Examining the impact of median arcuate ligament-induced celiac artery compression on target vessel patency, long-term survival and device integrity in fenestrated and branched endovascular repairs.

OBJECTIVE: To evaluate the impact of celiac artery (CA) compression by median arcuate ligament (MAL) on technical metrics and long-term CA patency in patients with complex aortic aneurysms undergoing fenestrated/branched endograft repairs (F/B-EVARs). METHODS: Single-center, retrospective review of patients undergoing fenestrated/branched endovascular aortic aneurysm repairs and requiring incorporation of the CA between 2013 and 2023. Patients were divided into two groups-those with (MAL+) and without (MAL-) CA compression-based on preoperative computed tomography angiography findings. MAL was classified in three grades (A, B, and C) based on the degree and length of stenosis. Patients with MAL grade A had ≤50% CA stenosis measuring ≤3 mm in length. Those with grade B had 50% to 80% CA stenosis measuring 3 to 8 mm long, whereas those with grade C had >80% stenosis measuring >8 mm in length. End points included device integrity, CA patency and technical success-defined as successful implantation of the fenestrated/branched device with perfusion of CA and no endoleak. RESULTS: One hundred and eighty patients with complex aortic aneurysms (pararenal, 128; thoracoabdominal, 52) required incorporation of the CA during fenestrated/branched endovascular aortic aneurysm repair. Majority (73%) were male, with a median age of 76 years (interquartile range [IQR], 69-81 years) and aneurysm size of 62 mm (IQR, 57-69 mm). Seventy-eight patients (43%) had MAL+ anatomy, including 33 patients with MAL grade A, 32 with grade B, and 13 with grade C compression. The median length of CA stenosis was 7.0 mm (IQR, 5.0-10.0 mm). CA was incorporated using fenestrations in 177 (98%) patients. Increased complexity led to failure in CA bridging stent placement in four MAL+ patients, but completion angiography showed CA perfusion and no endoleak, accounting for a technical success of 100%. MAL+ patients were more likely to require bare metal stenting in addition to covered stents (P = .004). Estimated blood loss, median operating room time, contrast volume, fluoroscopy dose and time were higher (P < .001) in MAL+ group. Thirty-day mortality was 3.3%, higher (5.1%) in MAL+ patients compared with MAL- patients (2.0 %). At a median follow-up of 770 days (IQR, 198-1525 days), endograft integrity was observed in all patients and CA events-kinking (n = 7), thrombosis (n = 1) and endoleak (n = 2) -occurred in 10 patients (5.6%). However, only two patients required reinterventions. MAL+ patients had overall lower long-term survival. CONCLUSIONS: CA compression by MAL is a predictor of increased procedural complexity during fenestrated/branched device implantation. However, technical success, long-term device integrity and CA patency are similar to that of patients with MAL- anatomy.

Technical approach, outcomes, and exposure-related complications in patients undergoing anterior lumbar interbody fusion.

OBJECTIVE: To describe our technique, evaluate access related complications and factors contributing to adverse outcomes in patients undergoing retroperitoneal anterior lumbar interbody fusion (ALIF). METHODS: We conducted a retrospective analysis of prospectively collected data on patients undergoing ALIF at our institution from January 2008 to December 2017. Access was performed by a vascular surgeon who remained present for the duration of the case. Data collected included patients' demographics, comorbidities, exposure related complications and ileus. Study end points included major adverse events and minor complications. Major adverse events included any vascular injuries requiring repair, bowel and ureter injuries, postoperative bleeding requiring reoperation, myocardial infarction, stroke, venous thromboembolism (pulmonary embolism/deep venous thrombosis), wound dehiscence, and death. Minor complications included postoperative paralytic ileus, urinary tract infections, and surgical site infections. The incidence of incisional hernia was also evaluated. RESULTS: During this period, 1178 patients (514 males and 664 females; mean age, 54.1 ± 13.8 years) underwent a total of 2352 levels ALIF at our institution (single level, 422 patients; 2 levels, 450; 3 levels, 205; 4 levels, 98; 5 levels, 6; 6 levels, 1; and 7 levels, 1). The median estimated blood loss was 25 mL (interquartile range, 25-50). There were 57 exposure-related complications (4.8%), including vascular injuries (venous, 13; arterial, 4) in 17 patients (1.4%), bowel injuries in three patients (serosa tear in two and arterial embolization with subsequent bowel ischemia in one). Eleven of the 13 venous injuries (84.6%) occurred while exposing the L4 to L5 lumbar level. Two of the four patients with arterial injuries developed acute limb ischemia requiring embolectomy. One embolized to the superior mesenteric artery and underwent bowel resection. Twenty patients (1.7%) developed venous thromboembolism, two of whom had sustained left iliac vein injury during exposure. Sixteen patients (1.4%) developed a retroperitoneal hematoma/seroma with nine requiring evacuation in the operating room. Thirty-six patients (3.1%) developed postoperative ileus, defined as an inability to tolerate diet on postoperative day 3. Four patients (0.4%) had a postoperative myocardial infarction, and two had a stroke and two (0.17%) died within the first 30 postoperative days. Thirty-one patients developed incisional complications, including surgical site infection in 24 and incisional hernia in 7. CONCLUSIONS: Our findings suggest that ALIF exposure can be performed safely with a relatively low overall complication rate. The majority of vascular injuries associated with this procedure are venous in nature, occurring predominantly while exposing the L4 to L5 level and can be safely addressed by an experienced vascular team.

