Using impedance planimetry to define the end of a peroral endoscopic myotomy.

INTRODUCTION: Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic option for management of achalasia. Adequate distal myotomy is necessary for relief of symptoms, but when too long may also increase risk of reflux. The objective of this study is to evaluate clinical outcomes after POEM and final length of gastric myotomy using impedance planimetry (EndoFLIP). METHODS: A retrospective review of 34 consecutive patients undergoing POEM with EndoFLIP were included. EndoFLIP measurements, including esophagogastric junction distensibility index (DI), minimum diameter (Dmin), and cross-sectional area (CSA) were recorded at 30- and 40-mL balloon-fill pre- and post- myotomy. The myotomy was considered complete when DI ≥ 3.4 mm2/mmHg. Postoperative Eckardt score (ES) was determined at initial postoperative visit and most recent follow-up. Linear and logistic regression were used to evaluate the association between gastric myotomy length and post-myotomy EndoFLIP measurements on postoperative ES and GERD. Wilcoxon rank-sum test was used to compare gastric myotomy lengths and EndoFLIP parameters in relation to clinical success and development of GERD, and paired t-test to compare EndoFLIP measurements and ES pre- and post-myotomy. RESULTS: Final length of gastric myotomy measured 1 cm in 1 (2.9%), 1.5 cm in 11 (32.4%), 2.0 cm in 19 (55.9%), and 2.5 cm in 3 (8.8%) patients. Mean preoperative ES was 6.6 ± 2.2. All patients achieved ES < 3 postoperatively, which was maintained in 88.5% of patients at a median of 7.5 months of follow-up. Gastric myotomy length and post-myotomy EndoFLIP values were not associated with postoperative Eckardt scores or GERD. DISCUSSION: Early and late symptom relief was achieved in 100 and 88.5% of patients, respectively, at a gastric myotomy length of 1-2.5 cm. Using EndoFLIP to define a completed myotomy at DI of 3.4 mm2/mmHg yielded variable lengths of gastric myotomy.

Outcomes of light and midweight synthetic mesh use in clean-contaminated and contaminated ventral incisional hernia repair: an ACHQC comparative analysis.

BACKGROUND: Use of macroporous synthetic mesh in contaminated ventral hernia repair has become more frequent. The objective of this study is to compare the outcomes of ventral incisional hernia repair with permanent synthetic mesh in contaminated fields to those in a clean field. METHODS: The Abdominal Core Health Quality Collaborative registry, a prospectively updated longitudinal hernia-specific national database, was retrospectively queried for adults who underwent open ventral incisional hernia repair using light or medium-weight synthetic mesh and classified as clean (CDC Class I) or contaminated (CDC Class II/III). Univariate analysis was used to compare demographic information, hernia characteristics, and operative details. Odds ratios (OR) were calculated using multivariable logistic regression for the primary outcome of 30-day surgical site infection (SSI) and secondary outcomes of 30-day surgical site occurrence (SSO), SSO requiring procedural intervention (SSO-PI), and clinical recurrence at one year. RESULTS: 7219 cases met criteria for inclusion; 13.2% of these were contaminated. 83.4% of patients had follow-up data at 30 days and 20.8% at 1 year. The adjusted OR for 30-day SSI in contaminated fields compared to clean was 2.603 (95% CI 1.959-3.459). OR for 30-day SSO was 1.275 (95% CI 1.017-1.600) and 2.355 (95%CI 1.817-3.053) for 30-day SSO-PI. OR for recurrence at one year was 1.489 (95%CI 0.892-2.487). Contaminated cases had higher rates of mesh infection (3.9% vs 0.8%, p < 0.001) and mesh removal (7.3 vs 2.5%, p < 0.001) at 1 year. CONCLUSIONS: After adjusting for baseline differences, patients undergoing ventral incisional hernia repair using light or midweight synthetic mesh in contaminated fields have higher odds of 30-day SSI, SSO, and SSO-PI than those performed in clean wounds. The odds of recurrence did not statistically differ and further studies with long-term outcomes are needed to better evaluate the best treatment options for this patient population.

