Diosmin and its glycocalyx restorative and anti-inflammatory effects on injured blood vessels.

The endothelium, a crucial homeostatic organ, regulates vascular permeability and tone. Under physiological conditions, endothelial stimulation induces vasodilator endothelial nitric oxide (eNO) release and prevents adhesion molecule accessibility and leukocyte adhesion and migration into vessel walls. Endothelium dysfunction is a principal event in cardiovascular disorders, including atherosclerosis. Minimal attention is given to an important endothelial cell structure, the endothelial glycocalyx (GCX), a negatively charged heterogeneous polysaccharide that serves as a protective covering for endothelial cells and enables endothelial cells to transduce mechanical stimuli into various biological and chemical activities. Endothelial GCX shedding thus plays a role in endothelial dysfunction, for example by increasing vascular permeability and decreasing vessel tone. Consequently, there is increasing interest in developing therapies that focus on GCX repair to limit downstream endothelium dysfunction and prevent further downstream cardiovascular events. Here, we present diosmin (3',5,7-trihydroxy-4'-methoxyflavone-7-rhamnoglucoside), a flavone glycoside of diosmetin, which downregulates adhesive molecule expression, decreases inflammation and capillary permeability, and upregulates eNO expression. Due to these pleiotropic effects of diosmin on the vasculature, a possible unidentified mechanism of action is through GCX restoration. We hypothesize that diosmin positively affects GCX integrity along with GCX-related endothelial functions. Our hypothesis was tested in a partial ligation left carotid artery (LCA) mouse model, where the right carotid artery was the control for each mouse. Diosmin (50 mg/kg) was administered daily for 7 days, 72 h after ligation. Within the ligated mice LCAs, diosmin treatment elevated the activated eNO synthase level, inhibited inflammatory cell uptake, decreased vessel wall thickness, increased vessel diameter, and increased GCX coverage of the vessel wall. ELISA showed a decrease in hyaluronan concentration in plasma samples of diosmin-treated mice, signifying reduced GCX shedding. In summary, diosmin supported endothelial GCX integrity, to which we attribute diosmin's preservation of endothelial function as indicated by attenuated expression of inflammatory factors and restored vascular tone.

Fluorescent Imaging as a Component of Diagnosing Pyoderma Gangrenosum: A Case Report.

ABSTRACT: A 64-year-old White woman was admitted to the hospital with complaint of progressive right hip ulceration at the wound site following a total right hip arthroplasty. Initial history and physical examination gave a leading differential diagnosis of pyoderma gangrenosum. Until recently, the exclusion of infection for pyoderma gangrenosum has been largely clinical and supported by cultures/biopsies demonstrating the absence of infection. The MolecuLight i:X (MolecuLight, Toronto, Ontario, Canada) is a novel bedside fluorescent imaging device capable of determining the bacterial burden within a wound in real time. Fluorescent imaging excluded infection at the initial visit, and debridement was avoided. Subsequently, pathergy was avoided as well. The patient was started on topical clobetasol with hypochlorous acid-soaked dressings. She also received 80 mg daily of prednisone and high-dose vitamin D3 (10,000 IU). Recovery was complicated by a deep tunnel along the incisional line at 3 months postdiagnosis, which required slowing of the prednisone taper and the addition of colchicine. Repeat cultures grew Parvimonas, Pseudomonas, and Streptococcus species. Appropriate antibiotics were given. The patient was transitioned from prednisone to adalimumab and started on negative-pressure wound therapy. Negative-pressure wound therapy was discontinued at 5 months, and the wound resolved at 6 months.

Retrospective real-world comparative effectiveness of ovine forestomach matrix and collagen/ORC in the treatment of diabetic foot ulcers.