A prospective randomized comparison of contralateral snare versus retrograde gate cannulation in endovascular aneurysm repair.

OBJECTIVE: The objective of this study was to compare snare vs the standard retrograde gate cannulation method during endovascular aneurysm repair to determine the most efficient technique and to evaluate whether time was affected by graft design or the surgeon's experience. METHODS: This was a prospective randomized study involving single-center elective endovascular aneurysm repairs. Patients were randomized to the snare or retrograde group in a 1:1 ratio. The initial method was attempted for 15 minutes; if it was unsuccessful, the team switched to the alternative technique for an additional 15 minutes. The protocol continued until success was achieved. Data collected on demographic, anatomic, and procedural factors were analyzed for statistically significant differences. RESULTS: A total of 101 patients were included. Average age was 75.3 years, and 82% were male; 49 patients were randomized to snare and 52 to retrograde cannulation. The groups were overall similar. Median cannulation times were 3.9 minutes for the snare and 2.7 minutes for the retrograde technique (P = .13). The snare group attempts were successful within the initial 15-minute period in all but one patient (98% success). In the retrograde group, 5 of the 52 (10%) crossed over to snare. This difference did not reach statistical significance (P = .11). A difference was seen in the extremes of cannulation times. The surgeon's experience and graft design were not found to have significant effects on cannulation times. Further analysis of the retrograde group patients with long cannulation time found a relative breakpoint at the 5-minute mark. In those exceeding this time mark, the chance of eventual cannulation within 15 minutes dropped to 67%. In this group, median time to cannulation was 12.2 minutes for retrograde compared with 7.1 minutes for snare after crossover. CONCLUSIONS: Gate cannulation was successful using both methods with no statistical difference between the two in median time. Retrograde cannulation was found to be more likely to have short times. If cannulation by retrograde technique had not been achieved in the first 5 minutes, the chances of eventual success dropped significantly, and crossover to snare was more efficient. This finding suggests that one should consider an alternative method of gate cannulation if it has not been accomplished within this time.

Preoperative Inferior Mesenteric Artery Embolization: A Valid Method to Reduce the Rate of Type II Endoleak after EVAR?

BACKGROUND: Type II endoleak is the most commonly encountered endoleak after endovascular abdominal aortic aneurysm repair (EVAR). Some have advocated preoperative inferior mesenteric artery (IMA) embolization as a valid method for reducing the incidence of this endoleak, but controversies exist. We sought to demonstrate the impact of IMA embolization using a meta-analysis of currently available studies combined with our own experience. METHODS: We conducted an institutional review board-approved, retrospective analysis of all patients undergoing IMA embolization before EVAR between the years 2010 and 2015 and used as a control a similar group of patients with patent IMA. We divided patients from our own experience and 5 other studies into 2 groups: those who did not undergo IMA embolization (control) before EVAR and those who did. Rates of type II endoleaks, aneurysm sac regression, and secondary interventions were analyzed. RESULTS: A total of 620 patients from 6 studies were analyzed, including 258 patients who underwent an attempted IMA embolization before EVAR with a cumulative success rate of 99.2% (range, 93.8% to 100%). There was 1 fatality associated with IMA embolization. A meta-analysis showed that preoperative IMA embolization protected against type II endoleaks compared to the control group (odds ratio [OR], 0.31 [0.17-0.57]; P < 0.001, I2 = 43%). Furthermore, the rate of secondary intervention was significantly lower in the treatment group (OR, 0.12 [0.004-0.36]; P < 0.001, I2 = 0%). After IMA embolization, type II endoleak resulted from patent lumbar arteries in all 62 patients with persistent endoleak. CONCLUSIONS: Preoperative embolization of the IMA protects against the development of type II endoleaks and secondary interventions and may potentially lead to a rapid aneurysm sac regression. The procedure can be performed with a high technical success rate and minimal complications and should be considered in patients with IMA >3 mm before EVAR. A randomized trial, however, is required to clearly delineate the clinical significance of this technique.

