A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia.

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).

A phase I study to evaluate the safety, tolerance and pharmacokinetics of anti-Shiga toxin hyperimmune equine F (ab')2 fragments in healthy volunteers.

AIMS: Shiga toxin-producing Escherichia coli-haemolytic uraemic syndrome (STEC-HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab')2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. METHODS: A single-centre, randomized, phase 1, single-blind, placebo-controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts (n = 4) to receive a single INM004 dose of 2 or 4 mg kg-1, or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4 mg kg-1 repeated every 24 h, or placebo (INM004:placebo ratio of 5:1). RESULTS: Eight subjects (57.1%) experienced mild treatment-emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24 h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2 h after infusion, with median Cmax values of 45.1 and 77.7 µg mL-1 for 2 and 4 mg kg-1, respectively. The serum concentration of INM004 declined in a biphasic manner (t1/2 range 30.7-52.9 h). Systemic exposures increased with each subsequent dose in a dose-proportional manner, exhibiting accumulation. Geometric median Cmax and AUC values were 149 and 10 300 µg h mL-1, respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2 mg kg-1 showed neutralizing capacity against Stx1 and Stx2 in in vitro assays. CONCLUSIONS: The results obtained in this first-in-human study support progression into the phase 2 trial in children with HUS.

Maternal responsiveness and toddler body mass index z-score: Prospective analysis of maternal and child mealtime interactions.

Responsive feeding, where parents are guided by children's hunger and satiation cues and provide appropriate structure and support for eating, is believed to promote healthier weight status. However, few studies have assessed prospective associations between observed parental feeding and toddler growth. We characterized toddler growth from 18 to 36 months and, in a subset of families, examined whether observed maternal responsiveness to toddler satiation cues and encouraging prompts to eat at 18 and 24 months were associated with toddler body mass index z-score (BMIz) from 18 to 36 months. Participants included 163 toddlers and their mothers with overweight/obesity who had participated in a lifestyle intervention during pregnancy. Anthropometrics were measured at 18, 24, and 36 months. In a subsample, mealtime interactions were recorded in families' homes at 18 (n = 77) and 24 (n = 75) months. On average, toddler BMIz remained stable from 18 to 36 months with 31.3% (n = 51) categorized with a healthy weight, 56.4% (n = 92) with at risk for overweight and 12.3% (n = 20) with overweight. Fewer maternal prompts to eat at 18 months was associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p = .002). Higher child weight status at 12 months was also associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p < .001). Neither 24-month maternal prompts nor 18 or 24 month responsiveness to satiation cues were associated with toddler BMIz. In this diverse sample, weight status was relatively stable from 18 to 36 months. Maternal prompts to eat measured earlier in toddlerhood and prior child weight status were associated with toddler BMIz.

Caffeine exposure ameliorates acute ischemic cell death in avian developing retina.

In infants, the main cause of blindness is retinopathy of prematurity that stems in a hypoxic-ischemic condition. Caffeine is a psychoactive compound that at low to moderate concentrations, selectively inhibits adenosine A1 and A2A receptors. Caffeine exerts beneficial effects in central nervous system of adult animal models and humans, whereas it seems to have malefic effect on the developing tissue. We observed that 48-h exposure (during synaptogenesis) to a moderate dose of caffeine (30 mg/kg of egg) activated pro-survival signaling pathways, including ERK, CREB, and Akt phosphorylation, alongside BDNF production, and reduced retinal cell death promoted by oxygen glucose deprivation in the chick retina. Blockade of TrkB receptors and inhibition of CREB prevented caffeine protection effect. Similar signaling pathways were described in previously reported data concerning chemical preconditioning mechanism triggered by NMDA receptors activation, with low concentrations of agonist. In agreement to these data, caffeine increased NMDA receptor activity. Caffeine decreased the levels of the chloride co-transporter KCC2 and delayed the developmental shift on GABAA receptor response from depolarizing to hyperpolarizing. These results suggest that the caffeine-induced delaying in depolarizing effect of GABA could be facilitating NMDA receptor activity. DPCPX, an A1 adenosine receptor antagonist, but not A2A receptor inhibitor, mimicked the effect of caffeine, suggesting that the effect of caffeine occurs through A1 receptor blockade. In summary, an in vivo caffeine exposure could increase the resistance of the retina to ischemia-induced cell death, by triggering survival pathways involving CREB phosphorylation and BDNF production/TrkB activation.

