Compressibility in lattice Boltzmann on standard stencils: effects of deviation from reference temperature.

With growing interest in the simulation of compressible flows using the lattice Boltzmann (LB) method, a number of different approaches have been developed. These methods can be classified as pertaining to one of two major categories: (i) solvers relying on high-order stencils recovering the Navier-Stokes-Fourier equations, and (ii) approaches relying on classical first-neighbour stencils for the compressible Navier-Stokes equations coupled to an additional (LB-based or classical) solver for the energy balance equation. In most cases, the latter relies on a thermal Hermite expansion of the continuous equilibrium distribution function (EDF) to allow for compressibility. Even though recovering the correct equation of state at the Euler level, it has been observed that deviations of local flow temperature from the reference can result in instabilities and/or over-dissipation. The aim of the present study is to evaluate the stability domain of different EDFs, different collision models, with and without the correction terms for the third-order moments. The study is first based on a linear von Neumann analysis. The correction term for the space- and time-discretized equations is derived via a Chapman-Enskog analysis and further corroborated through spectral dispersion-dissipation curves. Finally, a number of numerical simulations are performed to illustrate the proposed theoretical study. This article is part of the theme issue 'Fluid dynamics, soft matter and complex systems: recent results and new methods'.

Stability of the lattice kinetic scheme and choice of the free relaxation parameter.

The lattice kinetic scheme (LKS), a modified version of the classical single relaxation time (SRT) lattice Boltzmann method, was initially developed as a suitable numerical approach for non-Newtonian flow simulations and a way to reduce memory consumption of the original SRT approach. The better performances observed for non-Newtonian flows are mainly due to the additional degree of freedom allowing an independent control over the relaxation of higher-order moments, independently from the fluid viscosity. Although widely applied to fluid flow simulations, no theoretical analysis of LKS has been performed. The present work focuses on a systematic von Neumann analysis of the linearized collision operator. Thanks to this analysis, the effects of the modified collision operator on the stability domain and spectral behavior of the scheme are clarified. Results obtained in this study show that correct choices of the "second relaxation coefficient" lead, to a certain extent, to a more consistent dispersion and dissipation for large values of the first relaxation coefficient. Furthermore, appropriate values of this parameter can lead to a larger linear stability domain. At moderate and low values of viscosity, larger values of the free parameter are observed to increase dissipation of kinetic modes, while leaving the acoustic modes untouched and having a less pronounced effect on the convective mode. This increased dissipation leads in general to less pronounced sources of nonlinear instability, thus improving the stability of the LKS.

Theoretical and numerical analysis of the lattice kinetic scheme for complex-flow simulations.

The lattice kinetic scheme (LKS) is a modified version of the classical single relaxation time lattice Boltzmann method. Although used for many applications, especially when large variations in viscosity are involved, a thorough analysis of the scheme has not been provided yet. In the context of this work, the macroscopic behavior of this scheme is evaluated through the Chapman-Enskog analysis. It is shown that the additional degree of freedom provided in the scheme allows for an independent control of higher-order moments. These results are further corroborated by numerical simulations. The behavior of this numerical scheme is studied for selected external and internal flows to clarify the effect of the free parameter on the different moments of the distribution function. It is shown that it is more stable than SRT (single relaxation time) when confronted to fully periodic under-resolved simulations (especially for λ≈1). It can also help minimize the error coming from the viscosity-dependence of the wall position when combined with the bounce-back approach; although still present, viscosity-dependence of the wall position is reduced. Furthermore, as shown through the multiscale analysis, specific choices of the free parameter can cancel out the leading-order error. Overall, the LKS is shown to be a useful and efficient alternative to the SRT method for simulating numerically complex flows.

Extensive analysis of the lattice Boltzmann method on shifted stencils.

