Volatile organic compounds in bile can distinguish pancreatic cancer from chronic pancreatitis: a prospective observational study.

BACKGROUND: Early and accurate diagnosis of pancreatic cancer is important. Our aim was to identify potential volatile organic compounds (VOCs) in the bile that can help distinguish pancreatic cancer from chronic pancreatitis. METHODS: In this prospective observational study, bile was aspirated from patients undergoing endoscopic retrograde cholangiopancreatography for chronic pancreatitis and pancreatic cancer, and the gaseous headspace was analyzed using mass spectrometry. RESULTS: The study included a discovery cohort of 57 patients (46 pancreatic cancer, 11 chronic pancreatitis) and a validation cohort of 31 patients (19 and 12, respectively). Using logistic regression analysis, the model [0.158 × age + 9.747 × log (ammonia) - 3.994 × log (acetonitrile) + 5.044 × log (trimethylamine) - 30.23] successfully identified patients with pancreatic cancer with a sensitivity of 93.5 % and specificity of 100 % (likelihood ratio 40.9, area under the curve 0.98, 95 % confidence interval 0.95 - 1.00). The diagnostic accuracy of this model was confirmed in the second independent validation cohort. CONCLUSION: The measurement of VOCs in bile helped to accurately distinguish pancreatic cancer from chronic pancreatitis.

Volatile organic compounds in plasma for the diagnosis of esophageal adenocarcinoma: a pilot study.

BACKGROUND AND AIMS: A noninvasive screening test that can detect esophageal adenocarcinoma (EAC) at an earlier stage could improve the prognosis associated with EAC. The role of plasma volatile organic compounds (VOCs) for the diagnosis of EAC has not been previously studied. METHODS: Plasma samples were collected from subjects with EAC and GERD before endoscopy. Twenty-two preselected VOCs were analyzed with selected ion flow tube mass spectrometry. RESULTS: The headspaces from 39 plasma samples (20 EAC, 19 GERD) were analyzed. The levels of 9 VOCs (acetonitrile, acrylonitrile, carbon disulfide, isoprene, 1-heptene, 3-methylhexane, [E]-2-nonene, hydrogen sulfide, and triethylamine) were significantly altered in EAC patients compared with GERD patients. A multivariable logistic regression analysis was performed to build a model for the prediction of EAC. The model identified patients with EAC with an area under the curve of 0.83 (95% confidence interval, 0.67-0.98). CONCLUSIONS: Plasma VOCs may be useful in diagnosing EAC. Larger studies are needed to confirm our pilot study observations.

Treatment Efficacy of Integrative Family and Systems Treatment (I-FAST) With and Without Consultation: The Role of Model Training in the Sustainability of Evidence-Based Family Treatments.

This study examined the efficacy of the Integrative Family and Systems Treatment (I-FAST) training model that seeks to support development of model expertise within the agency in the context of facilitating the sustainability of evidence-based family treatment within community mental health settings. A quasi-experimental design was used to examine treatment outcomes of I-FAST among agencies that received ongoing Consultation and agencies that received No Consultation upon completion of I-FAST training. χ (2) analyses and independent samples t test analyses showed that there were no significant differences between the two groups on clients who had achieved reliable change on Problem Severity and Functioning based on parents' assessments. Significance of this study is discussed in the context of the role of evidence-based family therapy (EBFT) training in facilitating its sustainability in community mental health settings.

Volatile organic compounds in bile for early diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis: a pilot study.

BACKGROUND: The diagnosis of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) is particularly difficult. The role of volatile organic compounds (VOCs) for diagnosis of CCA in patients with PSC is not known. OBJECTIVE: Our aim was to identify potential VOCs in the headspaces (gas above the sample) in bile that may predict CCA in patients with PSC. DESIGN: Prospective cross-sectional study. SETTING: Referral center. PATIENTS: A total of 32 patients undergoing ERCP for PSC and for CCA complicating PSC. INTERVENTIONS: ERCP, bile aspiration. MAIN OUTCOME MEASUREMENTS: Selected ion flow tube mass spectrometry was used to analyze the concentration of 22 prevalent VOCs in bile samples. Logistic regression analysis was performed to build a predictive model for diagnosis of CCA. RESULTS: Levels of several compounds (ethanol, acrylonitrile, acetonitrile, acetaldehyde, benzene, carbon disulfide, dimethyl sulfide, 2-propranolol) were significantly different in patients with CCA complicating PSC compared with those having PSC (P < .05). By using receiver operating characteristic curve analysis, we developed a model for the diagnosis of CCA adjusted for age and sex based on VOC levels of acrylonitrile, 3-methyl hexane, and benzene. The model (2.3239*log [acrylonitrile] + 0.9871*log [3-methyl hexane] + 0.8448*log [benzene]) < -0.12 identified the patients with CCA (area under the curve [AUC] = 0.89), with 90.5% sensitivity and 72.7% specificity (P = .02). LIMITATIONS: Sample size. CONCLUSION: The measurement of VOCs in biliary fluid may be useful to diagnose CCA in patients with PSC. A larger study with a longitudinal study design is required to confirm our pilot observations to diagnose CCA early in patients with PSC. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01565460.).

