Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method.

BACKGROUND: Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients. METHODS: This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland-Altman plots and Passing-Bablok regressions. RESULTS: The Bland-Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%). CONCLUSIONS: In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay.

Guidelines: Anaesthesia in the context of COVID-19 pandemic.

OBJECTIVES: The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. METHODS: The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions. RESULTS: The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. CONCLUSION: We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.

Cholangitis lenta: An underdiagnosed lesion associated with severe cholestasis following liver transplantation.

BACKGROUND: Cholangitis lenta (CL) represents a specific histological lesion associated with severe cholestasis and related to sepsis. Despite being well known by pathologists, CL has been poorly studied in liver transplantation (LT). METHODS: We performed a retrospective 12-year analysis of the incidence, risk factors, and outcome of CL in LT recipients. Biopsy samples performed within 3 months after LT underwent blinded rereading to identify recipients with CL. RESULTS: Among 587 LT performed, 45 (7.7%) developed CL. Of these, 7 (15.6%) had no signs of clinical sepsis at the time of biopsy, but further investigations revealed positive cultures. Independent factors associated with CL were sepsis at the time of LT (OR = 3.62 [95%CI = 1.63-8.06]), donor age (OR = 1.05 [1.03-1.08]), and operative time (OR = 1.23 [95%CI = 1.02-1.48]). Cholangitis lenta was associated with increased severe morbidity (71.1% vs 33.0%, P < .001), 90-day mortality (24.4% vs 5.9%, P < .001) and decreased one-year graft (62.1% vs 89.4%, P < .001) and patient survival (55.6% vs 87.9%, P < .001). CONCLUSION: Cholangitis lenta represents a possible lesion associated with cholestasis after LT, which strongly affects its outcome. In the event of an unexplained post-transplant cholestasis, the diagnosis of CL must be considered, even in the absence of clinically evident sepsis.

Liver Transplantation for Acute Liver Failure Attributed to Leptospirosis: A Report of Two Cases.

BACKGROUND: Leptospirosis is a zoonosis caused by pathogenic spirochetes of the genus Leptospira. Although it may be limited to nonspecific fever, leptospirosis may also be responsible for neurological symptoms or fulminant diseases such as Weil's disease. Diagnosis is challenging due to the difficulty in isolating the organism and the delays required for performing the serological test. CASE PRESENTATION: Two cases of leptospirosis are presented here. The clinical picture differed from a real Weil's disease in the first case and from a neuro-leptospirosis in the second. However, both patients underwent liver transplantation because of the severity of the associated acute liver failure. Unfortunately, one of the cases had a fatal outcome. CONCLUSION: Antibiotic treatment for leptospirosis should not be delayed by the lack of a positive serology test for this potentially lethal disease. In the context of a history of exposure to risk factors for leptospirosis, a negative serology must be repeated 7 days to 2 weeks following the first test. Although not always present, acute liver injury may, in rare cases, require liver transplantation.

One-year outcome after neurosurgery for intracranial tumor in elderly patients.

BACKGROUND: The number of elderly patients proposed for brain tumor removal is increasing. Only few data on long-term functional prognosis after intracranial surgery are available. MATERIALS AND METHODS: Prospective, observational study of all patients greater than 70 year of age operated for intracranial tumors. Two scales for health status evaluation were used: Karnofsky Performance Scale (KPS) and Activities of Daily Living (ADL) score. Data were expressed as medians (first to third quartiles). The primary endpoint was the probability to remain nondependant (ADL>3 and KPS≥70%) after 1 year. RESULTS: Between 2003 and 2007, 90 patients were included: 46 (51.1%) meningioma, 17 (18.9%) high-grade glioma, and 11 (12.2%) metastasis. At hospital admission, age was 73.50 years (71.25-76.00), American Society of Anesthesiology score 2 (2 to 3), KPS 80% (70-90), ADL 5.5 (4.5 to 6.0). Two patients died during the first 28 days, 3 others during the first year. Both KPS and ADL decreased after 1 year: KPS 80% (70 to 90; mean: 80%) at hospital admission versus 80% (60 to 90) at 1 year (mean: 70%), P=0.003; ADL 5.5 (4.5 to 6.0) at hospital admission versus 5.0 (3.25 to 5.50) at 1 year, P=0.001. In multivariate analysis, 2 preoperative parameters were associated with autonomy at 1 year: the ADL at hospital admission and meningioma as histologic type. CONCLUSIONS: In this series of elderly patients, intracranial tumor surgery was associated with low 1-year mortality. Meningioma was associated with a better postoperative functional outcome. Preoperative ADL score was a predictive of functional evolution 1 year after the surgery.

Is thenar tissue hemoglobin oxygen saturation in septic shock related to macrohemodynamic variables and outcome?