A Dedicated Surveillance Program Improves Compliance with Endovascular Aortic Aneurysm Repair Follow-up.

BACKGROUND: Current recommendations suggest lifetime follow-up for endovascular aortic aneurysm repair (EVAR) patients to avoid consequences associated with endoleak and aneurysm enlargement. Follow-up compliance has been reported between 43% and 92%, with most single-center studies citing successful follow-up surveillance at less than 60%. We investigated follow-up completeness with a defined surveillance program and subsequent secondary intervention prevalence from a single center. METHODS: Our surveillance program notified patients of the need for follow-up imaging and surgeon review. Data were obtained from retrospective review of a prospective database, including operative and follow-up details, follow-up imaging completeness, endoleak incidence, and secondary intervention prevalence. RESULTS: Five hundred seventeen patients received elective EVAR from 2005 to 2015. Surveillance was achieved in 425 (82.3%). Mean number of follow-up studies was 4.2 ± 2.9 and median time to first follow-up was 36 days. Four hundred forty-eight patients (86.7%) had freedom from intervention. Sixty-nine unique patients (13.3%) had 107 secondary interventions. Median time to first secondary intervention in 69 patients was 476 days. Mean number of imaging studies for secondary intervention patients was 6.1 ± 3.9, compared with mean 3.4 ± 2.3 for patients without (P < 0.001). Overall mortality was 24.6% (n = 127), including 32 deaths of unknown cause (6.2% overall) and 95 of non-EVAR-related causes (18.3%). No aneurysm-related deaths were reported. CONCLUSIONS: Regular post-EVAR surveillance through a dedicated program resulted in a high rate of follow-up compliance, 13.3% rate of secondary intervention, and low aneurysm-related mortality. Careful lifetime surveillance remains important in long-term care following elective EVAR.

The effects of Gremlin1 on human umbilical cord blood hematopoietic progenitors.

Bone morphogenetic proteins (BMPs) support malignant hematopoiesis in CML. Conversely, the multi-functional BMP antagonist Gremlin1 supports self-renewing cancer stem cells of other malignancies. Inhibition of BMP signaling in CML, or of Gremlin1 in solid tumors, may therefore have therapeutic potential. However, since BMPs regulate hematopoietic stem cell (HSC) decisions in the stem cell niche, it is necessary to determine how Gremlin1 influences normal HSC. We examined the effects of Gremlin1 on long-term culture-initiating cells (LTC-IC) and transplantable hematopoietic stem cells (SCID-repopulating cells: SRC) in human umbilical cord blood. Gremlin1 inhibited BMP signaling, downregulated BMP-6 and cyclin E2 expression and upregulated hairy and enhancer of split-1 (HES-1; a Notch transcriptional target) and Hedgehog interacting protein-1 (HHIP-1; an inhibitor of Hedgehog signaling). The functional effects of Gremlin1 on SRC, i.e. skewing of their myelopoietic:lymphopoietic potential towards B lymphopoiesis without affecting long-term engraftment potential, were entirely consistent with changes in gene expression induced by Gremlin1. Since both BMPs and Gremlin1 are secreted by osteoblasts in vivo, our studies provide potential insights into the molecular regulation of hematopoiesis in the stem cell niche. These results also suggest that Gremlin1 (and possibly its mimetics that may be developed for therapeutic use) may not adversely affect normal human hematopoietic stem cell survival, though they may reduce their myelopoietic potential.

Feasibility and outcome of partial open surgical fenestrated stent graft explantation, radical debridement, and in situ reconstruction for late graft infection.

