Didier Delefosse

Plasma proteome to look for diagnostic biomarkers of early bacterial sepsis after liver transplantation: a preliminary study.

Background:While outcome continuously improves after liver transplantation, sepsis remains the leading cause of early postoperative mortality. Diagnosis of infections remains particularly difficult in these patients. This study used plasma profiling coupling Proteinchip array with surface-enhanced laser desorption ionization time-of-fly mass spectrometry to search for biomarkers of postoperative sepsis in patients who underwent liver transplantation. Methods:Diagnosis of sepsis at day 5 relied on widely accepted clinical signs and positive culture of microbiologic samples. Profiles of day 5 plasma were obtained from SELDI-TOF CM10 chip (BioRad, Marnes-la-Coquette, France) analysis. Mean peak intensity of proteins was compared between septic and nonseptic plasma by U test followed by analysis of the area under the receiver-operating characteristic for the significant peaks. Diagnostic performance of significant proteins was established in a derivation set and in a validation set. Results:In the derivation set of 31 patients with and 30 without infection, 23 plasma protein peaks were differentially expressed between patients with and without sepsis. Combination of five peaks allowed sepsis diagnosis with a positive likelihood ratio of 12.5 and a C-statistics of 0.72, 95% CI 0.57–0.85. In the validation set of 31 patients with infection and 34 without infection, the five peaks were differentially expressed as well and allowed day 5 sepsis diagnosis with a positive likelihood ratio of 5.1 and C-statistics of 0.74 (0.58–0.85). Conclusion:A combination of five plasma protein peaks may provide material for useful diagnostic biomarkers of postoperative sepsis in patients undergoing liver transplantation. However, these proteins remain to be identified.

Late onset of cortical blindness in a patient with severe preeclampsia related to retained placental fragments.

A 33-yr-old, gravida 2, para 1 parturient was admitted at 38 weeks’ gestation with a chief complaint of abdominal pain. Preeclampsia was diagnosed by the presence of elevated systemic arterial blood pressure (170/100 mmHg) and proteinuria. Physical examination revealed hyperreflexic limbs. Blood tests showed a moderate elevation in liver enzymes (aspartate aminotransferase, 121 U/l) and hyperuricemia (343 M). Hypertension was controlled with intravenous nicardipine, and an emergent cesarean delivery was performed on the day of admission, using general anesthesia. The patient recovered rapidly from anesthesia, and the results of a neurologic examination performed 2 h later were normal, except for hyperreflexic limbs. The patient’s clinical condition worsened during the first three postoperative days (POD), with the onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome (aspartate aminotransferase, 4,238 U/l; platelet count, 50,000/ml; and hemolysis, confirmed by elevated nonconjugated bilirubin concentration [59 M] and decreased haptoglobin concentration). Respiratory distress with severe hypoxemia related to pulmonary edema occurred on POD1, requiring tracheal intubation, mechanical ventilation, and sedation. Acute renal failure (oliguria and creatinine clearance 5 ml/min) was observed on POD2. A transesophageal echocardiogram ruled out left ventricular dysfunction, and pulmonary artery monitoring was used to optimize hemodynamic status. A head computed tomography (CT) scan without contrast, performed on POD 1 to eliminate intracerebral hemorrhage as a possible diagnosis, was within the normal limits. Three days after admission, a sudden decrease in arterial blood pressure led to the diagnosis of intraabdominal hemorrhage, as well as a subcapsular hematoma of the liver. At this time, CT scan morphology of the uterus was considered normal, with a hyperdensity in the uterine cavity, only suggesting a small amount of intrauterine blood. Intraabdominal blood was surgically evacuated, but the liver was left intact since the Glisson capsule was not ruptured. The patient’s condition improved gradually thereafter. Arterial blood pressure, renal and respiratory function, liver enzyme concentration, and platelet count were all normal by 15 days after delivery. Intravenous sedation was stopped after 1 week, but recovery was slow, and the level of consciousness was sufficient to allow tracheal extubation on POD 14 only. The patient was sleepy, able to be aroused only after verbal stimulation, and confused. The results of a cerebral CT scan performed at this time were normal, and an electroencephalogram revealed diffuse slow waves. The patient’s state of consciousness improved gradually, and she was able to perform everyday tasks such as washing, eating without any help, and pouring water into a glass. The results of formal neurologic examinations, repeated several times during this period, were normal. Three weeks after delivery, hypertension recurred, and treatment with nicardipine was reinitiated. On POD 26, the patient was suddenly unable to perform routine tasks because of complete blindness. Results of a funduscopic examination were normal, pupils were symmetrical and reacted normally to light, and the patient did not react to threat. The results of the remainder of her neurologic examination were normal. Electroencephalography revealed focal posterior paroxysmal spike activity that was unresponsive to intravenous clonazepam and sodium valproate and could only be suppressed with intravenous phenytoin. Head CT scan revealed bilateral occipital hypodensity. Axial T2-weighted magnetic resonance (MR) images with fluid-attenuated inversion recovery sequences showed bilateral hypersignal in the occipital, temporal, and parietal regions, suggesting focal cerebral edema (fig. 1). A recurrence of preeclampsia was suspected. Ultrasound evaluation of the uterus detected echogenic fragments in the uterine cavity. These were removed during a hysteroscopic procedure with general anesthesia. Histologic analysis revealed the presence of placental tissues, including necrotized villi. The patient’s clinical condition rapidly improved after surgery. She was able to distinguish bright light 12 h after curettage, and she could identify the shape of usual items after 48 h. Visual function was considered normal by the ophthalmologist after 4 days. Within 1 week, arterial blood pressure was normalized, level of consciousness was improved, and electroencephalographic abnormalities disappeared. A week later, occipital hypersignal on T2-weighted MR imaging had nearly disappeared. The patient was discharged 38 days after cesarean section delivery.