Volatile Organic Compounds in Urine for Noninvasive Diagnosis of Malignant Biliary Strictures: A Pilot Study.

BACKGROUND: The use of volatile organic compounds (VOCs) in bile was recently studied and appeared promising for diagnosis of malignancy. Noninvasive diagnosis of malignant biliary strictures by using VOCs in urine has not been studied. AIM: To identify potential VOCs in urine to diagnose malignant biliary strictures. METHODS: In this prospective cross-sectional study, urine was obtained immediately prior to ERCP from consecutive patients with biliary strictures. Selected-ion flow-tube mass spectrometry was used to analyze the concentration of VOCs in urine samples. RESULTS: Fifty-four patients with biliary strictures were enrolled. Fifteen patients had malignant stricture [six cholangiocarcinoma (CCA) and nine pancreatic cancer], and 39 patients had benign strictures [10 primary sclerosing cholangitis (PSC) and 29 with benign biliary conditions including chronic pancreatitis and papillary stenosis]. The concentration of several compounds (ethanol and 2-propanol) was significantly different in patients with malignant compared with benign biliary strictures (p < 0.05). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of malignant biliary strictures adjusted for age and gender based on VOC levels of 2-propranol, carbon disulfide, and trimethyl amine (TMA). The model [-2.4191 * log(2-propanol) + 1.1617 * log(TMA) - 1.2172 * log(carbon disulfide)] ≥ 7.73 identified the patients with malignant biliary stricture [area under the curve (AUC = 0.83)], with 93.3 % sensitivity and 61.5 % specificity (p = 0.009). Comparing patients with CCA and PSC, the model [38.864 * log(ethane) - 3.989 * log(1-octene)] ≤ 169.9 could identify CCA with 80 % sensitivity and 100 % specificity (AUC = 0.9). CONCLUSIONS: Measurement of VOCs in urine may diagnose malignant biliary strictures noninvasively.

The breathprints in patients with liver disease identify novel breath biomarkers in alcoholic hepatitis.

BACKGROUND & AIMS: Selected-ion flow-tube mass spectrometry can precisely identify trace gases in the human breath, in the parts-per-billion range. We investigated whether concentrations of volatile compounds in breath samples correlate with the diagnosis of alcoholic hepatitis (AH) and the severity of liver disease in patients with AH. METHODS: We recruited patients with liver disease from a single tertiary care center. The study population was divided between those with AH with cirrhosis (n = 40) and those with cirrhosis with acute decompensation from etiologies other than alcohol (n = 40); individuals without liver disease served as control subjects (n = 43). We used selected-ion flow-tube mass spectrometry to identify and measure 14 volatile compounds in breath samples from fasted subjects. We used various statistical analyses to compare clinical characteristics and breath levels of compounds among groups and to test the correlation between levels of compounds and severity of liver disease. Logistic regression analysis was performed to build a predictive model for AH. RESULTS: We identified 6 compounds (2-propanol, acetaldehyde, acetone, ethanol, pentane, and trimethylamine [TMA]) whose levels were increased in patients with liver disease compared with control subjects. Mean concentrations of TMA and pentane (TAP) were particularly high in breath samples from patients with AH, compared with those with acute decompensation or control subjects (for both, P < .001). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of AH based on breath levels of TAP. TAP scores of 36 or higher identified the patients with AH (area under the receiver operating characteristic curves = 0.92) with 90% sensitivity and 80% specificity. The levels of exhaled TMA had a low level of correlation with the severity of AH based on model for end-stage liver disease score (r = 0.38; 95% confidence interval, 0.07-0.69; P = .018). CONCLUSIONS: Based on levels of volatile compounds in breath samples, we can identify patients with AH vs patients with acute decompensation or individuals without liver disease. Levels of exhaled TMA moderately correlate with the severity of AH. These findings might be used in diagnosis of AH or in determining patient prognosis.

