRRT resulted in faster decrease in endotoxin levels, but we observed no improvements in clinical, physiological, or biological parameters

Near-infrared spectroscopy StO monitoring to assess the therapeutic effect of drotrecogin alfa (activated) on microcirculation in patients with severe sepsis or septic shock

Sepsis is a leading cause of death despite appropriate management. There is increasing evidence that microcirculatory alterations might persist independently from macrohemodynamic improvement and are related to clinical evolution. Future efforts need to be directed towards microperfusion monitoring and treatment. This study explored the utility of thenar muscle oxygen saturation (StO) and its changes during a transient vascular occlusion test (VOT) to measure the microcirculatory response to drotrecogin alfa (activated) (DrotAA) in septic patients. A prospective, observational study was performed in three general intensive care units at three university hospitals. We studied 58 patients with recent onset of severe sepsis or septic shock and at least two organ dysfunctions. Thirty-two patients were treated with DrotAA and 26 were not treated because of formal contraindication. StO was monitored using near-infrared spectroscopy (NIRS), and VOT was performed to obtain deoxygenation (DeOx) and reoxygenation (ReOx) slopes. Measurements were obtained before DrotAA was started and were repeated daily for a 96-hour period. Patients' characteristics, outcome, severity, and baseline values of StO, DeOx, and ReOx did not differ between groups. Treated patients significantly improved DeOx and ReOx values over time, whereas control patients did not. In treated patients, ReOx improvements were correlated to norepinephrine dose reductions. Early clinical response (SOFA improvement after 48 hours of treatment) was not associated to changes in VOT-derived slopes. In the treated group, the relative improvement of DeOx within 48 hours was able to predict mortality (AUC 0.91, p < 0.01). In patients with severe sepsis or septic shock, DrotAA infusion was associated with improvement in regional tissue oxygenation. The degree of DeOx amelioration after 2 days in treated patients predicted mortality with high sensitivity and specificity. Thus, StO derived variables might be useful to evaluate the microcirculatory response to treatment of septic shock

Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study

Purpose: Our aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics. Materials and methods: We performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time dependent analysis comparing survivors and non-survivors. Results: During the study period kinetics of CRP as well as its relative changes, CRP-ratio, was significantly different between survivors and non-survivors (p = 0.026 and p = 0.005, respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the initial value while it was 96% in non-survivors. The kinetics of other studied variables did not distinguish between survivors and non-survivors. In survivors the bacterial load also decreased markedly. Adequate initial antibiotic therapy was associated with lower mortality (p = 0.025) and faster CRP decrease (p = 0.029). Conclusions: C-reactive protein kinetics can be used to identify VAP patients with poor outcome as soon as four days after the initiation of treatment. (C) 2017 Elsevier Inc. All rights reserve

The poetic view of I. A. Bunin. On the basis of story analyses

V diplomové práci se zabýváme Hngvostylistickým rozborem povídkové tvorby Ivana Alexejeviče Bunina včetně kompozice s cílem dojít k určení principů jeho povídek, a tedy formulovat dimenzi básnicko-filozofickou. Příkladem takového rozboru může být např. analýza Buninovy básně z roku 1916 v závěru článku A. K. Žolkovského.! V této diplomové práci se konkrétně jedná o povídky IIepe6aJl (1892- 1898), 3UMHUU COH (1918), O oypaKe EMelle, KaKou 6blUlell 6cex yMHee (1921), B HeKomopOM l1apcm6e (1923), Cmapblu nopm (1927), IIep6a5l lllo606b (1930). Pro srovnání doplňujeme práci o kapitolu s ukázkou jiného, deníkového žánru, ve kterém se, stejně jako ve většině rozebíraných povídek, vyskytují hláskově instrumentované a rytmizované úseky, třebaže /(He6HuK (1917-1918) a OKa5lHHble OHU (1918-1919) nejsou díla čistě umělecká. V rámci analýzy provádíme rozbor fonetický, v němž zkoumáme, jak je využito vokálů a konsonantů, jejich distribuce k vyjádření významu a expresivity. Kromě hláskové instrumentace si všímáme rytmizace a jejího vztahu k sémantice textu. Důležitou se zde jeví rovněž pozornost zaměřená na sémanticko-Iexikální rovinu, tedy na sémantiku slov a jejich výběr, a na syntax. Na základě takového rozboru charakterizujeme autorovo básnické myšlení a podstatu toho, v čem tkví často zdůraňované mistrovství Buninova..

Biomarker kinetics in the prediction of VAP diagnosis : results from the BioVAP study

Altres ajuts: This study was partially supported by an unrestricted grant from Thermo Fisher Scientific providing free of charge the kits for PCT and MR-proADM measurement without any role in the analysis of the data.Prediction of diagnosis of ventilator-associated pneumonia (VAP) remains difficult. Our aim was to assess the value of biomarker kinetics in VAP prediction. We performed a prospective, multicenter, observational study to evaluate predictive accuracy of biomarker kinetics, namely C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM), for VAP management in 211 patients receiving mechanical ventilation for >72 h. For the present analysis, we assessed all (N = 138) mechanically ventilated patients without an infection at admission. The kinetics of each variable, from day 1 to day 6 of mechanical ventilation, was assessed with each variable's slopes (rate of biomarker change per day), highest level and maximum amplitude of variation (Δ max). A total of 35 patients (25.4 %) developed a VAP and were compared with 70 non-infected controls (50.7 %). We excluded 33 patients (23.9 %) who developed a non-VAP nosocomial infection. Among the studied biomarkers, CRP and CRP ratio showed the best performance in VAP prediction. The slope of CRP change over time (adjusted odds ratio [aOR] 1.624, confidence interval [CI] [1.206, 2.189], p = 0.001), the highest CRP ratio concentration (aOR 1.202, CI [1.061, 1.363], p = 0.004) and Δ max CRP (aOR 1.139, CI [1.039, 1.248], p = 0.006), during the first 6 days of mechanical ventilation, were all significantly associated with VAP development. Both PCT and MR-proADM showed a poor predictive performance as well as temperature and white cell count. Our results suggest that in patients under mechanical ventilation, daily CRP monitoring was useful in VAP prediction. Trial registration NCT02078999 The online version of this article (doi:10.1186/s13613-016-0134-8) contains supplementary material, which is available to authorized users