Medication for addiction treatment and acute care utilization in HIV-positive adults with substance use disorders.

Medication for addiction treatment (MAT) could reduce acute care utilization in HIV-positive individuals with substance use disorders. The study objective was to determine if HIV-positive people with substance use disorders treated with MAT report less acute care utilization than those not receiving MAT. We assessed the association between MAT and acute care utilization among HIV-positive individuals with alcohol or opioid use disorder. Acute care utilization 6 months later was defined as any past 3-month self-reported (1) emergency department (ED) visit and (2) hospitalization. Of 153 participants, 88% had alcohol use disorder, 41% had opioid use disorder, and 48 (31%) were treated with MAT. Fifty-five (36%) participants had an ED visit and 38 (25%) participants had a hospitalization. MAT was not associated with an ED visit (AOR 1.12, 95% CI 0.46-2.75) or hospitalization (AOR 1.09, 95% CI 0.39-3.04). MAT was not associated with acute care utilization. These results highlight the need to increase MAT prescribing in HIV-positive individuals with substance use disorders, and to address the many factors that influence acute care utilization.

The Italian version of rheumatoid arthritis pain scale (IT-RAPS): psychometric properties on community and clinical samples.

This paper describes the validation process of the Italian version of the Rheumatoid Arthritis Pain Scale (ITRAPS), describing its translation and adaptation to Italian culture. The cultural adaptation and validation were based on data from a sample of people affected by rheumatoid arthritis (RA). The process required a forward and backward translation of the original language, reviewed by an expert panel. The adapted version of the RAPS was then tested on a community and clinical sample, in order to test its psychometric properties. The IT-RAPS was submitted to 122 people affected by RA. The data was analyzed using Cronbach's coefficient alpha and the Pearson product-moment correlation coefficients. The IT-RAPS showed an internal consistency reliability coefficient of 0.96. This is the first study reporting the validation and cross-cultural adaptation of the RAPS in Italian. The study's findings provided support for the IT-RAPS as a reliable and valid measurement of multidimensional pain in RA patients.

Analysis of Circulating Mediators of Bone Remodeling in Prader-Willi Syndrome.

We tested the hypothesis that the levels of bone remodeling mediators may be altered in Prader-Willi syndrome (PWS). We assessed RANKL, OPG, sclerostin, DKK-1 serum levels, and bone metabolism markers in 12 PWS children (7.8 ± 4.3 years), 14 PWS adults (29.5 ± 7.2 years), and 31 healthy controls matched for sex and age. Instrumental parameters of bone mineral density (BMD) were also evaluated. Lumbar spine BMD Z-scores were reduced in PWS children (P < 0.01), reaching osteopenic levels in PWS adults. PWS patients showed lower 25(OH)-vitamin D serum levels than controls (P < 0.001). Osteocalcin was increased in PWS children but reduced in adults respect to controls (P < 0.005 and P < 0.01, respectively). RANKL levels were higher in both pediatric and PWS adults than controls (P < 0.004), while OPG levels were significantly reduced (P < 0.004 and P < 0.006, respectively). Sclerostin levels were increased in children (P < 0.04) but reduced in adults compared to controls (P < 0.01). DKK-1 levels did not show significant difference between patients and controls. In PWS patients, RANKL, OPG, and sclerostin significantly correlated with metabolic and bone instrumental parameters. Consistently, with adjustment for age, multiple linear regression analysis showed that BMD and osteocalcin were the most important predictors for RANKL, OPG, and sclerostin in children, and GH and sex steroid replacement treatment in PWS adults. We demonstrated the involvement of RANKL, OPG, and sclerostin in the altered bone turnover of PWS subjects suggesting these molecules as markers of bone disease and new potential pharmacological targets to improve bone health in PWS.

Diabetes stigma is associated with negative treatment appraisals among adults with insulin-treated Type 2 diabetes: results from the second Diabetes MILES - Australia (MILES-2) survey.

