GPER deficiency impedes murine myocutaneous revascularization and wound healing.

Estrogens regulate numerous physiological and pathological processes, including wide-ranging effects in wound healing. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ER ß ), that typically regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), that predominantly mediates rapid "non-genomic" signaling. Estrogen modulates the expression of various genes involved in epidermal function and regeneration, inflammation, matrix production, and protease inhibition, all critical to wound healing. Our previous work demonstrated improved myocutaneous wound healing in female mice compared to male mice. In the current study, we employed male and female GPER knockout mice to investigate the role of this estrogen receptor in wound revascularization and tissue viability. Using a murine myocutaneous flap model of graded ischemia, we measured real-time flap perfusion via laser speckle perfusion imaging. We conducted histologic and immunohistochemical analyses to assess skin and muscle viability, microvascular density and vessel morphology. Our results demonstrate that GPER is crucial in wound healing, mediating effects that are both dependent and independent of sex. Lack of GPER expression is associated with increased skin necrosis, reduced flap perfusion and altered vessel morphology. These findings contribute to understanding GPER signaling in wound healing and suggest possible therapeutic opportunities by targeting GPER.

Endovascular repair of bilateral common iliac artery aneurysms using intraoperative positioning system.

Intraoperative positioning system (IOPS; Centerline Biomedical, Inc) is a novel technology that allows for real-time intravascular navigation of endovascular devices using an electromagnetic field. In this report, we describe the use of IOPS for effective treatment of bilateral common iliac artery aneurysms with endovascular aortoiliac repair using iliac branch endoprostheses. Our experience suggests that this technology has the potential to reduce radiation and contrast use in endovascular procedures, although its application is currently limited. To the best of our knowledge, this is the first reported case of bilateral internal iliac cannulations for iliac branch endoprosthesis placement using IOPS.

Racial and sex disparities in inpatient outcomes of patients with ruptured abdominal aortic aneurysms in the United States.

BACKGROUND: Ruptured abdominal aortic aneurysm (AAA) is a medical emergency that requires immediate surgical intervention. The aim of this analysis was to identify the sex- and race-specific disparities that exist in outcomes of patients hospitalized with this condition in the United States using the National Inpatient Sample (NIS) to identify targets for improvement and support of specific patient populations. METHODS: In this descriptive, retrospective study, we analyzed the patients admitted with a primary diagnosis of ruptured AAA between January 1, 2016, and December 31, 2020, using the NIS database. We compared demographics, comorbidities, and in-hospital outcomes in AAA patients, and compared these results between different racial groups and sexes. RESULTS: A total of 22,395 patients with ruptured AAA were included for analysis. Of these, 16,125 patients (72.0%) were male, and 6270 were female (28.0%). The majority of patients (18,655 [83.3%]) identified as Caucasian, with the remaining patients identifying as African American (1555 [6.9%]), Hispanic (1095 [4.9%]), Asian or Pacific Islander (470 [2.1%]), or Native American (80 [0.5%]). Females had a higher risk of mortality than males (OR, 1.7; 95% confidence interval [CI], 1.45-1.96; P < .001) and were less likely to undergo endovascular aortic repair (OR, 0.70; 95% CI, 0.61-0.81; P < .001) or fenestrated endovascular aortic repair (OR, 0.71; 95% CI, 0.55-0.91; P = .007). Relative to Caucasian race, patients who identified as African American had a lower risk of inpatient mortality (OR, 0.50; 95% CI, 0.37-0.68; P < .001). CONCLUSIONS: In this retrospective study of the NIS database from 2016 to 2020, females were less likely to undergo endovascular intervention and more likely to die during their initial hospitalization. African American patients had lower rates in-hospital mortality than Caucasian patients, despite a higher burden of comorbidities. Future studies are needed to elucidate the potential factors affecting racial and sex disparities in ruptured AAA outcomes, including screening practices, rupture risk stratification, and more personalized guidelines for both elective and emergent intervention.

A hybrid approach to previously excluded, expanding internal iliac artery aneurysms.