Evaluation of common clinical and hemodynamic parameters to pulmonary capillary wedge pressures in patients undergoing right heart catheterization.

Introduction: A cornerstone of heart failure assessment is the right heart catheterization and the pulmonary capillary wedge pressure measurement it can provide. Clinical and hemodynamic parameters such as weight and jugular venous distention are less invasive measures often used to diagnose, manage, and treat these patients. To date, there is little data looking at the association of these key parameters to measured pulmonary capillary wedge pressure (PCWP). This is a large, retrospective, secondary analysis of a right heart catheterization database comparing clinical and hemodynamic parameters against measured PCWP in heart failure patients. Methods: A total of 538 subjects were included in this secondary analysis. Spearman's Rho analysis of each clinical and hemodynamic variable was used to compare their association to the documented PCWP. Variables analyzed included weight, body mass index (BMI), jugular venous distention (JVD), creatinine, edema grade, right atrial pressure (RAP), pulmonary artery systolic pressure (PASP), systemic vascular resistance, pulmonary vascular resistance, cardiac output (thermal and Fick), systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, oxygen saturation (SpO2), and pulmonary artery diastolic pressure (PADP). Results: Ten out of 17 selected parameters had a statistically significant association with measured PCWP values. PADP had the strongest association (0.73, p<0.0001), followed by RAP and PASP (0.69, p<0.0001 and 0.67, p<0.0001, respectively). Other significant parameters included weight (0.2, p<0.001), BMI (0.2, p<0.001), SpO2 (-0.17, p<0.0091), JVD (0.24, p<0.005) and edema grade (0.2, p<0.0001). Conclusion: This retrospective analysis clarifies the associations of commonly used clinical and hemodynamic parameters to the clinically used gold standard for volume assessment in heart failure patients, PCWP.

Evaluation of Treatment Differences Between Men and Women Undergoing Ventral Hernia Repair: An Analysis of the Abdominal Core Health Quality Collaborative.

BACKGROUND: Sex is emerging as an important clinical variable associated with surgical outcomes and decision making. However, its relevance in regard to baseline and treatment differences in primary and incisional ventral hernia repair remains unclear. STUDY DESIGN: This is a retrospective cohort study using the Abdominal Core Health Quality Collaborative database to identify elective umbilical, epigastric, or incisional hernia repairs. Propensity matching was performed to investigate confounder-adjusted treatment differences between men and women. Treatments of interest included surgical approach (minimally invasive or open), mesh use, mesh type, mesh position, anesthesia type, myofascial release, fascial closure, and fixation use. RESULTS: A total of 8,489 umbilical, 1,801 epigastric, and 16,626 incisional hernia repairs were identified. Women undergoing primary ventral hernia repair were younger (umbilical 46.4 vs 54 years, epigastric 48.7 vs 52.7 years), with lower BMI (umbilical 30.4 vs 31.5, epigastric 29.2 vs 31.1), and less likely diabetic (umbilical 9.9% vs 11.4%, epigastric 6.8% vs 8.8%). Women undergoing incisional hernia repair were also younger (mean 57.5 vs 59.1 years), but with higher BMI (33.1 vs 31.5), and more likely diabetic (21.4% vs 19.1%). Propensity-matched analysis included 3,644 umbilical, 1,232 epigastric, and 12,480 incisional hernias. Women with incisional hernia were less likely to undergo an open repair (60.2% vs 63.4%, p < 0.001) and have mesh used (93.8% vs 94.8%, p = 0.02). In umbilical and incisional hernia repairs, women had higher rates of intraperitoneal mesh placement and men had higher rates of preperitoneal and retro-muscular mesh placement. CONCLUSIONS: Small but statistically significant treatment differences in operative approach, mesh use, and mesh position exist between men and women undergoing ventral hernia repair. It remains unknown whether these treatment differences result in differing clinical outcomes.

