Contemporary outcomes for arterial reconstruction with non-saphenous vein cryo-preserved conduits.

OBJECTIVE: Cryopreserved (CP) products are utilized during challenging cases when autogenous or prosthetic conduit use is not feasible. Despite decades of experience with cadaveric greater saphenous vein (GSV), there is limited available data regarding the outcomes and patency of other CP products, specifically arterial and deep venous grafts. This study was designed to evaluate outcomes of non-GSV CP conduits in patients undergoing urgent, emergent, and elective arterial reconstruction at our institution. We hypothesized that non-GSV CP allografts have adequate patency and outcomes and are therefore a feasible alternative to GSV in settings where autologous graft is unavailable or prosthetic grafts are contraindicated. METHODS: This study was approved by the Institutional Review Board at our institution. We retrospectively reviewed charts of patients undergoing arterial reconstructions using CP conduits from 2010 to 2022. Data collected included demographics, comorbidities, smoking status, indications for surgery, indication for CP conduit use, anatomic reconstruction, urgency of procedure, and blood loss. Time-to-event outcomes included primary and secondary graft patency rates, follow-up amputations, and mortality; other complications included follow-up infection/reinfection and 30-day complications, including return to the operating room and perioperative mortality. Time-to-event analyses were evaluated using product-limit survival estimates. RESULTS: Of 96 identified patients receiving CP conduits, 56 patients received non-GSV conduits for 66 arterial reconstructions. The most common type of non-GSV CP product used was femoral artery (31 patients), followed by aorto-iliac artery (22 patients), and femoral vein (19 patients), with some patients receiving more than one reconstruction or CP product. Patients were mostly male (75%), with a mean age of 63.1 years and a mean body mass index of 26.7 kg/m2. Indications for CP conduit use included infection in 53 patients, hostile environment in 36 patients, contaminated field in 30 patients, tissue coverage concerns in 30 patients, inadequate conduit in nine patients, and patient preference in one patient. Notably, multiple patients had more than one indication. Most surgeries (95%) were performed in urgent or emergent settings. Supra-inguinal reconstructions were most common (53%), followed by extra-anatomic bypasses (47%). Thirty-day mortality occurred in 10 patients (19%). Fifteen patients (27%) required return to the operating room for indications related to the vascular reconstructions, with 10 (18%) cases being unplanned and five (9%) cases planned/staged. Overall survival at 6, 12, and 24 months was 80%, 68%, and 59%, respectively. Primary patency at 6, 12, and 24 months was 86%, 70%, and 62%, respectively. Amputation freedom at 6 months, 12 months, and 24 months was 98%, 95%, and 86%, respectively for non-traumatic indications. CONCLUSIONS: Non-GSV CP products may be used in complex arterial reconstructions when autogenous or prosthetic options are not feasible or available.

Duodenocaval Fistula from an Inferior Vena Cava Filter Perforation.

Background: This article describes a rare case of inferior vena cava (IVC) filter perforation into the duodenum in a patient presenting with abdominal pain. Case report: A 55 year old woman presented with abdominal pain four years after an IVC filter placement. Workup demonstrated an IVC filter strut perforating the duodenum. The filter was removed via laparotomy, the duodenum was closed primarily, and the IVC was repaired. The patient was discharged home on post-operative day five and is doing well. Conclusions: Most extraluminal perforations of IVC filter struts are asymptomatic. Rare filter associated duodenal perforations may present with non-specific abdominal symptoms. If no other diagnosis can be attributed to the patient's presentation, direct removal of the filter and repair of the duodenum are indicated.

Portal Hypertension Due to a Traumatic Arteriovenous Fistula in a Patient With a Celiac Artery Aneurysm.

This article describes a rare case of a traumatic splenic arteriovenous fistula (AVF) causing portal hypertension in a patient presenting with abdominal pain, diarrhea, and melena. A 78-year-old was admitted to the hospital with abdominal pain. The patient's history was notable for prior laparotomy and left nephrectomy for a gunshot wound. Workup demonstrated portal hypertension with a dilated splenic vein with aneurysmal changes and a saccular celiac artery aneurysm. Celiac angiogram demonstrated a communication between celiac and portal circulation. The patient underwent laparotomy with ligation of the splenic artery and resection of the celiac artery aneurysm. In conclusion, splenic AVFs are relatively rare in clinical practice. Once the diagnosis is established, operative intervention is required to avoid complications of portal hypertension. Surgical ligation has been used in this case with a successful outcome.

