Vascular persistence following precision micropuncture.

OBJECTIVE: The success of engineered tissues continues to be limited by time to vascularization and perfusion. Recently, we described a simple microsurgical approach, termed micropuncture (MP), which could be used to rapidly vascularize an adjacently placed scaffold from the recipient macrovasculature. Here we studied the long-term persistence of the MP-induced microvasculature. METHODS: Segmental 60 µm diameter MPs were created in the recipient rat femoral artery and vein followed by coverage with a simple Type 1 collagen scaffold. The recipient vasculature and scaffold were then wrapped en bloc with a silicone sheet to isolate intrinsic vascularization. Scaffolds were harvested at 28 days post-implantation for detailed analysis, including using a novel artificial intelligence (AI) approach. RESULTS: MP scaffolds demonstrated a sustained increase of vascular density compared to internal non-MP control scaffolds (p < 0.05) secondary to increases in both vessel diameters (p < 0.05) and branch counts (p < 0.05). MP scaffolds also demonstrated statistically significant increases in red blood cell (RBC) perfused lumens. CONCLUSIONS: This study further highlights that the intrinsic MP-induced vasculature continues to persist long-term. Its combination of rapid and stable angiogenesis represents a novel surgical platform for engineered scaffold and graft perfusion.

Retromuscular drain output at removal does not influence adverse outcome rate in open ventral hernia repairs.

BACKGROUND: Retromuscular drains are commonly placed during retromuscular hernia repair (RHR) to decrease postoperative wound complications and help mesh in-growth. Drains are traditionally removed when output is low but the relationship between drain output at the time of removal and postoperative complications has yet to be delineated. This study aimed to investigate outcomes of RHR patients with drain removal at either high or low output volume. METHODS: An institutional review board-approved retrospective chart review evaluated adult patients undergoing open RHR with retromuscular drain placement between 2013 and 2022 at a single academic medical center. Patients were stratified into low output drainage (LOD, < 50 mL/day) or high output drainage (HOD, ≥ 50 mL/day) groups based on volume on the day of drain removal. RESULTS: We identified 336 patients meeting inclusion criteria: 58% LOD (n = 195) and 42% HOD (n = 141). Demographics and risk factors pertaining to hernia complexity were similar between cohorts. Low-drain output at the time of removal was associated with a significantly longer drain duration (6.3 ± 4.5 vs. 4.4 ± 1.6 days, p < 0.001) and postoperative hospital stay (5.9 ± 3.6 vs. 4.8 ± 2.8 days, p < 0.001). With a 97% 30-day follow-up, incidence of surgical site occurrence (SSO) was not statistically different between groups (29.2% LOD, 26.2% HOD, p = 0.63). Surgical site infection and SSO requiring procedural intervention was also not statistically significant between cohort. At 1-year follow-up, hernia recurrence rates were the same between groups (4.2% LOD, 1.4% HOD, p = 0.25). CONCLUSION: Following open ventral hernia repair with retromuscular mesh placement, the rate of postoperative wound complications was not statistically different based on volume of drain output day of removal. These results suggest that removing drains earlier despite higher output is safe and has no effect on short- or long-term hernia outcomes.

Over-the-Scope-Clips Can Be Fired Safely Over a Guidewire: Proof of Concept in an Ex-Vivo Porcine Model.