Standard lattice Boltzmann methods (LBMs) are based on a symmetric discretization of the phase space, which amounts to study the evolution of particle distribution functions (PDFs) in a reference frame at rest. This choice induces a number of limitations when the simulated flow speed gets closer to the sound speed, such as velocity-dependent transport coefficients. The latter issue is usually referred to as a Galilean invariance defect. To restore the Galilean invariance of LBMs, it was proposed to study the evolution of PDFs in a comoving reference frame by relying on asymmetric shifted lattices [N. Frapolli, S. S. Chikatamarla, and I. V. Karlin, Phys. Rev. Lett. 117, 010604 (2016)].PRLTAO0031-900710.1103/PhysRevLett.117.010604 From the numerical viewpoint, this corresponds to overcoming the rather restrictive Courant-Friedrichs-Lewy conditions on standard LBMs and modeling compressible flows while keeping memory consumption and processing costs to a minimum (therefore using the standard first-neighbor stencils). In the present work systematic physical error evaluations and stability analyses are conducted for different discrete equilibrium distribution functions (EDFs) and collision models. Thanks to them, it is possible to (1) better understand the effect of this solution on both physics and stability, (2) assess its viability as a way to extend the validity range of LBMs, and (3) quantify the importance of the reference state as compared to other parameters such as the equilibrium state and equilibration path. The results clearly show that, in theory, the concept of shifted lattices allows the scheme to deal with arbitrarily high values of the nondimensional velocity. Furthermore, just like the zero-Mach flow for the standard stencils, it is observed that setting the shift velocity to the fluid velocity results in optimal physical and numerical properties. In addition, a detailed analysis of the obtained results shows that the properties of different collision models and EDFs remain unchanged under the shift of stencil. In other words, by introducing a velocity shift in the stencil, the optimal operating point, in terms of physics and numerics, will also be shifted by the same vector regardless of the EDF or collision model considered. Eventually, while limited to the D2Q9 stencil with the nine possible first-neighbor shifts, the present study and corresponding conclusions can be extended to other stencils and velocity shifts in a straightforward manner.

The obesity supine death syndrome (OSDS).

The obesity supine death syndrome refers to a catastrophic cascade of cardiorespiratory complications resulting from the supine positioning of a morbidly obese subject which can ultimately lead to death. It was first described in 1977 in two massively obese patients who were forced to lie down for medical procedures. But surprisingly, despite the current worldwide epidemic of obesity, very few cases have been reported yet. It can be assumed that the syndrome is poorly recognized in clinical practice and may participate in the high rate of unexplained death in morbidly obese patients. Based on the previously published cases and on those we met, this review aims at helping clinicians to early detect at-risk patients, to correctly diagnose this dramatic syndrome and to understand the underlying pathophysiology. More importantly, the main objective is to convince the attending clinicians that they have to do everything in their power to prevent obesity supine death syndrome occurrence by maintaining morbidly obese patients in the sitting or upright position whenever possible. When the syndrome unfortunately occurs, the best therapeutic approach is based on the immediate return to sitting position.

A novel type of semi-active jet turbulence grid.

This article describes a novel approach to generate increased turbulence levels in an incoming flow. It relies on a cost-effective and robust semi-active jet grid, equipped with flexible tubes as moving elements attached onto tube connections placed at the intersections of a fixed, regular grid. For the present study, these flexible tubes are oriented in counter-flow direction in a wind tunnel. Tube motion is governed by multiple interactions between the main flow and the jets exiting the tubes, resulting in chaotic velocity fluctuations and high turbulence intensities in the test section. After describing the structure of the turbulence generator, the turbulent properties of the airflow downstream of the grid in both passive and active modes are measured by hot-wire anemometry and compared with one another. When activating the turbulence generator, turbulence intensity, turbulent kinetic energy, and the Taylor Reynolds number are noticeably increased in comparison with the passive mode (corresponding to simple grid turbulence). Furthermore, the inertial subrange of the turbulent energy spectrum becomes wider and closely follows Kolmogorov's -5/3 law. These results show that the semi-active grid, in contrast to passive systems, is capable of producing high turbulence levels, even at low incoming flow velocity. Compared to alternatives based on actuators driven by servo-motors, the production and operation costs of the semi-active grid are very moderate and its robustness is much higher.

Fluid-Structure Simulations of a Ruptured Intracranial Aneurysm: Constant versus Patient-Specific Wall Thickness.

Computational Fluid Dynamics is intensively used to deepen the understanding of aneurysm growth and rupture in order to support physicians during therapy planning. However, numerous studies considering only the hemodynamics within the vessel lumen found no satisfactory criteria for rupture risk assessment. To improve available simulation models, the rigid vessel wall assumption has been discarded in this work and patient-specific wall thickness is considered within the simulation. For this purpose, a ruptured intracranial aneurysm was prepared ex vivo, followed by the acquisition of local wall thickness using µCT. The segmented inner and outer vessel surfaces served as solid domain for the fluid-structure interaction (FSI) simulation. To compare wall stress distributions within the aneurysm wall and at the rupture site, FSI computations are repeated in a virtual model using a constant wall thickness approach. Although the wall stresses obtained by the two approaches-when averaged over the complete aneurysm sac-are in very good agreement, strong differences occur in their distribution. Accounting for the real wall thickness distribution, the rupture site exhibits much higher stress values compared to the configuration with constant wall thickness. The study reveals the importance of geometry reconstruction and accurate description of wall thickness in FSI simulations.