A Hybrid Approach in the Management of a Large Pancreaticoduodenal Artery Aneurysm.

Pancreaticoduodenal artery aneurysms (PDAA) are rare and represent a small fraction of known visceral aneurysms. We describe a case of a 79-year-old male with an 82 mm PDAA in the setting of chronic celiac artery occlusion. The patient was treated with an open repair. Due to the large size of the aneurysm and the dense adhesions to the surrounding tissues, vascular control of the superior mesenteric artery (SMA) was achieved by endovascular balloon occlusion and the aneurysm repaired with resection and primary aneurysmorrhaphy. The patient had an uneventful postoperative course.

Total endovascular aortic arch repair using the Terumo Aortic triple-branch arch endograft.

OBJECTIVE: To evaluate the feasibility and outcomes of total endovascular repair of aortic arch aneurysms using a novel triple-branch arch endograft. METHODS: Retrospective review of the clinical data and outcomes of 3 patients with arch aneurysms treated at a single institution using a custom-made triple-branch aortic endograft (Terumo Aortic, Sunrise, FL) between 2015 and 2020. The device has 3 internal branches corresponding to the principal branches of the standard aortic arch, obviating the need for any surgical revascularization. This initial experience represents the first three cases ever performed in the world using this endograft. RESULTS: All procedures were technically successful. There were no strokes, in-hospital, or 1 year mortality. All 3 patients required secondary re-interventions. One patient died 14 months after the index procedure due to endocarditis unrelated to the arch repair. CONCLUSION: The initial experience with the Terumo Aortic triple-branch endograft for treatment aortic arch aneurysms showed that, while the procedure is technically feasible, there remain significant anatomic and mechanical challenges in the endovascular repair of this segment of the thoracic aorta. Further refinements of endograft design and identification of optimal bridging stent technology are needed.

Gamma Radiation-Induced Rib Necrosis and Stereotactic Radiosurgery Failure.

Stereotactic radiosurgery, or SRS, uses focused beams of gamma radiation targeted to specific areas of the body and has been used for multiple forms of non-small cell lung cancer. In this article, the authors describe two incidental cases of osteonecrosis in patients who had previously undergone stereotactic radiosurgery with recurrence of tumor. While this is a known side effect of traditional radiation therapy, it has not been described in the context of stereotactic radiosurgery. Further, these lesions were immediately deep to a rib, which may have shielded the lesion, and led to SRS failure. Osteonecrosis of the rib is a rare clinical entity but has been found to occur with glucocorticoid use, bisphosphonates, radiation therapy, and radiofrequency ablation. In the authors' review of the literature on SRS for lung cancer and intrathoracic pathology, rib osteonecrosis was not described and has not been mentioned as a possible side effect. Patients who have undergone thoracic stereotactic radiotherapy may develop side effects of traditional radiotherapy. We identified two patients who developed rib osteonecrosis though that has not been previously described as an adverse effect of stereotactic radiotherapy. The patients described in this case did not have any radiographic evidence of disease on imaging, suggesting that further research is warranted on the diagnosis and management of this rare disease entity.

Laparoscopic Repair of Extraperitoneal Ureteral Inguinal Hernia With Mesh Placement.

Ureteral inguinal hernias are a well-described entity, within the spectrum of sliding hernias, with over 140 cases described since 1880. Though herniation of the ureter is relatively rare and complete ureteric obstruction is infrequent, a massive herniation may cause complete obstruction, leading to hydronephrosis. Management of these hernias is challenging and poses a significant danger of inadvertent injury and entrapment of a tortuous ureter. When faced with this type of hernia, extreme care should be taken to perform the appropriate preoperative workup and thoroughly plan the surgical approach. The present case describes a patient with a known ureteral inguinal hernia, who underwent a laparoscopic repair of the hernia with mesh placement.

Pneumomediastinum After Dental Filling: A Rare Case Presentation.