Volatile organic compounds in bile can diagnose malignant biliary strictures in the setting of pancreatic cancer: a preliminary observation.

BACKGROUND: Ascertaining the nature of biliary strictures is challenging. The role of volatile organic compounds (VOCs) in bile in determining the cause of biliary strictures is not known. OBJECTIVE: To identify potential VOCs in the headspaces (gas above the sample) of bile in patients with malignant biliary strictures from pancreatic cancer. DESIGN: Prospective cross-sectional study. SETTING: Referral center. PATIENTS: Prospective study in which bile was aspirated in 96 patients undergoing ERCP for benign and malignant conditions. MAIN OUTCOME MEASUREMENTS: Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze the headspace and to build a predictive model for pancreatic cancer. RESULTS: The headspaces from 96 bile samples were analyzed, including 24 from patients with pancreatic cancer and 72 from patients with benign biliary conditions. The concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and trimethylamine [TMA]) were increased in patients with pancreatic cancer compared with controls (P < .05). By using receiver-operating characteristic curve analysis, we developed a model for the diagnosis of pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl sulfide, and acetaldehyde. The model [10.94 + 1.8229* log (acetaldehyde) + 0.7600* log (acetone) - 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) - 2.1401 * log (trimethylamine) ≥ 10] identified the patients with pancreatic cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9% specificity. LIMITATIONS: Sample size. CONCLUSIONS: The measurement of biliary fluid VOCs may help to distinguish malignant from benign biliary strictures. Further studies are warranted to validate these observations. (Clinical Trial Registration Number NCT01565460.).

Detection ofClostridioides difficileinfection by assessment of exhaled breath volatile organic compounds.

Clostridioides difficileinfection (CDI) is the leading cause of hospital-acquired infective diarrhea. Current methods for diagnosing CDI have limitations; enzyme immunoassays for toxin have low sensitivity andClostridioides difficilepolymerase chain reaction cannot differentiate infection from colonization. An ideal diagnostic test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection. Assessing volatile organic compounds (VOCs) in exhaled breath may be a useful test for identifying CDI. To identify a wide selection of VOCs in exhaled breath, we used thermal desorption-gas chromatography-mass spectrometry to study breath samples from 17 patients with CDI. Age- and sex-matched patients with diarrhea and negativeC.difficiletesting (no CDI) were used as controls. Of the 65 VOCs tested, 9 were used to build a quadratic discriminant model that showed a final cross-validated accuracy of 74%, a sensitivity of 71%, a specificity of 76%, and a receiver operating characteristic area under the curve of 0.72. If these findings are proven by larger studies, breath VOC analysis may be a helpful adjunctive diagnostic test for CDI.

Exhaled Breath Analysis Using Selected Ion Flow Tube Mass Spectrometry and Disease Severity in Heart Failure.

Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). The ability of VOCs to predict long term cardiovascular mortality and morbidity has not been independently verified. In 55 patients admitted with acute decompensated heart failure (ADHF), we measured exhaled breath acetone and pentane levels upon admission and after 48 h of diuresis. In a separate cohort of 51 cardiac patients undergoing cardiopulmonary exercise testing (CPET), we measured exhaled breath acetone and pentane levels before and at peak exercise. In the ADHF cohort, admission acetone levels correlated with lower left ventricular ejection fraction (LVEF, r = -0.297, p = 0.035). Greater weight loss with diuretic therapy correlated with a greater reduction in both acetone levels (r = -0.398, p = 0.003) and pentane levels (r = -0.309, p = 0.021). In patients with above-median weight loss (≥4.5 kg), patients demonstrated significantly greater percentage reduction in acetone (59% reduction vs. 7% increase, p < 0.001) and pentane (23% reduction vs. 2% reduction, p = 0.008). In the CPET cohort, admission acetone and pentane levels correlated with higher VE/VCO2 (r = 0.39, p = 0.005), (r = 0.035, p = 0.014). However, there were no significant correlations between baseline or peak exercise acetone and pentane levels and peak VO2. In longitudinal follow-up with a median duration of 33 months, patients with elevated exhaled acetone and pentane levels experienced higher composite adverse events of death, ventricular assist device implantation, or orthotopic heart transplantation. In patients admitted with ADHF, higher exhaled breath acetone levels are associated with lower LVEF and poorer outcomes, and greater reductions in exhaled breath acetone and pentane tracked with greater weight loss. Exhaled acetone and pentane may be novel biomarkers in heart failure worthy of future investigation.