Decrease in pulse pressure and stroke volume variations after mini-fluid challenge accurately predicts fluid responsiveness†.

BACKGROUND: Dynamic indices, such as pulse pressure variation (PPV), are inaccurate predictors of fluid responsiveness in mechanically ventilated patients with low tidal volume. This study aimed to test whether changes in continuous cardiac index (CCI), PPV, and stroke volume variation (SVV) after a mini-fluid challenge (100 ml of fluid during 1 min) could predict fluid responsiveness in these patients. METHODS: We prospectively studied 49 critically ill, deeply sedated, and mechanically ventilated patients (tidal volume <8 ml kg(-1) of ideal body weight) without cardiac arrhythmias, in whom a fluid challenge was indicated because of circulatory failure. The CCI, SVV (PiCCO™; Pulsion), and PPV (MP70™; Philips) were measured before and after 100 ml of colloid infusion during 1 min, and then after the additional infusion of 400 ml during 14 min. Responders were defined as subjects with a ≥15% increase in cardiac index (transpulmonary thermodilution) after the full (500 ml) fluid challenge. Areas under the receiver operating characteristic curves (AUCs) and the grey zones were determined for changes in CCI (ΔCCI100), SVV (ΔSVV100), and PPV (ΔPPV100) after 100 ml fluid challenge. RESULTS: Twenty-two subjects were responders. The ΔCCI100 predicted fluid responsiveness with an AUC of 0.78. The grey zone was large and included 67% of subjects. The ΔSVV100 and ΔPPV100 predicted fluid responsiveness with AUCs of 0.91 and 0.92, respectively. Grey zones were small, including ≤12% of subjects for both indices. CONCLUSIONS: The ΔSVV100 and ΔPPV100 predict fluid responsiveness accurately and better than ΔCCI100 (PiCCO™; Pulsion) in patients with circulatory failure and ventilated with low volumes.

Mathematical coupling of data between global-end diastolic volume index and cardiac index calculated by the PiCCO device: myth or reality?

BACKGROUND: Aim of the study was to investigate whether cardiac index (CI) and global end diastolic volume index (GEDVi) determined from the same thermodilution curve are mathematically coupled during the infusion of an inotropic agent in critically ill patients. METHODS: Seventeen patients were prospectively studied. CI and GEDVi were evaluated in triplicate by the transpulmonary thermodilution technique with the PiCCO system before and 20 to 30 minutes after increases in dobutamine infusion rate. Mixed linear model was used to determine the within-subject correlation coefficient between changes in CI and GEDVi induced by changes in dobutamine infusion rate. RESULTS: Dobutamine administration significantly increased CI by 48±35%, whereas the average increase in GEDVi was only 8.2±12.3% but statistically significant (P<0.0001). The increase of GEDVi in response to dobutamine infusion was unexpected given that dobutamine has no recognized effect on right and left ventricular dimensions. Intriguingly, we observed a significant correlation coefficient, in individual patients, between changes in CI and GEDVi (r=0.58, P=0.002). CONCLUSION: Our study provides evidence that changes in GEDVi are mathematically coupled to changes in CI during dobutamine infusion. Therefore, clinicians using PiCCO device to evaluate GEDVi must be aware of the underlying formula to avoid placing undue reliance on artifactual correlations due to mathematical coupling.

Neuodevelopmental outcomes for children transplanted under the age of 3 years.

UNLABELLED: Our previous investigations on neurodevelopmental outcomes for intestinal transplanted infants revealed that while some children were able to achieve a normal developmental outcomes, most children suffered from significant motor delays and several experienced severe cognitive delays. In our current investigation, we were especially interested in children who are transplanted before the age of 3 years because the impact of the chronic illness and nutrition impairment on the infant's developing brain may be more severe than those children who receive a liver transplant. METHODS: We evaluated 34 infants using the Bayley Scales of Infant Development. Twenty-seven children received a liver/intestine or multivisceral transplant and seven received a liver transplant. RESULTS: Comparison of the two groups revealed that children receiving an intestine/multivisceral transplant have much poorer outcomes. Seventy-four percent of these children were significantly delayed mentally compared to only 57.14% of the liver transplant infants. Furthermore, 42.86% of the liver-transplanted infants were actually functioning in the normal range posttransplant. The intestinal/multivisceral transplant infants' motor development shows the most striking difference, with 96.3% being severely delayed as compared to liver transplant infants in whom only 71% experienced serious delays. The neurodevelopmental impact of organ failure and transplant before the age of 3 years may depending on the type of organ transplant. Our study found that it may be more likely to expect a good outcome for liver transplant patients than for intestinal and multivisceral transplanted infants. This difference maybe due to the overall severity of the disease and the possible impact of nutritional deficits early in infancy.