Aortic stent graft infection is a rare, but potentially lethal, complication of endovascular aortic aneurysm repair. Definitive treatment is complete stent graft explanation with in-line or extra-anatomical reconstruction. However, several factors can render such an operation unsafe, including the patient's overall fitness for surgery and partial incorporation of graft with a resulting robust inflammatory process, especially around the visceral vessels. We present the case of a 74-year-old man with a history of an infected fenestrated stent graft that was managed with partial explantation, wide debridement, and in situ reconstruction using a rifampin-soaked graft and a 360° omental wrap with good results.

Bilateral renal forniceal rupture due to retroperitoneal hematoma after femoral venous access.

Retroperitoneal hematoma is a potential complication of femoral venous access that rarely leads to bilateral ureteral obstruction. We present the case of a 73-year-old woman who underwent an ablation procedure for atrial fibrillation complicated by laceration of an aberrant obturator artery during femoral venous cannulation, leading to a compressive retroperitoneal hematoma, bilateral ureteral obstruction, acute renal failure, and renal forniceal rupture. The patient was successfully treated with embolization of the inferior epigastric artery and aberrant obturator artery, hematoma evacuation, and ureteral stent placement. This case illustrates a rare complication of arterial laceration during femoral venous access without ultrasound guidance.

Technical approach and outcomes of failed infrarenal endovascular aneurysm repairs rescued with fenestrated and branched endografts.

BACKGROUND: Endovascular rescue of failed infrarenal repair (EVAR) has emerged as an attractive option to stent graft explantation. The procedure, however, is underutilized due to limited devices accessibility and the challenges associated with their implantation in this patient population. The purpose of this study was to report our outcomes and discuss our approach to rescuing previously failed infrarenal endovascular aneurysm repairs (EVAR) with fenestrated/branched endografts (f/b-EVAR). METHODS: A retrospective analysis of prospectively collected data of consecutive patients with failed EVAR rescued with f/b-EVAR at our institution from November 2013 to March 2019 was conducted. The study primary end point was technical success; defined as the implantation of the device with no type I a/b or type III endoleak or conversion to open repair. Secondary endpoints included major adverse events (MAEs), graft patency and reintervention rates. RESULTS: During this time, 202 patients with complex aortic aneurysms were treated with f/b-EVAR. Of these, 19 patients (Male: 17, mean age 79 ± 7 years) underwent repair for failed EVAR. The median time from failed repair to f/b-EVAR was 48 (30, 60) months. Treatment failure was attributed to stent graft migration in 9 (47.4%) patients, disease progression in 5 (26.3%), short initial neck in 3 (15.8%) and unable to be determined in 2 (10.5%). Three patients were treated urgently with surgeon modified stent graft. Technical success was achieved in 18 patients (95%), including two who had undergone emergent repair for rupture. Seventy-two targeted vessels (97.3%) were successfully incorporated. Sixteen (84.2%) patients required a thoracoabdominal repair to achieve a durable seal. Major adverse events (MAEs) occurred in 3 patients (15.7%) including paralysis and death in one (5.3%), compartment syndrome and temporary dialysis in another and laparotomy with snorkeling of one renal and bypass of the other in the third patient. Median (IQR) hospital length of stay was 3 (2, 4) days. Late reintervention, primary target vessel patency and primary assisted patency rates were 5.3%, 98.6% and 100%, respectively. CONCLUSION: Implantation of f/b-EVAR in patients with failed previous EVAR is a challenging undertaking that can be performed safely with a high technical success and low reintervention rates.

Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells.

Estrogen promotes the growth of breast cancer via estrogen receptors (ER). Earlier studies showed that the opioid receptor antagonist naloxone inhibits MCF-7 breast cancer growth in mice. We examined the cellular and molecular mechanism of naloxone antagonism of ERalpha activity in human MCF-7 cells. Naloxone (100 nmol/L) inhibited 17beta-estradiol (E2)-induced (10 nmol/L) MCF-7 cell proliferation by 65% and mitogen-activated protein kinase/extracellular signal-regulated kinase phosphorylation. Naloxone blocked the E2-induced activation of ERalpha, with 85% inhibition after 5 minutes and 100% recovery after 60 minutes. This assay is based on quantitation of E2-activated nuclear ERalpha binding to the immobilized coactivator peptide. A significant decrease in E2-induced ERalpha transactivation was observed in the presence of naloxone in the estrogen response element-luciferase reporter assay (P < 0.05, E2 versus E2 + naloxone). Naloxone also blocked E2-induced down-regulation of ERalpha mRNA at 30 minutes and 6 hours. Although naloxone inhibits ERalpha activity directly, it also induces a cross-talk between mu-opioid receptor (MOR) and ERalpha. Immunoprecipitates with anti-MOR antibody showed the presence of ERalpha in cells incubated with E2 in the presence of naloxone but not in cells incubated with E2 or naloxone alone. Higher amounts of ERalpha associated with MOR after 60 minutes compared with 10 minutes of incubation. Naloxone inhibited E2-bovine serum albumin-FITC binding to plasma membrane-associated ERalpha and also inhibited the direct binding of [3H]E2 to ERalpha. Thus, naloxone modulates ERalpha activity directly as well as indirectly via MOR. This study suggests that naloxone-like compounds can be developed as novel therapeutic molecules for breast cancer therapy.

