Contact investigation based on serial interferon-gamma release assays (IGRA) in children from the hematology-oncology ward after exposure to a patient with pulmonary tuberculosis.

BACKGROUND: Interferon-gamma release assays (IGRAs) have high specificity and sensitivity for the diagnosis of tuberculosis (TB) infection. However, their role as a screening tool in children with immunodeficiency disorders is still unclear. In the present study, we performed a contact investigation using serial IGRAs on children with immunodeficiency conditions exposed to a contagious TB patient. METHODS: Children who were exposed to a contagious TB case underwent serial QuantiFERON(®) TB Gold In-Tube (QFT-GIT) and T-SPOT(®).TB (T-SPOT) testing. RESULTS: Eighteen children were tested. At the first testing, only two children (11 %) were positive to T-SPOT. Indeterminate results were more frequent with QFT-GIT (35 %) than with T-SPOT (12 %). In the multivariable analysis, a statistically significant association of lymphocyte count <500 cells/mm(3) (p < 0.00005) and low age (p = 0.03) with indeterminate results for the QFT-GIT test but not for T-SPOT (p = 0.10 and p = 0.88, respectively) was found. At the end of October 2012, 15 of the 18 children were alive and none developed active TB disease. CONCLUSION: T-SPOT provided more determinate results and was less influenced by low age and lymphocytopenia than QFT-GIT in this population of immunodeficient children. These findings suggest that T-SPOT is a more accurate test for the identification of TB infection in young children with lymphocytopenia and should be preferred to QFT-GIT under such specific conditions.

Type 1 diabetes and measles, mumps and rubella childhood infections within the Italian Insulin-dependent Diabetes Registry.

AIMS: Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results. METHODS: This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used. RESULTS: The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269). CONCLUSIONS: According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility.

[Assessment of the impact of cancer in the Vercelli Local Health Authority from 2002 to 2009]. / Incidenza oncologica nell'ASL VC di Vercelli dal 2002 al 2009.

The object of the study is to provide an epidemiological overview of the impact of neoplasms in an area that has no cancer registry. A descriptive study was conducted within the Local Health Authority of Vercelli. To estimate the number of cases, hospital discharge documents (including passive mobility) were used and integrated with the archives of pathology. The number of cases was calculated on the basis of SIR (specific rates of the Vercelli Local Health Authority divided by age in the years 2002-2009 in comparison with new cases of cancer in the city of Turin from 2005 to 2007, used as standard population). All readings were expressed including intervals of confidence at 95%. For tumors of low lethality for males, extending the period of observation confirms the excess for bladder cancer (SIR = 1.1, 1.07 to 1.21) and lymphoma aggregate (SIR = 1.4, 1.2 to 1.6). for females: thyroid (SIR = 1.5, 1.3 to 1.65) and lymphomas (SIR = 1.25, 1.1 to 1.4). In addition to these tumors in both sexes is observed to decrease colorectal cancer but excess for leukemias and brain. The extension of the study is intended as the base for the creation of a cancer register that will be established, naturally integrating further sources of information. In all cases, data observed indicated several epidemiological peculiarities in the region, probably linked to specific characteristics of local exposure, which should be addressed in terms of Public Health.

[Comparison of the leukaemia incidence in two cohorts of farmers and traders in the Vercelli province of Italy, 2002-2009]. / Confronto delle incidenze di leucemia di due coorti d'agri- coltori e di commercianti della provincia di Vercelli dal 2002 al 2009.

This study aims to investigate the incidence of leukaemia between 2002 and 2009 (ICDIX 204-208) among farmers active in the Vercelli province (North West Italy), during the period: 1962-1991. The farmer cohort (14397 subjects, 78 cases) was compared with a retail trader cohort (4565 subjects, 11 cases) who were Vercelli province residents as well, but not exposed to the risk factors associated with professional farming. A proportional hazard Cox model shows among the farmers, an approximately double leukaemia incidence with respect to traders (Hazard Ratio = 1,90 P-value 0,043 IC95% 1,00-3,60). Moreover men's incidence appears approximately to double that of women (Hazard Ratio = 1,92 P-value 0,003 IC95% 1,25-2,95).

Major childhood infectious diseases and other determinants associated with type 1 diabetes: a case-control study.

The objective of the study was to evaluate the association between infectious diseases and other events pertaining to childhood medical history and type 1 diabetes. A case-control study was carried out, taking as cases 159 type 1 diabetic patients (0-29 years) recorded from 1988 to 2000 within the population registry of the Pavia province (North Italy). As controls 318 non-diabetic subjects were matched by age and sex. A questionnaire was administered by standardised interviewers. Data were analysed by conditional logistic regression. Viral childhood diseases (OR 4.29; 95%CI 1.57-11.74) and bottle feeding (OR 1.83; 95%CI 1.08-3.09) were directly correlated to type 1 diabetes; an inverse correlation was found for vitamin D administration during lactation (0-14 years) (OR 0.31; 95%CI 0.11-0.86) and for history of scarlet fever in both sexes and age groups (OR 0.19; 95%CI 0.08-0.46). Most associations of the studied variables confirm already known findings. The significant inverse correlation of type 1 diabetes with scarlet fever history is a peculiar finding, the meaning of which is still obscure, although it has been recently described that streptococcal A infections are regulated by HLA class II alleles.

A technical note about Phidel: a new software for evaluating magnetic induction field generated by power lines.

The Regional Environment Protection Agency of Friuli Venezia Giulia (ARPA FVG, Italy) has performed an analysis on existing software designed to calculate magnetic induction field generated by power lines. As far as the agency's requirements are concerned the tested programs display some difficulties in the immediate processing of electrical and geometrical data supplied by plant owners, and in certain cases turn out to be inadequate in representing complex configurations of power lines. Phidel, an innovative software, tackles and works out all the above-mentioned problems. Therefore, the obtained results, when compared with those of other programs, are the closest to experimental measurements. The output data can be employed both in the GIS and Excel environments, allowing the immediate overlaying of digital cartography and the determining of the 3 and 10 muT bands, in compliance with the Italian Decree of the President of the Council of Ministers of 8 July 2003.

ELF field in the proximity of complex power line configuration measurement procedures.

The issue of how to measure magnetic induction fields generated by various power line configurations, when there are several power lines that run across the same exposure area, has become a matter of interest and study within the Regional Environment Protection Agency of Friuli Venezia Giulia. In classifying the various power line typologies the definition of double circuit line was given: in this instance the magnetic field is determined by knowing the electrical and geometric parameters of the line. In the case of independent lines instead, the field is undetermined. It is therefore pointed out how, in the latter case, extracting previsional information from a set of measurements of the magnetic field alone is impossible. Making measurements throughout the territory of service has in several cases offered the opportunity to define standard operational procedures.

Stratified gray-scale median analysis and color mapping of the carotid plaque: correlation with endarterectomy specimen histology of 28 patients.

BACKGROUND AND PURPOSE: To determine whether a stratified gray-scale median (GSM) analysis of the carotid plaque combined with color mapping could predict plaque histology better than an overall GSM measurement. METHODS: Thirty-one carotid plaques derived from 28 patients undergoing carotid endarterectomy were investigated by ultrasound. GSMs of the whole plaque were used as measurement of echogenicity. A profile of the regional GSM as a function of distance from the plaque surface could be generated. Plaque pixels were further mapped into 3 different colors depending on their GSM value. RESULTS: Plaques with large calcifications presented the highest GSM values, and those with large hemorrhagic areas or with a predominant necrotic core exhibited the lowest. Fibrous plaques had intermediate GSM values. A necrotic core located in a juxtalumenal position was associated with significantly lower GSM values (P=0.009) and with a predominant red color (GSM <50) at the surface (P=0.0019). With respect to the thickness of the fibrous cap and the position of the necrotic core, the sensitivity and specificity of the predominant red color of the whole plaque was respectively 45% and 67% and 53% and 75%; considering the predominant red color of the surface, the sensitivity and specificity increased to 73% and 67% and 84% and 75%, respectively. CONCLUSIONS: The stratified GSM measurement combined with color mapping showed a good correlation with the different histopathological components and further allowed identification with good accuracy of determinants of plaque instability. This approach should be investigated in a prospective, natural history study.

Quantification of upper limb skills in elderly rehabilitative inpatients: a controlled study.

BACKGROUND: Aging has a recognized degenerative effect on the functionality of the hand in terms of strength and dexterity. Despite this, there are few studies in literature that quantify the upper limb skills in the elderly. AIM: The aim was to present quantitative data regarding upper limb functionality in the elderly and to quantify the effect of aging on them, considering the influence of the comorbidities, of the global level of autonomy, of the cognitive status and of the mood, which are typically compromised in the elderly. DESIGN: It was a controlled study. SETTING: It was settled in the Rehabilitation Unit of the "Santa Maria alle Fonti" Medical Center, part of the Don Carlo Gnocchi ONLUS Foundation. POPULATION: Thirty-five elderly inpatients (aged 78.6±7.5 years) compared to 30 healthy young adults (aged 30±3.9 years). METHODS: A task consisting in 12 trials of grasping of rulers was administered to each subject and studied with a video analysis software. To assess the comorbidities, the global level of autonomy, the cognitive status and the mood, we respectively used the Cumulative Illness Rating Scale (CIRS), the Functional Independence Measure (FIM™), the Mini Mental State Examination (MMSE) and the Geriatric Depression Scale in the 15-items version (GDS-15). The scores obtained in these scales were correlated to the mean times of trials execution. RESULTS: The motor performance was significantly worse in the inpatients group compared to the control group in terms of time to complete single tasks (which was on average three times higher in the inpatients group) and of respect of the starting sound stimulus, with more subjects from the inpatients group anticipating the starting signal. This worsening of the motor performance was significantly correlated to the severity of comorbidities and to the global level of autonomy. No significant differences emerged for the correctness of the performance and significant differences were not correlated with depression or cognitive impairment. CONCLUSION: This study provides quantifiable data regarding upper limb skills in the elderly inpatient, allowing comparisons with other future studies of the rehabilitative environment. CLINICAL REHABILITATION IMPACT: It suggests the relevance of considering the severity of comorbidities and the global level of autonomy in the assessment of upper limb skills in the elderly.

Differentiation potentiates oxidant injury to mitochondria by hydrogen peroxide in Friend's erythroleukemia cells.

Oxidative damage to mitochondrial functions was investigated upon non-lethal treatment with H2O2 of Friend's erythroleukemia cells induced to differentiate, in comparison with the parental cell line. Both respiration and maximal ATP synthase capacity were more severely diminished by H2O2 in induced cells. The effects were mediated by intracellular redox-active iron and OH. radicals. Specifically, the mechanisms of the selective oxidant injury to F0F1 ATP synthase observed in differentiating cells likely involved impairment of F0-F1 coupling sensitive to oligomycin. We suggest a Fenton-like reaction of H2O2 with iron ions, more available in the differentiating cells, as occurring at the surface and/or in the lipid bulk phase of the inner mitochondrial membrane, thus injuring subunits responsible for the coupling of F0F1 ATP synthase through generation in situ of the actual damaging species. Besides, we propose heme iron as the most likely candidate for such reaction in induced cells actively synthesizing heme. In accordance, pretreatment of uninduced cells with hemin made H2O2-damage qualitatively identical.

Severe energy impairment consequent to inactivation of mitochondrial ATP synthase as an early event in cell death: a mechanism for the selective sensitivity to H2O2 of differentiating erythroleukemia cells.

Irreversible damage to Friend's erythroleukemia cells was caused by induction of endogenous heme biosynthesis with the differentiating agent N,N'-hexamethylene bisacetamide followed by a 30-min exposure to 0.25 mM H2O2. Early irreversible ATP depletion was observed concomitant with oxidative inactivation of the mitochondrial ATP synthase. Cell proliferative capacity was also impaired within 2 h of the treatment, and progressive delayed cell lethality, starting 2 h after the insults, was also found. Based on the prevention provided by specific antioxidants and on the absence of malodialdehyde production, all the effects were ascribed to the oxidant action of .OH radicals, or closely related species, generated through iron-catalyzed reactions of H2O2, which apparently caused site-directed oxidative modifications of iron-binding proteins, in particular mitochondrial ATP synthase, rather than peroxidation of membrane lipids. Similar effects were mimicked even in the parental cell line when oligomycin was used to inhibit selectively mitochondrial ATP synthase activity, thereby lowering the enzyme activity to a level similar to that found in H2O2-damaged differentiating cells. Hence, induction of erythroid differentiation makes the mitochondrial ATP synthase a major target of H2O2 by enhancing the availability of redox-active iron in the local environment of the enzyme. Subsequent oxidative inactivation of the mitochondrial ATP synthase, resulting in severe energy impairment, leads to loss of cell growth capacity. Erythroleukemia cells may serve as a model system for the combination of two selective properties: (1) the capacity for carrying out efficient heme synthesis and/or for undergoing iron overload-like state; and (2) subsequent enhanced sensitivity to reactive oxygen species generators. Early severe mitochondrial dysfunction and energy impairment may be a major part of the mechanism of the sensitivity.

Distribution of protein gene product 9.5 (PGP 9.5) in the vertebrate retina: evidence that immunoreactivity is restricted to mammalian horizontal and ganglion cells.

Using light microscopic immunocytochemistry, we have studied the distribution of protein gene product 9.5 (PGP 9.5), a neuron-specific protein first extracted from human brain (Doran et al., '83:J. Neurochem. 40:1542-1547), in the vertebrate retina. Retinas were obtained from frog, chicken, rat, rabbit, cow, cat, dog, and human. No immunoreactivity was observed in frog and only a faint staining was present in chicken. In mammalian retinas, a strong positive reaction was restricted to horizontal and ganglion cells, with minor interspecies variations. Immunostaining was present throughout the cell body and the dendritic tree in horizontal cells. At the level of retinal ganglion cells, immunolabel was particularly abundant in cell bodies and axons forming the optic nerve. Only the main dendrites were stained, the remainder of the dendritic tree giving rise to a diffuse punctate reaction in the inner plexiform layer. In rats, displaced amacrine cells, which are known to contribute largely (40-50%) to the total neuronal population within the ganglion cell layer (Perry, '81: Neuroscience 6:931-944) were not immunoreactive, as demonstrated from (i) analysis of the morphology, cell size and cell density of immunoreactive neurons in wholemounts; (ii) colocalization of retrograde label and PGP 9.5 immunoreactivity in about 80% of ganglion cells after injection of peroxidase into the optic nerve; and (iii) reduction of immunoreactivity in the inner plexiform and ganglion cell layers following optic nerve transection. Western blot analysis of extracts from rabbit retinas indicated that the immunoreactive species is PGP 9.5 or a closely related molecule. Recent studies have demonstrated that PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase (Wilkinson et al., '89:Science 246:670-673). The present results, therefore, suggest that differences in the ubiquitination process exist between retinal neurons.

Long-term acetyl-L-carnitine treatment in Alzheimer's disease.

In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.

Time course, localization and pharmacological modulation of immediate early inducible genes, brain-derived neurotrophic factor and trkB messenger RNAs in the rat brain following photochemical stroke.

A focal, unilateral thrombotic stroke was produced in the rat sensorimotor cortex. The time course of expression and localization of the immediate early inducible genes: c-fos, c-jun, zif268; nerve growth factor, brain-derived neurotrophic factor and the related tyrosine kinase high-affinity receptor (trkB) messenger RNAs were studied by in situ hybridization. The levels of messenger RNAs for c-fos, zif268, brain-derived neurotrophic factor (but not nerve growth factor) and trkB were consistently increased in cortex ipsilaterally to the lesion, while c-jun messenger RNA content was only slightly increased. The brain-derived neurotrophic factor messenger RNA was increased from 2 to 18 h following the stroke, mainly in cells having a normal morphological appearance. The trkB messenger RNA displayed temporal and spatial increases similar to brain-derived neurotrophic factor messenger RNA. The time course and pattern of expression of immediate early inducible gene and trophic factor messenger RNAs did not clearly support a causal relationship between these two families of factors. The observed messenger RNA increases were greatly attenuated by the non-competitive N-methyl-D-aspartate-sensitive glutamate receptor antagonist (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine , but substantially unaffected by the non-N-methyl-D-aspartate receptor antagonist 2,3-dihydroxy-6-nitrosulphanoylbenzoquinoxaline. The results suggest a major contribution of N-methyl-D-aspartate-sensitive glutamate receptor activation to the transcriptionally directed events subsequent to stroke. Future studies should clarify the contribution of these processes to either the progression of neuronal degeneration or the establishment of protective compensatory responses.

Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells.

Five young patients with Niemann-Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30-40% of the assays.

Rate of progression and prognostic factors in Alzheimer's disease: a prospective study.

OBJECTIVE: To study rate of progression and correlates of cognitive and functional/behavioral deterioration in Alzheimer patients. DESIGN: A 1-year multicenter prospective study. SETTING: Outpatients and inpatients at geriatric institutions. PATIENTS: Fifty-six patients with a clinical diagnosis of Alzheimer's disease according to DSM-III criteria of Primary Degenerative Dementia. MAIN OUTCOME MEASURES: Blessed Dementia Scale (BDS) and Blessed Information-Memory-Concentration test (BIMC) measured at baseline, third, sixth, and twelfth month. RESULTS: The mean annual (+/- SD) rate of progression of our sample was 3.5 (+/- 3.7) points on the BDS and 2.6 (+/- 4.9) on the BIMC, with a wide range of variability. The level of cognitive impairment (BIMC score) at baseline predicted functional and behavioral deterioration: the better the initial BIMC score, the less the rate of negative change of BDS (r = 0.37, P = 0.006). Furthermore, the younger the patients at the disease onset, the faster the progression of cognitive impairment (r = 0.48, P = 0.0003), with men having a slower rate of progression (P = 0.004) than women. CONCLUSIONS: The present study confirms previous findings showing a wide individual variability in rate of progression of cognitive and functional/behavioral impairment as assessed by BIMC and BDS. The cognitive profile may predict the clinical evolution better than the functional and behavioral status, with patients with an earlier onset and women having a faster deterioration.