Background and Objectives: To assist in achieving optimal position when deploying over-the-scope (OTS)-clips, the concept of cannulating the defect with a guidewire, backloading the endoscope onto the wire, and firing the OTS-clip over the wire with subsequent wire removal has been demonstrated. The safety of this technique has not been evaluated. Methods: An ex-vivo porcine foregut model was utilized. Biopsy punches were used to create 3-mm diameter full-thickness gastrointestinal tract defects through which a guidewire was threaded. An endoscope was backloaded over the wire and OTS-clips (OVESCO, Tuebingen, Germany) were fired over the mucosal defect and wire. The wire was removed through the endoscope and the removal difficulty was graded using a Likert scale. This process was repeated for each unique combination of nine OTS-clip types, two wire types, four wire angles, and three tissue types. Statistical analysis included t test and ANOVA. Results: Two hundred sixteen OTS-clip firings with wire removal attempts were performed with the following Likert score breakdown: 1 - No difficulty (80.6%), 2 - mild difficulty (16.2%), 3 - moderate difficulty (2.3%), 4 - extreme difficulty (0.9%), and 5 - unable to remove (0%). Statistically significant differences were noted in removal difficulty between OTS-clip sizes (p < 0.05). No differences were identified between clip teeth types, wire types, tissue types, and wire angles (p > 0.05). Conclusion: In this ex-vivo model, the guidewire was successfully removed through the endoscope in all cases. This technique can be employed to facilitate OTS-clip closure of gastrointestinal tract defects, but further study is indicated before wide clinical implementation.

Esophagogastric Junction Outflow Obstruction and Hiatal Hernia: Is Hernia Repair Alone Sufficient?

Introduction: Esophagogastric junction outflow obstruction (EGJOO) is attributed to primary/idiopathic causes or secondary/mechanical causes, including hiatal hernias (HH). While patients with HH and EGJOO (HH+EGJOO) may undergo HH repair without myotomy, it is unclear if an underlying motility disorder is missed by therapy which addresses only the secondary EGJOO cause. The goal of this study was to determine if HH repair alone is sufficient management for HH+EGJOO patients. Methods: A retrospective review of patients who underwent HH repair between January 1, 2016 and January 31, 2020 was performed. Patients who underwent high-resolution esophageal manometry(HREM) within one year before HH repair were included. Patients with and without EGJOO on pre-operative HREM were compared. Results: Sixty-three patients were identified. Pre-operative HREM findings included: 43 (68.3%) normal, 13 (20.6%) EGJOO, 4 (6.3%) minor disorder or peristalsis, 2 (3.2%) achalasia, and 1 (1.6%) major disorder of peristalsis. No differences between patients with EGJOO or normal findings on pre-operative manometry were found in pre-operative demographics/risk factors, pre-operative symptoms, and pre-operative HREM, except higher integrated relaxation pressure in EGJOO patients. No differences were noted in length of stay, 30-day complications, long-term persistent symptoms, or recurrence with mean follow-up of 26-months. Of the 3 (23.1%) EGJOO patients with persistent symptoms, 2 underwent HREM demonstrating persistent EGJOO and none required endoscopic/surgical myotomy. Conclusion: Most HH+EGJOO patients experienced symptom resolution following HH repair alone and none required additional intervention to address a missed primary motility disorder. Further study is required to determine optimal management of patients with persistent EGJOO following HH repair.

Is preparation of a sterile operative field before percutaneous endoscopic gastrostomy necessary? A cost-effectiveness analysis.

BACKGROUND: Despite the non-sterile nature of the alimentary tract, percutaneous endoscopic gastrostomy (PEG) procedures are often performed after creating a sterile surgical field to reduce infection risk. Our group has previously demonstrated no statistically significant difference in the rate of surgical site infection (SSI) following PEG performed with or without sterile operative fields. The purpose of this study is to evaluate the cost-effectiveness of working with or without sterile operative fields during PEG. METHODS: A decision tree model of PEG with and without sterile operative fields was created to evaluate the cost-effectiveness of these two methods. The primary outcome was incremental cost-effectiveness ratio with a ceiling willingness to pay threshold assumed of $100,000 per quality-adjusted life year (QALY). Costs were from the perspective of the healthcare system with a time horizon for the model of 90 days. Sensitivity analyses were performed on all model parameters. RESULTS: In the base case analysis, sterile operative field PEG was cost-effective resulting in 0.2225 QALYs at an expected cost of $2,099. PEG procedures without a sterile operative field yielded less QALYs (0.2224) at a higher cost ($2,199) and were dominated. These procedures became cost-effective when the expected cost was < $1618 (e.g., $140 less than sterile operative field PEG) or when the SSI rate was < 1.6% (e.g., 0.2% higher than sterile operative field PEG) while holding all other variables constant. CONCLUSION: PEG procedures performed without a sterile operative field can be cost-effective compared to procedures performed with a sterile operative field if the rates of SSI remain similar. Cost savings from foregoing a sterile operative field appear to be offset if the SSI rate increases > 0.2% above that of sterile operative field PEG procedures.