Key processes, ingredients and components of successful systems collaboration: working with severely emotionally or behaviorally disturbed children and their families.

Systems collaboration has repeatedly been cited as a component of successful social service delivery. Through qualitative data, this study explored the process involved in inter-agency collaboration when providing Integrative Family and Systems Treatment (I-FAST) for families with severely emotionally or behaviorally disturbed children. Data were collected through a series of eight focus groups with 26 agency collaborators across 11 counties in Ohio. Data analysis revealed two emergent phenomena: the process of developing collaboration, consisting of making initial contact, a trial period and developing trust; and the key ingredients of collaboration, focusing on interpersonal and professional qualities. Implications of each theme are discussed.

Biomarkers for the Evaluation of Pouch Inflammation: A Systematic Review.

Background: Ileal pouch inflammation is a common problem following ileal pouch-anal anastomosis (IPAA). Despite its prevalence, diagnosis remains multimodal and requires endoscopy. The use of biomarkers in the prediction of and/or association with pouchitis has not been well characterized. We performed a systematic review to summarize the available evidence. Method: A search of Ovid, MEDLINE, Cochrane Library, EMBASE, and Web of Science was conducted. Inclusion criteria included studies evaluating biomarkers for the evaluation and prediction of inflammation in patients with IPAA utilizing pouchoscopy as the gold standard. Exclusion criteria included studies on the role of the microbiome or genetic markers. Results: A total of 28 studies, 5 case-control studies, and 23 observational cohort studies were identified. Fecal biomarkers were assessed in 23 studies, of which fecal calprotectin was the most commonly studied with sensitivities ranging from 57% to 92% and specificities from 19% to 92%. Six studies examined serum biomarkers. None of the serum biomarkers demonstrated a high sensitivity or specificity in association with pouch inflammation. Six studies described the longitudinal assessment of biomarkers. Of these studies, only three reported a predictive role of biomarkers in diagnosing endoscopic inflammation. Conclusions: Biomarkers have emerged as a potential option to improve the management of pouchitis given the relative ease of sampling compared to pouchoscopy. Unfortunately, the evaluated biomarkers have not consistently demonstrated accuracy in predicting inflammation. Moreover, these biomarkers have not been reliably shown to be sensitive or specific in association with endoscopic pouch inflammation to merit their widespread use in clinical practice.

Diagnosis of Clostridioides difficile infection by analysis of volatile organic compounds in breath, plasma, and stool: A cross-sectional proof-of-concept study.

Clostridioides difficile infection (CDI) is an important infectious cause of antibiotic-associated diarrhea, with significant morbidity and mortality. Current diagnostic algorithms are based on identifying toxin by enzyme immunoassay (EIA) and toxin gene by real-time polymerase chain reaction (PCR) in patients with diarrhea. EIA's sensitivity is poor, and PCR, although highly sensitive and specific, cannot differentiate infection from colonization. An ideal test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection, and assess prognosis and recurrence. The study of volatile organic compounds (VOCs) has the potential to be an ideal diagnostic test. The presence of VOCs accounts for the characteristic odor of stool in CDI but their presence in breath and plasma has not been studied yet. A cross-sectional proof-of-concept study analyzing VOCs using selected ion flow tube mass spectrometry (SIFT-MS) was done on breath, stool, and plasma of patients with clinical features and positive PCR for CDI (cases) and compared with patients with clinical features but a negative PCR (control). Our results showed that VOC patterns in breath, stool, and plasma, had good accuracy [area under the receiver operating characteristic curve (ROC) 93%, 86%, and 91%, respectively] for identifying patients with CDI.

The breath print represents a novel biomarker of malnutrition in pulmonary arterial hypertension: A proof of concept study.