Diagnosis, Management, and Outcome of Aortitis at a Single Center.

BACKGROUND: Aortitis is a rare condition with inflammatory or infectious etiology that can be difficult to diagnose due to the highly variable clinical presentation and nonspecific symptoms. However, current literature on the diagnosis, management, and prognosis of aortitis is extremely scarce. METHODS: We retrospectively reviewed all patients' charts who were diagnosed with giant cell arteritis, Takayasu arteritis, or noninfectious aortitis presenting at a single center between January 1, 2009, and April 17, 2015. Data collected included demographics, medical history, comorbidities, laboratory and imaging data, management, and outcome. RESULTS: Among the included 15 patients presenting with aortitis at our center, 53% were diagnosed with Takayasu arteritis, 33% with idiopathic inflammatory aortitis, and 13% with giant cell arteritis. All patients received steroid treatment, 67% received adjunctive immunosuppressants or immunomodulators, and 33% underwent interventional procedures. Based on clinical presentation and laboratory and imaging findings at the last follow-up visit for each patient, 67% showed improvement, 27% had no change in disease activity, and 7% had a progression of the disease. CONCLUSIONS: Takayasu arteritis was found to be more common than idiopathic inflammatory aortitis and giant cell arteritis among our 15 cases diagnosed with aortitis. All patients received medical therapy and 33% received interventional procedures, leading to 67% improvement of disease activity or related complications. This article also offers a comprehensive review of the diagnosis, management, and outcome of aortitis, supplementing the very limited literature on this disease.

Duplex imaging of residual venous obstruction to guide duration of therapy for lower extremity deep venous thrombosis.

BACKGROUND: Clinical trials have shown that the presence of ultrasound-identified residual venous obstruction (RVO) on follow-up scanning may be associated with an elevated risk for recurrence, thus providing a potential tool to help determine the optimal duration of anticoagulant therapy. We performed a systematic review to evaluate the clinical utility of post-treatment duplex imaging in predicting venous thromboembolism (VTE) recurrence and in adjusting duration of anticoagulation. METHODS: The Ovid MEDLINE Database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were queried for the terms residual thrombus or obstruction, duration of therapy, deep vein thrombosis, deep venous thrombosis, DVT, venous thromboembolism, VTE, antithrombotic therapy, and anticoagulation, and 228 studies were selected for review. Six studies determined the rate of VTE recurrence on the basis of the presence or absence of RVO. RESULTS: Findings on venous ultrasound scans frequently remained abnormal in 38% to 80% of patients, despite at least 3 months of therapeutic anticoagulation. In evaluating for VTE recurrence, the definition of RVO varied widely in the literature. Some studies have shown an association between RVO and VTE recurrence, whereas other studies have not. Overall, the presence of RVO is a mild risk factor for recurrence (odds ratio, 1.3-2.0), but only when surveillance imaging is performed soon after the index deep venous thrombosis (3 months). CONCLUSIONS: RVO is a mild risk factor for VTE recurrence. The presence or absence of ultrasound-identified RVO has a limited role in guiding the duration of therapeutic anticoagulation. Further research is needed to evaluate its utility relative to other known risk factors for VTE recurrence.

Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells.

In mucopolysaccharidosis-I (MPS-I), alpha-L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem-cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical FGF-2-FGFR1-HS interactions, resulting in defective FGF-2-induced proliferation and survival of Hurler multipotent progenitor cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS-cytokine receptor interactions may represent a mechanism by which accumulated HS contributes to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate.