History matching of a complex epidemiological model of human immunodeficiency virus transmission by using variance emulation.

Complex stochastic models are commonplace in epidemiology, but their utility depends on their calibration to empirical data. History matching is a (pre)calibration method that has been applied successfully to complex deterministic models. In this work, we adapt history matching to stochastic models, by emulating the variance in the model outputs, and therefore accounting for its dependence on the model's input values. The method proposed is applied to a real complex epidemiological model of human immunodeficiency virus in Uganda with 22 inputs and 18 outputs, and is found to increase the efficiency of history matching, requiring 70% of the time and 43% fewer simulator evaluations compared with a previous variant of the method. The insight gained into the structure of the human immunodeficiency virus model, and the constraints placed on it, are then discussed.

Mediastinal mass with Dysphagia in an elderly patient.

We report the use of endoscopic techniques for successful diagnosis in a case of atypical esophageal tuberculosis. Tuberculosis of the esophagus is an unusual presentation of this disease, having been estimated to occur in 0.15% of the people who die of tuberculosis. A few cases of possible primary tuberculous esophagitis have been described. This report describes a patient with dysphagia who appeared to have esophageal tuberculosis without HIV and in the absence of other signs of tuberculosis. The patient responded promptly to treatment with tuberculostatics.

Hypoxaemic reperfusion ameliorates the histopathological changes in the pig brain after a severe global cerebral ischaemic insult.

BACKGROUND AND PURPOSE: We have recently shown that hypoxaemic reperfusion, after an ischaemic brain insult, improves neurological outcome and decreases lipid peroxidation. In the present study, we investigated the effect of hypoxaemic reperfusion on brain histopathological changes. METHODS: Sixteen pigs subjected to a 10-min global cerebral ischaemia were either hypoxaemically (PaO2 = 35 mmHg, hypoxaemic reperfusion (HR) group, n = 8) or hyperoxaemically (PaO2 > 300 mmHg, control (C) group, n = 8) reperfused. The brains were removed 24 h after reperfusion and six neuropathological abnormalities were evaluated blindly and scored semi-quantitatively (0: normal to 3: severe injury) on eight representative regions of the brain. The overall cumulative score of the abnormalities and their regional prevalence, as well as the neurological outcome, were compared between the two groups. RESULTS: The neuronal degeneration, assessed in terms of cumulative score (P = 0.002) and regional prevalence (P = 0.025 to P = 0.041), was lower in the HR group than in the C group. Spongy degeneration attained statistically significant difference only in cerebellum (P = 0.002) and inflammation only in hippocampus (P = 0.046) but the difference in the cumulative score of these abnormalities was not statistically significant. The difference of the three neurological assessments over time was statistically significant between the two groups, i.e. after resuscitation (P = 0.001), at 8 h (P = 0.006) and at 24 h (P = 0.001) after reperfusion. CONCLUSIONS: Hypoxaemic reperfusion during resuscitation from a severe global ischaemic cerebral insult is associated with statistically significantly fewer histopathological changes of the brain than in controls. This is associated with a superior neurological outcome.

The effect of hypoxemic reperfusion on cerebral protection after a severe global ischemic brain insult.

