Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

Background: In the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease. Methods: The concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated. Results: The final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model. Conclusions: Pancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity

Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds' (VOCs) pattern when compared to controls. Patients 10-17 years of age, were divided into four groups: Crohn's disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non-invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects the large part of SCD patients and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL) and osteoclast recruitment (Rank) with up-regulation of Il6 as pro-resorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). In order to interfer with the development of SBD, zoledronic-acid, a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R exposed mice. Zoledronic-acid markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc) and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared to either normoxic or single H/R episode SCD mice. Zoledronic-acid used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment and increased osteoclast activity resulted from local hypoxia, oxidative stress and the release of pro-resorptive cytokine such as IL6. Zoledronic acid might act on both osteoclast and osteoblast compartment as multimodal therapy to prevent SBD

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings

Gli addotti all'emoglobina nel monitoraggio biologico delle esposizioni professionale: il caso del cobalto e della dimetilformammide

Un gruppo di lavoratori esposti a nanoparticelle di cobalto e ossido di cobalto è stato coinvolto al fine di caratterizzare la cinetica del cobalto nelle urine, nel sangue intero e nella globina. In una prima fase è stata confermata la piuttosto rapida cinetica del cobalto in campioni di urine (emivita di poche ore). La seconda fase ha comportato la raccolta di campioni di urine, una volta alla settimana per 16 settimane consecutive al fine di avere un’indicazione sui livelli medi di esposizione individuale e rapportarla alle concentrazioni del cobalto nella globina. I risultati hanno messo in evidenza una relazione lineare molto stretta tra la media delle concentrazioni del cobalto nei campioni di urina raccolti nei 4 mesi precedenti e le concentrazioni del metallo nella globina. Anche il sangue intero ha presentato concentrazioni di cobalto in relazione lineare con i risultati della globina. Questo dato contrastava con i dati della letteratura che suggerivano una emivita del cobalto nel sangue piuttosto breve. In una terza fase abbiamo raccolto campioni di sangue al termine dell’ultima giornata lavorativa prima delle vacanze natalizie e dopo 18 giorni (cioè all’inizio della ripresa del lavoro) al fine di valutare il tempo di decadimento del cobalto nella globina e la sua emivita nel sangue intero. I risultati hanno messo in evidenza che l’emivita del cobalto nel sangue è di circa 10 giorni e che nella globina decade lentamente in logico parallelismo alla distruzione dei globuli rossi

Valutazione dello stress lavoro correlato:esperienze gestionali ed applicative nell'AOUI di Verona

Sono stati somministrati a 817 dipendenti ospedalieri il questionario strumento operatore HSE per la valutazione dello stress lavorativo, il questionario MOHQ per valutare il benessere lavorativo e il GHQ-12 per verificare la presenza di disagio psichico. La maggior intensità di rischio psicosociale è stata evidenziata per l'area chirurgica, rispetto a quella medica e rispetto ai servizi ospedalieri, per i soggetti con età inferiore ai 30 aa e per quelli con più di 50 aa, per il personale infermieristico rispetto ai medici

Urinary excretion of the metabolites of n-hexane and its isomers during occupational exposure

Environmental exposure to commercial hexane (n-hexane, 2-methylpentane, and 3-methylpentane) was tested in several work places in five shoe factories by taking three grap-air samples during the afternoon shift. Individual exposure ranges were 32-500 mg/m3 for n-hexane, 11-250 mg/m3 for 2-methylpentane, and 10-204 mg/m3 for 3-methylpentane. The metabolites of commercial hexane in the urine of 41 workers were measured at the end of the work shift. 2-Hexanol, 2,5-hexanedione, 2,5-dimethylfuran, and gamma-valerolactone were found as n-hexane metabolites and 2-methyl-2-pentanol and 3-methyl-2-pentanol as 2-methylpentane and 3-methylpentane metabolites. The presence of metabolites in the urine was correlated with occupational exposure to solvents. n-Hexane exposure was correlated more positively with 2-hexanol and 2,5-hexanedione than with 2,5-dimethylfuran and gamma-valerolactone. A good correlation was also found between total n-hexane metabolites and n-hexane exposure. 2-Methyl-2-pentanol and 3-methyl-2-pentanol were highly correlated with 2-methylpentane and 3-methylpentane exposure. The results suggest that the urinary excretion of hexane metabolites may be used for monitoring occupational exposure to n-hexane and its isomers

Concentration of ethylene oxide in the alveolar air of occupationally exposed workers

Ethylene oxide was tested in environmental air and in the alveolar air of 10 workers employed in a hospital sterilizer unit at hourly intervals during the work shift. Alveolar ethylene oxide concentrations (Ca) were correlated with environmental concentration (Ci) in all the workers studied (r = 0.89-0.99). The ratio between alveolar and environmental concentration (Ca/Ci) given by the slope of the regression line obtained for all the data collected was 0.24. This means that the alveolar retention of ethylene oxide, expressed as 1 - (Ca/Ci), corresponded, on average, to about 75% of the environmental concentration

Composti particolari: diossine, idrocarburi policiclici aromatici (IPA), policlorobifenili (PCB), solfuro di carbonio, formaldeide

Profilo tossicologico di: diossine, idrocarburi policiclici aromatici (IPA), policlorobifenili (PCB), solfuro di carbonio, formaldeid

Purge and Trap analysis of toluene in blood: comparison with the Head Space method

A procedure for the determination of toluene in blood by the Purge and Trap method is described. The method, which had not been previously employed for the determination of volatile organic substances in biological fluids, has a linear range which extends up to at least 1500 micrograms/L, and gives results in excellent agreement with the conventional Head Space method; the detection limit was not exactly determined, but is estimated to be less than 7.5 micrograms/L, much better than for the Head Space method. Using the Purge and Trap method, we have observed the accumulation of toluene in the blood of experimental subjects as a result of a weekly exposure to toluene