Crowdsourcing Skin Demarcations of Chronic Graft-Versus-Host Disease in Patient Photographs: Training Versus Performance Study.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a significant cause of long-term morbidity and mortality in patients after allogeneic hematopoietic cell transplantation. Skin is the most commonly affected organ, and visual assessment of cGVHD can have low reliability. Crowdsourcing data from nonexpert participants has been used for numerous medical applications, including image labeling and segmentation tasks. OBJECTIVE: This study aimed to assess the ability of crowds of nonexpert raters-individuals without any prior training for identifying or marking cGHVD-to demarcate photos of cGVHD-affected skin. We also studied the effect of training and feedback on crowd performance. METHODS: Using a Canfield Vectra H1 3D camera, 360 photographs of the skin of 36 patients with cGVHD were taken. Ground truth demarcations were provided in 3D by a trained expert and reviewed by a board-certified dermatologist. In total, 3000 2D images (projections from various angles) were created for crowd demarcation through the DiagnosUs mobile app. Raters were split into high and low feedback groups. The performances of 4 different crowds of nonexperts were analyzed, including 17 raters per image for the low and high feedback groups, 32-35 raters per image for the low feedback group, and the top 5 performers for each image from the low feedback group. RESULTS: Across 8 demarcation competitions, 130 raters were recruited to the high feedback group and 161 to the low feedback group. This resulted in a total of 54,887 individual demarcations from the high feedback group and 78,967 from the low feedback group. The nonexpert crowds achieved good overall performance for segmenting cGVHD-affected skin with minimal training, achieving a median surface area error of less than 12% of skin pixels for all crowds in both the high and low feedback groups. The low feedback crowds performed slightly poorer than the high feedback crowd, even when a larger crowd was used. Tracking the 5 most reliable raters from the low feedback group for each image recovered a performance similar to that of the high feedback crowd. Higher variability between raters for a given image was not found to correlate with lower performance of the crowd consensus demarcation and cannot therefore be used as a measure of reliability. No significant learning was observed during the task as more photos and feedback were seen. CONCLUSIONS: Crowds of nonexpert raters can demarcate cGVHD images with good overall performance. Tracking the top 5 most reliable raters provided optimal results, obtaining the best performance with the lowest number of expert demarcations required for adequate training. However, the agreement amongst individual nonexperts does not help predict whether the crowd has provided an accurate result. Future work should explore the performance of crowdsourcing in standard clinical photos and further methods to estimate the reliability of consensus demarcations.

A novel algorithm for cardiovascular screening using conjunctival microcirculatory parameters and blood biomarkers.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case-control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

Peripheral Nerve Entrapments in Cancer Pain.

Peripheral nerve entrapments can occur anywhere in the head and body and can cause significant pain. Cancer pain can be caused by these entrapments, triggered by a variety of etiologies, including tumor invasion, surgical trauma, chemotherapy, or scarring. Knowing the cause of pain can help the physician treat the problem effectively, and will decrease unnecessary and potentially worsening surgeries and high dose opioid therapies, as well as unnecessary pain. A knowledgeable interventional pain physician can diagnose and treat these nerves entrapments in the most effective manner, providing improved pain relief and quality of life.Key points Nerve entrapments can occur throughout the body in cancer patients due to multiple etiologies such as tumor invasion, surgical trauma, or cancer therapy. The problem of nerve entrapments in cancer pain is under-recognized. Patients with nerve entrapment syndromes frequently complain of a burning tingling sensation and other paresthesias in the nerve distribution which can progress to a complete loss of sensory and motor function. Diagnostic tools include history and physical exam, imaging, nerve conduction studies as well as diagnostic nerve injections/blocks. Treatment of nerve entrapments can range from neuropathic pain medications to nerve blocks and nerve ablations to surgical decompression.

Assessment of the conjunctival microcirculation for patients presenting with acute myocardial infarction compared to healthy controls.

Microcirculatory dysfunction occurs early in cardiovascular disease (CVD) development. Acute myocardial infarction (MI) is a late consequence of CVD. The conjunctival microcirculation is readily-accessible for quantitative assessment and has not previously been studied in MI patients. We compared the conjunctival microcirculation of acute MI patients and age/sex-matched healthy controls to determine if there were differences in microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. Results are for all vessels as they were not sub-classified into arterioles or venules. The conjunctival microcirculation was assessed in 56 controls and 59 inpatients with a presenting diagnosis of MI. Mean vessel diameter for the controls was 21.41 ± 7.57 µm compared to 22.32 ± 7.66 µm for the MI patients (p < 0.001). Axial velocity for the controls was 0.53 ± 0.15 mm/s compared to 0.49 ± 0.17 mm/s for the MI patients (p < 0.001). Wall shear rate was higher for controls than MI patients (162 ± 93 s-1 vs 145 ± 88 s-1, p < 0.001). Blood volume flow did not differ significantly for the controls and MI patients (153 ± 124 pl/s vs 154 ± 125 pl/s, p = 0.84). This pilot iPhone and slit-lamp assessment of the conjunctival microcirculation found lower axial velocity and wall shear rate in patients with acute MI. Further study is required to correlate these findings further and assess long-term outcomes in this patient group with a severe CVD phenotype.