Previously excluded internal iliac artery (IIA) aneurysms can continue to expand and pose a risk of rupture. In this case series, we present three patients with previously excluded, expanding IIA aneurysms after endovascular stent coverage or open surgical ligation of the proximal IIA. We describe a hybrid approach to treat these patients safely and effectively.

A novel, microvascular evaluation method and device for early diagnosis of peripheral artery disease and chronic limb-threatening ischemia in individuals with diabetes.

Objective: A novel transdermal arterial gasotransmitter sensor (TAGS) has been tested as a diagnostic tool for lower limb microvascular disease in individuals with and without diabetes mellitus (DM). Methods: The TAGS system noninvasively measures hydrogen sulfide (H2S) emitted from the skin. Measurements were made on the forearm and lower limbs of individuals from three cohorts, including subjects with DM and chronic limb-threatening ischemia, to evaluate skin microvascular integrity. These measurements were compared with diagnosis of peripheral artery disease (PAD) using the standard approach of the toe brachial index. Other measures of vascular health were made in some subjects including fasting blood glucose, hemoglobin A1c, plasma lipids, blood pressure, estimated glomerular filtration, and body mass index. Results: The leg:arm ratio of H2S emissions correlated with risk factors for microvascular disease (ie, high-density lipoprotein levels, estimated glomerular filtration rate, systolic blood pressure, and hemoglobin A1c). The ratios were significantly lower in symptomatic DM subjects being treated for chronic limb-threatening ischemia (n = 8, 0.48 ± 0.21) compared with healthy controls (n = 5, 1.08 ± 0.30; P = .0001) and with asymptomatic DM subjects (n = 4, 0.79 ± 0.08; P = .0086). The asymptomatic DM group ratios were also significantly lower than the healthy controls (P = .0194). Using ratios of leg:arm transdermal H2S measurement (17 subjects, 34 ratios), the overall accuracy to identify limbs with severe PAD had an area under the curve of the receiver operating curve of 0.93. Conclusions: Ratios of transdermal H2S measurements are lower in legs with impaired microvascular function, and the decrease in ratio precedes clinically apparent severe microvascular disease and diabetic ulcers. The TAGS instrument is a novel, sensitive tool that may aid in the early detection and monitoring of PAD complications and efforts for limb salvage.

Hydrogen sulfide and miR21 are suitable biomarkers of hypoxic exposure.

Hypoxia is the reduction of alveolar partial pressure of oxygen ([Formula: see text]). Military members and people who practice recreational activities from moderate to high altitudes are at risk for hypoxic exposure. Hypoxemia's signs and symptoms vary from asymptomatic to severe responses, such as excessive hypoxic ventilatory responses and residual neurobehavioral impairment. Therefore, it is essential to identify hypoxia-induced biomarkers to indicate people with exposure to hypoxia. Advances have been made in understanding physiological responses to hypoxia, including elevations in circulating levels of endothelin 1 (ET-1) and microRNA 21 (miR-21) and reduction in circulating levels of hydrogen sulfide (H2S). Although the levels of these factors change upon exposure to hypoxia, it is unclear if these changes are sustained on return to normoxia. We hypothesize that hypoxia-induced ET-1 and miR-21 remain elevated, whereas hypoxia-reduction in H2S sustains after returning to normoxic conditions. To test this hypothesis, we exposed male rats to 6 h of 12% O2 and measured circulating levels of ET-1 and miR-21, pre, during, and posthypoxia. We found that ET-1 plasma levels increased in response to hypoxia but returned to normal levels within 30 min after the restoration of normoxia. miR-21 plasma levels and transdermal H2S emissions decreased in response to hypoxia, remaining decreased on return to normoxia, thus following the biomarker criteria. Therefore, this study supports a unique role for plasma miR21 and transdermal H2S as hypoxia biomarkers that could be used to identify individuals after exposure to hypoxia.

Sex differences in murine myocutaneous flap revascularization.

