Monitoring the venous circulation: novel techniques and applications.

PURPOSE OF REVIEW: Venous pressure is an often-unrecognized cause of patient morbidity. However, bedside assessment of PV is challenging. We review the clinical significance of venous pressure measurement, existing techniques, and introduce the Venous Excess Ultrasound (VExUS) Score as a novel approach using doppler ultrasound to assess venous pressure. RECENT FINDINGS: Studies show clear associations between elevated venous pressure and adverse outcomes in critically ill patients. Current venous pressure measurement techniques include physical examination, right heart catheterization (RHC), two-dimensional ultrasound, and a variety of labor-intensive research-focused physiological maneuvers. Each of these techniques have specific shortcomings, limiting their clinical utility. To address these gaps, Beaubien-Souligny et al. introduced the VExUS Score, a novel doppler ultrasound-based method that integrates IVC diameter with doppler measurements of the hepatic, portal, and renal veins to generate a venous congestion assesment. Studies show strong correlations between VExUS score and RHC measurements, and well as an association between VExUS score and improvement in cardiorenal acute kidney injury, diuretic response, and fluid status shifts. However, studies in noncardiac populations have been small, heterogenous, and inconclusive. SUMMARY: Early studies evaluating the use of doppler ultrasound to assess venous congestion show promise, but further research is needed in diverse patient populations and clinical settings.

Reliability and reproducibility of the venous excess ultrasound (VExUS) score, a multi-site prospective study: validating a novel ultrasound technique for comprehensive assessment of venous congestion.

Though the novel venous excess ultrasound (VExUS) score is increasingly used as a noninvasive means of venous congestion measurement, the inter-rater reliability (IRR), inter-user reproducibility (IUR), and utility of concurrent ECG have not been evaluated. We conducted a multicenter study of the IRR, IUR, and utility of ECG for VExUS interpretation between four attending physicians of diverse specialties, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR for scans with and without ECG. Eighty-four paired VExUS exams from 42 patients, 60 of which had a concurrent ECG tracing, were interpreted. They showed substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p < 0.001), and IUR, with a KS 0.63 and ICC of 0.8. There was greater agreement among images with an ECG tracing. These results suggest that ECG-augmented VExUS may be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds.

Correlation between the VExUS score and right atrial pressure: a pilot prospective observational study.

Venous congestion is an under-recognized contributor to mortality in critically ill patients. Unfortunately, venous congestion is difficult to measure, and right heart catheterization (RHC) has been considered the most readily available means for measuring venous filling pressure. Recently, a novel "Venous Excess Ultrasound (VExUS)" score was developed to noninvasively quantify venous congestion using inferior vena cava (IVC) diameter and Doppler flow through the hepatic, portal, and renal veins. A preliminary retrospective study of post-cardiac surgery patients showed promising results, including a high positive-likelihood ratio of high VExUS grade for acute kidney injury. However, studies have not been reported in broader patient populations, and the relationship between VExUS and conventional measures of venous congestion is unknown. To address these gaps, we prospectively assessed the correlation of VExUS with right atrial pressure (RAP), with comparison to inferior vena cava (IVC) diameter. Patients undergoing RHC at Denver Health Medical Center underwent VExUS examination before their procedure. VExUS grades were assigned before RHC, blinding ultrasonographers to RHC outcomes. After controlling for age, sex, and common comorbidities, we observed a significant positive association between RAP and VExUS grade (P < 0.001, R2 = .68). VExUS had a favorable AUC for prediction of a RAP ≥ 12 mmHg (0.99, 95% CI 0.96-1) compared to IVC diameter (0.79, 95% CI 0.65-0.92). These results suggest a strong correlation between VExUS and RAP in a diverse patient population, and support future studies of VExUS as a tool to assess venous congestion and guide management in a spectrum of critical illnesses.

Water-Holding and Transport Properties of Skin Stratum Corneum of Infants and Toddlers Are Different from Those of Adults: Studies in Three Geographical Regions and Four Ethnic Groups.