Assessment of the conjunctival microcirculation in adult patients with cyanotic congenital heart disease compared to healthy controls.

PURPOSE: Congenital heart disease (CHD) is the most common live birth defect and a proportion of these patients have chronic hypoxia. Chronic hypoxia leads to secondary erythrocytosis resulting in microvascular dysfunction and increased thrombosis risk. The conjunctival microcirculation is easily accessible for imaging and quantitative assessment. It has not previously been studied in adult CHD patients with cyanosis (CCHD). METHODS: We assessed the conjunctival microcirculation and compared CCHD patients and matched healthy controls to determine if there were differences in measured microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. The axial velocity was estimated by applying the 1D + T continuous wavelet transform (CWT). Results are for all vessels as they were not sub-classified into arterioles or venules. RESULTS: 11 CCHD patients and 14 healthy controls were recruited to the study. CCHD patients were markedly more hypoxic compared to the healthy controls (84% vs 98%, p = 0.001). A total of 736 vessels (292 vs 444) were suitable for analysis. Mean microvessel diameter (D) did not significantly differ between the CCHD patients and controls (20.4 ± 2.7 µm vs 20.2 ± 2.6 µm, p = 0.86). Axial velocity (Va) was lower in the CCHD patients (0.47 ± 0.06 mm/s vs 0.53 ± 0.05 mm/s, p = 0.03). Blood volume flow (Q) was lower for CCHD patients (121 ± 30pl/s vs 145 ± 50pl/s, p = 0.65) with the greatest differences observed in vessels >22 µm diameter (216 ± 121pl/s vs 258 ± 154pl/s, p = 0.001). Wall shear rate (WSR) was significantly lower for the CCHD group (153 ± 27 s-1 vs 174 ± 22 s-1, p = 0.04). CONCLUSIONS: This iPhone and slit-lamp combination assessment of conjunctival vessels found lower axial velocity, wall shear rate and in the largest vessel group, lower blood volume flow in chronically hypoxic patients with congenital heart disease. With further study this assessment method may have utility in the evaluation of patients with chronic hypoxia.

Quantitative assessment of the conjunctival microcirculation using a smartphone and slit-lamp biomicroscope.

PURPOSE: The conjunctival microcirculation is a readily-accessible vascular bed for quantitative haemodynamic assessment and has been studied previously using a digital charge-coupled device (CCD). Smartphone video imaging of the conjunctiva, and haemodynamic parameter quantification, represents a novel approach. We report the feasibility of smartphone video acquisition and subsequent haemodynamic measure quantification via semi-automated means. METHODS: Using an Apple iPhone 6 s and a Topcon SL-D4 slit-lamp biomicroscope, we obtained videos of the conjunctival microcirculation in 4 fields of view per patient, for 17 low cardiovascular risk patients. After image registration and processing, we quantified the diameter, mean axial velocity, mean blood volume flow, and wall shear rate for each vessel studied. Vessels were grouped into quartiles based on their diameter i.e. group 1 (<11 µm), 2 (11-16 µm), 3 (16-22 µm) and 4 (>22 µm). RESULTS: From the 17 healthy controls (mean QRISK3 6.6%), we obtained quantifiable haemodynamics from 626 vessel segments. The mean diameter of microvessels, across all sites, was 21.1µm (range 5.8-58 µm). Mean axial velocity was 0.50mm/s (range 0.11-1mm/s) and there was a modestly positive correlation (r 0.322) seen with increasing diameter, best appreciated when comparing group 4 to the remaining groups (p < .0001). Blood volume flow (mean 145.61pl/s, range 7.05-1178.81pl/s) was strongly correlated with increasing diameter (r 0.943, p < .0001) and wall shear rate (mean 157.31 s-1, range 37.37-841.66 s-1) negatively correlated with increasing diameter (r - 0.703, p < .0001). CONCLUSIONS: We, for the first time, report the successful assessment and quantification of the conjunctival microcirculatory haemodynamics using a smartphone-based system.

Do Pain Medicine Fellowship Programs Provide Education in Practice Management? A Survey of Pain Medicine Fellowship Programs.