BACKGROUND AND PURPOSE: Reactive oxygen species contribute to membrane lipid peroxidation and neuronal death and have been implicated in anoxic encephalopathy. We tested whether hypoxemic reperfusion (HR) after global cerebral ischemia would improve neurological recovery. METHODS: Two groups of pigs (n = 11 in each group) were subjected to a model of a 10-min global cerebral and systemic ischemia to compare the effect of hypoxemic reperfusion (group HR) with the classical hyperoxemic control (group C). A third group not subjected to ischemia served as control to the control group (n = 6, group CC), but received hyperoxygenation at the respective period of reperfusion. The outcome was evaluated by means of neurological assessment and the extent of lipid peroxidation measuring the plasma malonaldehyde (MDA) together with hydroxyalkenals (HALK). RESULTS: Animals of group HR exhibited a significantly superior neurological outcome compared with those of group C at all three consecutive assessments after reperfusion (post-resuscitation P = 0.006, at 8 h P = 0.003, and at 24 h P = 0.007). The levels of MDA and HALK are lower in the HR group than in group C (P = 0.029). Additionally, in the CC group these molecules increased significantly early at hyperoxygenation (P = 0.02). A faster lactate metabolism in the HR group was observed during reperfusion, though non-significant. CONCLUSIONS: Hypoxemic reperfusion during resuscitation from a severe global ischemic cerebral insult improves the neurological outcome compared with classic hyperoxemic reperfusion. This is additionally confirmed by the decreased production of the molecules of lipid peroxidation. In the absence of preceding ischemia, these molecules may increase by simple over-oxygenation.

Prevention of infection in multiple trauma patients by high-dose intravenous immunoglobulins.

OBJECTIVE: To investigate the activity of intravenous immunoglobulin (IVIG) as a prophylactic agent against infection in trauma victims. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: A 20-bed university intensive care unit. PATIENTS: Thirty-nine trauma patients with injury severity scores (ISSs) of 16-50. INTERVENTIONS: Penicillin was given at the time of admission and continued at least until day 4. Twenty-one patients received IVIG and 18 patients received human albumin at 1 g/kg in four divided doses (days 1, 2, 3, and 6). The two groups had similarities in age, gender, Acute Physiology and Chronic Health Evaluation II score, risk of death, and Glasgow Coma Scale score, but differing ISSs (p = .02), at the time of admission. Blood was collected on days 1, 4, and 7. MEASUREMENTS AND MAIN RESULTS: Clinical variables related to infection were recorded. The complement components C3c, C4 and CH50, IgG, and the fractions of IgG were measured. The serum bactericidal activity (SBA) was assessed at 37 degrees C (98.6 degrees F) and 40 degrees C (104.0 degrees F) at the time of admission and during the course of IVIG administration. Controlling for ISS, IVIG-treated patients had fewer pneumonias (p = .003) and total non-catheter-related infections (p = .04). Catheter-related infections (p = .76), length of stay in the intensive care unit, antibiotic days, and infection-related mortality did not differ between the two groups. A significantly increased trend in IgG and its subclasses was shown on days 4 and 7 in the IVIG group but not in the control group (p<.000001). No important differences were noted in complement fractions. The SBA of the groups was similar on day 1, but significantly higher on days 4 and 7 (p<.000001) in the IVIG group, remaining so controlling for complement and ISS. SBA was higher at 40 degrees C (104.0 degrees F) compared with 37 degrees C (98.6 degrees F) (p<.0001) under all three conditions. In both groups, low SBA (on days 1, 4, and 7) was associated with increased risk of pneumonia (p<.01) and non-catheter-related infections (p = .06 for day 1; p<.01 for days 4 and 7). CONCLUSIONS: Trauma patients receiving high doses of IVIG exhibit a reduction of septic complications and an improvement of SBA. Early SBA measurement may represent an index of susceptibility to infection.

Brain eigenfrequency shifting as a sensitive index of cerebral compliance in an experimental model of epidural hematoma in the rabbit: preliminary study.

