Prediction of anemia in real-time using a smartphone camera processing conjunctival images.

Anemia is defined as a low hemoglobin (Hb) concentration and is highly prevalent worldwide. We report on the performance of a smartphone application (app) that records images in RAW format of the palpebral conjunctivae and estimates Hb concentration by relying upon computation of the tissue surface high hue ratio. Images of bilateral conjunctivae were obtained prospectively from a convenience sample of 435 Emergency Department patients using a dedicated smartphone. A previous computer-based and validated derivation data set associating estimated conjunctival Hb (HBc) and the actual laboratory-determined Hb (HBl) was used in deriving Hb estimations using a self-contained mobile app. Accuracy of HBc was 75.4% (95% CI 71.3, 79.4%) for all categories of anemia, and Bland-Altman plot analysis showed a bias of 0.10 and limits of agreement (LOA) of (-4.73, 4.93 g/dL). Analysis of HBc estimation accuracy around different anemia thresholds showed that AUC was maximized at transfusion thresholds of 7 and 9 g/dL which showed AUC values of 0.92 and 0.90 respectively. We found that the app is sufficiently accurate for detecting severe anemia and shows promise as a population-sourced screening platform or as a non-invasive point-of-care anemia classifier.

Prediction of anemia and estimation of hemoglobin concentration using a smartphone camera.

Anemia, defined as a low hemoglobin concentration, has a large impact on the health of the world's population. We describe the use of a ubiquitous device, the smartphone, to predict hemoglobin concentration and screen for anemia. This was a prospective convenience sample study conducted in Emergency Department (ED) patients of an academic teaching hospital. In an algorithm derivation phase, images of both conjunctiva were obtained from 142 patients in Phase 1 using a smartphone. A region of interest targeting the palpebral conjunctiva was selected from each image. Image-based parameters were extracted and used in stepwise regression analyses to develop a prediction model of estimated hemoglobin (HBc). In Phase 2, a validation model was constructed using data from 202 new ED patients. The final model based on all 344 patients was tested for accuracy in anemia and transfusion thresholds. Hemoglobin concentration ranged from 4.7 to 19.6 g/dL (mean 12.5). In Phase 1, there was a significant association between HBc and laboratory-predicted hemoglobin (HBl) slope = 1.07 (CI = 0.98-1.15), p<0.001. Accuracy, sensitivity, and specificity of HBc for predicting anemia was 82.9 [79.3, 86.4], 90.7 [87.0, 94.4], and 73.3 [67.1, 79.5], respectively. In Phase 2, accuracy, sensitivity and specificity decreased to 72.6 [71.4, 73.8], 72.8 [71, 74.6], and 72.5 [70.8, 74.1]. Accuracy for low (<7 g/dL) and high (<9 g/dL) transfusion thresholds was 94.4 [93.7, 95] and 86 [85, 86.9] respectively. Error trended with increasing HBl values (slope 0.27 [0.19, 0.36] and intercept -3.14 [-4.21, -2.07] (p<0.001) such that HBc tended to underestimate hemoglobin in higher ranges and overestimate in lower ranges. Higher quality images had a smaller bias trend than lower quality images. When separated by skin tone results were unaffected. A smartphone can be used in screening for anemia and transfusion thresholds. Improvements in image quality and computational corrections can further enhance estimates of hemoglobin.

Nondisplaced pubic ramus fracture associated with exsanguination and death.

We present a case of an elderly man who sustained non-displaced fractures through the right superior and inferior pubic rami after a fall from standing and had a tragic outcome. While minimally displaced pubic ramus fractures are typically stable and require only symptomatic treatment, there have been reports, such as this one, of low-energy pubic rami fractures resulting in massive hemorrhage. Despite aggressive resuscitation and embolization of the right obturator artery, our patient ultimately died during his hospitalization. This report highlights the need to maintain a high index of suspicion for intrapelvic bleeds even in patients with nondisplaced pubic rami fractures. Rapid recognition and treatment of intrapelvic bleeds can be lifesaving.

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain.

Continuous noninvasive measurement of pulsus paradoxus complements medical decision making in assessment of acute asthma severity.

BACKGROUND: Pulsus paradoxus (PP) is a pathophysiologic parameter that is indicative of asthma severity. The ability of PP to categorize acutely asthmatic patients in accordance with the earlier National Asthma Education and Prevention Program (NAEPP) expert panel report 1 guidelines was determined. METHODS: An arterial tonometric BP monitor, which was interfaced to an analog-digital converter, executed a periodic amplitude analysis algorithm, which computed PP in real time. The PP measurement was compared to the criterion standard of emergency physicians in determining the hospital admission vs hospital discharge disposition following the NAEPP standardized treatment. Receiver operating characteristics (ROCs) were calculated, and the PP threshold, which maximized sensitivity and specificity, was identified. In a separate laboratory investigation, PP was induced in a healthy volunteer by inspiration through a fixed resistance. Plethysmographic waveform changes, induced by PP, were measured by a second analog-to-digital converter that was connected to a pulse oximeter. RESULTS: A total of 79 patients were enrolled in the study, of whom 63 met a priori inclusion criteria and had uninterrupted data acquisition. The mean PP for patients who were appropriately discharged from the hospital was 9.1 mm Hg (95% confidence interval [CI], 7.3 to 10.9 mm Hg) and differed from the PP of 17.6 mm Hg (95% CI, 13.5 to 21.8; p < 0.001) for patients admitted to the hospital/relapsed. The sensitivity and specificity for physician disposition were 0.83 and 0.89, respectively, and for PP values were 0.78 and 0.78, respectively. The Wilcoxon area under the ROC curve was 0.82 (95% CI, 0.64 to 0.99) following treatment. The risk ratio was 5.32 for hospital admission among patients with a PP of > 11.3 mm Hg. Changes in the photoplethysmography peak height were correlated to PP from the BP monitor by a regression line with a slope of 0.01 V/mm Hg. CONCLUSIONS: Continuous PP can aid in determining disposition among emergency department (ED) patients with acute asthma. ED physicians equipped with a PP monitor would be able to objectify the work of breathing and would more closely adhere to NAEPP guidelines. The possibility that a PP detection algorithm could reside in a pulse oximeter warrants further investigation.

T cell epitope identification for bovine vaccines: an epitope mapping method for BoLA A-11.

T cell responses play an important role in immunity to parasites and other microbial agents of infectious diseases, therefore a number of T cell-directed vaccines are in development. Computer-driven algorithms that facilitate the discovery of T cell epitopes from protein and genome sequences are now being used to accelerate preclinical studies of human vaccines. Similar tools are not yet available for predicting T cell epitopes for animal vaccines, but there may be sufficient data available to begin the process of compiling the algorithms. We describe the construction of a novel mathematical 'matrix' that describes the properties of bovine major histocompatibility complex (BoLA) system antigen (BoLA) A-11 peptide ligands, developed for use with EpiMatrix, an existing T cell epitope-mapping algorithm. An alternative means of developing BoLA matrices, using the pocket profile method, is also discussed. Matrices such as the one described here may be used to develop T cell epitope-mapping tools for cattle and other ruminants. Epitope-mapping algorithms offer a significant advantage over other methods of epitope selection, such as the screening of synthetic overlapping peptides, because high throughput screening can be performed in silico, followed by ex vivo confirmatory studies. Furthermore, using epitope-mapping algorithms, putative T cell epitopes can be derived directly from genomic sequences, allowing researchers to circumvent labor-intensive cloning steps in the genome-to-vaccine discovery pathway.