Drotrecogin alfa (activated) may attenuate severe sepsis-associated encephalopathy in clinical septic shock

INTRODUCTION: Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction induced by the immuno-inflammatory response to infection. Elevated levels of the brain-specific S100B protein are present in many septic patients and reflect the severity of SAE. Adjunctive treatment with drotrecogin alfa (activated) (DrotAA), the human recombinant form of activated protein C, has been shown to improve mortality in patients with severe sepsis-induced organ failure. We studied the effect of DrotAA on S100B levels in patients with acute septic shock who presented with increased baseline values of this biomarker. METHODS: All patients received standard goal-directed resuscitation treatment. Patients with pre-existing or acute neurological disorders were excluded. Based on the Glasgow coma scale (GCS), patients were classified into two groups: GCS ≥ 13 and GCS <13. DrotAA was given as a continuous infusion of 24 μg/kg/h for 96 h. S100B was measured before sedation and the start of DrotAA (0 h) and at 32 h, 64 h and 96 h and at corresponding time points in patients not treated with DrotAA. The lower limit of normal was < 0.5 μg/L. RESULTS: Fifty-four patients completed the study. S100B was increased in 29 (54%) patients. Twenty-four patients (9 with GCS ≥ 13 and 15 with GCS <13) received DrotAA. S100B levels in DrotAA-treated patients with a GCS <13, though higher at baseline than in untreated subjects (1.21 ± 0.22 μg/L vs. 0.95 ± 0.12 μg/L; P = 0.07), progressively and significantly decreased during infusion (0.96 ± 0.22 μg/L at 32 h, P = 0.3; 0.73 ± 0.12 μg/L at 64 h, P < 0.05; and 0.70 ± 0.13 μg/L at 96 h, P < 0.05 vs. baseline). This patient group had also significantly lower S100B values at 64 h and at 96 h than their untreated counterparts. In the patients with a GCS ≥ 13, S100B levels were not influenced by DrotAA treatment. CONCLUSIONS: S100B-positivity is present in more than half of the patients with septic shock. When increased S100B levels are used as a surrogate for SAE, adjunctive DrotAA treatment seems to beneficially affect the evolution of severe SAE as discriminated by an admission GCS <13

The influence of personality on the effect of iTBS after being stressed on cortisol secretion

Over the last years, individualization of repetitive Transcranial Magnetic Stimulation (rTMS) parameters has been a focus of attention in the field of non-invasive stimulation. It has been proposed that in stress-related disorders personality characteristics may influence the clinical outcome of rTMS. However, the underlying physiological mechanisms as to how personality may affect the rTMS response to stress remains to be clarified. In this sham-controlled crossover study, after being stressed by the Trier Social Stress Test, 38 healthy females received two sessions of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex. To take possible personality influences into account, they also completed the Temperament and Character Inventory. Mood and salivary cortisol were assessed throughout the experimental protocol. Overall, two iTBS sessions did not significantly alter mood or influenced cortisol secretion. When taking into account personality features, higher scores on the character dimension Cooperativeness was related to decreased cortisol output, only when active iTBS was administered after the social stressor. In line with other studies, personality features such as the character dimension Cooperativeness may be of particular interest to explain individual neurobiological responses to neurostimulation

Multicentre performance evaluation of the E170 Module for MODULAR ANALYTICS

The E170 module was evaluated at 13 sites in an international multicentre study. The objective of the study was to assess the analytical performance of 49 analytes, and to collect feedback on the system's reliability and practicability. The typical, within-run coefficients of variation (CVs) for most of the quantitative assays ranged between 1 and 2% while a range of 2-4% was achieved with the infectious disease methods. Total precision CVs were found to be within the manufacturer's expected performance ranges, demonstrating good concordance of the system's measuring channels and a high reproducibility during the 2-4-week trial period. The functional sensitivity of 11 selected assays met the clinical requirements (e.g., thyreotroponin (TSH) 0.008 mU/l, troponin T 0.02 µg/l, total prostate-specific antigen (PSA) 0.03 µg/l). The E170 showed no drift during an 8-hour period and no relevant reagent carryover. Accuracy was confirmed by ring trial experiments and method comparisons vs. Elecsys® 2010. The reliability and practicability of the system's hardware and software met with, or even exceeded, the evaluator's requirements. Workflow studies showed that E170 can cover the combined workload of various routine analysers in a variety of laboratory environment. Throughput and sample processing time requirements were achieved while personnel ‘hands-on-time' could be reduce

Serum Anti-Müllerian Hormone Is Significantly Altered by Downregulation With Daily Gonadotropin-Releasing Hormone Agonist: A Prospective Cohort Study