Neurodevelopmental outcomes of infant multivisceral transplant recipients: a longitudinal study.

UNLABELLED: This longitudinal investigation compares cognitive and physical capabilities of transplant recipients, both before and after receiving an intestinal transplant. METHODS: Using the Bayley Scales of Infant Development, we conducted pretransplant and posttransplant assessments on nine children (4 males, 5 females) who received either an isolated intestine, combined intestine and liver, or multivisceral transplants, with a mean age at transplant of 18 months (range 8-29) and a mean time posttransplant of 2 months (range 1-4 months). RESULTS: Scores on the Mental Developmental Index reflected that a majority (55.6%) of patients who scored in the significantly delayed range prior to transplant remained in the significantly delayed classification after receiving a transplant. In addition, 33.3% showed a decrease in their mental classification; either from "mildly delayed" to "significantly delayed" or from "within normal limits" to "mildly delayed". Results on the Motor Developmental Index demonstrated that 78% of recipients had significant delays both before and after receiving a transplant, while 11.1% fell one standard deviation after transplantation. We found that the majority of children who experience developmental delays prior to transplant are still experiencing delays when they are discharged from inpatient care. In addition, those children receiving multivisceral transplantations, as opposed to an isolated bowel, may be at a much greater risk of developing and retaining both cognitive and physical delays. Early neurodevelopmental evaluations of these patients is essential for early parental education and compliance with early intervention services to maximize potential recovery and ability to obtain normal development.

Neurodevelopmental outcomes of infant intestinal transplant recipients.

Little is known about the impact of intestinal transplantation on development of the infant brain. In this study we report four neurodevelopmental studies on children receiving either liver or intestinal/multivisceral transplants. Our preliminary investigation examined the pretransplant status of 27 infants, who were either liver or intestinal/multivisceral candidates, using the Bayley Scales of Infant Development. A second study examined 23 infants after liver or intestinal/multivisceral transplant. A third study included pre- and posttransplant evaluations on 5 multivisceral infant transplants. In the fourth study, 10 children were tested several years after intestinal/multivisceral transplantation. Some children are able to achieve a normal development. However, even several years posttransplant most children can still experience significant cognitive delays. Children receiving a transplant during infancy may also suffer severe motor delays. Infants undergoing intestinal/multivisceral transplantation show significantly more cognitive delays than those undergoing single-organ liver transplantation. In addition, multivisceral transplanted infants are more likely to continue to be severely developmentally delayed at the time of hospital discharge. With improved survival rates for infant transplants, both cognitive and motor development must be evaluated to determine the need for early intervention. In addition, educating families on the importance of compliance with intervention services outside the hospital is essential to maximize long-term neurodevelopmental outcomes for these infants.

Tropoelastin biosynthesis by corneal cells. Epithelial inhibition of keratocyte tropoelastin biosynthesis.

The vertebrate cornea is an avascular tissue and does not contain elastic fibers. We tested the capacity of corneal epithelial cells and stromal keratocytes to synthesize tropoelastin. Explant cultures and cell cultures were obtained from these two cell types in standard culture conditions. Their elastin-synthetic activity was compared to skin explant cultures and to dermal fibroblast cell cultures. Both corneal cell types synthesized tropoelastin as shown by the incorporation of a radioactive precursor followed by immunoprecipitation of tropoelastin. When serial cultures of keratocytes were tested, tropoelastin biosynthesis strongly increased after the 3rd passage and was at the 9th passage more than the double of that of the first passage. When cocultures were studied with or without cell contact, epithelial cells partially inhibited tropoelastin biosynthesis by keratocytes. This inhibition was somewhat stronger (-36%, p < 0.005) with cell-to-cell contact than keeping separate epithelial cells and keratocytes bathing in the same medium (-18%, p < 0.005). When human skin fibroblasts were substituted for keratocytes with cell-to-cell contact, their tropoelastin biosynthesis was also inhibited by corneal epithelial cells (-42%, p < 0.005), to the same extent as for keratocytes. In Transwell culture, this inhibition was again somewhat lower (-36%, p < 0.005). Some diffusible factor produced by epithelial cells is apparently involved. The epithelial inhibition of tropoelastin biosynthesis by stromal keratocytes might represent one of the mechanisms keeping corneal stroma exempt of elastin fibers.