AIM: To explore factors associated with negative insulin appraisals among adults with Type 2 diabetes, including perceived and experienced diabetes stigma. METHODS: The second Diabetes MILES - Australia study (MILES-2) is a national survey of adults with diabetes, focused on behavioural and psychosocial issues. Subgroup analyses were conducted on the responses of 456 adults with insulin-treated Type 2 diabetes (38% women; mean ± sd age: 61.2 ± 8.8 years; diabetes duration: 14.5 ± 7.5 years; years using insulin: 6.4 ± 5.5). Participants completed validated measures of perceived and experienced diabetes stigma (Type 2 Diabetes Stigma Assessment Scale), insulin appraisals [Insulin Treatment Appraisal Scale (ITAS)] and known correlates of insulin appraisals: diabetes-specific distress (Problem Areas In Diabetes scale) and diabetes-specific self-efficacy (Confidence in Diabetes Self-care scale). A multiple linear regression was conducted (N = 279) to determine the contribution of those variables found to be associated with ITAS Negative scores. RESULTS: Univariable analyses revealed negative insulin appraisals were associated with demographic and self-care characteristics (age, employment status, BMI, years using insulin, injections per day), self-efficacy, diabetes-specific distress and diabetes stigma (all P < 0.01). Number of injections per day [regression coefficient [95% confidence interval]: 0.74 [0.08, 1.40]; P = 0.028], self-efficacy [-0.12 [-0.19, -0.06]; P < 0.001] and diabetes stigma [0.39 (0.31, 0.46); P < 0.001) significantly and independently contributed to the final multivariable model, explaining 58% of the variance in ITAS Negative scores. The independent contribution of diabetes-specific distress was suppressed following the inclusion of diabetes stigma. CONCLUSIONS: This study represents the first step in understanding the relationship between perceived and experienced diabetes stigma and negative insulin appraisals, and provides quantitative evidence for the strong, independent relationship between these two important constructs.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Measuring Type 1 diabetes stigma: development and validation of the Type 1 Diabetes Stigma Assessment Scale (DSAS-1).

AIMS: To develop and validate a self-report measure designed to assess perceived and experienced stigma for adults with Type 1 diabetes: the Type 1 Diabetes Stigma Assessment Scale (DSAS-1). METHODS: A large item-pool (64 items) was drafted based on qualitative data from interviews with 27 adults with Type 1 diabetes. Eleven adults with Type 1 diabetes completed the draft questionnaire (responding to items using a five-point Likert scale), and participated in cognitive debriefing interviews. Based on their feedback, the item-pool was reduced and refined. Adults with Type 1 diabetes (N=898) completed an online survey including the draft stigma questionnaire (41 items) and other validated measures. Psychometric validation included principal components analysis and confirmatory factor analysis (split samples), internal consistency reliability assessment and Spearman's rho correlations. RESULTS: Scale reduction techniques resulted in 19 items (α=0.93). An unforced three-factor solution suggested three subscales: Treated Differently (six items, α=0.89); Blame and Judgement (six items, α=0.88); and Identity Concerns (seven items, α=0.89). This was corroborated with a confirmatory factor analysis, which demonstrated reasonable model fit with the three factors; less so for a single-factor model. Satisfactory concurrent, convergent and discriminant validity were demonstrated. CONCLUSIONS: The 19-item DSAS-1 is a valid and reliable measure of the perceptions and experiences of Type 1 diabetes stigma. This novel, relatively brief measure has satisfactory psychometric properties. The DSAS-1 is now available for investigations into the nature and magnitude of the relationships between diabetes stigma and diabetes self-care behaviours and outcomes.

Lack of evidence of rotavirus-dependent molecular mimicry as a trigger of coeliac disease.

New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human-transglutaminase protein and the dodecapeptide (260-271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti-pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy-proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no-CD children and 107 blood donors. Using enzyme-linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A-IgG antibodies against the synthetic peptides pVP7, the human transglutaminase-derived peptide (476-487 aa) which shows a homology with VP7 protein and a control peptide. The triple-layered RV particles (TLPs) containing the VP7 protein and the double-layered RV-particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV-TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0·6, P = 0·1). Biopsy-proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non-specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD.

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α.

UNLABELLED: In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. INTRODUCTION: Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. METHODS: Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. RESULTS: DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. CONCLUSIONS: Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. These cytokines could represent new pharmacological targets for OI patients.

Suicidal ideation reported by adults with Type 1 or Type 2 diabetes: results from Diabetes MILES-Australia.