BACKGROUND: We hypothesized that there is a gap between expectations and actual training in practice management for pain medicine fellows. Our impression is that many fellowships rely on residency training to provide exposure to business education. Unfortunately, pain management and anesthesiology business education are very different, as the practice settings are largely office- versus hospital-based, respectively. OBJECTIVE: Because it is unclear whether pain management fellowships are providing practice management education and, if they do, whether the topics covered match the expectations of their fellows, we surveyed pain medicine program directors and fellows regarding their expectations and training in business management. STUDY DESIGN: A survey. SETTING: Academic pain medicine fellowship programs. METHODS: After an exemption was obtained from the University of Texas Medical Branch Institutional Review Board (#13-030), an email survey was sent to members of the Association of Pain Program Directors to be forwarded to their fellows. Directors were contacted 3 times to maximize the response rate. The anonymous survey for fellows contained 21 questions (questions are shown in the results). RESULTS: Fifty-nine of 84 program directors responded and forwarded the survey to their fellows. Sixty fellows responded, with 56 answering the survey questions. LIMITATIONS: The responder rate is a limitation, although similar rates have been reported in similar studies. CONCLUSIONS: The majority of pain medicine fellows receive some practice management training, mainly on billing documentation and preauthorization processes, while most do not receive business education (e.g., human resources, contracts, accounting/financial reports). More than 70% of fellows reported that they receive more business education from industry than from their fellowships, a result that may raise concerns about the independence of our future physicians from the industry. Our findings support the need for enhanced and structured business education during pain fellowship. KEY WORDS: Business education, practice management, fellowship training, curriculum development, knowledge gaps, private practice.

Mapping of arterial location for the design of automated identification and analysis algorithms in whole body MRA.

Technological and medical advances have led to the realisation of full body imaging, with systemic diagnostic approaches becoming increasingly more prevalent. In the imaging of atherosclerotic disease, contrast -enhanced whole-body MRA has been demonstrated to enable detection of stenosis with a high sensitivity and specificity. Characterization of the systemic cardiovascular disease burden has significant prognostic value. A whole-body acquisition does however generate a large volume of three-dimensional data and as such there are expected to be significant advantages in developing automated techniques for the analysis of these images. Improved radiological workflow, reduced analysis time and increased analytical standardization are expected to be among the benefits offered by this approach. As part of a process of automated software development this study aimed to collect and validate arterial location ground truth. The data will be used to inform the development of semi-automated vascular identity tools, and allow the potential for the further development of semi-automated anatomically informed cardiovascular disease analysis and reporting.

Ancient Ephemeroptera-Collembola symbiosis fossilized in amber predicts contemporary phoretic associations.

X-ray computed tomography is used to identify a unique example of fossilized phoresy in 16 million-year-old Miocene Dominican amber involving a springtail being transported by a mayfly. It represents the first evidence (fossil or extant) of phoresy in adult Ephemeroptera and only the second record in Collembola (the first is also preserved in amber). This is the first record of Collembola using winged insects for dispersal. This fossil predicts the occurrence of similar behaviour in living springtails and helps explain the global distribution of Collembola today.

A minute fossil phoretic mite recovered by phase-contrast X-ray computed tomography.

High-resolution phase-contrast X-ray computed tomography (CT) reveals the phoretic deutonymph of a fossil astigmatid mite (Acariformes: Astigmata) attached to a spider's carapace (Araneae: Dysderidae) in Eocene (44-49 Myr ago) Baltic amber. Details of appendages and a sucker plate were resolved, and the resulting three-dimensional model demonstrates the potential of tomography to recover morphological characters of systematic significance from even the tiniest amber inclusions without the need for a synchrotron. Astigmatids have an extremely sparse palaeontological record. We confirm one of the few convincing fossils, potentially the oldest record of Histiostomatidae. At 176 µm long, we believe this to be the smallest arthropod in amber to be CT-scanned as a complete body fossil, extending the boundaries for what can be recovered using this technique. We also demonstrate a minimum age for the evolution of phoretic behaviour among their deutonymphs, an ecological trait used by extant species to disperse into favourable environments. The occurrence of the fossil on a spider is noteworthy, as modern histiostomatids tend to favour other arthropods as carriers.

Computed tomography recovers data from historical amber: an example from huntsman spiders.

Computed tomography (CT) methods were applied to a problematic fossil spider (Arachnida: Araneae) from the historical Berendt collection of Eocene (ca. 44-49 Ma) Baltic amber. The original specimens of Ocypete crassipes Koch and Berendt 1854 are in dark, oxidised amber and the published descriptions lack detail. Despite this, they were subsequently assigned to the living Pantropical genus Heteropoda Latreille, 1804 and are ostensibly the oldest records of huntsman spiders (Sparassidae) in general. Given their normally large size, and presumptive ability to free themselves more easily from resin, it would be surprising to find a sparassid in amber and traditional (optical) methods of study would likely have left O. crassipes as an equivocal record--probably a nomen dubium. However, phase contrast enhanced X-ray CT revealed exquisite morphological detail and thus 'saved' this historical name by revealing characters which confirm that it's a bona fide member both of Sparassidae and the subfamily Eusparassinae. We demonstrate here that CT studies facilitate taxonomic equivalence even between recent spiders and unpromising fossils described in older monographs. In our case, fine structural details such as eye arrangement, cheliceral dentition, and leg characters like a trilobate membrane, spination and claws, allow a precise referral of this fossil to an extant genus as Eusparassus crassipes (Koch and Berendt 1854) comb. nov.

Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy.

Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4(+) T-cell depletion and the effect of HAART on the restoration of CD4(+) T cells in GALT. Severe depletion of intestinal CD4(+) T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4(+) T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4(+) T cells, despite the delay in comparison to peripheral blood CD4(+) T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4(+) T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4(+) T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4(+) T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.