The retrospective pragmatic real-world data (RWD) study compared the healing outcomes of diabetic foot ulcers (DFUs) treated with either ovine forestomach matrix (OFM) (n = 1150) or collagen/oxidised regenerated cellulose (ORC) (n = 1072) in out-patient wound care centres. Median time to wound closure was significantly (P = .0015) faster in the OFM group (14.6 ± 0.5 weeks) relative to the collagen/ORC group (16.4 ± 0.7). A sub-group analysis was performed to understand the relative efficacy in DFUs requiring longer periods of treatment and showed that DFUs treated with OFM healed up to 5.3 weeks faster in these challenging wounds. The percentage of wounds closed at 36 weeks was significantly improved in OFM treated DFUs relative to the collagen/ORC. A Cox proportional hazards analysis showed OFM-treated wounds had a 18% greater probability of healing versus wounds managed with collagen/ORC, and the probability increased to 21% when the analysis was adjusted for multiple variables. This study represents the first large retrospective RWD analysis comparing OFM and collagen/ORC and supports the clinical efficacy of OFM in the treatment of DFUs.

Understanding wound care from a venous and lymphatic perspective.

The uncertainty due to COVID-19 surrounding live events has remained present and persistent. Therefore, this year, the American Vein & Lymphatic Society (AVLS) Annual Congress will be a virtual-only event that will take place on 15 October 2020. It will include a live-streamed session will complement the fundamental knowledge of providing wound care for patients. On-demand content will allow attendees to participate at their own pace, watching as much or as little as they want each day, potentially earning AMA PRA Category 1 CreditsTM.

Wound Care: Multicenter Feasibility Study.

OBJECTIVES: The aims of this study were to determine a sound recruitment strategy for multisite wound studies to address the rising prevalence and incidence of chronic wounds and to identify appropriate adult patient populations with wounds of interest and establish partnerships with their clinicians and clinical services as a model for a multisite wound care feasibility study. DESIGN: A pilot multisite recruitment feasibility study. SETTING: Three wound clinics located in a large, Midwestern metropolitan area. PARTICIPANTS AND INTERVENTION: A convenience sample of 3 staff and 3 patients with lower-extremity wounds from each clinic was interviewed. Medical records of all patients with lower-extremity wounds seen during 1 week at each clinic were reviewed. Outcome measures included characteristics of patients being treated at the 3 wound care clinics (patient demographics and wound characteristics) and wound treatments used. Barriers and opportunities that could be addressed in recruitment and other research strategies were identified. MAIN RESULTS: Barriers and facilitators for future research were identified and varied within and between clinics. Patients reported they were willing to participate in future research, although fewer were willing if the study was blinded. Patients received a variety of treatments within and across clinics. Medical record reviews provided further information about wound clinic patients, wound characteristics, and barriers and facilitators for future study. CONCLUSIONS: Characteristics of wound clinic patients and their wounds were found to vary by site, suggesting tailored recruitment methods by site within multisite wound care studies may be most productive. This study suggests successful recruitment strategies for future wound care intervention research.

Case Report: The effect of automated manual lymphatic drainage therapy on lymphatic contractility in 4 distinct cases.

Introduction: Automated manual lymphatic drainage therapy (AMLDT) is available for home use in the form of a pneumatic mat of 16 pressurized air channels that inflate and deflate to mimic the stretch and release action of manual lymphatic drainage therapy. Four cases (a patient with complex regional pain syndrome and lymphedema, a healthy patient, a breast cancer survivor with chronic pain, and a patient with a history of abdominal surgery) underwent near-infrared fluorescence lymphatic imaging (NIRFLI) with AMLDT to evaluate the effect of AMLDT on lymphatic pumping and pain. Methods: Each patient received 32-36 injections of 25 µg indocyanine green (ICG) on the anterior and posterior sides of their body and underwent 1 h of NIRFLI to assess the drainage of ICG laden lymph toward regional nodal basins at baseline. Each patient lay supine on the mat for 1 h of AMLDT with NIRFLI to assess lymphatic flow during treatment. A final NIFRFLI assessment was done 30-60 min posttreatment with the patient in the supine and prone position. Patients reported baseline and posttreatment pain using the Visual Analogue Scale. An imager analyzed NIRFLI images using ImageJ (US National Institutes of Health). Using time stamps of the first and last images to determine time lapsed and the number of pulses observed in a timeframe, pulsing frequency (pulses/min) was obtained to assess lymphatic function. Results: All 4 cases completed the NIRFLI and AMLDT without complications; all 3 patients with baseline pain reported reduced pain posttreatment. AMLDT appeared to alter lymphatic contractility, with both increased and decreased pulsing frequencies observed, including in nonaffected limbs. Pulsing frequencies were very heterogeneous among patients and varied within anatomic regions of the same patient. Discussion: This proof-of-concept study suggests that AMLDT may impact lymphatic contractility. Further research on its effect on lymphatic function is warranted.