Sex differences in susceptibility to ischemia/reperfusion injury have been documented in humans. Premenopausal women have a lower risk of ischemic heart disease than age-matched men, whereas after menopause, the risk is similar or even higher in women. However, little is known about the effects of sex on myocutaneous ischemia/reperfusion. To explore sex differences in wound revascularization, we utilized a murine myocutaneous flap model of graded ischemia. A cranial-based, peninsular-shaped, myocutaneous flap was surgically created on the dorsum of male and female mice. Physiological, pathological, immunohistochemical, and molecular parameters were analyzed. Flaps created on female mice were re-attached to the recipient site resulting in nearly complete viability at post-operative day 10. In contrast, distal full-thickness myocutaneous necrosis was evident at 10 days post-surgery in male mice. Over the 10 day study interval, laser speckle imaging documented functional revascularization in all flap regions in female mice, but minimal distal flap reperfusion in male mice. Day 10 immunostained histologic sections confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice. RT-PCR demonstrated significant differences in growth factor and metabolic gene expression between female and male mice at day 10. In conclusion, in a graded-ischemia wound healing model, flap revascularization was more effective in female mice. The recognition and identification of sex-specific wound healing differences may lead to a better understanding of the underlying mechanisms of myocutaneous revascularization and drive novel discovery to improve soft tissue wound healing following tissue transfer for traumatic injury and cancer resection.

Pneumothorax, pneumomediastinum, and dysphonia complicating awake transcarotid artery revascularization.

A 59-year-old woman presented with advanced, symptomatic carotid artery stenosis in the setting of severe medical comorbidities including coronary artery disease, congestive heart failure with recent admission for exacerbation, and diabetes mellitus. She underwent awake transcarotid artery revascularization because of her medically high-risk status. Postoperatively, she was noted to have developed pneumothorax, pneumomediastinum, and dysphonia, thought to be secondary to entrained air during the course of low neck dissection for carotid artery exposure in the setting of partial airway obstruction and high negative intrathoracic pressures during the procedure. After conservative treatment, she ultimately enjoyed complete clinical resolution. This case demonstrates an unusual complication of awake transcarotid artery revascularization.

Effects of a standardized emergency department protocol on after-hours use of venous duplex ultrasound.

OBJECTIVE: Vascular laboratory (VL) venous duplex ultrasound is the "gold standard" for diagnosis of lower extremity deep venous thrombosis (DVT), which is linked to many morbid conditions. Decreasing night and weekend use of VL services in the emergency department (ED) represents a potentially viable means of reducing costs as skilled personnel must remain on call and receive a wage premium when activated. We investigated the effects of workflow changes that required ED providers to use a computerized decision-making tool, integrated into the electronic medical record, to calculate a Wells score for each patient considered for an after-hours venous duplex ultrasound study for suspected DVT. METHODS: The rate of VL use and study positivity before and after implementation of the decision-making tool were examined in addition to measures of ED throughput, rate of concomitant pulmonary embolism, disposition of examined patients from the ED, observed thrombus distribution in duplex ultrasound studies positive for DVT, and calculated personnel costs of after-hours VL use. RESULTS: A total of 391 after-hours, ED-initiated venous duplex ultrasound studies were obtained during the 4-year study period (n = 213 before intervention, n = 178 after intervention; P = .12). Whereas the period immediately after the start of the intervention saw a decrease in VL use, this was not sustained. Studies performed after the intervention were not more likely to be positive for acute DVT (12.2% vs 18%; P = .1179). The average Wells score was 2.8 (range, 0-6). VL personnel were called in 347 times during the 4-year period, with a total cost of $14,643.40. Nurse-ordered studies were significantly more likely to be positive, with 22% revealing acute DVT compared with 12% for physician-ordered studies (P = .042). The intervention resulted in significant improvements in ED throughput, with time between triage and study request falling from 226 minutes to 165 minutes (P < .001). Observed thrombus distribution revealed involvement of the most proximal external iliac system in a minority of cases (11%), whereas most thrombi (89%) were limited to the femoropopliteal, calf, and superficial venous systems. CONCLUSIONS: A requirement for ED providers to document a Wells score before obtaining an after-hours venous duplex ultrasound study resulted in only a transient decrease in VL use but improved ED throughput. Studies ordered by nurses were significantly more likely to be positive, possibly as a result of consistent protocol adherence compared with the physicians. Future studies may warrant investigation into this provider variance.