Comparison of clinical symptoms and bioimpedance to pulmonary capillary wedge pressure in heart failure.

Introduction: Clinical symptoms of heart failure commonly include fatigue, edema, and shortness of breath. Unfortunately, clinical monitoring has proven unreliable in predicting congestion and the need for hospitalization. Biosensing wearables have been developed as a potential adjunct to clinical signs and symptoms to detect congestion before it becomes severe thus preventing a heart failure hospitalization. Hypothesis: Clinical signs and symptoms of heart failure will correlate with thoracic bioimpedance measurements (ZOE®) and pulmonary capillary wedge pressure (PCWP). Methods: One hundred and fifty-five subjects undergoing right heart catheterization (RHC) were prospectively enrolled. A Zo value (ohms) was obtained, jugular venous pressure (JVP) was estimated, edema graded, and shortness of breath (SOB) assessed in all subjects. RHC was performed by a scheduled cardiologist per routine. One-way ANOVA was performed to assess the relationship between variables. A Pearson correlation coefficient was used to compare the Zo value and PCWP. Results: Neither estimated JVP (cmH2O) (p = 0.65, n = 110) nor edema scores (p = 0.12, n = 110) demonstrated a significant relationship to PCWP. The presence of subjective SOB also did not demonstrate a significant association with PCWP (p = 0.99, n = 110). There was no correlation between ZOE® and PCWP (r = -0.08, p = 0.56, n = 56). Conclusions: These findings support the idea that traditional measures for monitoring heart failure patients are limited.

Noninvasive Venous Waveform Analysis Correlates With Pulmonary Capillary Wedge Pressure and Predicts 30-Day Admission in Patients With Heart Failure Undergoing Right Heart Catheterization.

BACKGROUND: Heart failure is the leading cause of hospitalization in the elderly and readmission is common. Clinical indicators of congestion may not precede acute congestion with enough time to prevent hospital admission for heart failure. Thus, there is a large and unmet need for accurate, noninvasive assessment of congestion. Noninvasive venous waveform analysis in heart failure (NIVAHF) is a novel, noninvasive technology that monitors intravascular volume status and hemodynamic congestion. The objective of this study was to determine the correlation of NIVAHF with pulmonary capillary wedge pressure (PCWP) and the ability of NIVAHF to predict 30-day admission after right heart catheterization. METHODS AND RESULTS: The prototype NIVAHF device was compared with the PCWP in 106 patients undergoing right heart catheterization. The NIVAHF algorithm was developed and trained to estimate the PCWP. NIVA scores and central hemodynamic parameters (PCWP, pulmonary artery diastolic pressure, and cardiac output) were evaluated in 84 patients undergoing outpatient right heart catheterization. Receiver operating characteristic curves were used to determine whether a NIVA score predicted 30-day hospital admission. The NIVA score demonstrated a positive correlation with PCWP (r = 0.92, n = 106, P < .0001). The NIVA score at the time of hospital discharge predicted 30-day admission with an AUC of 0.84, a NIVA score of more than 18 predicted admission with a sensitivity of 91% and specificity of 56%. Residual analysis suggested that no single patient demographic confounded the predictive accuracy of the NIVA score. CONCLUSIONS: The NIVAHF score is a noninvasive monitoring technology that is designed to provide an estimate of PCWP. A NIVA score of more than 18 indicated an increased risk for 30-day hospital admission. This noninvasive measurement has the potential for guiding decongestive therapy and the prevention of hospital admission in patients with heart failure.

Therapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch.