BACKGROUND/OBJECTIVE: Epidermal structure, function, and composition are different in white infants and adults. We investigated whether ethnicity and location contribute to differences in functional and clinical measurements of skin barrier function during the first years of life and in adults. METHODS: Children (n = 397, ages 3-49 mos) and women (n = 117, mean age 31 yrs) were enrolled at independent centers in Beijing, China (ethnic Chinese), Skillman, New Jersey (white, African American), and Mumbai, India (ethnic South Asian). Water barrier properties of the stratum corneum were assessed using high-frequency conductance and transepidermal water loss (TEWL) on the dorsal forearm and upper inner arm. Digital imaging was used to evaluate facial erythema and scaling. RESULTS: Despite differences in local climate, TEWL was similar in adults. In children, conductance and TEWL decreased monotonically from age 3 months to 4 years. In children from Beijing, TEWL values were higher in both arm locations than in children in Mumbai and Skillman. No significant differences were observed in TEWL or conductance between the white and African American groups. CONCLUSION: In general, TEWL and conductance were greater on the upper inner arm than the dorsal forearm. Erythema and scaling were observed most often in subjects from Beijing and most infrequently in subjects from Mumbai. Stratum corneum water barrier properties were different in children and adults. Although there may be differences in these properties between ethnic groups in childhood, TEWL values were similar in adults across the three geographic locations and four ethnicities.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Venous excess ultrasonography (VExUS) captures dynamic changes in volume status surrounding hemodialysis: A multicenter prospective observational study.

Background: The evaluation of volume status is essential to clinical decision-making, yet multiple studies have shown that physical exam does not reliably estimate a patient's intravascular volume. Venous excess ultrasound score (VExUS) is an emerging volume assessment tool that utilizes inferior vena cava (IVC) diameter and pulse-wave Doppler waveforms of the portal, hepatic and renal veins to evaluate venous congestion. A point-of-care ultrasound exam initially developed by Beaubein-Souligny et al., VExUS represents a reproducible, non-invasive and accurate means of assessing intravascular congestion. VExUS has recently been validated against RHC-the gold-standard of hemodynamic evaluation for volume assessment. While VExUS scores were shown to correlate with elevated cardiac filling pressures (i.e., right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP)) at a static point in time, the ability of VExUS to capture dynamic changes in volume status has yet to be elucidated. We hypothesized that paired VExUS examinations performed before and after hemodialysis (HD) would reflect changes in venous congestion in a diverse patient population. Methods: Inpatients with end-stage renal disease undergoing intermittent HD were evaluated with transabdominal VExUS and lung ultrasonography before and following HD. Paired t-tests were conducted to assess differences between pre-HD and post-HD VExUS scores, B-line scores and dyspnea scores. Results: Fifty-six patients were screened for inclusion in this study. Ten were excluded due to insufficient image quality or incomplete exams, and forty-six patients (ninety-two paired ultrasound exams) were included in the final analysis. Paired t-test analysis of pre-HD and post-HD VExUS scores revealed a mean VExUS grade change of 0.82 (p<0.001) on a VExUS scale ranging from 0 to 4. The mean difference in B-line score following HD was 0.8 (p=0.001). There was no statistically significant difference in subjective dyspnea score (p=0.41). Conclusions: Large-volume fluid removal with HD was represented by changes in VExUS score, highlighting the utility of the VExUS exam to capture dynamic shifts in intravascular volume status. Future studies should evaluate change in VExUS grade with intravenous fluid or diuretic administration, with the ultimate goal of evaluating the capacity of a standardized bedside ultrasound protocol to guide inpatient volume optimization.

Documentation of impaired epidermal barrier in mild and moderate diaper dermatitis in vivo using noninvasive methods.

The presence of irritants from feces and urine with the concurrent mechanical friction and occlusion creates an environment in the diapered area that renders the skin prone to diaper dermatitis. Besides being a source of discomfort to the infant, these skin irritations pose a risk of secondary infections. In this study, we used noninvasive in vivo techniques to define measurable parameters that correlate with diaper dermatitis pathophysiology. In 35 infants (16 with mild or moderate and 19 without diaper dermatitis) we compared skin of diapered areas afflicted with diaper dermatitis to lesion-free diapered sites and to skin outside the diapered area (thigh). Our findings show significantly elevated cutaneous erythema, pH, and hydration, with significantly compromised water barrier function in involved areas compared to nonlesional sites both within and outside the diapered area. Furthermore, skin pH in nonlesional diapered skin for the diaper dermatitis cohort was significantly higher compared to the nondiapered sites. These observations are consistent with the current understanding of pathological skin changes in diaper dermatitis. In this study, we demonstrate that noninvasive methods can document relevant parameters to diaper dermatitis in vivo.

Binge eating and emotional eating behaviors among adolescents and young adults with bipolar disorder.