INTRODUCTION: The study objectives were to evaluate septic shock-induced alterations in skeletal muscle hemoglobin oxygenation saturation (StO2) using near-infrared spectroscopy (NIRS) and forearm skin blood flow velocity using laser Doppler (LD) to determine the relationship of macroperfusion and microperfusion parameters, and to test the relationship of the worst NIRS parameters during the first 24 hours of shock with 28-day prognosis. METHODS: A prospective, observational study was performed in a 21-bed university hospital surgical intensive care unit. Forty-three septic shock patients with at least another organ failure underwent a 3-minute, upper arm (brachial artery) vascular occlusion test (VOT). Microperfusion parameters (thenar eminence StO2 and forearm LD skin blood flow) were collected on days 1, 2 and 3, before (baseline StO2 and LD values) and during the 3-minute VOT with calculation of occlusion and reperfusion slopes for StO2 and LD. Daily Sequential Organ Failure Assessment (SOFA) score, macrohemodynamic parameters (systolic arterial blood pressure, cardiac output (pulmonary artery catheter or transesophageal Doppler), mixed venous oxygen saturation (pulmonary artery or superior vena cava catheter)) and metabolic parameters (pH, base excess, lactate) were determined. RESULTS: Baseline StO2 (82% (75 to 88) vs. 89% (85 to 92), P = 0.04) and reperfusion slope (2.79%/second (1.75 to 4.32) vs. 9.35%/second (8.32 to 11.57), P < 0.0001) were lower in septic shock patients than in healthy volunteers. StO2 reperfusion slope correlated with occlusion slope (P < 0.0001), cardiac output (P = 0.01) and LD reperfusion slope (P = 0.08), and negatively with lactate level (P = 0.04). The worst StO2 reperfusion slope during the first day of shock was lower in nonsurvivors than in survivors (P = 0.003) and improved significantly the predictive value of Simplified Acute Physiology Score II and SOFA scores. CONCLUSIONS: The alteration of StO2 reperfusion slope in septic shock patients compared with healthy volunteers was related with macrohemodynamic, microhemodynamic and metabolic parameters. The addition of the worst value of the day 1 StO2 reperfusion slope improved the outcome prediction of Simplified Acute Physiology Score II and SOFA scores.

Cardiac troponin and skeletal muscle oxygenation in severe post-partum haemorrhage.

INTRODUCTION: Cardiac troponin has been shown to be elevated in one-half of the parturients admitted for post-partum haemorrhage. The purpose of the study was to assess whether increased cardiac troponin was associated with a simultaneous alteration in haemoglobin tissue oxygen saturation in peripheral muscles in post-partum haemorrhage. METHODS: Tissue haemoglobin oxygen saturation of thenar eminence muscle (StO2) was measured via near-infrared spectroscopy technology. Two sets of StO2 parameters (both isolated baseline and during forearm ischaemia-reperfusion tests) were collected at two time points: upon intensive care unit admission and prior to intensive care unit discharge. Comparisons were performed using Wilcoxon paired tests, and univariate associations were assessed using logistic regression model and Wald tests. RESULTS: The 42 studied parturients, admitted for post-partum haemorrhage, had clinical and biological signs of severe blood loss. Initial cardiac troponin I was increased in 24/42 parturients (0.43 +/- 0.60 microrg/l). All measured parameters of muscular haemoglobin oxygen saturation, including Srecovery, were also altered at admission and improved together with improved haemodynamics, when bleeding was controlled. Multivariate analysis showed that muscular Srecovery <3%/second at admission was strongly associated with increased cardiac troponin. CONCLUSIONS: Our study confirmed the high incidence of increased cardiac troponin, and demonstrated the simultaneous impairment in the reserve of oxygen delivery to peripheral muscles in parturients admitted for severe post-partum haemorrhage.

Contribution to structural intensity tool: application to the cancellation of ECG interference in diaphragmatic EMG.

This paper is concerned with the problem of localizing the typical features of a signal when it is observed with noise in order to align a set of curves. Structural intensity (SI) is a recent tool that computes the "density" of the location of the modulus maxima of a wavelet representation along various scales in order to identify singularities of an unknown signal. As a contribution to this novel approach we establish a modified SI using the Berkner transform which allows maxima linkage to insure accurate localization of singularities. An application to cancellation of ECG interference in diaphragmatic EMG is also proposed.

Non-invasive detection of respiratory muscles activity during assisted ventilation.

The instantaneous pressure applied by the respiratory muscles [Pmus(t)] of a patient under ventilatory support may be continuously assessed with the help of a model of the passive respiratory system updated cycle by cycle. Inspiratory activity (IA) is considered present when Pmus goes below a given threshold. In six patients, we compared IA with (i) inspiratory activity (IAref) obtained from esophageal pressure and diaphragmatic EMG and (ii) that (IAvent) detected by the ventilator. In any case, a ventilator support onset coincides with an IA onset but the opposite is not true. IA onset is always later than IAref beginning ((0.21 +/- 0.10 s) and IA end always precedes IAref end (0.46 +/- 0.16 s). These results clearly deteriorate when the model is not updated.

Ventilatory support: a dynamical systems approach.

Misunderstanding of the dynamical behavior of the ventilatory system, especially under assisted ventilation, may explain the problems encountered in ventilatory support monitoring. Proportional assist ventilation (PAV) that theoretically gives a breath by breath assistance presents instability with high levels of assistance. We have constructed a mathematical model of interactions between three objects: the central respiratory pattern generator modelled by a modified Van der Pol oscillator, the mechanical respiratory system which is the passive part of the system and a controlled ventilator that follows its own law. The dynamical study of our model shows the existence of two crucial behaviors, i.e. oscillations and damping, depending on only two parameters, namely the time constant of the mechanical respiratory system and a cumulative interaction index. The same result is observed in simulations of spontaneous breathing as well as of PAV. In this last case, increasing assistance leads first to an increase of the tidal volume (VT), a further increase in assistance inducing a decrease in VT, ending in damping of the whole system to an attractive fixed point. We conclude that instabilities observed in PAV may be explained by the different possible dynamical behaviors of the system rather than changes in mechanical characteristics of the respiratory system.