Simplified prediction rule for prognosis of patients with severe community-acquired pneumonia in ICUs.

STUDY OBJECTIVES: To develop a simplified prognostic prediction rule for patients admitted to ICUs for severe community-acquired pneumonia (CAP). SETTING: Six ICUs in the north of France. PATIENTS: Five hundred five patients admitted to ICUs over a 9-year period (from 1987 to 1995) for severe CAP. INTERVENTIONS: Retrospective prognosis analysis and multivariate analysis using a credit scoring technique. MEASUREMENTS: The primary outcome measure was ICU mortality. RESULTS: Among the 505 patients, 472 were eligible for the prognosis study. The ICU mortality rate was 22.9%. Multivariate analysis identified, on the basis of the patient's medical history and initial examination on ICU admission, six independent predictors of mortality: age > or = 40 years, anticipated death within 5 years, nonaspiration pneumonia, chest radiograph involvement > 1 lobe, acute respiratory failure requiring mechanical ventilation, and septic shock. An initial risk score based on these factors classified patients into three risk classes of increasing mortality: 4% in class I, 25% in class II, and 60% in class III. Multivariate analysis of events occurring during ICU stay identified three independent predictors of mortality: hospital-acquired lower respiratory tract superinfections, nonspecific CAP-related complications, and sepsis-related complications. An adjustment risk score based on these factors was essential to accurately predict the final outcome of patients in the initial risk class II. CONCLUSIONS: As an aid to clinicians in stratifying the prognosis of patients with severe CAP, the simplified prediction rule used in this study could be useful for therapeutic decisions and appropriate care.

Community-acquired pneumonia in the intensive care unit: epidemiological and prognosis data in older people.

OBJECTIVES: To compare epidemiological data, etiology, and prognosis of severe community-acquired pneumonia (CAP) in the intensive care unit (ICU) according to age (< or > or = 65 years) and to determine prognostic factors of CAP in older people. DESIGN: A retrospective (1987-1992) and prospective (1993-95) multicenter study. SETTING: Six ICUs in the north of France. PATIENTS: Five hundred five patients admitted to an ICU for severe CAP. MEASUREMENTS: Patient characteristics were compared with regard to age. Prognosis of CAP in older patients was studied by stepwise discriminant analysis. RESULTS: Two hundred seventy-eight patients (55%) were aged 65 years or older. Comparison of epidemiological data between older and younger patients revealed a higher prevalence of women (38% vs 29%), more severe underlying comorbidities (anticipated death within 5 years: 59% vs 26%), and more frequent chronic respiratory insufficiency (48% vs 33%) in the older patients. In this study group, 224 organisms were isolated from 172 patients (62%); those identified most frequently were Gram-negative bacilli (34%), S. pneumoniae (32%), and Staphylococcus sp. (19%). Compared with younger patients, no significant differences in bacteriological data were observed. However, crude and attributable mortality rates were significantly higher in the older patients (33% vs 21% and 30% vs 19%, respectively). Prognosis analysis identified four independent predictors of mortality in the older patients: initial septic shock (relative risk (RR) = 3), sepsis-related complications (RR = 4.3), hospital-acquired lower respiratory tract superinfections (RR = 2), and nonspecific pneumonia-related complications (RR = 2.8). CONCLUSION: The bacterial etiology provides some approaches to empirical therapy for older patients with severe community-acquired pneumonia. In addition, the inappropriateness of withholding intensive care for reasons of age alone is emphasized.

Community-acquired aspiration pneumonia in intensive care units. Epidemiological and prognosis data.

Over a 9-yr period, among 505 patients exhibiting severe community-acquired pneumonia and admitted into a total of six medical ICUs in the north of France, we collected 116 patients (23%) meeting the usual criteria for aspiration pneumonia. Main medical grounds of ICU admission were respiratory distress in 54 patients and neurological disturbances in 62 patients. The main underlying risk factor for aspiration pneumonia was drug overdose (39%). Mechanical ventilation was required for 73 patients. Initial shock was present in 15 patients. Pulmonary involvement was bilateral in 27 patients. There were 94 aerobic organisms isolated from 70 patients (60%), the most frequent being gram-negative bacilli (n = 38), Staphyloccus spp. (n = 27) and Streptococcus pneumoniae (n = 22). Overall mortality was 22%, but only 11 (11%) deaths were directly or indirectly related to aspiration pneumonia. Stepwise multivariate analysis identified four independent predictors of mortality: ineffective initial antimicrobial therapy (p = 0.0001), positive initial blood culture (p = 0.0001), hospital-acquired lower respiratory tract superinfections (p = 0.0054), and use of inotropic support (p = 0.0078). The importance of prevention of hospital-acquired superinfections and permanent optimization of our antimicrobial strategies warranting efficacy of the initial antimicrobial therapy is underlined.