Research Question: What is the effect of gonadotropin-releasing hormone (GnRH)-agonist treatment on serum anti-Müllerian hormone (AMH)?Design: This prospective cohort study conducted in a tertiary university hospital comprised patients (n = 52) who self-administered daily triptorelin (0.1 mg/0.1 mL) subcutaneously for 14 days from menstrual cycle day 21 ± 3, between July 2015 and March 2016. Enrolled women were 18–43 years old, considered normal ovarian responders, with a planned GnRH agonist controlled ovarian stimulation protocol. The primary endpoint was to evaluate the effect of GnRH agonist on serum AMH levels after 7 and 14 days of treatment.Results: Under GnRH agonist treatment, serum AMH was significantly decreased vs. baseline on day 7 (mean change from baseline: −0.265 ng/mL; 95% confidence interval [CI], −0.395 to −0.135 ng/mL; p &lt; 0.001). On day 14, serum AMH was significantly increased (mean change from baseline: 0.289 ng/mL; 95% CI, 0.140–0.439 ng/mL; p &lt; 0.001). Although the median change in AMH from baseline was only −14.9% on day 7 and +17.4% on day 14, from day 7 to 14 AMH significantly increased by 0.55 ng/mL (43.8%; p &lt; 0.001), which is of paramount clinical importance. A linear, mixed-effect model demonstrated that GnRH agonist treatment for 7 and 14 days had a highly significant effect on serum AMH concentration after adjustment for confounding factors (age, body mass index, baseline antral follicle count, and visit). AMH assay precision was excellent (four aliquots/sample); coefficient of variation was 1.2–1.4%.Conclusions: GnRH agonist treatment had a clinically significant effect on serum AMH, dependent on treatment duration. The clear V-shaped response of AMH level to daily GnRH agonist treatment has important clinical implications for assessing ovarian reserve and predicting ovarian response, thus AMH measurements under GnRH agonist downregulation should be interpreted with great caution

High prolactin levels are associated with more delirium in septic patients

Purposes: We investigated whether high prolactin levels were associated with delirium in septic patients because neuropsychiatric disorders are frequently associated with hyperprolactinemia. Materials and methods: Prolactin levels were measured daily for 4 days in 101 patients with sepsis. Delirium was assessed using the Richmond Agitation Sedation Scale and the Confusion Assessment Method in the ICU. Results: Delirium developed in 79 patients (78%) and was more common in patients older than 65 years. Prolactin levels were higher in patients with delirium than in those without over the 4 days of observation (P = .032). In patients with delirium, higher prolactin levels were associated with a lower incidence of nosocomial infection (P = .006). Multivariable logistic regression showed that the Sequential Organ Failure Assessment score at intensive care unit admission (odds ratio, 1.24; 95% confidence interval, 1.04-1.48; P = .002) and the combined effect of prolactin levels with age (odds ratio, 1.018; 95% confidence interval, 1.01-1.031; P = .006) were associated with the development of delirium. Conclusions: High prolactin levels may be a risk factor for delirium in septic patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Serum S100B protein could help to detect cerebral complications associated with extracorporeal membrane oxygenation (ECMO)

Background: To investigate if serum S100B protein levels could early detect cerebral complications under treatment extracorporeal membrane oxygenation (ECMO). Methods: Serum S100B levels were measured over 5 days in 32 patients with cardiogenic and septic shock, including 15 patients who treated by ECMO and 17 who did not. Cerebral complications included hemorrhage, stroke, encephalopathy with myoclonus, and brain death. Delirium was identified by the positive Confusion Assessment Method in the ICU. Results: S100B levels were elevated in 24/32 patients (75 %) at ICU admission. Five patients developed cerebral complications (2 hemorrhages with 1 brain death, 1 encephalopathy with myoclonus in the ECMO group and 2 strokes in the non-ECMO group). At day 5, S100B levels were higher in the 5 patients with cerebral complications than in the 27 without cerebral complications, regardless of ECMO (0.426 [0.421, 0.652] vs. 0.102 [0.085, 0.135] μg/L, p = 0.011). S100B levels were also more elevated in 3 patients with than in 12 without cerebral complications associated with ECMO (0.799 [0.325, 0.965] vs. 0.102 [0.09, 0.607] μg/L, p = 0.033). S100B levels were not associated with delirium after sedation withdrawal. Conclusions: Measurement serum S100B could be useful to detect cerebral complications in deeply sedated patients associated with ECMO but not for monitoring delirium after sedation withdrawal. © 2013 Springer Science+Business Media.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Accuracy and reproducibility of automated estradiol-17 beta and progesterone assys using native serum samples: results obtained in the Belgian external assessment scheme