Vascular procedures, such as stenting, angioplasty, and bypass grafting, often fail due to intimal hyperplasia (IH), wherein contractile vascular smooth muscle cells (VSMCs) dedifferentiate to synthetic VSMCs, which are highly proliferative, migratory, and fibrotic. Previous studies suggest MAPK-activated protein kinase 2 (MK2) inhibition may limit VSMC proliferation and IH, although the molecular mechanism underlying the observation remains unclear. We demonstrated here that MK2 inhibition blocked the molecular program of contractile to synthetic dedifferentiation and mitigated IH development. Molecular markers of the VSMC contractile phenotype were sustained over time in culture in rat primary VSMCs treated with potent, long-lasting MK2 inhibitory peptide nanopolyplexes (MK2i-NPs), a result supported in human saphenous vein specimens cultured ex vivo. RNA-Seq of MK2i-NP-treated primary human VSMCs revealed programmatic switching toward a contractile VSMC gene expression profile, increasing expression of antiinflammatory and contractile-associated genes while lowering expression of proinflammatory, promigratory, and synthetic phenotype-associated genes. Finally, these results were confirmed using an in vivo rabbit vein graft model where brief, intraoperative treatment with MK2i-NPs decreased IH and synthetic phenotype markers while preserving contractile proteins. These results support further development of MK2i-NPs as a therapy for blocking VSMC phenotype switch and IH associated with cardiovascular procedures.

Hemodynamic Parameters in the Assessment of Fluid Status in a Porcine Hemorrhage and Resuscitation Model.

BACKGROUND: Measuring fluid status during intraoperative hemorrhage is challenging, but detection and quantification of fluid overload is far more difficult. Using a porcine model of hemorrhage and over-resuscitation, it is hypothesized that centrally obtained hemodynamic parameters will predict volume status more accurately than peripherally obtained vital signs. METHODS: Eight anesthetized female pigs were hemorrhaged at 30 ml/min to a blood loss of 400 ml. After each 100 ml of hemorrhage, vital signs (heart rate, systolic blood pressure, mean arterial pressure, diastolic blood pressure, pulse pressure, pulse pressure variation) and centrally obtained hemodynamic parameters (mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output) were obtained. Blood volume was restored, and the pigs were over-resuscitated with 2,500 ml of crystalloid, collecting parameters after each 500-ml bolus. Hemorrhage and resuscitation phases were analyzed separately to determine differences among parameters over the range of volume. Conformity of parameters during hemorrhage or over-resuscitation was assessed. RESULTS: During the course of hemorrhage, changes from baseline euvolemia were observed in vital signs (systolic blood pressure, diastolic blood pressure, and mean arterial pressure) after 100 ml of blood loss. Central hemodynamic parameters (mean pulmonary artery pressure and pulmonary capillary wedge pressure) were changed after 200 ml of blood loss, and central venous pressure after 300 ml of blood loss. During the course of resuscitative volume overload, changes were observed from baseline euvolemia in mean pulmonary artery pressure and central venous pressure after 500-ml resuscitation, in pulmonary capillary wedge pressure after 1,000-ml resuscitation, and cardiac output after 2,500-ml resuscitation. In contrast to hemorrhage, vital sign parameters did not change during over-resuscitation. The strongest linear correlation was observed with pulmonary capillary wedge pressure in both hemorrhage (r2 = 0.99) and volume overload (r2 = 0.98). CONCLUSIONS: Pulmonary capillary wedge pressure is the most accurate parameter to track both hemorrhage and over-resuscitation, demonstrating the unmet clinical need for a less invasive pulmonary capillary wedge pressure equivalent.

Physiology and clinical utility of the peripheral venous waveform.

The peripheral venous system serves as a volume reservoir due to its high compliance and can yield information on intravascular volume status. Peripheral venous waveforms can be captured by direct transduction through a peripheral catheter, non-invasive piezoelectric transduction, or gleaned from other waveforms such as the plethysmograph. Older analysis techniques relied upon pressure waveforms such as peripheral venous pressure and central venous pressure as a means of evaluating fluid responsiveness. Newer peripheral venous waveform analysis techniques exist in both the time and frequency domains, and have been applied to various clinical scenarios including hypovolemia (i.e. hemorrhage, dehydration) and volume overload.

A brief report on the effects of vasoactive agents on peripheral venous waveforms in a porcine model.

OBJECTIVES: Non-invasive venous waveform analysis (NIVA) is a recently described, novel technique to assess intravascular volume status. Waveforms are captured with a piezoelectric sensor; analysis in the frequency domain allows for calculation of a "NIVA value" that represents volume status. The aim of this report was to determine the effects of vasoactive agents on the venous waveform and calculated NIVA values. DESIGN: Porcine experimental model. SETTING: Operating theatre. PARTICIPANTS: A piezoelectric sensor was secured over the surgically exposed saphenous vein in eight anesthetized pigs. MAIN OUTCOME MEASURES: NIVA value, pulmonary capillary wedge pressure (PCWP), and mean arterial pressure prior to and post intravenous administration of 150-180 µg of phenylephrine or 100 µg of sodium nitroprusside. RESULTS: Phenylephrine led to a decrease in NIVA value (mean 9.2 vs. 4.6, p < 0.05), while sodium nitroprusside led to an increase in NIVA value (mean 9.5 vs. 11.9, p < 0.05). Mean arterial pressure increased after phenylephrine (p < 0.05) and decreased after sodium nitroprusside (p < 0.05). PCWP did not change significantly after phenylephrine (p = 0.25) or sodium nitroprusside (p = 0.06). CONCLUSIONS: Vasoactive agents lead to changes in non-invasively obtained venous waveforms in euvolemic pigs, highlighting a potential limitation in the ability to NIVA to estimate static volume in this setting. Further studies are indicated to understand the effects of vasoactive agents in the setting of hypovolemia and hypervolemia.

Non-Invasive Venous waveform Analysis (NIVA) for volume assessment during complex cranial vault reconstruction: A proof-of-concept study in children.

BACKGROUND: Non-Invasive Venous waveform Analysis (NIVA) is novel technology that captures and analyzes changes in venous waveforms from a piezoelectric sensor on the wrist for hemodynamic volume assessment. Complex cranial vault reconstruction is performed in children with craniosynostosis and is associated with extensive blood loss, potential life-threatening risks, and significant morbidity. In this preliminary study, we hypothesized that NIVA will provide a reliable, non-invasive, quantitative assessment of intravascular volume changes in children undergoing complex cranial vault reconstruction. OBJECTIVE: To present proof-of-concept results of a novel technology in the pediatric population. METHODS: The NIVA prototype was placed on each subject's wrist, and venous waveforms were collected intraoperatively. Estimated blood loss and fluid/blood product administration were recorded in real time. Venous waveforms were analyzed into a NIVA value and then correlated, along with mean arterial pressure (MAP), to volume changes. Concordance was quantified to determine if the direction of change in volume was similar to the direction of change in MAP or change in NIVA. RESULTS: Of 18 patients enrolled, 14 had usable venous waveforms, and there was a significant correlation between change in NIVA value and change in volume. Change in MAP did not correlate with change in volume. The concordance between change in MAP and change in volume was less than the concordance between change in NIVA and change in volume. CONCLUSION: NIVA values correlate more closely to intravascular volume changes in pediatric craniofacial patients than MAP. This initial study suggests that NIVA is a potential safe, reliable, non-invasive quantitative method of measuring intravascular volume changes for children undergoing surgery.

Primary Tumor Resection Offers Survival Benefit in Patients with Metastatic Midgut Neuroendocrine Tumors.

