A case of large airway and orbital hemangiomas with facial capillary malformation.

Infantile hemangiomas (IHs) are the most common pediatric vascular tumors, although their genetic etiology is largely unknown. Congenital capillary malformations (CMs) are associated with known somatic pathogenic variants, including GNAQ, GNA11, PIK3CA, and PIK3R1. Co-occurrence of a facial CM such as port wine stain and IH is not associated with any recognized vascular anomaly syndromes and rarely reported in the literature. We describe a case of a 5-week-old female patient with a large facial CM and extensive IHs of the lower lip, airway, and orbit who presented with airway compromise and responded to propranolol therapy.

Body site distribution of pediatric-onset morphea and association with extracutaneous manifestations.

BACKGROUND: The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized. OBJECTIVE: To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations. METHODS: A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software. RESULTS: A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4). LIMITATIONS: Retrospective nature and the inclusion of only patients with clinical photographs. CONCLUSION: The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed.

What global diastolic function is, what it is not, and how to measure it.

Despite Leonardo da Vinci's observation (circa 1511) that "the atria or filling chambers contract together while the pumping chambers or ventricles are relaxing and vice versa," the dynamics of four-chamber heart function, and of diastolic function (DF) in particular, are not generally appreciated. We view DF from a global perspective, while characterizing it in terms of causality and clinical relevance. Our models derive from the insight that global DF is ultimately a result of forces generated by elastic recoil, modulated by cross-bridge relaxation, and load. The interaction between recoil and relaxation results in physical wall motion that generates pressure gradients that drive fluid flow, while epicardial wall motion is constrained by the pericardial sac. Traditional DF indexes (τ, E/E', etc.) are not derived from causal mechanisms and are interpreted as approximating either stiffness or relaxation, but not both, thereby limiting the accuracy of DF quantification. Our derived kinematic models of isovolumic relaxation and suction-initiated filling are extensively validated, quantify the balance between stiffness and relaxation, and provide novel mechanistic physiological insight. For example, causality-based modeling provides load-independent indexes of DF and reveals that both stiffness and relaxation modify traditional DF indexes. The method has revealed that the in vivo left ventricular equilibrium volume occurs at diastasis, predicted novel relationships between filling and wall motion, and quantified causal relationships between ventricular and atrial function. In summary, by using governing physiological principles as a guide, we define what global DF is, what it is not, and how to measure it.

Skin Pigmentation Affects ViOptix T.Ox Performance in Variably Pigmented Preclinical Model of Flap Ischemia and Congestion.

Background: Free flap monitoring is more difficult in patients with dark skin because ischemia and congestion can be masked by pigmentation. For this reason, adjunct methods such as cutaneous near-infrared spectroscopy are of elevated importance in patients with highly pigmented skin. The purpose of this experiment is to determine if ViOpitx T.Ox performance is affected by cutaneous pigmentation. Methods: Swine with naturally occurring areas of nonpigmented and pigmented skin were used. Pigmentation of each animal was assessed using spectrophotometry and histopathology. During normoxemia, tissue oxygenation (StO2) measurements were taken of nonpigmented and pigmented skin using the T.Ox device. A bicolor pedicled rectus abdominis myocutaneous flap was raised, and T.Ox probe was adhered to adjacent areas of opposite coloration on the same flap. StO2 was measured continuously during reversible episodes of flap ischemia and congestion (n = 4 swine, n = 6 flaps). Results: There was not a significant difference between baseline StO2 values of nonpigmented (49% ± 7.9%) and pigmented skin (47% ± 6.2%). The absolute change in StO2 was significantly larger during both ischemia (6%) and congestion (16%) in nonpigmented skin compared with adjacent pigmented skin. Conclusions: T.Ox detects flap ischemia and congestion in both highly pigmented and nonpigmented skin. However, surgeons need to be aware that StO2 changes related to complete flap ischemia or congestion may be much more subtle than what is seen in nonpigmented skin. This study establishes a novel internally controlled porcine model that isolates the impact of skin pigmentation when assessing cutaneous devices measuring tissue oxygenation.