Myocutaneous revascularization following graded ischemia in lean and obese mice.

BACKGROUND: Murine models of diabetes and obesity have provided insight into the pathogenesis of impaired epithelialization of excisional skin wounds. However, knowledge of postischemic myocutaneous revascularization in these models is limited. MATERIALS AND METHODS: A myocutaneous flap was created on the dorsum of wild type (C57BL/6), genetically obese and diabetic (ob/ob, db/db), complementary heterozygous (ob+/ob-, db+/db-), and diet-induced obese (DIO) mice (n=48 total; five operative mice per strain and three unoperated mice per strain as controls). Flap perfusion was documented by laser speckle contrast imaging. Local gene expression in control and postoperative flap tissue specimens was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Image analysis of immunochemically stained histologic sections confirmed microvascular density and macrophage presence. RESULTS: Day 10 planimetric analysis revealed mean flap surface area necrosis values of 10.8%, 12.9%, 9.9%, 0.4%, 1.4%, and 23.0% for wild type, db+/db-, ob+/ob-, db/db, ob/ob, and DIO flaps, respectively. Over 10 days, laser speckle imaging documented increased perfusion at all time points with revascularization to supranormal perfusion in db/db and ob/ob flaps. In contrast, wild type, heterozygous, and DIO flaps displayed expected graded ischemia with failure of perfusion to return to baseline values. RT-PCR demonstrated statistically significant differences in angiogenic gene expression between lean and obese mice at baseline (unoperated) and at day 10. CONCLUSION: Unexpected increased baseline skin perfusion and augmented myocutaneous revascularization accompanied by a control proangiogenic transcriptional signature in genetically obese mice compared to DIO and lean mice are reported. In future research, laser speckle imaging has been planned to be utilized in order to correlate spatiotemporal wound reperfusion with changes in cell recruitment and gene expression to better understand the differences in wound microvascular biology in lean and obese states.

There is no benefit to universal carotid artery duplex screening before a major cardiac surgical procedure.

BACKGROUND: Perioperative stroke is a devastating complication after cardiac surgery. In an attempt to minimize this complication, many cardiac surgeons routinely preoperatively order carotid artery duplex scans to assess for significant carotid stenosis. We hypothesize that the routine screening of preoperative cardiac surgery patients with carotid artery duplex scans detects few patients who would benefit from carotid intervention or that a significant carotid stenosis reliably predicts stroke risk after cardiac surgery. METHODS: A retrospective review identified 1,499 patients who underwent cardiac surgical procedures between July 1999 and September 2010. Data collected included patient demographics, comorbidities, history of previous stroke, preoperative carotid artery duplex scan results, location of postoperative stroke, and details of carotid endarterectomy (CEA) procedures before, in conjunction with, or after cardiac surgery. Statistical methods included univariate analysis and Fisher's exact test. RESULTS: Twenty-six perioperative strokes were identified (1.7%). In the 21 postoperative stroke patients for whom there is complete carotid artery duplex scan data, 3 patients had a hemodynamically significant lesion (>70%) and 1 patient underwent unilateral carotid CEA for bilateral disease. Postoperative strokes occurred in the anterior cerebral circulation (69.2%), posterior cerebral circulation (15.4%), or both (15.4%). Patient comorbidities, preoperative carotid artery duplex scan screening velocities, or types of cardiac surgical procedure were not predictive for stroke. Thirteen patients (0.86%) underwent CEA before, in conjunction with, or after cardiac surgery. Two of these patients had symptomatic disease, 1 of whom underwent CEA before and the other after his cardiac surgery. Of the 11 asymptomatic patients, 2 underwent CEA before, 3 concurrently, and 6 after cardiac surgery. Left main disease (≥50% stenosis), previous stroke, and peripheral vascular disease were found to be statistically significant predictors of carotid revascularization. A cost analysis of universal screening resulted in an estimated net cost of $378,918 during the study period. CONCLUSIONS: The majority of postoperative strokes after cardiac surgery are not related to extracranial carotid artery disease and they are not predicted by preoperative carotid artery duplex scan screening. Consequently, universal carotid artery duplex scan screening cannot be recommended and a selective approach should be adopted.