OBJECTIVE: To verify brain eigenfrequency shifting after the occurrence of a lesion producing mass effect into the cranial vault. DESIGN: Experimental animal study. SETTING: Laboratory of experimental surgery affiliated with a university critical care department. SUBJECTS: Six adult male New Zealand white rabbits. INTERVENTIONS: A Camino ICP monitor was placed in the parenchyma, and a 5-Fr balloon-tipped catheter and accelerometer were placed into the epidural space. MEASUREMENTS: Before and after the introduction of successive 0.1-mL increments of autologous blood into the balloon, intracranial pressure (ICP) was recorded along with the accelerometer signal obtained during free vibration of the skull triggered by a calibrated hammer. Fast Fourier transformation of the digitized signal provided the eigenfrequency spectrum. The eigenfrequency showing the sharpest decrease after the initial 0.1-mL volume addition was considered as the best frequency, and its variation in response to subsequent 0.1-mL increments represents the brain eigenfrequency shifting. MAIN RESULTS: Brain eigenfrequency shifting to lower values occurs for small blood volume increments (up to 0.2 mL). When volume addition becomes >0.3 mL, brain eigenfrequency shifting to higher values is exhibited. The decrease in best frequency after the initial introduction of 0.1 mL is statistically significant (p = .003), in a range of volume in which no significant intracranial pressure difference appears. The respective variation of ICP is explained using a quadratic curve. For volumes of 0 to 0.1 mL, the change in ICP is not statistically significant (p = .08). CONCLUSIONS: Changes of the brain's physical characteristics by mass addition in the cranial vault can be expressed by brain eigenfrequency shifting. The method seems advantageous because it reliably detects mass additions at low levels where no ICP change occurs. Additionally, it provides serial measurements, and it is less invasive than the currently used methods for intracranial compliance.

The regional production of cytokines and lactate in sepsis-related multiple organ failure.

In order to explore whether an organ-specific pattern in cytokine and lactate concentrations exists in patients with multiple organ failure (MOF), we measured the cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and lactate in blood taken from the hepatic vein, pulmonary capillaries, and peripheral veins of 10 patients with MOF with hepatic involvement (MOF-HI), eight patients with MOF and adult respiratory distress syndrome (MOF-ARDS), and five head-injured patients (controls). Ten additional patients participated in a study of arteriovenous pulmonary concentration gradients of these substances. For statistical analysis, nonparametric tests and analysis of variance (ANOVA) were used. The regional concentrations of these substances exhibited a different pattern in the two MOF groups. In the MOF-HI group, mean +/- SD cytokines IL-1beta and IL-6 (pg/ml) were respectively 216 +/- 100 and 461 +/- 343 in the hepatic sinusoidal blood; 149 +/- 52 and 293 +/- 204 in pulmonary capillary blood; and 148 +/- 105 and 234 +/- 162 in peripheral venous blood. In the MOF-ARDS group the corresponding levels were 180 +/- 103 and 235 +/- 124; 235 +/- 94 and 280 +/- 108; and 130 +/- 77 and 194 +/- 127. The TNF-alpha levels also exhibited the same pattern. The mean +/- SD corresponding levels (mmol/L) for lactate in the MOF-HI group were 3.1 +/- 1.8, 1.5 +/- 0.3, and 1.2 +/- 0.6, and in the MOF-ARDS group were 1.1 +/- 0.9, 1.8 +/- 1.1, and 1.0 +/- 0.2, respectively. The differences in the levels of all substances between the liver and lungs in the two MOF groups were statistically significant (p < 0.003). In the study of transpulmonary gradients it was shown that the levels of cytokine and lactate were lower in arterial blood than in mixed venous blood in MOF-HI patients, whereas the opposite was true in MOF-ARDS patients. In this study, we found that in MOF, cytokines and lactate are secreted from the most severely affected organs.

Drainage tube endoscopy: a contribution to the management of severe acute pancreatitis?

Peritoneal lavage is one of the interventional approaches that have gained some attention in the early, toxaemic phase of acute pancreatitis. Additionally some kind of drainage is necessary for suppurative collections that characterize the late phase of the disease. In both the above situations tube plugging is a common problem and it is usually associated with a relapse of the patient's septic state and newly formed collection(s) on abdominal CT. Two cases are presented, in early and in late phases respectively, in which drainage tube adoscopy (DTE) re-established tube patency and ensured drainage. DTE may represent an alternative to surgery or to CT-guided paracentesis and evacuation of newly formed intra-abdominal collections secondary to tube obstruction.