BACKGROUND: This study investigates nutritional behavior among adolescents and young adults with bipolar disorder (BP) in comparison to those without history of major psychiatric disorder. METHODS: 131 participants (82 BP, 49 controls) with a mean age of 16.11 ± 1.61 years were included. The self-reported Quick Weight, Activity, Variety & Excess (WAVE) Screener was used to assess dietary habits, yielding a total nutritional score as well as Excess, Variety, and Household Food Insecurity subscale scores. Specifically, the Variety subscale was used to measure daily consumption of essential nutrients; the Excess subscale measured unhealthy eating behaviors such as binge eating and excessive intake of fat and sugar; and the Household Food Insecurity subscale was used to detect food insecurity. Within-group analysis was conducted on participants with BP to identify correlates of unhealthy diet. RESULTS: BP participants scored significantly lower than controls on the WAVE (t=2.62, p=0.010), specifically the Excess subscale (t=3.26, p=0.001). This was related to higher prevalence of binge eating and emotional eating behaviors among participants with BP compared to controls. Within-group analyses showed that self-reported emotional dysregulation/impulsivity was associated with maladaptive nutritional behaviors (t=3.38, p=0.035). LIMITATIONS: Cross-sectional design. Within-group analyses were underpowered. Diet quality was measured using a brief self-report screener. CONCLUSION: Adolescents and young adults with BP have poorer nutritional behaviors compared to controls, and this difference is related to stress-induced eating. This demonstrates the need to screen for stress-induced eating and to intervene when needed in order to optimize nutritional behaviors among adolescents and young adults with BP.

Using novel in vitro NociOcular assay based on TRPV1 channel activation for prediction of eye sting potential of baby shampoos.

The transient receptor potential vanilloid type 1 (TRPV1) channel is one of the most well-characterized pain-inducing receptors. The purpose of this study was to predict human eye stinging of 19 baby bath and shampoo formulations by studying TRPV1 activity, as measured by increase in intracellular free Ca(2+). The NociOcular test, a novel recombinant neuronal in vitro model with high expression of functional TRPV1 channels, was used to test formulations containing a variety of surfactants, preservatives, and fragrances. TRPV1-specific Ca(2+) influx was abolished when the TRPV1 channel antagonist capsazepine was applied to the cells prior to shampoo samples. The positive control, an adult shampoo that contains cocamide monoethanolamine (CMEA), a known stinging ingredient, was the most active sample tested in the NociOcular test. The negative control, a marketed baby shampoo, was negative in the NociOcular and human tests. Seven of the formulations induced stinging in the human test, and of those six were positive in the NociOcular test. Twelve formulations were classified as nonstinging in the human test, and of those ten were negative in the NociOcular test. There was no correlation between the clinical stinging results for the baby formulations and the data generated from other in vitro eye irritation assays (cytosensor microphysiometer, neutral red uptake, EpiOcular, transepithelial permeability). Our data support that the TRPV1 channel is a principal mediator of eye-stinging sensation induced by baby bath and shampoo formulations and that the NociOcular test may be a valuable in vitro tool to predict human eye-stinging sensation.

Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression.

The skin is under continual assault from a variety of damaging environmental factors such as ultraviolet irradiation and atmospheric pollutants, and as organisms age the cumulative damage exceeds the capacity of endogenous antioxidant defenses resulting in chronic inflammation and premature aging. Botanical extracts such as Feverfew containing naturally occurring antioxidants could replenish the depleted cutaneous stores and perhaps forestall these degenerative changes. A parthenolide-depleted extract of Feverfew (PD-Feverfew), which was free of sensitization potential, was found to possess free radical scavenging activity against a wide range of reactive oxygen species and with greater activity than Vitamin C. In vitro, PD-Feverfew restored cigarette smoke-mediated depletion of cellular thiols, attenuated the formation of UV-induced hydrogen peroxide and reduced pro-inflammatory cytokine release. In vivo, topical PD-Feverfew reduced UV-induced epidermal hyperplasia, DNA damage and apoptosis. In a clinical study PD-Feverfew treatment significantly reduced erythema versus placebo 24 h post-UV exposure. Through the ability to scavenge free radicals, preserve endogenous antioxidant levels, reduce DNA damage and induce DNA repair enzymes, which can help repair damaged DNA, parthenolide-depleted extract of Feverfew may protect skin from the numerous external aggressions encountered daily by the skin and reduce the damage to oxidatively challenged skin.