The performance of 11 fingertip pulse oximeters during hypoxemia in healthy human participants with varied, quantified skin pigment.

BACKGROUND: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation. METHODS: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%. Skin pigmentation was assessed subjectively using a perceived Fitzpatrick Scale (pFP) and objectively using the individual typology angle (ITA) via spectrophotometry at nine anatomical sites. FINDINGS: Five of 11 devices had a root mean square error (ARMS) > 3%, falling outside the acceptable FDA performance range. Nine devices demonstrated worse performance in participants in the darkest skin pigmentation category compared with those in the lightest category. A commonly used subjective skin colour scale frequently miscategorised participants as being darkly pigmented when compared to objective quantification of skin pigment by ITA. INTERPRETATION: Fingertip pulse oximeters have variable performance, frequently not meeting regulatory requirements for clinical use, and occasionally contradicting claims made by manufacturers. Most devices showed a trend toward worse performance in participants with darker skin pigment. Regulatory standards do not adequately account for the impact of skin pigmentation on device performance. We recommend that the pFP and other non-standardised subjective skin colour scales should no longer be used for defining diversity of skin pigmentation. Reliable methods for characterising skin pigmentation to improve diversity and equitable performance of pulse oximeters are needed. FUNDING: This study was conducted as part of the Open Oximetry Project funded by the Gordon and Betty Moore Foundation, Patrick J McGovern Foundation, and Robert Wood Johnson Foundation. The UCSF Hypoxia Research Laboratory receives funding from multiple industry sponsors to test the sponsors' devices for the purposes of product development and regulatory performance testing. Data in this paper do not include sponsor's study devices. All data were collected from devices procured by the Hypoxia Research Laboratory for the purposes of independent research. No company provided any direct funding for this study, participated in study design or analysis, or was involved in analysing data or writing the manuscript. None of the authors own stock or equity interests in any pulse oximeter companies. Dr Ellis Monk's time utilised for data analysis, reviewing and editing was funded by grant number: DP2MH132941.

Low-cost augmented reality goggles enable precision fluorescence-guided cancer surgery.

Disparities in surgical outcomes often result from subjective than objective decisions dictated by surgical training, experience, and available resources. To improve outcomes, surgeons have adopted advancements in robotics, endoscopy, and intra-operative imaging including fluorescence-guided surgery (FGS), which highlight tumors in real-time without using ionizing radiation. However, like many medical innovations, technical, economic, and logistic challenges have hindered widespread adoption of FGS beyond high-resource centers. To overcome these impediments, we developed the fully-wearable and battery-powered fluorescence imaging augmented reality Raspberry Pi-based goggle system (FAR-Pi). Novel device design ensures distance-independent coalignment between real and augmented FAR-Pi views and offers higher spatial resolution, depth of focus, and fluorescence detection sensitivity than existing bulkier, pricier, and wall-powered technologies. When paired with pan-tumor targeting fluorescent agents such as LS301, FAR-Pi objectively identifies tumors in vivo. As an open-source, affordable, and adaptable system, FAR-Pi is poised to democratize access to FGS and improve health outcomes worldwide.

Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage.

Postpartum hemorrhage (PPH) is both the leading and most preventable cause of maternal mortality. PPH is currently diagnosed through visual estimation of blood loss or vital sign analysis of shock index (ratio of heart rate to systolic blood pressure). Visual assessment underestimates blood loss, particularly in the setting of internal bleeding, and compensatory mechanisms stabilize hemodynamics until hemorrhage is massive, beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels to shunt blood to the central organs, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The device was first tested using flow phantoms across a range of physiologically relevant flow rates and demonstrated a linear response. Subsequent testing occurred in swine hemorrhage studies (n=6) by placing the device on the posterior side of the swine's front hock and withdrawing blood from the femoral vein at a constant rate. Resuscitation with intravenous crystalloids followed the induced hemorrhage. The mean LSFI vs. percent estimated blood volume loss had an average correlation coefficient of -0.95 during the hemorrhage phase and 0.79 during resuscitation, both of which were superior to the performance of the shock index. With continued development, this noninvasive, low-cost, and reusable device has global potential to provide an early alert of PPH when low-cost and accessible management strategies are most effective, helping to reduce maternal morbidity and mortality from this largely preventable problem.

Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage.

Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom models and a strong correlation coefficient with blood loss averaged across subjects (>0.9) in a large animal model, with superior performance to vital sign metrics.

Venous Malformations: A Journey Through Their Multifaceted Clinical Presentations.

Venous malformations are the most common congenital vascular malformations. Because venous malformations can be complex, difficult to treat, and associated with late complications, it is important to know the basics of the different types of venous malformations and clinical differential diagnosis. Patients with complex lesions may be best served by a specialty vascular anomalies clinic.

The thermodynamics of diastole: kinematic modeling-based derivation of the P-V loop to transmitral flow energy relation with in vivo validation.

Pressure-volume (P-V) loop-based analysis facilitates thermodynamic assessment of left ventricular function in terms of work and energy. Typically these quantities are calculated for a cardiac cycle using the entire P-V loop, although thermodynamic analysis may be applied to a selected phase of the cardiac cycle, specifically, diastole. Diastolic function is routinely quantified by analysis of transmitral Doppler E-wave contours. The first law of thermodynamics requires that energy (ε) computed from the Doppler E-wave (εE-wave) and the same portion of the P-V loop (εP-V E-wave) be equivalent. These energies have not been previously derived nor have their predicted equivalence been experimentally validated. To test the hypothesis that εP-V E-wave and εE-wave are equivalent, we used a validated kinematic model of filling to derive εE-wave in terms of chamber stiffness, relaxation/viscoelasticity, and load. For validation, simultaneous (conductance catheter) P-V and echocadiographic data from 12 subjects (205 total cardiac cycles) having a range of diastolic function were analyzed. For each E-wave, εE-wave was compared with εP-V E-wave calculated from simultaneous P-V data. Linear regression yielded the following: εP-V E-wave=αεE-wave+b (R2=0.67), where α=0.95 and b=6e(-5). We conclude that E-wave-derived energy for suction-initiated early rapid filling εE-wave, quantitated via kinematic modeling, is equivalent to invasive P-V-defined filling energy. Hence, the thermodynamics of diastole via εE-wave generate a novel mechanism-based index of diastolic function suitable for in vivo phenotypic characterization.

Research Techniques Made Simple: Scientific Communication using Twitter.

The scientific process depends on social interactions: communication and dissemination of research findings, evaluation and discussion of scientific work, and collaboration with other scientists. Social media, and specifically, Twitter has accelerated the ability to accomplish these goals. We discuss the ways that Twitter is used by scientists and provide guidance on navigating the academic Twitter community.

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo.

SIGNIFICANCE: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. AIM: We aim to demonstrate label-free imaging of suspected melanoma CTCs. APPROACH: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. RESULTS: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. CONCLUSIONS: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma.

Hyperspectral imaging and characterization of allergic contact dermatitis in the short-wave infrared.

Short-wave infrared hyperspectral imaging is applied to diagnose and monitor a case of allergic contact dermatitis (ACD) due to poison ivy exposure in one subject. This approach directly demonstrates increased tissue fluid content in ACD lesional skin with a spectral signature that matches the spectral signature of intradermally injected normal saline. The best contrast between the affected and unaffected skin is achieved through a selection of specific wavelengths at 1070, 1340 and 1605 nm and combining them in a pseudo-red-green-blue color space. An image derived from these wavelengths normalized to unaffected skin defines a "tissue fluid index" that may aid in the quantitative diagnosis and monitoring of ACD. Further clinical testing of this promising approach towards disease detection and monitoring with tissue fluid content quantification is warranted.

Focal dynamic thermal imaging for label-free high-resolution characterization of materials and tissue heterogeneity.