BACKGROUND: The breath print is a quantitative measurement of molecules in exhaled breath and represents a new frontier for biomarker identification. It is unknown whether this state-of-the-art, noninvasive method can detect malnutrition. We hypothesize that individuals with malnutrition will present with a distinguishable breath print. METHODS: We conducted a retrospective chart review on patients with previously analyzed breath samples to identify malnutrition. Breath was analyzed by selected-ion flow-tube mass spectrometry. Registered dietitians conducted a retrospective chart review to collect malnutrition diagnoses and nutrition status indicators. Patients were categorized into one of four groups: pulmonary arterial hypertension (PAH), PAH with malnutrition (PAH-Mal), control, and control with malnutrition (Control-Mal), based on the malnutrition diagnosis present in the patient's chart. Principle component analysis was conducted to characterize the breath print. A logistic regression model with forward selection was used to detect the best breath predictor combination of malnutrition. RESULTS: A total of 74 patients met inclusion criteria (PAH: 52; PAH-Mal: 10; control: 10; Control-Mal: 2). Levels of 1-octene (PAH-Mal, 5.1 ± 1.2; PAH, 12.5 ± 11.2; P = 0.005) and ammonia (PAH-Mal, 14.6 ± 15.8; PAH, 56.2 ± 64.2; P = 0.013) were reduced in PAH-Mal compared with PAH. The combination of 1-octene (P = 0.010) and 3-methylhexane (P = 0.045) distinguished malnutrition in PAH (receiver operating characteristic area under the curve: 0.8549). CONCLUSIONS: This proof of concept study provides the first evidence that the breath print is altered in malnutrition. Larger prospective studies are needed to validate these results and establish whether breath analysis may be a useful tool to screen for malnutrition in the clinical setting.

Effect of hydrocarbons on the morphology of synthesized niobium carbide nanoparticles.

Niobium carbide nanoparticles were synthesized by flowing methane, ethylene, or acetylene gas through a plasma generated from an arc discharge between two niobium electrodes. Varying methane, ethylene, and acetylene concentrations were employed in the studies to investigate their effects on niobium carbide nanoparticle morphology. Transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), and selected area diffraction pattern (SADP) were used to investigate the synthesized NbC nanoparticles, whereupon it was found that these nanoparticles adopt cubic morphology with methane gas, a mixture of cubes and cuboctahedron morphology with ethylene gas, and solely a cuboctahedron morphology with acetylene gas. The change in particle morphology might be attributed to either the ethylene and acetylene free radicals or the increase in carbon concentration effecting the relative growth rates of the {111} and {100} facets on a NbC seed crystal.

Cutaneous larva migrans in infants in the Adelaide Hills.

Four infants aged between 8 and 13 months presented between November 2002 and May 2006 with dermatitis of the lower abdomen, perineum or buttocks. All lived in semi-rural properties in the Adelaide Hills and had not travelled outside South Australia. Wandering thread-like serpiginous tracks were evident on examination, consistent with a diagnosis of cutaneous larva migrans. No abnormalities were detected on full blood examination, Strongyloides stercoralis serology or faecal analysis. Treatment with oral albendazole resulted in rapid resolution of symptoms. An epidemiological survey was undertaken which suggested possums or millipedes may have been the source of nematode larvae, the precise nature of which is unclear but could include Parastrongyloides trichosuri and Rhabditis necromena.

Comparison of volatile organic compound profiles in exhaled breath versus plasma headspace in different diseases.

Breath analysis is the study of volatile organic compounds (VOC's) in exhaled breath. This analysis provides information on the body's condition. In this study we investigated the relationship between 22 VOC's detected in exhaled breath and plasma headspace using a selected ion flow tube mass spectrometer (SYFT-MS). We compared pairs of exhaled breath and plasma samples from patients with pulmonary hypertension inflammatory bowel disease (IBD), and IBD patients after J-pouch surgery (pouch group). Half of the measured VOC's from exhaled breath were significantly associated with the VOC's from plasma headspace. Interestingly, six breath VOC's (trimethyl amine (FDR p = 0.02), hydrogen sulfide (FDR p = 7.64 × 10-30), ethanol (FDR p = 1.56 × 10-4), dimethyl sulfide (FDR p = 5.70 × 10-19), benzene (FDR p = 8.40 × 10-27), and acetaldehyde (FDR p = 4.27 × 10-17)) and two plasma headspace VOC's (1-Octene (FDR p = 0.02) and 2-propanol (FDR p = 2.47 × 10-9)) were able to differentiate between the three groups. Breath and plasma headspace share a similar signature with significant association in half of the measured VOCs. The disease discriminatory capacity of breath and plasma headspace appear to be different. Therefore, using the VOC's print from both breath and plasma headspace may better help diagnose patients.

Breath Metabolomics Provides an Accurate and Noninvasive Approach for Screening Cirrhosis, Primary, and Secondary Liver Tumors.

