Translational bioinformatics in the era of real-time biomedical, health care and wellness data streams.

Monitoring and modeling biomedical, health care and wellness data from individuals and converging data on a population scale have tremendous potential to improve understanding of the transition to the healthy state of human physiology to disease setting. Wellness monitoring devices and companion software applications capable of generating alerts and sharing data with health care providers or social networks are now available. The accessibility and clinical utility of such data for disease or wellness research are currently limited. Designing methods for streaming data capture, real-time data aggregation, machine learning, predictive analytics and visualization solutions to integrate wellness or health monitoring data elements with the electronic medical records (EMRs) maintained by health care providers permits better utilization. Integration of population-scale biomedical, health care and wellness data would help to stratify patients for active health management and to understand clinically asymptomatic patients and underlying illness trajectories. In this article, we discuss various health-monitoring devices, their ability to capture the unique state of health represented in a patient and their application in individualized diagnostics, prognosis, clinical or wellness intervention. We also discuss examples of translational bioinformatics approaches to integrating patient-generated data with existing EMRs, personal health records, patient portals and clinical data repositories. Briefly, translational bioinformatics methods, tools and resources are at the center of these advances in implementing real-time biomedical and health care analytics in the clinical setting. Furthermore, these advances are poised to play a significant role in clinical decision-making and implementation of data-driven medicine and wellness care.

Preliminary investigation of the treatment of equine medial femoral condylar subchondral cystic lesions with a transcondylar screw.

OBJECTIVE: To determine if medial femoral condylar (MFC) subchondral cystic lesions (SCL) causing lameness will demonstrate radiographic evidence of healing and lameness reduction after placement of a transcondylar screw in lag fashion. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 20) with lameness attributed to a MFC SCL. METHODS: A 4.5 mm screw was inserted in lag fashion across MFC SCL in horses with hindlimb lameness. Post-operative radiography and lameness examinations were performed at 30-60 day intervals after surgery for 120 days, and SCL radiographic area and lameness were graded. Treatment was considered successful if lameness was eliminated and the radiographic area of the SCL on a caudocranial projection decreased ≥ 50% by 120 days. RESULTS: Twenty-six limbs were treated. Nine horses (11 limbs) had autologous adjunctive biologics placed into the SCL. Lameness was reduced by 1-2 grades by 60 days after surgery in 18 horses and was eliminated in 15 horses by 120 days, at which time the SCL area had decreased ≥ 50% and work had resumed without lameness (mean follow-up, 12 months). Biologic therapies had no impact on treatment success. Treatment was less successful in horses >3 years of age. CONCLUSIONS: A MFC transcondylar screw decreases the area of a MFC SCL on craniocaudal radiographs and eliminates lameness in ∼ 75% of horses by 120 days. The simplicity and lack of specialized equipment required make this technique a useful option for the treatment of equine SCL causing lameness.

Withings Body Cardio versus Gold Standards of Pulse-Wave Velocity and Body Composition.

Home blood pressure monitors are widely used by consumers yet cardiovascular health may be better defined by pulse-wave velocity (PWV). So far, the Withings Body Cardio scale is the only consumer device that has been designed to measure PWV and body composition, including fat mass (FM) and fat-free mass (FFM), in the home setting. While one study has demonstrated that this device meets the acceptable accuracy standards of the ARTERY Society, no study has accounted for the gravitational effect of standing on a scale on aortic-leg PWV. PURPOSE: The purpose of this study was to assess the accuracy of PWV and body composition as determined by the Body Cardio scale. METHODS: Measurements of PWV and body composition in healthy, young males and females (n = 20) using the Body Cardio device were compared to PWV assessed by applanation tonometry (SphygmoCor) and body composition analysis determined by air displacement plethysmography (Bod Pod). Bland-Altman analysis and mean absolute percent error (MAPE) were used to assess accuracy. RESULTS: Data are reported as the mean bias (95% confidence interval). The Body Cardio overestimated PWV by 0.68 m/s (-0.16, 1.51) and FM by 2.91 kg (-2.91, 8.73). Body Cardio PWV and FM estimations had a MAPE of 9.7% and 25.8%, respectively. The Body Cardio underestimated body mass (BM) and FFM by 0.11 kg (-0.41, 0.18) and 2.87 kg (-9.04, 3.30), respectively. Body Cardio BM and FFM estimations had a MAPE of 0.15% and 5.6%, respectively. CONCLUSIONS: The Body Cardio scale provides accurate measures of BM and PWV; however, it should be used cautiously for measures of FM and FFM.

Comparative studies of 193-nm photodissociation and TOF-TOFMS analysis of bradykinin analogues: the effects of charge site(s) and fragmentation timescales.

The dissociation reactions of [M + H]+, [M + Na]+, and [M + Cu]+ ions of bradykinin (amino acid sequence RPPGFSPFR) and three bradykinin analogues (RPPGF, RPPGFSPF, PPGFSPFR) are examined by using 193-nm photodissociation and post-source decay (PSD) TOF-TOF-MS techniques. The photodissociation apparatus is equipped with a biased activation cell, which allows us to detect fragment ions that are formed by dissociation of short-lived (<1 mus) photo-excited ions. In our previously reported photodissociation studies, the fragment ions were formed from ions dissociating with lifetimes that exceeded 10 mus; thus these earlier photofragment ion spectra and post-source decay (PSD) spectra [composite of both metastable ion (MI) and collision-induced dissociation (CID)] were quite similar. On the other hand, short-lived photo-excited ions dissociate by simple bond cleavage reactions and other high-energy dissociation channels. We also show that product ion types and abundances vary with the location of the charge on the peptide ion. For example, H+ and Na+ cations can bind to multiple polar functional groups (basic amino acid side chains) of the peptide, whereas Cu+ ions preferentially bind to the guanidino group of the arginine side-chain and the N-terminal amine group. Furthermore, when Cu+ is the charge carrier, the abundances of non-sequence informative ions, especially loss of small neutral molecules (H2O and NH3) is decreased for both photofragment ion and PSD spectra relative to that observed for [M + H]+ and [M + Na]+ peptide ions.