Pneumomediastinum and subcutaneous emphysema is an uncommon potentially life-threatening complication of dental procedures. Common causes of pneumomediastinum after dental procedures include tooth extraction, preparation, restorative treatment, endodontic treatment, and subgingival curettage that are associated with the use of handpieces and high-pressure air/water syringes. Herein, we present a case of pneumomediastinum with subcutaneous emphysema in a 40-year-old female who underwent two dental fillings and presented to our hospital with chief complain of facial swelling and odynophagia. The patient was managed conservatively, had an uneventful hospital course, and fully recovered. This case underlines the need for prompt diagnosis and management because of the risk of airway compromise, air embolism, and infection. The mechanism, clinical presentation, differential diagnosis, and complications are also reviewed.

Abdominal Apoplexy: A Case Study of Idiopathic Spontaneous Lesser Sac Hematoma.

Idiopathic spontaneous intraperitoneal hemorrhage (ISIH) is a rare event associated with high mortality. There have been multiple case reports of spontaneous rupture of middle colic pseudoaneurysms in the literature. Herein, we present a case of a 51-year-old female that presented with spontaneous rupture of the middle colic artery and associated massive intraabdominal hematoma without findings of a pseudoaneurysm. The patient underwent a computed tomography (CT) scan as an outpatient 24 hours prior to the onset of the bleeding due to abdominal pain without findings of hematoma or aneurysm of the mesenteric vessels. Subsequently, the patient underwent emergent exploratory laparotomy with findings of a massive hematoma in the lesser sac and spontaneous bleeding from the middle colic artery that was ligated. The patient had an uneventful postoperative course and fully recovered. To our knowledge, this is the second reported case of idiopathic bleeding from the middle colic artery without evidence of a pseudoaneurysm based on a current review of the literature.

Effect of Aging on Mitochondrial Energetics in the Human Atria.

Energy production in myocardial cells occurs mainly in the mitochondrion. Although alterations in mitochondrial functions in the senescent heart have been documented, the molecular bases for the aging-associated decline in energy metabolism in the human heart are not fully understood. In this study, we examined transcription profiles of genes coding for mitochondrial proteins in atrial tissue from aged (≥65 years old) and comorbidities-matched adult (<65 years old) patients with preserved left ventricular function. We also correlated changes in functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes with gene expression changes. There was significant alteration in the expression of 10% (101/1,008) of genes coding for mitochondrial proteins, with 86% downregulated (87/101). Forty-nine percent of the altered genes were confined to mitochondrial energetic pathways. These changes were associated with a significant decrease in respiratory capacity of mitochondria oxidizing glutamate and malate and functional activity of complex I activity that correlated with the downregulation of NDUFA6, NDUFA9, NDUFB5, NDUFB8, and NDUFS2 genes coding for NADH dehydrogenase subunits. Thus, aging is associated with a decline in activity of OXPHOS within the broader transcriptional downregulation of genes regulating mitochondrial energetics, providing a substrate for reduced energetic efficiency in the senescent human atria.

Synthetic peptide TEKKRRETVEREKE derived from ezrin induces differentiation of NIH/3T3 fibroblasts.

Synthetic 14 AA peptide (Gepon) derived from the hinge region of ezrin, a protein that links cell surface molecules to intracellular actin filaments, accelerates and facilitates wound and ulcer healing in clinical applications. However, the molecular mechanisms underlying this phenomenon and involved in enhanced healing of wounds with Gepon are not yet understood. The purpose of current study was to investigate intracellular signaling pathways involved in the effect of this peptide on wild type and genetically modified (CD44 KO) NIH/3T3 embryonic mouse fibroblasts. Gepon treatment of NIH/3T3 cells resulted in morphological and biochemical changes, characteristic of differentiated fibroblasts. While treatment of NIH/3T3 cells with TGF-ß1 triggered the activation of both canonical and non-canonical signaling pathways, exposure of fibroblasts to Gepon activated only the ERK1/2 dependent pathway without modulating SMAD dependent signaling pathway. Knocking out hyaluronic acid CD44 receptor did not change Gepon or TGF-ß1 dependent activation of intracellular signaling pathways and assembling of α-SMA-positive filaments. Gepon dependent differentiation of NIH/3T3 fibroblasts is based on activation of ERK1/2 kinase, non-canonical intracellular signaling pathway. Our data suggest that the treatment of fibroblasts with Gepon triggers activation of the non-canonical (SMAD independent) intracellular signaling pathway that involves ERK1/2kinase phosphorylation. Activation of the MAPK signaling pathway and the increase in formation of α-SMA containing stress filaments induced by Gepon were independent on presence of CD44 receptor in NIH/3T3 fibroblasts. Thus, our observation designates the significance and sufficiency of MAPK pathway mediated activation of fibroblasts with Gepon for healing of erosion, ulcers and wounds.