Testosterone-induced relaxation of coronary arteries: activation of BKCa channels via the cGMP-dependent protein kinase.

Androgens are reported to have both beneficial and detrimental effects on human cardiovascular health. The aim of this study was to characterize nongenomic signaling mechanisms in coronary artery smooth muscle (CASM) and define the ionic basis of testosterone (TES) action. TES-induced relaxation of endothelium-denuded porcine coronary arteries was nearly abolished by 20 nM iberiotoxin, a highly specific inhibitor of large-conductance, calcium-activated potassium (BK(Ca)) channels. Molecular patch-clamp studies confirmed that nanomolar concentrations of TES stimulated BK(Ca) channel activity by ∼100-fold and that inhibition of nitric oxide synthase (NOS) activity by N(G)-monomethyl-L-arginine nearly abolished this effect. Inhibition of nitric oxide (NO) synthesis or guanylyl cyclase activity also attenuated TES-induced coronary artery relaxation but did not alter relaxation due to 8-bromo-cGMP. Furthermore, we detected TES-stimulated NO production in porcine coronary arteries and in human CASM cells via stimulation of the type 1 neuronal NOS isoform. Inhibition of the cGMP-dependent protein kinase (PKG) attenuated TES-stimulated BK(Ca) channel activity, and direct assay determined that TES increased activity of PKG in a concentration-dependent fashion. Last, the stimulatory effect of TES on BK(Ca) channel activity was mimicked by addition of purified PKG to the cytoplasmic surface of a cell-free membrane patch from CASM myocytes (∼100-fold increase). These findings indicate that TES-induced relaxation of endothelium-denuded coronary arteries is mediated, at least in part, by enhanced NO production, leading to cGMP synthesis and PKG activation, which, in turn, opens BK(Ca) channels. These findings provide a molecular mechanism that could help explain why androgens have been reported to relax coronary arteries and relieve angina pectoris.

Activation of G protein-coupled estrogen receptor induces endothelium-independent relaxation of coronary artery smooth muscle.

Estrogens can either relax or contract arteries via rapid, nongenomic mechanisms involving classic estrogen receptors (ER). In addition to ERα and ERß, estrogen may also stimulate G protein-coupled estrogen receptor 1 (GPER) in nonvascular tissue; however, a potential role for GPER in coronary arteries is unclear. The purpose of this study was to determine how GPER activity influenced coronary artery reactivity. In vitro isometric force recordings were performed on endothelium-denuded porcine arteries. These studies were augmented by RT-PCR and single-cell patch-clamp experiments. RT-PCR and immunoblot studies confirmed expression of GPER mRNA and protein, respectively, in smooth muscle from either porcine or human coronary arteries. G-1, a selective GPER agonist, produced a concentration-dependent relaxation of endothelium-denuded porcine coronary arteries in vitro. This response was attenuated by G15, a GPER-selective antagonist, or by inhibiting large-conductance calcium-activated potassium (BK(Ca)) channels with iberiotoxin, but not by inhibiting NO signaling. Last, single-channel patch-clamp studies demonstrated that G-1 stimulates BK(Ca) channel activity in intact smooth muscle cells from either porcine or human coronary arteries but had no effect on channels isolated in excised membrane patches. In summary, GPER activation relaxes coronary artery smooth muscle by increasing potassium efflux via BK(Ca) channels and requires an intact cellular signaling mechanism. This novel action of estrogen-like compounds may help clarify some of the controversy surrounding the vascular effects of estrogens.