Evolution from static to dynamic label-free thermal imaging has improved bulk tissue characterization, but fails to capture subtle thermal properties in heterogeneous systems. Here, we report a label-free, high speed, and high-resolution platform technology, focal dynamic thermal imaging (FDTI), for delineating material patterns and tissue heterogeneity. Stimulation of focal regions of thermally responsive systems with a narrow beam, low power, and low cost 405 nm laser perturbs the thermal equilibrium. Capturing the dynamic response of 3D printed phantoms, ex vivo biological tissue, and in vivo mouse and rat models of cancer with a thermal camera reveals material heterogeneity and delineates diseased from healthy tissue. The intuitive and non-contact FDTI method allows for rapid interrogation of suspicious lesions and longitudinal changes in tissue heterogeneity with high-resolution and large field of view. Portable FDTI holds promise as a clinical tool for capturing subtle differences in heterogeneity between malignant, benign, and inflamed tissue.

Quantifying Diastolic Function: From E-Waves as Triangles to Physiologic Contours via the 'Geometric Method'.

Conventional echocardiographic diastolic function (DF) assessment approximates transmitral flow velocity contours (Doppler E-waves) as triangles, with peak (Epeak), acceleration time (AT), and deceleration time (DT) as indexes. These metrics have limited value because they are unable to characterize the underlying physiology. The parametrized diastolic filling (PDF) formalism provides a physiologic, kinematic mechanism based characterization of DF by extracting chamber stiffness (k), relaxation (c), and load (x o ) from E-wave contours. We derive the mathematical relationship between the PDF parameters and Epeak, AT, DT and thereby introduce the geometric method (GM) that computes the PDF parameters using Epeak, AT, and DT as input. Numerical experiments validated GM by analysis of 208 E-waves from 31 datasets spanning the full range of clinical diastolic function. GM yielded indistinguishable average parameter values per subject vs. the gold-standard PDF method (k: R2 = 0.94, c: R2 = 0.95, x o : R2 = 0.95, p < 0.01 all parameters). Additionally, inter-rater reliability for GM-determined parameters was excellent (k: ICC = 0.956 c: ICC = 0.944, x o : ICC = 0.993). Results indicate that E-wave symmetry (AT/DT) may comprise a new index of DF. By employing indexes (Epeak, AT, DT) that are already in standard clinical use the GM capitalizes on the power of the PDF method to quantify DF in terms of physiologic chamber properties.

The kinematic filling efficiency index of the left ventricle: contrasting normal vs. diabetic physiology.

An index of filling efficiency incorporating stiffness and relaxation (S&R) parameters has not been derived or validated, although numerous studies have focused on the effects of altered relaxation or stiffness on early rapid filling and diastolic function. Previous studies show that S&R parameters can be obtained from early rapid filling (Doppler E-wave) via kinematic modeling. E-wave contours are governed by harmonic oscillatory motion modeled via the parameterized diastolic filling (PDF) formalism. The previously validated model determines three (unique) oscillator parameters from each E-wave having established physiological analogues: x(o) (load), c (relaxation/viscoelasticity) and k (chamber stiffness). We define the dimensionless, filling-volume-based kinematic filling efficiency index (KFEI) as the ratio of the velocity-time integral (VTI) of the actual clinical E-wave contour fit via PDF to the VTI of the PDF model-predicted ideal E-wave contour having the same x(o) and k, but with no resistance to filling (c = 0). To validate the new index, Doppler E-waves from 36 patients with normal ventricular function, 17 diabetic and 19 well-matched non-diabetic controls, were analyzed. E-wave parameters x(o), c and k and KFEI were computed for each patient and compared. In concordance with prior human and animal studies in which c differentiated between normal and diabetic hearts, KFEI differentiated (p < 0.001) between nondiabetics (55.8% +/- 3.3%) and diabetics (49.1% +/- 3.3%). Thus, the new index introduces and validates the concept of filling efficiency, and, using diabetes as a working example, provides quantitative and mechanistic insight into how S&R affect ventricular filling efficiency.