Using noninvasive imaging to assess manual lymphatic drainage on lymphatic/venous responses in a spaceflight analog.

This retrospective case series (clinicaltrials.gov NCT06405282) used noninvasive imaging devices (NIID) to assess the effect of manual lymphatic drainage (MLD) on dermal/venous fluid distribution, perfusion, and temperature alterations of the head, neck, upper torso, and legs while in the 6-degree head-down tilt validated spaceflight analog. A lymphatic fluid scanner measured tissue dielectric constant levels. Near-infrared spectroscopy assessed perfusion, by measuring tissue oxygenation saturation. Long-wave infrared thermography measured tissue temperature gradients. Fifteen healthy, university students participated. NIID assessments were taken 1 minute after assuming the HDT position and then every 30 minutes, with MLD administered from 180 to 195 minutes. Subjects returned to the sitting position and were assessed at post-225 min NIID demonstrated significant changes from baseline (p < 0.01), although these changes at areas of interest varied. MLD had a reverse effect on all variables. NIID assessment supported the potential use of MLD to mitigate fluid shifts during a spaceflight analog.

Venous leg ulcers and prevalence of surgically correctable reflux disease in a national registry.

BACKGROUND: Chronic venous disorders are common, with varicose veins occurring in ∼40% of the population. Venous leg ulcers affect 1% to 2% of the population, with the prevalence increasing ≤4% for those aged >65 years. Both conditions are expensive and together are responsible for ≤2% of the annual healthcare budget expenditure of Western societies. The ESCHAR (effect of surgery and compression on healing and recurrence) and EVRA (early venous reflux ablation) trials demonstrated that surgical correction of superficial venous reflux reduced ulcer recurrence, resulted in faster healing times (EVRA), and was proved cost-effective. Largescale data regarding patients with chronic venous leg ulcers presenting to venous centers with treatable superficial venous insufficiency has not been previously reported. Our study was designed to evaluate the percentage of patients with leg ulcers presenting to dedicated vein centers who were found to have surgically correctable superficial venous insufficiency. METHODS: The American Vein & Lymphatic Society Patient Reported Outcome Venous Registry began collecting data in 2014 and is one of two national registries focused on chronic venous disorders. The database was queried first for the presence of an ulcer using the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification (C6 status). These de-identified data were further correlated by crossing the number of ulcers for the same limb using the revised venous clinical severity score (rVCSS). The demographics, index duplex ultrasound details, and rVCSS features for ulcer duration and compression use were analyzed. Once the presence of an ulcer had been validated by CEAP and rVCSS, the population was divided into groups according to the ultrasound-reported anatomic pathology (eg, normal, reflux, obstruction, reflux plus obstruction). The query was directed toward all patients seeking a venous evaluation at participating centers from January 2018 through January 2022. RESULTS: More than 270,000 unique patient records were reviewed. Of the 270,000 records, 163,027 (60%) had had duplex ultrasound scans available, for 1794 unique patients (1879 limbs), representing 1.1% with a leg wound. Of these patients, 55.4% were men and 44.6% were women. Group S included patients with isolated superficial pathology (n = 1291; 68.7%). Group M included patients with mixed superficial and deep pathology (n = 238; 12.7%). Group D included patients with isolated deep vein pathology (n = 58; 3.1%). Finally, group N included patients with leg wounds but no venous pathology (n = 292; 15.5%). The rVCSSs for groups S and M were significantly higher than those for group N. In group S, the dominant patterns involved the great saphenous vein (GSV) above the knee (54.8%), the small saphenous vein (30.7%), and the anterior accessory GSV (14.4%). The frequency of single, double, and triple axial vein reflux identified 1.45 vessels eligible for ablation treatment per limb. In group M, the dominant patterns involved the GSV above the knee (61.7%), the small saphenous vein (26.2%), and the anterior accessory GSV (12.1%), for 1.52 axial segments per limb. Of the 84.4% of venous ulcer patients, duplex ultrasound analysis revealed that 97% of this large subset had had surgically correctable disease. CONCLUSIONS: The American Vein & Lymphatic Society Patient Reported Outcome Venous Registry demonstrated that 85% of the leg wounds in the present study were venous in origin and 97% possessed surgically correctable disease. Our findings support early referral to dedicated vein centers with appropriate venous reflux management as a part of the multidisciplinary team caring for patients with venous leg ulcers.