End‐tidal oxygraphy during pre‐oxygenation in patients with severe diffuse emphysema

We hypothetised that the rate of pre‐oxygenation could be altered by the increase in lung volume and airflow obstruction observed in emphysema. End‐tidal oxygen concentration was monitored, using a paramagnetic oxygen analyser, during 10‐min pre‐oxygenation (tidal breathing of 100% oxygen) in 10 normal patients and in 10 patients with severe diffuse emphysema documented by computerised tomography. Emphysema was characterised by an important increase in functional residual capacity of the lungs [190 (23)% of predicted values] and a decrease in expiratory flow. The increase in end‐tidal oxygen concentration was slower in the emphysema group than in the control group (p = 0.0024). After 3 and 5 min of pre‐oxygenation, the end‐tidal fractional oxygen concentration was significantly lower in the emphysema group than the control group [mean (SD); value at 3 min: emphysema: 0.83 (0.06) vs. control: 0.91 (0.02), p = 0.0005]. Individual values of end‐tidal oxygen concentration measured after 3, 5 and 10 min of pre‐oxygenation were negatively correlated with functional residual capacity in the emphysema group, whereas no such correlation was found in the control group. These results suggest that pre‐oxygenation should be monitored in patients with diffuse emphysema to ensure that adequate pre‐oxygenation is achieved.

Prognostic Value of Preoperative Brain Natriuretic Peptide Serum Levels in Liver Transplantation.

Background Brain natriuretic peptide (BNP) serum concentration has been shown to be a preoperative predictor of postoperative outcome in high risk surgery. Whether it is able to predict early post-liver transplantation (LT) mortality in cirrhotic patients is unanswered. Methods Prospective monocenter observational study including all consecutive patients who received LT for cirrhosis and for whom a preoperative BNP serum dosage was available between January 2011 and December 2014. Results During the period, 207 cirrhotic patients among 525 LT were studied. The ICU and 180-day mortality rates were, respectively, 6% and 8%. Pre-LT BNP concentration, adjusted on model of end-stage liver disease (MELD) score, was an independent factor of ICU and 180-day mortality rates (for each 50 pg/mL increase; hazard ratio, 1035 [1.022-1.049]; P < 0.001 and 1.035 [1.014-1057]; P = 0.001). According to the receiver operator characteristic curve with an accuracy of 0.79 (0.66-0.93), the optimal cutoff value of pre-LT BNP serum level to predict ICU mortality was 155 pg/mL with a negative predictive value of 99%. All patients with MELD score exceeding 25 and pre-LT serum BNP level less than 155 pg/mL survived, whereas patients combining MELD score exceeding 25 and pre-LT BNP concentration exceeding 155 pg/mL had a 27% ICU mortality rate (P = 0.03). Conclusions In cirrhotic patients, pre-LT BNP serum level was an independent predictor of post-LT ICU mortality. With its excellent negative predictive value, the use of this biomarker in combination with MELD score could be useful to better predict post-LT early outcome.