&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;In 2005, a special survey in the Belgian External Quality Assessment focused on the performance of six automated immunoassay analysers most frequently used in Belgium for estradiol-17beta (E(2)) and progesterone. Results obtained were compared with values determined by reference method, isotope dilution-gas chromatograph/mass spectrometry (ID-GC/MS).&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Five fresh frozen serum samples, without additives, from single donors and three pools from pregnant women were distributed to all registered Belgian laboratories. Total variation, bias, linear relationship within the reported range and linear regression were investigated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Inter-laboratory coefficients of variation ranged from 4 to 49% for E(2) and from 6 to 45% for progesterone. Bias ranged from -26 to 239% for E(2) and from -23 to 81% for progesterone. Several systems showed an upward bias for one particular sample of at least 25%. Weighted linear regression showed overall bias ranging from -8% to 32% for E(2) and from 7% to 41% for progesterone.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Few automated methods succeed in having an excellent reproducibility for E(2) and progesterone. Given the high bias values it is suggested that, for performance testing, results be compared whenever possible with a reference method. The linear relationship as assessed by comparing results with those obtained by ID-GC/MS using samples from different donors was not assured for most methods.&lt;/p&gt;</p

Hypotension and a positive fluid balance are associated with delirium in patients with shock

The pathogenesis of delirium in critically ill patients is multifactorial. How hypotension and hypoxemia affect brain function and whether they can promote delirium remains unclear. A high cumulative positive fluid balance may also have a negative effect on brain function and promote delirium. We hypothesized that delirium would be more likely to develop in patients with low systemic arterial pressure, hypoxemia and a higher positive fluid balance, and investigated these associations in a prospective observational cohort study in patients with shock. After initial resuscitation, episodes of hypotension, defined as a mean arterial pressure (MAP) <65 mmHg or diastolic pressure <60 mmHg, and hypoxemia, defined as peripheral oxygen saturation (SpO2) <90% for more than one minute or any arterial oxygen concentration (PaO2) <90 mmHg, were recorded during the first 5 days of the ICU stay. Fluid balance was evaluated daily and the 5-day cumulative fluid balance recorded. Delirium was assessed using the Confusion Assessment Method for the ICU. A total of 252 patients were admitted with shock during the study period; 185 (73%) developed delirium. Patients who developed delirium also had more episodes of hypotension with a low MAP (p = 0.013) or diastolic pressure (p = 0.018) during the first five days of the ICU stay than those who did not. Patients with a higher cumulative fluid balance during the same period were also more likely to develop delirium (p = 0.01); there was no significant difference in the occurrence of hypoxemia between groups. Joint modeling, combining a linear-mixed model and an adjusted Cox survival model showed that low diastolic pressure (alpha effect = -0.058 ±0.0013, p = 0.043) and a positive cumulative fluid balance (alpha effect = 0.04±0.003, p = 0.021) were independently associated with delirium. In conclusion, low diastolic pressure and a cumulative positive fluid balance but not hypoxemia were independently associated with development of delirium in patients with shock.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cortisol Is an Associated-Risk Factor of Brain Dysfunction in Patients with Severe Sepsis and Septic Shock

Objectives. To investigate cortisol levels in brain dysfunction in patients with severe sepsis and septic shock. Methods. In 128 septic and sedated patients, we studied brain dysfunction including delirium and coma by the evaluation of Richmond Agitation Sedation Scale (RASS), the Confusion Method Assessment in the ICU (CAM-ICU) after sedation withdrawal and the measurement of serum S100B biomarker of brain injury. Serum cortisol and S100B were measured within 12 hours after ICU admission and daily over the next four days. Results. Brain dysfunction was observed in 50% (64/128) before but in 84% (107/128) of patients after sedation withdrawal, and was more common in the patients older than 57 years (P = 0.009). Both cortisol (P = 0.007) and S100B levels (P = 0.028) were higher in patients with than patients without brain dysfunction. Cortisol levels were associated with ICU mortality (hazard ratio = 1.17, P = 0.024). Multivariate logistic regression showed that cortisol (odds ratio (OR): 2.34, 95% CI (2.01, 3.22), P = 0.02) and the combination effect of cortisol with age (OR: 1.004, 95% CI (1.002, 1.93), P = 0.038) but not S100B were associated with brain dysfunction. Conclusions. Cortisol was an associated-risk factor of brain dysfunction in patients with severe sepsis and septic shock