Ovine Forestomach Matrix in the Surgical Management of Complex Lower-Extremity Soft-Tissue Defects.

BACKGROUND: Chronic lower-extremity defects may lead to major amputations and have severe consequences on patient quality of life and mortality. Dermal matrices have become part of the reconstructive ladder and are often deployed in these scenarios to quickly build neodermis, especially in volumetric defects over exposed bone and tendon initially, to allow for subsequent closure by means of split-thickness skin grafting (STSG) or secondary intention. Ovine forestomach matrix (OFM) is a decellularized extracellular matrix (ECM) bioscaffold available in both sheet and particulate forms that can be used as a dermal matrix in various soft-tissue reconstruction procedures. METHODS: This retrospective case series evaluated the use of OFM products in the surgical reconstruction of 50 cases (n = 50) comprised of challenging lower-extremity defects from seven healthcare centers. Patient records were reviewed to identify comorbidities, defect cause, defect size, presence of exposed structures, Centers for Disease Control and Prevention contamination score, Wagner grade, OFM graft use, time to 100% granulation tissue, STSG use, overall time to heal, and postoperative complications. The primary study outcomes were time (days) to 100% granulation tissue formation, with secondary outcomes including overall time to wound closure (weeks), STSG take at 1 week, and complications. RESULTS: The results of this case series demonstrate OFM as a clinically effective treatment in the surgical management of complex lower-extremity soft-tissue defects with exposed structures in patients with multiple comorbidities. One application of OFM products was effective in regenerating well-vascularized neodermis, often in the presence of exposed structures, with a mean time to 100% granulation of 26.0 ± 22.2 days. CONCLUSIONS: These data support the use of OFM as a safe, cost-effective, and clinically effective treatment option for coverage in complex soft-tissue wounds, including exposed vital structures, and to shorten the time to definitive wound closure in complicated patient populations.

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3-4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center's:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3-4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Albumin, oral contraceptives, and venous thromboembolism risk in astronauts.

A venous thromboembolism (VTE) event occurred in a female astronaut during long-duration spaceflight. Multiple factors may have contributed to this risk, including the use of combined (progestin + estrogen) oral contraceptives (cOC). Biochemistry data from 65 astronauts were evaluated for associations with cOC use and with sex. The female astronauts who used cOCs had lower concentrations of serum albumin and higher concentrations of transferrin, a protein involved in the clotting cascade, than the male astronauts and the female astronauts who were not taking cOCs (P < 0.001). The women who used cOCs had higher serum concentrations of the acute phase reactant ceruloplasmin and cortisol during flight (P < 0.001) than the men and the women who were not taking cOCs; they also had higher calculated whole blood viscosity than women not taking cOCs (P < 0.001). Lower circulating concentrations of albumin, higher concentrations of transferrin, and elevated markers of inflammation all could contribute to an increased risk of VTE during spaceflight. These changes, in association with a higher blood viscosity, can directly affect endothelial glycocalyx integrity and hypercoagulability status, both of which contribute to VTE risk in terrestrial populations.NEW & NOTEWORTHY We report here evidence of an association between oral contraceptive use and serum albumin, among other factors, which potentially increase the risk of venous thromboembolism in astronauts. These findings highlight potential risks to astronaut health while providing potential alternative countermeasures for decreasing VTE risk during spaceflight. These findings also highlight an underrecognized potential mechanism for hypoalbuminemia to increase VTE risk in terrestrial populations.