Evaluation of direct-to-consumer low-volume lab tests in healthy adults.

BACKGROUND: Clinical laboratory tests are now being prescribed and made directly available to consumers through retail outlets in the USA. Concerns with these test have been raised regarding the uncertainty of testing methods used in these venues and a lack of open, scientific validation of the technical accuracy and clinical equivalency of results obtained through these services. METHODS: We conducted a cohort study of 60 healthy adults to compare the uncertainty and accuracy in 22 common clinical lab tests between one company offering blood tests obtained from finger prick (Theranos) and 2 major clinical testing services that require standard venipuncture draws (Quest and LabCorp). Samples were collected in Phoenix, Arizona, at an ambulatory clinic and at retail outlets with point-of-care services. RESULTS: Theranos flagged tests outside their normal range 1.6× more often than other testing services (P < 0.0001). Of the 22 lab measurements evaluated, 15 (68%) showed significant interservice variability (P < 0.002). We found nonequivalent lipid panel test results between Theranos and other clinical services. Variability in testing services, sample collection times, and subjects markedly influenced lab results. CONCLUSION: While laboratory practice standards exist to control this variability, the disparities between testing services we observed could potentially alter clinical interpretation and health care utilization. Greater transparency and evaluation of testing technologies would increase their utility in personalized health management. FUNDING: This work was supported by the Icahn Institute for Genomics and Multiscale Biology, a gift from the Harris Family Charitable Foundation (to J.T. Dudley), and grants from the NIH (R01 DK098242 and U54 CA189201, to J.T. Dudley, and R01 AG046170 and U01 AI111598, to E.E. Schadt).

Peptide sequencing by MALDI 193-nm photodissociation TOF MS.

Ultraviolet photodissociation time-of-flight (TOF) mass spectrometry (MS) is described as a method for determination of peptide ion primary structure. Monoisotopic selection and bond-specific activation, combined with the rapidity of TOF MS analysis, render this technique invaluable to the rapidly expanding field of proteomics. Photofragment ion spectra of model peptides acquired using both post-source decay (PSD) focusing and TOF-TOF experimental methods are exhibited. Advantages of 193-nm photodissociation for de novo sequencing of peptide ions are discussed.

Treatment of dabigatran-associated bleeding: case report and review of the literature.

Dabigatran etexilate is a competitive, direct thrombin inhibitor that works in the coagulation cascade to ultimately prevent thrombus formation. It is recommended by the 2012 American College of Chest Physicians evidence-based clinical practice guidelines as first-line therapy over vitamin k antagonists for long-term antithrombotic therapy in patients with paroxysmal or persistent nonrheumatic atrial fibrillation who are at intermediate to high risk of stroke and systemic embolism (grade 2B). However, serious postmarketing events involving life-threatening bleeding are emerging with no antidote for reversal of the anticoagulant effect being available for use. Potential reversal agents are being used in clinical practice with questionable efficacy and safety profiles. We report a case involving an 84-year-old male with acute kidney injury who developed life-threatening gastrointestinal and surgical site bleeding secondary to dabigatran accumulation. Use of the Naranjo probability scale indicated a probable cause between the bleeding event and dabigatran use. After discontinuation of drug therapy, fresh frozen plasma, recombinant coagulation factor VIIa, and cryoprecipitate were administered as potential reversal agents with negligible benefit. However, this patient appeared to slowly benefit with administration of continuous venovenous hemodialysis. Based upon our experience with this patient and literature review, the most effective treatment algorithm for dabigatran-associated bleeding may be to utilize hemodialysis initially.

Comparison of radiography and computed tomography to evaluate metacarpo/metatarsophalangeal joint pathology of paired limbs of thoroughbred racehorses with severe condylar fracture.

OBJECTIVE: To compare the orthogonal radiographic (OR) and computed tomographic (CT) appearance of paired Thoroughbred racehorse limbs with severe condylar fracture. STUDY DESIGN: In vitro study. SAMPLE POPULATION: Cadaveric paired limbs with severe condylar fracture (n=11 horses). METHODS: Four standard radiographic and multiple transverse CT images were obtained of the fractured and contralateral limbs centering on the metacarpo/metatarsophalangeal (fetlock) joints. Radiographs and CT images were graded by 4 raters, and interobserver agreement was calculated. Imaging evaluations were supplemented by fetlock joint dissection. A consensus description of actual injury and the detection accuracy of OR and CT for that injury was determined. Results- Rater agreement for OR and CT for most pathologic features was good or excellent. OR was similar to CT for the detection of condylar and diaphyseal third metacarpal and metatarsal (MC/MT3) fractures, diaphyseal fractures of the first phalanx (P1), and fracture location on the condyle. CT was superior to OR for detection of MC/MT3 proximal fissures and articular comminution, condylar small cracks and lucencies, and proximal sesamoid fractures. OR was superior to CT for detection of proximal P1 dorsal fractures. Both OR and CT were poor at detecting palmar/planter proximal P1 fractures and coalescing cracks in the subchondral bone of MC/MT3. CONCLUSIONS: CT is better than OR for detection of pathology in limbs with condylar fractures, but does not detect every pathologic feature. CLINICAL RELEVANCE: CT provides superior information of pathology in Thoroughbred racehorses with condylar fractures.