Can prolonged expiration manoeuvres improve the prediction of arterial PCO2 from end-tidal PCO2?

We have studied, in 16 patients undergoing thoracoabdominal oesophagectomy, if two prolonged expiration manoeuvres improve prediction of arterial PCO2 (PaCO2) from end-tidal PCO2 (PE' CO2). PE' CO2, PCO2 at the end of a simple prolonged expiration (PE1 CO2), and PCO2 at the end of a prolonged expiration preceded by sustained hyperinflation of the lungs (PE2 CO2), were measured during laparotomy, in the lateral thoracotomy position during two-lung ventilation, and after transition to one-lung ventilation. (PaCO2-PE' CO2) was 1.3 (SD 0.4) kPa during laparotomy and this remained stable throughout the study. Both manoeuvres decreased the mean arterial to peak expired PCO2 difference, particularly during one-lung ventilation. However, PE1 CO2 and PE2 CO2 did not agree more closely with PaCO2 than PE' CO2 at any stage of the study. We conclude that these manoeuvres did not improve estimation of PaCO2 from PE' CO2.

Behavioral treatment of conversion disorder in adolescence. A case example of Globus Hystericus.

The present single case study evaluated the efficacy of a cognitive-behavioral intervention for the treatment of a patient diagnosed with globus hystericus, a conversion disorder characterized by a perceived lump in the throat. The patient was a non-mentally retarded 12-year-old female who refused to swallow solids because she thought that her throat muscles would involuntarily constrict and result in choking. She lost approximately .5 lbs. per week during the 6 months prior to treatment. Improvements in weight gain were demonstrated consequent to the implementation of behavior therapy, with weight gain being particularly pronounced after contingency contracting was added to therapy. Weight gain was maintained at 1, 6, and 10 months posttreatment.

Severe community-acquired pneumonia in ICUs: prospective validation of a prognostic score.

OBJECTIVE: To determine predictors of intensive care unit (ICU) mortality in patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific prognostic index, and to evaluate this index prospectively. DESIGN: Combined retrospective and prospective clinical study over two periods: January 1987-December 1992 and January 1993-December 1994. SETTING: Four medical ICUs in the north of France. PATIENTS: Derivation cohort: 335 patients admitted to one ICU were retrospectively studied to determine prognosis factors and to develop a pneumonia-specific prognostic index. Validation cohort: 125 consecutive patients, admitted to four ICUs, were prospectively enrolled to evaluate this index. RESULTS: In the derivation cohort, 16 predictors of mortality were identified and assigned a value directly proportional to their magnitude in the mortality model: aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09), serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or = 3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29), underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52), acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67), immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5). An index was obtained by adding each patient's points. According to a receiver operating characteristic curve, the cut-off value of this index was 2.5. In the validation cohort, an index of > or = 2.5 could predict death with a positive predictive value of 0.92, sensitivity 0.61, and specificity 0.98. CONCLUSION: This index, which performs well in classifying patients at high-risk of death, may help physicians in initial patient care (appropriateness of the initial antimicrobial therapy) and guide future clinical research (analysis and design of therapeutic trials).

Treatment of relapsing and refractory adult acute myeloid leukemia according to in vitro clonogenic leukemic cell drug sensitivity.

In an attempt to improve the results of treatment in patients with relapsing or refractory acute myeloid leukemia (AML), we conducted a pilot study using a two-drug salvage regimen according to the in vitro clonogenic leukemic cell (CFU-L) drug sensitivity. Fourteen patients were included in the study, 10 with relapsing and 4 with refractory AML. Drug exposure was assessed for daunorubicin, cytosine arabinoside, etoposide, mitoxantrone and amsacrine. The two drugs with the best inhibitory effect on CFU-L were selected for the treatment. A complete remission was achieved in only 4 patients and a partial remission in 3 patients. Although the number of patients is too small for appropriate statistical analysis and for a definite conclusion to be drawn, the observed response rate with directed therapy did not appear better than that expected from empiric salvage regimen.