Drug compliance and unreported drugs in the elderly.

A random sample of 46 general practitioners of the Unitá Sanitaria Locale in Torino recruited 802 elderly outpatients and collected information about complaints and current drug treatment. Within a week each patient received a home interview and details were collected on drug compliance and use of drugs other than those reported by the general practitioners. On average, each patient was taking 3.6 drugs, of which 2.9 were correctly reported by the general practitioners and 0.7 were unreported. Among the most prescribed therapeutic groups there were drugs with a narrow therapeutic index (cardiovascular drugs, diuretics, psychotropic agents) and substances whose efficacy has never been fully documented ("cerebroactive-vasoactive" agents). Age and number of complaints were positively and significantly correlated with number of prescribed drugs. Nearly half of the sample (44.4%)--more frequently women and people with higher education--were taking one or more drugs not detected by the general practitioners, often benzodiazepines taken over a long period for anxiety or insomnia. Full compliance occurred for 81.5% of the prescriptions and 59.9% of patients were correctly taking all prescribed drugs. Compliance was lower for prescriptions of the general practitioners compared with other doctors' prescriptions (eg, hospital doctor, private doctor) and probability of taking correctly all the prescribed drugs decreased with the number of medicines concurrently taken. The most common reason for noncompliance was fear of side effects.

Glucocorticoids depress activity-dependent expression of BDNF mRNA in hippocampal neurones.

Glucocorticoid hormones are important regulators of brain development and ageing, and can impair the capacity of hippocampal neurones to survive various neurological insults. Here we show that dexamethasone, a synthetic glucocorticoid, prevents activity-dependent increases of brain-derived neurotrophic factor (BDNF) mRNA in cultures of rat hippocampal neurones. In situ hybridization was used to evaluate the levels of BDNF mRNA. Up-regulation of BDNF mRNA triggered by depolarization with high potassium, or exposure to the glutamate receptor agonist kainic acid, resulted both from higher levels of expression in neurones and from new recruitment of cells. These data suggest that the known ability of glucocorticoids to exacerbate neuronal injury following ischaemia and other metabolic insults could be due to antagonism of regulatory mechanisms governing neurotrophin levels in the brain.

Photochemical stroke and brain-derived neurotrophic factor (BDNF) mRNA expression.

In situ hybridization and Northern blotting were used to study the expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat brain following photochemical stroke. A focal thrombotic lesion of the sensorimotor cortex was produced by intravenously injecting the light-sensitive dye rose bengal and exposing the skull to a controlled beam of light. Four hours after the light exposure the level of BDNF mRNA was increased in the hippocampus and cortex ipsilateral and perifocal to the lesion. The stroke-induced BDNF mRNA increase was prevented by the non-competitive glutamate receptor blocker dizocilpine (MK-801). The results indicate that the activation of N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors is involved in the stroke-triggered stimulation of BDNF mRNA increase.

Sepsis score and acute-phase protein response as predictors of outcome in septic surgical patients.

In a series of 135 patients with severe surgical infections, we determined the sepsis score and the plasma level of the acute-phase proteins alpha-1-acid glycoprotein, alpha 1-antitrypsin, complement factor B, and C3. The initial sepsis score was a strong determinant of survival: in survivors it was significantly lower than in nonsurvivors. Only 8% of patients with a sepsis score above 20 survived. At the onset of severe sepsis, the plasma levels of all four acute-phase proteins were significantly lower in nonsurvivors. A significant elevation of C3a levels in the plasma of both surviving and nonsurviving patients indicated marked consumption of complement components in all patients with severe sepsis. A linear equation was developed to predict survival: sepsis index of survival (SIS) % = 121 + 0.26 (complement factor B) + 0.36 (alpha-1-acid glycoprotein)-6 (sepsis score). Based on our analysis, at the onset of severe sepsis, an SIS of 50% or more can correctly predict 88% of survivors and an SIS less than 50% can correctly predict 86% of nonsurvivors several days in advance of clinical outcome.