Hepatocellular carcinoma (HCC) and secondary liver tumors, such as colorectal cancer liver metastases are significant contributors to the overall burden of cancer-related morality. Current biomarkers, such as alpha-fetoprotein (AFP) for HCC, result in too many false negatives, necessitating noninvasive approaches with improved sensitivity. Volatile organic compounds (VOCs) detected in the breath of patients can provide valuable insight into disease processes and can differentiate patients by disease status. Here, we investigate whether 22 VOCs from the breath of 296 patients can distinguish those with no liver disease (n = 54), cirrhosis (n = 30), HCC (n = 112), pulmonary hypertension (n = 49), or colorectal cancer liver metastases (n = 51). This work extends previous studies by evaluating the ability for VOC signatures to differentiate multiple diseases in a large cohort of patients. Pairwise disease comparisons demonstrated that most of the VOCs tested are present in significantly different relative abundances (false discovery rate P < 0.1), indicating broad impacts on the breath metabolome across diseases. A predictive model developed using random forest machine learning and cross validation classified patients with 85% classification accuracy and 75% balanced accuracy. Importantly, the model detected HCC with 73% sensitivity compared with 53% for AFP in the same cohort. An added value of this approach is that influential VOCs in the predictive model may provide insight into disease etiology. Acetaldehyde and acetone, both of which have roles in tumor promotion, were considered important VOCs for differentiating disease groups in the predictive model and were increased in patients with cirrhosis and HCC compared to patients with no liver disease (false discovery rate P < 0.1). Conclusion: The use of machine learning and breath VOCs shows promise as an approach to develop improved, noninvasive screening tools for chronic liver disease and primary and secondary liver tumors.

Successful treatment of pulmonary mucormycosis in a renal transplant recipient with limited pulmonary reserve by combined medical and surgical therapy.

Mucormycosis is a rare opportunistic fungal infection in renal transplant recipients which is associated with exceedingly high mortality when inadequately treated. Risk factors for this infection include diabetes, neutropaenia and immunosuppression. We report a case of pulmonary mucormycosis in a renal allograft recipient with type 2 diabetes and limited pulmonary reserve. The patient was successfully treated with lobectomy and liposomal amphotericin B with preservation of pulmonary and allograft functions. Early recognition of this infection is warranted before dissemination, which carries a poor prognosis.

Non-enzymatic hydrogen sulfide production from cysteine in blood is catalyzed by iron and vitamin B6.

Hydrogen sulfide (H2S) plays important roles in metabolism and health. Its enzymatic generation from sulfur-containing amino acids (SAAs) is well characterized. However, the existence of non-enzymatic H2S production from SAAs, the chemical mechanism, and its biological implications remain unclear. Here we present non-enzymatic H2S production in vitro and in blood via a reaction specific for the SAA cysteine serving as substrate and requires coordinated catalysis by Vitamin B6, pyridoxal(phosphate), and iron under physiological conditions. An initial cysteine-aldimine is formed by nucleophilic attack of the cysteine amino group to the pyridoxal(phosphate) aldehyde group. Free or heme-bound iron drives the formation of a cysteine-quinonoid, thiol group elimination, and hydrolysis of the desulfurated aldimine back to pyridoxal(phosphate). The reaction ultimately produces pyruvate, NH3, and H2S. This work highlights enzymatic production is inducible and robust in select tissues, whereas iron-catalyzed production contributes underappreciated basal H2S systemically with pathophysiological implications in hemolytic, iron overload, and hemorrhagic disorders.

Breath analysis in gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Volatile organic compounds (VOCs) are generated during pathologic processes, and their assessment can be used to diagnose and monitor a variety of diseases. Given the role of the microbiome in graft-versus-host disease (GVHD), we hypothesized that microorganisms producing volatile metabolites may alter VOCs expelled in breath in patients with gastrointestinal (GI) GVHD. In this pilot study, exhaled breath samples were obtained from 19 patients with grade 2 to 4 acute GI GVHD, 10 patients with no GVHD at day 100, and 10 healthy control subjects; the samples were analyzed by using mass spectrometry. Overall, nine (47%) patients had grade 2 GVHD, eight (42%) patients had grade 3 GVHD, and two (11%) patients had grade 4 GVHD; 26% had upper GI, 21% had lower GI, and 53% had both upper and lower GI manifestations. Stepwise canonical discriminant analysis identified 5 VOCs distinguishing patients with and without GI GVHD: 2-propanol, acetaldehyde, dimethyl sulfide, isoprene, and 1-decene (Wilks' Λ, 0.43; F statistic, 6.08; P = .001). The model correctly classified 89% (17 of 19) and 90% (9 of 10) of patients with and without GI GVHD, respectively. Breath analysis is a feasible and promising noninvasive method to detect acute GI GVHD. Further study of serial breath analysis and the gut microbiome in a larger cohort are ongoing to validate these findings.