Chamber-specific differences in human cardiac fibroblast proliferation and responsiveness toward simvastatin.

Fibroblasts, the most abundant cells in the heart, contribute to cardiac fibrosis, the substrate for the development of arrythmogenesis, and therefore are potential targets for preventing arrhythmic cardiac remodeling. A chamber-specific difference in the responsiveness of fibroblasts from the atria and ventricles toward cytokine and growth factors has been described in animal models, but it is unclear whether similar differences exist in human cardiac fibroblasts (HCFs) and whether drugs affect their proliferation differentially. Using cardiac fibroblasts from humans, differences between atrial and ventricular fibroblasts in serum-induced proliferation, DNA synthesis, cell cycle progression, cyclin gene expression, and their inhibition by simvastatin were determined. The serum-induced proliferation rate of human atrial fibroblasts was more than threefold greater than ventricular fibroblasts with faster DNA synthesis and higher mRNA levels of cyclin genes. Simvastatin predominantly decreased the rate of proliferation of atrial fibroblasts, with inhibition of cell cycle progression and an increase in the G0/G1 phase in atrial fibroblasts with a higher sensitivity toward inhibition compared with ventricular fibroblasts. The DNA synthesis and mRNA levels of cyclin A, D, and E were significantly reduced by simvastatin in atrial but not in ventricular fibroblasts. The inhibitory effect of simvastatin on atrial fibroblasts was abrogated by mevalonic acid (500 µM) that bypasses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition. Chamber-specific differences exist in the human heart because atrial fibroblasts have a higher proliferative capacity and are more sensitive to simvastatin-mediated inhibition through HMG-CoA reductase pathway. This mechanism may be useful in selectively preventing excessive atrial fibrosis without inhibiting adaptive ventricular remodeling during cardiac injury.

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF.

TGF-ß1-mediated differentiation of fibroblasts is associated with increased mitochondrial content and cellular respiration.

OBJECTIVS: Cytokine-dependent activation of fibroblasts to myofibroblasts, a key event in fibrosis, is accompanied by phenotypic changes with increased secretory and contractile properties dependent on increased energy utilization, yet changes in the energetic profile of these cells are not fully described. We hypothesize that the TGF-ß1-mediated transformation of myofibroblasts is associated with an increase in mitochondrial content and function when compared to naive fibroblasts. METHODS: Cultured NIH/3T3 mouse fibroblasts treated with TGF-ß1, a profibrotic cytokine, or vehicle were assessed for transformation to myofibroblasts (appearance of α-smooth muscle actin [α-SMA] stress fibers) and associated changes in mitochondrial content and functions using laser confocal microscopy, Seahorse respirometry, multi-well plate reader and biochemical protocols. Expression of mitochondrial-specific proteins was determined using western blotting, and the mitochondrial DNA quantified using Mitochondrial DNA isolation kit. RESULTS: Treatment with TGF-ß1 (5 ng/mL) induced transformation of naive fibroblasts into myofibroblasts with a threefold increase in the expression of α-SMA (6.85 ± 0.27 RU) compared to cells not treated with TGF-ß1 (2.52 ± 0.11 RU). TGF-ß1 exposure increased the number of mitochondria in the cells, as monitored by membrane potential sensitive dye tetramethylrhodamine, and expression of mitochondria-specific proteins; voltage-dependent anion channels (0.54 ± 0.05 vs. 0.23 ± 0.05 RU) and adenine nucleotide transporter (0.61 ± 0.11 vs. 0.22 ± 0.05 RU), as well as mitochondrial DNA content (530 ± 12 µg DNA/106 cells vs. 307 ± 9 µg DNA/106 cells in control). TGF-ß1 treatment was associated with an increase in mitochondrial function with a twofold increase in baseline oxygen consumption rate (2.25 ± 0.03 vs. 1.13 ± 0.1 nmol O2/min/106 cells) and FCCP-induced mitochondrial respiration (2.87 ± 0.03 vs. 1.46 ± 0.15 nmol O2/min/106 cells). CONCLUSIONS: TGF-ß1 induced differentiation of fibroblasts is accompanied by energetic remodeling of myofibroblasts with an increase in mitochondrial respiration and mitochondrial content.