Adjuvant use of acoustic pressure wound therapy for treatment of chronic wounds: a retrospective analysis.

PURPOSE: Small studies have indicated that the addition of acoustic pressure wound therapy (APWT) to conventional wound care may hasten healing of chronic wounds. We evaluated our early clinical experience using APWT as an adjunct to conventional wound care. DESIGN: The study was a retrospective chart review of consecutive patients receiving APWT in addition to conventional wound care in a hospital-based, primarily outpatient setting. METHODS: Medical records of all patients treated with APWT between August 2006 and October 2007 were reviewed. Analysis included the 41 patients with 52 wounds who received APWT at least 2 times per week during the study period. Statistical comparisons were made for wound dimensions, tissue characteristics, and pain at start versus end of APWT. RESULTS: Thirty-eight percent of wounds (N = 20) healed completely with a mean 6.8 weeks of APWT. Median wound area and volume decreased significantly (88% [P < .0001] and 100% [P < .0001], respectively) from start to end of APWT. The proportion of wounds with greater than 75% granulation tissue increased from 26% (n = 12) to 80% (n = 41) (P < .0001), and normal periwound skin increased from 25% (n = 13) to 54% (n = 28) (P = .0001). Presence of greater than 50% fibrin slough decreased from 50% (n = 24) to 9% (n = 4) of wounds (P = .006). CONCLUSIONS: This early experience supplementing conventional wound care with APWT suggests it may promote healing in chronic wounds, where the ordered cellular and molecular processes leading to healing have stalled.

A multi-institutional survey of newer surgery faculty on the impacts of education debt and debt repayment strategies.

BACKGROUND: The cost associated with becoming a physician is significant, and studies have shown that surgeons, in particular, accrue higher debts than matched controls from other specialties, and the public. These findings, along with the current era of economic turmoil, prompted our investigation into the effects of educational debt on the career, family and lifestyle choices of recently graduated surgeons. Our goal was to query young surgical faculty about the education debt carried, the burden it presents as they embark on a career, and the financial management strategies employed to pay down their debt. STUDY DESIGN: This study is a one-time, cross-sectional survey of regular and adjunct faculty from the University of Minnesota and the Mayo Clinic-Rochester. Participation was voluntary and responses were collected anonymously via SurveyMonkey. Respondents were sorted into two groups: those with and without education debt at the time of residency graduation. We compared these groups on a number of variables. RESULTS: Of the 111 respondents (111/152, 73% response rate), 69 (62.2%) carried debt at the time of graduation from residency. The median educational debt at graduation was $100,000, and surgeons with educational debt carried a significantly higher burden of consumer and total debt than those without educational debt at graduation (p < 0.001). This continued after graduation with 74% (51/69) of residents with debt at graduation falling below the benchmark 36% debt-to-income ratio, and 45% (17/32) of those without debt at graduation in this same high risk financial situation. CONCLUSIONS: Educational debt places a large financial responsibility on the shoulders of most newer faculty. The debt-to-income ratio demonstrated through our results was considerable for both study groups, and unwise according to financial literature. This is of utmost importance to leaders in academe, as salaries are generally lower than private practice colleagues. This can begin in residency with explicit and practical information on surgeon reimbursement, income ranges, and revenue sources (faculty, clinical), debt repayment strategies, and overall training on financial matters early in their residency.