Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

AIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

Methicillin-Resistant Staphylococcus aureus-Associated Diarrhea in a Critically Ill Burn Patient.

Described in surgical patients after antibiotic use in the 1950s and 1960s, Staphylococcus aureus (S. aureus) enterocolitis is a rare form of nosocomial diarrhea. However, S. aureus is not routinely tested like Clostridium difficile (C. difficile). We report a case of methicillin-resistant S. aureus (MRSA) enterocolitis found on stool culture in a 22-week pregnant female with a previously negative nasal MRSA culture, and a total burn surface area greater than 60%. She also developed necrotizing MRSA pneumonia and bacteremia. After starting broad-spectrum antibiotic for the necrotizing pneumonia with subsequent acute respiratory distress syndrome, the patient exhibited large voluminous diarrhea that tested positive for MRSA and negative for C. difficile in the stool culture. Similar to other reports of high-volume diarrhea, the diarrhea resolved quickly with enteral vancomycin. S. aureus should be considered along with C. difficile during the workup of nosocomial diarrhea, especially with exposure to broad-spectrum antibiotics in the critically ill patient.

Lessons Learned From Two Survivors of Greater Than 90% TBSA Full-Thickness Burn Injuries Using NovoSorb Biodegradable Temporizing Matrix™ and Autologous Skin Cell Suspension, RECELL™: A Case Series.

Since autologous split-thickness skin grafts are scarce and lab skin growth requires a significant amount of time, there are limited available treatment approaches for patients with full-thickness burns greater than 90% TBSA. Additionally, to achieve the primary goal of skin coverage and resuscitation, there must exist a balance between fluid loss and metabolic derangement. Allografts and xenografts have traditionally been used early in the process to achieve these goals. Currently, novel approaches to treatment consider the additional use of synthetic dermal substitutes and autologous skin cell suspension to improve outcomes. This case series describes the treatment course of patients with greater than 90% TBSA full-thickness burn injuries using a staged, multifaceted approach of using NovoSorb Biodegradable Temporizing Matrix™ as the primary dermal substitute in conjunction with a RECELL™ Autologous Cell Suspensions Device applied with autograft and allograft to achieve improved resuscitation, limiting fluid loss, and finally skin coverage. Allograft and NovoSorb Biodegradable Temporizing Matrix™ were used early to cover excised burns, resulting in improved metabolic control by limiting the systemic inflammatory response syndrome and fluid loss. Both patients survived using this approach.

Salivary Biomarkers for Detection of Oral Squamous Cell Carcinoma in a Taiwanese Population.

PURPOSE: This study evaluated the discriminatory power of salivary transcriptomic and proteomic biomarkers in distinguishing oral squamous cell carcinoma cases from controls and potentially malignant oral disorders (PMOD). EXPERIMENTAL DESIGN: A total of 180 samples (60 OSCC patients, 60 controls, and 60 PMOD patients) were used in the study. Seven transcriptomic markers (IL8, IL1ß, SAT1, OAZ1, DUSP1, S100P, and H3F3A) were measured using qPCR, and two proteomic markers (IL8 and IL1ß) were evaluated by ELISA. RESULTS: Among 7 transcriptomic markers, transcript level of DUSP1 was significantly lower in OSCC patients than in controls and PMOD patients. Between the proteomic markers, the protein concentration of IL8 and IL1ß was significantly higher in OSCC patients than controls and dysplasia patients. Univariate fractional polynomial (FP) models revealed that salivary IL8 protein (IL8p) has the highest AUC value between OSCC patients and controls (0.74) and between OSCC and PMOD patients (0.72). Applying a 2-marker FP model, salivary IL8p combined with IL1ß gave the best AUC value for discrimination between OSCC patients and controls, as well as the IL8p combined with H3F3A mRNA, which gave the best AUC value for discrimination between OSCC and PMOD patients. Multivariate models analysis combining salivary analytes and risk factor exposure related to oral carcinogenesis formed the best combinatory variables for differentiation between OSCC versus PMOL (AUC = 0.80), OSCC versus controls (AUC = 0.87), and PMOD versus controls (AUC = 0.78). CONCLUSIONS: The combination of transcriptomic and proteomic salivary markers is of great value for oral cancer detection and differentiation from PMOD patients and controls. Clin Cancer Res; 22(13); 3340-7. ©2016 AACR.