BACKGROUND: Approximately 35% of patients with midgut neuroendocrine tumors (MNET) present with distant metastases. Although successful resection of these metastatic foci improves overall survival (OS), the role of primary tumor resection (PTR) in patients with unresectable metastatic disease is unclear. The aim of this study is to evaluate prevalence and survival impact of PTR in patients with unresectable metastatic MNET. PATIENTS AND METHODS: A retrospective cohort study of patients with metastatic MNET was performed using the National Cancer Database (2004-2014). Demographic and clinicopathologic variables were compared between patients who did and did not undergo PTR. Survival analysis was performed using Kaplan-Meier and log-rank tests. Multivariable regression analysis was used to assess factors associated with PTR and all-cause mortality. RESULTS: The cohort included 4076 patients; 2520 (61.8%) underwent PTR. Patients more likely to undergo PTR were younger and diagnosed earlier, underwent treatment at a nonacademic facility, lived on the West Coast or in the Central USA, and presented with smaller lower-grade small bowel primary tumors. Median OS was improved for patients who underwent PTR compared with those who did not (71 vs. 29 months, p < 0.001). On multivariable analysis, younger age, Black race, higher income, later year of diagnosis, treatment at an academic facility, private insurance, fewer comorbidities, small bowel primary, lower grade, and PTR (hazard ratio 0.63, 95% confidence interval 0.51-0.78, p < 0.001) were associated with lower mortality. CONCLUSIONS: PTR was associated with improved OS. Further study is needed to understand how clinicians select patients for PTR.

Non-invasive venous waveform analysis (NIVA) for volume assessment in patients undergoing hemodialysis: an observational study.

BACKGROUND: Accurate assessment of volume status to direct dialysis remains a clinical challenge. Despite current attempts at volume-directed dialysis, inadequate dialysis and intradialytic hypotension (IDH) are common occurrences. Peripheral venous waveform analysis has recently been developed as a method to accurately determine intravascular volume status through algorithmic quantification of changes in the waveform that occur at different volume states. A noninvasive method to capture peripheral venous signals is described (Non-Invasive Venous waveform Analysis, NIVA). The objective of this proof-of-concept study was to characterize changes in NIVA signal with dialysis. We hypothesized that there would be a change in signal after dialysis and that the rate of intradialytic change in signal would be predictive of IDH. METHODS: Fifty subjects undergoing inpatient hemodialysis were enrolled. A 10-mm piezoelectric sensor was secured to the middle volar aspect of the wrist on the extremity opposite to the access site. Signals were obtained fifteen minutes before, throughout, and up to fifteen minutes after hemodialysis. Waveforms were analyzed after a fast Fourier transformation and identification of the frequencies corresponding to the cardiac rate, with a NIVA value generated based on the weighted powers of these frequencies. RESULTS: Adequate quality (signal to noise ratio > 20) signals pre- and post- dialysis were obtained in 38 patients (76%). NIVA values were significantly lower at the end of dialysis compared to pre-dialysis levels (1.203 vs 0.868, p < 0.05, n = 38). Only 16 patients had adequate signals for analysis throughout dialysis, but in this small cohort the rate of change in NIVA value was predictive of IDH with a sensitivity of 80% and specificity of 100%. CONCLUSIONS: This observational, proof-of-concept study using a NIVA prototype device suggests that NIVA represents a novel and non-invasive technique that with further development and improvements in signal quality may provide static and continuous measures of volume status to assist with volume directed dialysis and prevent intradialytic hypotension.

A cell permeant phosphopeptide mimetic of Niban inhibits p38 MAPK and restores endothelial function after injury.

Vascular injury leads to membrane disruption, ATP release, and endothelial dysfunction. Increases in the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and decreases in the phosphorylation of Niban, a protein implicated in ER stress and apoptosis, are associated with vascular injury. A cell permeant phosphopeptide mimetic of Niban (NiPp) was generated. The effects of NiPp in restoring endothelial function were determined ex vivo using intact rat aortic tissue (RA) after pharmacological activation of p38 MAPK and also in multiple clinically relevant injury models. Anisomycin (Aniso) increased p38 MAPK phosphorylation and reduced endothelial-dependent relaxation in RA. Treatment with NiPp prevented Ansio-induced reduction in endothelial function and increases in p38 MAPK phosphorylation. NiPp treatment also restored endothelial function after stretch injury (subfailure stretch), treatment with acidic Normal Saline (NS), and P2X7R activation with 2'(3')-O-(4-Benzoylbenzoyl)adenosine 5'-triphosphate (BzATP). Aged, diseased, human saphenous vein (HSV) remnants obtained from patients undergoing coronary bypass surgical procedures have impaired endothelial function. Treatment of these HSV segments with NiPp improved endothelial-dependent relaxation. Kinome screening experiments indicated that NiPp inhibits p38 MAPK. These data demonstrate that p38 MAPK and Niban signaling have a role in endothelial function, particularly in response to injury. Niban may represent an endogenous regulator of p38 MAPK activation. The NiPp peptide may serve as an experimental tool to further elucidate p38 MAPK regulation and as a potential therapeutic for endothelial dysfunction.

Observational Study of Noninvasive Venous Waveform Analysis to Assess Intracardiac Filling Pressures During Right Heart Catheterization.

BACKGROUND: Outpatient monitoring and management of patients with heart failure (HF) reduces hospitalizations and health care costs. However, the availability of noninvasive approaches to assess congestion is limited. Noninvasive venous waveform analysis (NIVA) uses a unique physiologic signal, the morphology of the venous waveform, to assess intracardiac filling pressures. This study is a proof of concept analysis of the correlation between NIVA value and pulmonary capillary wedge pressure (PCWP) and the ability of the NIVA value to predict PCWP > 18 mmHg in subjects undergoing elective right heart catheterization (RHC). PCWP was also compared across common clinical correlates of congestion. METHODS AND RESULTS: A prototype NIVA device, which consists of a piezoelectric sensor placed over the skin on the volar aspect of the wrist, connected to a data-capture control box, was used to collect venous waveforms in 96 patients during RHC. PCWP was collected at end-expiration by an experienced cardiologist. The venous waveform signal was transformed to the frequency domain (Fourier transform), where a ratiometric algorithm of the frequencies of the pulse rate and its harmonics was used to derive a NIVA value. NIVA values were successfully captured in 83 of 96 enrolled patients. PCWP ranged from 4-40 mmHg with a median of 13 mmHg. NIVA values demonstrated a linear correlation with PCWP (r = 0.69, P < 0.05). CONCLUSIONS: This observational proof-of-concept study using a prototype NIVA device demonstrates a moderate correlation between NIVA value and PCWP in patients undergoing RHC. NIVA, thus, represents a promising developing technology for noninvasive assessment of congestion in spontaneously breathing patients.

Non-Invasive Venous waveform Analysis (NIVA) for monitoring blood loss in human blood donors and validation in a porcine hemorrhage model.

STUDY OBJECTIVE: There is an unmet need for a non-invasive approach to diagnose hemorrhage early, before changes in vital signs occur. Non-Invasive Venous waveform Analysis (NIVA) uses a unique physiological signal (the peripheral venous waveform) to assess intravascular volume. We hypothesized changes in the venous waveform would be observed with blood loss in healthy adult blood donors and characterized hemorrhage using invasive monitoring in a porcine model. DESIGN: Prospective observational study. SETTING: American Red Cross donation center. PATIENTS: 50 human blood donors and 12 non-donating controls; 7 Yorkshire pigs. INTERVENTIONS: A venous waveform capturing prototype (NIVA device) was secured to the volar aspect of the wrist in human subjects. A central venous catheter was used to obtain hemodynamic indices and venous waveforms were obtained using the prototype NIVA device over the saphenous vein during 400 mL of graded hemorrhage in a porcine model. MEASUREMENTS: Venous waveforms were transformed from the time to the frequency domain. The ratiometric power contributions of the cardiac frequencies were used to calculate a NIVA value representative of volume status. MAIN RESULTS: A significant decrease in NIVA value was observed after 500 mL of whole blood donation (p < .05). A ROC curve for the ability of the NIVA to detect 500 mL of blood loss demonstrated an area under the curve (AUC) of 0.94. In the porcine model, change in NIVA value correlated linearly with blood loss and with changes in hemodynamic indices. CONCLUSIONS: This study provides proof-of-concept for a potential application of NIVA in detection of blood loss. NIVA represents a novel physiologic signal for detection of early blood loss that may be useful in early triage and perioperative management.

The Role of Vitamin A in Wound Healing.

Vitamin A is an essential micronutrient that comes in multiple forms, including retinols, retinals, and retinoic acids. Dietary vitamin A is absorbed as retinol from preformed retinoids or as pro-vitamin A carotenoids that are converted into retinol in the enterocyte. These are then delivered to the liver for storage via chylomicrons and later released into the circulation and to its biologically active tissues bound to retinol-binding protein. Vitamin A is a crucial component of many important and diverse biological functions, including reproduction, embryological development, cellular differentiation, growth, immunity, and vision. Vitamin A functions mostly through nuclear retinoic acid receptors, retinoid X receptors, and peroxisome proliferator-activated receptors. Retinoids regulate the growth and differentiation of many cell types within skin, and its deficiency leads to abnormal epithelial keratinization. In wounded tissue, vitamin A stimulates epidermal turnover, increases the rate of re-epithelialization, and restores epithelial structure. Retinoids have the unique ability to reverse the inhibitory effects of anti-inflammatory steroids on wound healing. In addition to its role in the inflammatory phase of wound healing, retinoic acid has been demonstrated to enhance production of extracellular matrix components such as collagen type I and fibronectin, increase proliferation of keratinocytes and fibroblasts, and decrease levels of degrading matrix metalloproteinases.

Normal Saline solutions cause endothelial dysfunction through loss of membrane integrity, ATP release, and inflammatory responses mediated by P2X7R/p38 MAPK/MK2 signaling pathways.

Resuscitation with 0.9% Normal Saline (NS), a non-buffered acidic solution, leads to increased morbidity and mortality in the critically ill. The goal of this study was to determine the molecular mechanisms of endothelial injury after exposure to NS. The hypothesis of this investigation is that exposure of endothelium to NS would lead to loss of cell membrane integrity, resulting in release of ATP, activation of the purinergic receptor (P2X7R), and subsequent activation of stress activated signaling pathways and inflammation. Human saphenous vein endothelial cells (HSVEC) incubated in NS, but not buffered electrolyte solution (Plasma-Lyte, PL), exhibited abnormal morphology and increased release of lactate dehydrogenase (LDH), adenosine triphosphate (ATP), and decreased transendothelial resistance (TEER), suggesting loss of membrane integrity. Incubation of intact rat aorta (RA) or human saphenous vein in NS but not PL led to impaired endothelial-dependent relaxation which was ameliorated by apyrase (hydrolyzes ATP) or SB203580 (p38 MAPK inhibitor). Exposure of HSVEC to NS but not PL led to activation of p38 MAPK and its downstream substrate, MAPKAP kinase 2 (MK2). Treatment of HSVEC with exogenous ATP led to interleukin 1ß (IL-1ß) release and increased vascular cell adhesion molecule (VCAM) expression. Treatment of RA with IL-1ß led to impaired endothelial relaxation. IL-1ß treatment of HSVEC led to increases in p38 MAPK and MK2 phosphorylation, and increased levels of arginase II. Incubation of porcine saphenous vein (PSV) in PL with pH adjusted to 6.0 or less also led to impaired endothelial function, suggesting that the acidic nature of NS is what contributes to endothelial dysfunction. Volume overload resuscitation in a porcine model after hemorrhage with NS, but not PL, led to acidosis and impaired endothelial function. These data suggest that endothelial dysfunction caused by exposure to acidic, non-buffered NS is associated with loss of membrane integrity, release of ATP, and is modulated by P2X7R-mediated inflammatory responses.