AIMS: To examine the prevalence and correlates of suicidal ideation (SI) in a community-based sample of adults with Type 1 or Type 2 diabetes. METHODS: Participants were 3338 adults aged 18-70 years with Type 1 diabetes (n = 1376) or Type 2 diabetes (non-insulin: n = 1238; insulin: n = 724) from a national survey administered to a random sample registered with the National Diabetes Services Scheme. Depression and SI were assessed using the Patient Health Questionnaire, and diabetes-specific distress with the Problem Areas In Diabetes scale. Separate logistic regression analyses by diabetes type/treatment were used to determine relative contribution to SI. RESULTS: Overall, we observed a SI rate of 14% in our sample. Participants with Type 2 diabetes using insulin reported more frequent depressive symptoms, and were more likely to report recent SI (19%) compared with those with either Type 1 diabetes or Type 2 diabetes not using insulin (14 and 12%, respectively). After controlling for depression, there was little difference in the prevalence of SI between diabetes types/treatments, but higher diabetes-specific distress significantly increased the odds of SI. CONCLUSIONS: As SI is a significant risk factor for a suicide attempt, the findings have implications for healthcare professionals, pointing to the importance of adequate screening and action plans for appropriate follow-up of those reporting depression. Our findings are also indicative of the psychological toll of diabetes more generally, and the need to integrate physical and mental healthcare for people with diabetes.

Prevalence of celiac disease in patients with severe food allergy.

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.

Neurobehavioral Alterations in a Genetic Murine Model of Feingold Syndrome 2.

Feingold syndrome (FS) is an autosomal dominant disorder characterized by microcephaly, short stature, digital anomalies, esophageal/duodenal atresia, facial dysmorphism, and various learning disabilities. Heterozygous deletion of the miR-17-92 cluster is responsible for a subset of FS (Feingold syndrome type 2, FS2), and the developmental abnormalities that characterize this disorder are partially recapitulated in mice that harbor a heterozygous deletion of this cluster (miR-17-92∆/+ mice). Although Feingold patients develop a wide array of learning disabilities, no scientific description of learning/cognitive disabilities, intellectual deficiency, and brain alterations have been described in humans and animal models of FS2. The aim of this study was to draw a behavioral profile, during development and in adulthood, of miR-17-92∆/+ mice, a genetic mouse model of FS2. Moreover, dopamine, norepinephrine and serotonin tissue levels in the medial prefrontal cortex (mpFC), and Hippocampus (Hip) of miR-17-92∆/+ mice were analyzed.Our data showed decreased body growth and reduced vocalization during development. Moreover, selective deficits in spatial ability, social novelty recognition and memory span were evident in adult miR-17-92∆/+ mice compared with healthy controls (WT). Finally, we found altered dopamine as well as serotonin tissue levels, in the mpFC and Hip, respectively, of miR-17-92∆/+ in comparison with WT mice, thus suggesting a possible link between cognitive deficits and altered brain neurotransmission.

Paediatricians' attitudes toward pain in children with severe cognitive impairment. A regional survey.

INTRODUCTION: pain is a frequent and relevant problem in children with severe cognitive impairments. Assessing pain in these patients can be difficult. Specific observational tools such as the Collignon Giusiano Questionnaire or the Non-communicating Children's Pain Checklist ( NCCPC) are available, but their use is not widespread. Children with severe cognitive impairment are frequently in need of painful procedures but data about availability of procedural sedation in this setting are limited. OBJECTIVE OF THE STUDY: to evaluate paediatricians' attitudes toward pain in children with severe cognitive impairment by measuring the use of specific pain scales and the use of analgesia or procedural sedation in course of a frequent procedure such as botulinum toxin injection. METHODS: phone interview with the doctor on duty of 56 paediatric wards in 3 regions of the North East of Italy, addressing the routine use of pain scales, and the use of specific observational tools for non communicating children. A phone interview was also conducted in 4 centers routinely practicing botulinum toxin injection about the use of analgesia or procedural sedation. RESULTS: 1 centre out of 55 reported to use specific scales for children with cognitive impairment, specifically the Collignon Giusiano Questionnaire. No centre used procedural sedation for botulinum toxin injection. CONCLUSION: in the investigated area there is a lack of attention to pain in children with severe cognitive impairment. Specific educational efforts should be done to improve the quality of care in this setting.

[The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas]. / La heterogeneidad del flujo sanguíneo en resonancia magnética, biomarcador para clasificar por grados los astrocitomas cerebrales.

OBJECTIVES: To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. MATERIAL AND METHODS: We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (K(trans)), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. RESULTS: For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and K(trans), both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. CONCLUSIONS: The quantification of the volume parameters of the entire region of the tumor with BV, BF, and K(trans) is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions.