The association of comorbid depression with mortality and amputation risk in patients with chronic limb-threatening ischemia.

OBJECTIVE: There is increasing evidence that depression is a risk factor for worse outcomes in patients with peripheral artery disease. The association of depression in patients with chronic limb-threatening ischemia (CLTI) is not well described, nor is the impact of medical treatment for depression in this patient population. The objective of this study was to investigate the prevalence of depression in patients with CLTI, its association on major amputation and all-cause mortality, and whether medical antidepressant treatment is associated with improvement in these outcomes in patients with depression. METHODS: A retrospective review of all adult patients (≥18 years old) diagnosed with CLTI from January 1, 2007, to December 31, 2018, at a single academic medical center was performed. Collected data included patient demographics, comorbidities, and diagnosis of depression within 6 months of initial CLTI diagnosis. We also collected data on use of antidepressant medications. Outcomes evaluated were need for major lower extremity amputation and all-cause mortality. Multivariable logistic regression models estimated the adjusted effects of comorbid depression and antidepressant medication use on major amputation and all-cause mortality. Kaplan-Meier survival curves illustrated the probabilities of survival and limb salvage over time, stratified by diagnosis of comorbid depression. Multivariable Cox proportional hazards models estimated the adjusted effects of comorbid depression on time to major amputation and all-cause mortality, and the adjusted effect of antidepressant treatment on time to all-cause mortality. RESULTS: A total of 2987 patients with CLTI were identified. Mean age was 68.6 years (standard deviation, 12.9 years); 56.5% were male, and 43.5% were female. Comorbid depression within 6 months of CLTI diagnosis was present in 7.1% of the cohort (212 patients). In multivariable analysis, comorbid depression was associated with a 68% increase in the odds of major amputation (adjusted odds ratio [aOR], 1.68; 95% confidence interval [CI], 1.19-2.37; P < .01), a 164% increase in the odds of all-cause mortality among patients not taking antidepressants (aOR, 2.64; 95% CI, 1.31-5.32; P = .03), and only a 6% increase in the odds of all-cause mortality among patients taking antidepressants (aOR, 1.06; 95% CI, 0.72-1.55; P = .99). The effect of comorbid depression on mortality varied significantly by whether or not the patient was taking an antidepressant medication (P = .02). CONCLUSIONS: Comorbid depression in the patient population with CLTI is associated with a worse prognosis for major lower extremity amputation overall, and a worse prognosis for all-cause mortality among patients not taking an antidepressant. Furthermore, antidepressant treatment in the presence of comorbid depression in this patient population is associated with an improvement in the odds of all-cause mortality, illustrating the potential importance of medical management of depression.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

A Contemporary Comparison of Cyanoacrylate, Radiofrequency, and Endovenous Laser Ablation on Healing of Active Venous Ulceration.

BACKGROUND: The goal of this study is to compare the healing rates of active lower extremity venous ulcers for patients receiving one of 3 ablation methods, compare their complications, and identify factors affecting successful healing and prevention of recurrence. METHODS: For this study, data were collected retrospectively on 146 patients at a single institution, tertiary referral center, with an active venous ulcer who underwent ablation therapy via cyanoacrylate (VenaSeal), radiofrequency (RFA), or endovenous laser ablation (EVLA) from 2010 to 2020. RESULTS: The study showed a nonsignificant difference in days to ulcer healing postintervention between ablative techniques, with 80.8 days for cyanoacrylate ablation (n = 15), 70.07 for RFA (n = 44), and 67.04 days for EVLA (n = 79). A similar, nonsignificant trend was observed for ulcer recurrence, with a rate of 35.7% (5/14) for cyanoacrylate ablation, 26.7% (20/75) for EVLA, and 23.1% (9/39) for RFA. The same nonsignificant trend occurred with deep venous thrombosis following the procedure in 6.3% (1/16) of cyanoacrylate ablation, 4.8% (4/84) of EVLA, and 2.2% (1/46) of RFA cases. The rate of endovenous glue induced thrombosis was also higher (6.3%) for cyanoacrylate than endovenous heat induced thrombosis in EVLA (3.6%) and RFA (2.2%). Cox proportional hazard was significant for compliance with compression therapy (hazard ratio [HR] 2.12, confidence interval [CI] 95% = 1.10-4.20, P = 0.031) and a lack of working with a wound clinic (HR 0.50, CI 95% = 0.33-0.75, P = 0.001) were associated with the decreased time to healing of ulcer but was not influenced by the presence of other comorbidities of smoking or diabetes mellitus. CONCLUSIONS: This study indicates a trend toward cyanoacrylate ablation having longer healing times and more complications compared to other ablation methods when used in patients with active venous ulcers. Compliance with compression treatment is predictive of venous ulcer healing and working with a wound clinic had significantly longer healing times.

Racial Disparities in the Risk for Thromboembolic Events in COVID-19 Patients during the Height of the SARS-CoV-2 Pandemic and Impact on Outcomes.

BACKGROUND: The primary objective of this study is to assess the risk of thromboembolic events (TEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) and study the impact of TEs on hospital course and mortality risk during the initial height of the severe acute respiratory syndrome coronavirus-2 pandemic. METHODS: A retrospective review of all adult inpatients (≥ 18 years old) with COVID-19 infection at a single academic institution from March 15, 2020 to July 1, 2020 was performed. Collected data included patient demographics, comorbidities, hospital admission type, TEs, laboratory values, use of anticoagulants/antiplatelet agents, hospital length of stay, and in-hospital mortality. A logistic regression was used to estimate associations between risk factors and TEs. RESULTS: A total of 826 inpatients with COVID-19 were identified. Of these, 56% were male, average age was 60.9 years, and race/ethnicity was reported as Hispanic in 51%, non-Hispanic Black in 25%, and non-Hispanic White in 18%. A total of 98 TEs were documented in 87 patients (10.5%). Hypertension, coronary artery disease, and chronic limb threatening ischemia were associated with an increased incidence of thromboembolism (P < 0.05). Hispanic patients had higher incidence of thromboembolism compared to White non-Hispanic patients (odds ratio {[OR] confidence interval [CI]}: 2.237 [1.053, 4.754], P = 0.036). As D-dimer increased, the odds of TE increased by 5.2% (OR [CI]: 1.052 [1.027, 1.077], P < 0.001). Patients with TEs had longer hospital stay (median 13 vs. 6 days, P < 0.001), higher likelihood of intensive care unit admission (63% vs. 33%, P < 0.001), and higher in-hospital mortality (28% vs. 16%, P = 0.006). Arterial TEs were associated with higher in-hospital mortality than venous TEs (37% vs. 15%, P = 0.027). CONCLUSIONS: During the initial height of the severe acute respiratory syndrome coronavirus-2 pandemic, TEs were relatively frequent in hospitalized patients with COVID-19. Racial disparities were seen with an increased proportion of minority patients admitted with respect to percentages seen in the general population. There was also a significantly increased incidence of TEs in Hispanic patients. TEs were associated with significantly longer hospital stay and higher in-hospital mortality. Patients with arterial TEs fared worse with significantly higher mortality than those with venous events. Inconsistencies in anticoagulation management early in the pandemic may have contributed to poor outcomes and more contemporary management outcomes need to be investigated.

Pilot study to assess the use of a fluorescence imaging system for assessment of amputation healing.

OBJECTIVE:: The purpose of this study was to use a fluorescence imaging system (FIS) (SPYElite, NOVADAQ, US) during lower extremity amputations and develop parameters to predict amputation healing, for which there are no proven, objective tests. We hypothesised that the FIS may identify areas of poor perfusion at the time of amputation and predict potential healing complications. There are no studies involving the FIS used in this study in lower extremity amputation. METHOD:: This prospective cohort study involved patients requiring either below- or above-knee-amputation at one, mid-western medical centre. The FIS was used as per manufacturer's instructions after wound closure and before dressing. Procedure and operative management was unchanged. Through the FIS, perfusion values were plotted along the amputation site to visualise and quantify intraoperative perfusion and to compare with 30-day postoperative amputation healing. RESULTS:: Surgeons determined that all of the 18 participants had adequate perfusion at surgical wound closure. At 30 days, two subjects had wound dehiscence or infection; these correlated with low perfusion values on the FIS imaging. A further six subjects had marginal or low perfusion values, but did not develop wound failure. CONCLUSION:: It is feasible to use the FIS during amputation, however it did not perfectly predict healing course based on vascular perfusion. There were interesting patterns of poor perfusion that correlated with areas of dehiscence or infection but other patients had reduced perfusion that healed well. Due to the small sample size, no discernible perfusion value differences existed between patients who healed and patients with healing complications. A future, larger study may show that the FIS can be predictive of patient healing and aid decisions for intraoperative revision.

Results for primary bypass versus primary angioplasty/stent for lower extremity chronic limb-threatening ischemia.

BACKGROUND: Long-term results comparing percutaneous transluminal angioplasty with or without stenting (PTA/S) and open surgical bypass for chronic limb-threatening ischemia (CLTI) in patients who have had no prior intervention are lacking. METHODS: All patients undergoing a first-time lower extremity revascularization for CLTI by vascular surgeons at our institution from 2005 to 2014 were retrospectively reviewed. Outcomes included perioperative complications, wound healing, restenosis, primary patency, reintervention, major amputation, RAS events (ie, reintervention, major amputation, or stenosis), and mortality. Outcomes were evaluated using χ2, Kaplan-Meier, and Cox regression analyses. RESULTS: Of the 2869 total lower extremity revascularizations performed between 2005 and 2014, there were 1336 that fit our criteria of a first-time lower extremity intervention for CLTI (668 bypass procedures and 668 PTA/S procedures). Bypass patients were younger (71 vs 72 years; P = .02) and more often male (62% vs 56%; P < .02). Total mean hospital length of stay (LOS) was significantly longer after a first-time bypass (10 vs 8 days; P < .001), as were mean preoperative LOS (4 vs 3 days; P < .01) and postoperative LOS (7 vs 5 days; P < .001). There was no difference in perioperative mortality (3% vs 3%; P = .63). Surgical site infection occurred in 10% of bypass patients. Freedom from reintervention was significantly higher in patients undergoing a first-time bypass procedure (62% vs 52% at 3 years; P = .04), as was freedom from restenosis (61% vs 45% at 3 years; P < .001). Complete wound healing at 6-month follow-up was significantly better after an initial bypass (43% vs 36%; P < .01). A Cox regression model of all patients showed that reintervention was predicted by a first-time PTA/S (hazard ratio, 1.6; 95% confidence interval, 1.3-2.1) and both preoperative femoropopliteal TransAtlantic Inter-Society Consensus (TASC) C and TASC D lesions (2.0 [1.3-3.1] and 1.8 [1.3-2.7], respectively). Major amputation among all patients was predicted by an initial presentation of gangrene (2.5 [1.3-5.0]), dialysis dependence (1.9 [1.3-2.9]), diabetes (2.0 [1.1-3.8]), and preoperative femoropopliteal TASC D lesions (2.1 [1.1-4.0]) and was not predicted by procedure type. CONCLUSIONS: In this retrospective analysis, bypass for the primary treatment of CLTI showed improved 6-month wound healing, higher freedom from restenosis, improved patency rates, significantly fewer reinterventions, and higher survival than PTA/S within 3 years; however, a bypass-first approach was associated with increased total hospital LOS and wound infection. Perioperative mortality and amputation rates were similar between procedure types.

Outcomes for forearm and upper arm arteriovenous fistula creation with the transposition technique.

OBJECTIVE: To study the outcomes of three different types of arteriovenous fistula (AVF) transpositions (forearm cephalic vein transposition [FACVT], upper arm cephalic vein transposition [UACVT], and upper arm basilic vein transposition [UABVT]) for dialysis patients in a single center. METHODS: A 6-year retrospective review, from 2006 to 2012, was conducted at a single institution in which the surgical outcomes for three different types of AVF transposition were reviewed. Preoperative duplex vein mapping was obtained in all patients to choose the best vein for access. RESULTS: There were 165 patients identified with 77 FACVTs, 52 UACVTs, and 36 UABVTs. Primary access maturation rates for the FACVT, UACVT, and UABVT groups were 86%, 90%, and 97%, respectively (P = .19). All transposed, matured primary AVFs were used after a mean of 9.9 weeks, without additional intervention. Primary 1-year patency for the FACVT, UACVT, and UABVT groups were 63%, 61%, and 70%, respectively (P = .71). Primary assisted 1-year patency for the FACVT, UACVT, and UABVT groups were 93%, 93%, and 100%, respectively (P > .999). Mean operating room times and time to intervention were not significantly different between the groups. The postoperative hematoma rate was 2% and wound infection rate was 2%. Multivariate analysis indicated no significant predictors of time to failure (P > .05). CONCLUSIONS: With low primary failure rates, reduced need for secondary interventions before maturation, and 1-year primary assisted patency rates in excess of 93%, our study showed that the transposition technique, in our experience, is superior to previously published literature in hemodialysis access creation.

Spontaneous Irs1 passenger mutation linked to a gene-targeted SerpinB2 allele.

In characterizing mice with targeted disruption of the SerpinB2 gene, we observed animals that were small at birth with delayed growth and decreased life expectancy. Although this phenotype cosegregated with homozygosity for the inactive SerpinB2 allele, analysis of homozygous SerpinB2-deficient mice derived from two additional independent embryonic stem (ES) cell clones exhibited no growth abnormalities. Examination of additional progeny from the original SerpinB2-deficient line revealed recombination between the small phenotype (smla) and the SerpinB2 locus. The locus responsible for smla was mapped to a 2.78-Mb interval approximately 30 Mb proximal to SerpinB2, bounded by markers D1Mit382 and D1Mit216. Sequencing of Irs1 identified a nonsense mutation at serine 57 (S57X), resulting in complete loss of IRS1 protein expression. Analysis of ES cell DNA suggests that the S57X Irs1 mutation arose spontaneously in an ES cell subclone during cell culture. Although the smla phenotype is similar to previously reported Irs1 alleles, mice exhibited decreased survival, in contrast to the enhanced longevity reported for IRS1 deficiency generated by gene targeting. This discrepancy could result from differences in strain background, unintended indirect effects of the gene targeting, or the minimal genetic interference of the S57X mutation compared with the conventionally targeted Irs1-KO allele. Spontaneous mutations arising during ES cell culture may be a frequent but underappreciated occurrence. When linked to a targeted allele, such mutations could lead to incorrect assignment of phenotype and may account for a subset of markedly discordant results from experiments independently targeting the same gene.

Comprehensive framework of factors accounting for worse aortic aneurysm outcomes in females: A scoping review.

Sex-based outcome studies have consistently documented worse results for females undergoing care for abdominal aortic aneurysms. This review explores the underlying factors that account for worse outcomes in the females sex. A scoping review of studies reporting sex-based disparities on abdominal aortic aneurysms was performed. The review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. Factors that account for worse outcomes in the females sex were identified, grouped into themes, and analyzed. Key findings of each study are reported and a comprehensive framework of these factors is presented. A total of 35 studies were identified as critical in highlighting sex-based disparities in care of patients with aortic aneurysms. We identified the following 10 interrelated themes in the chain of aneurysm care that account for differential outcomes in females: natural history, risk factors, pathobiology, biomechanics, screening, morphology, device design and adherence to instructions for use, technique, trial enrollment, and social determinants. Factors accounting for worse outcomes in the care of females with aortic aneurysms were identified and described. Some factors are immediately actionable, such as screening criteria, whereas device design improvement will require further research and development. This comprehensive framework of factors affecting care of aneurysms in females should serve as a blueprint to develop education, outreach, and future research efforts to improve outcomes in females.

Dual true and false lumen stent graft technique for endovascular repair of isolated common iliac artery aneurysm in chronic type A10 dissection.

A 52-year-old man presented with a chronic type A10 aortic dissection with subsequent aneurysmal degeneration of the left common iliac artery measuring up to 4.6 cm. He had previously undergone hemiarch replacement, which was complicated by renal failure. Owing to the presence of the growing aneurysm, he was unable to be listed for renal transplantation. He declined open operative repair. A novel dual true and false lumen stent graft technique using thoracic endografts was performed to successfully exclude the aneurysm. Follow-up imaging demonstrated aneurysm sac regression, with the patient subsequently undergoing renal transplantation.

Mimix hydroxyapatite cement use in the reconstruction of the craniofacial skeleton.

Reconstruction of the craniofacial skeleton has undergone a significant evolution during the past century. Initially, the use of autogenous bone grafts from various sites was the criterion standard. However, owing to donor site morbidity and lack of sufficient bone for large defects, surgeons have relied on various bone substitutes. Hydroxyapatite (HA) has served as an alternative to autogenous grafts, but questions regarding biocompatibility, risk of infection, and slow set times have hampered its acceptance. This article serves as a review of a single surgeon's experience using HA in the craniofacial skeleton. Eighteen patients receiving HA between March 2000 and November 2006 were observed. Sixteen underwent recontouring of skull-based bone defects, and 2 underwent recontouring for nasal and alveolar defects. The mean amount of HA used in each patient was 30.2 g. For large contour irregularities, the maximum thickness of HA used was 8 mm. The size of bone defects ameliorated averaged 4.8 cm(2). Complications occurred in 3 (16.7%) of 18 patients and included scalp hematoma and superficial cellulitis. In addition, 1 patient developed a facial abscess after placement along the alveolar floor, which necessitated removal. Hydroxyapatite represents a viable alternative to autogenous bone grafts when used in the correct manner. Hydroxyapatite should be used only for smaller defects or used in conjunction with absorbable plates when attempting to fill larger defects. Use of HA for nasal piriform augmentation or alveolar bone grafting should not be considered owing to problems with late infections.

Outcomes of a single-center experience with classification and treatment of endothermal heat-induced thrombosis after endovenous ablation.

OBJECTIVE: Endothermal heat-induced thrombosis (EHIT) is a known complication of endothermal venous ablation procedures. EHIT can lead to deep vein thrombosis/pulmonary embolism, which cause significant disability and, rarely, death. Other studies have evaluated risk factors for EHIT. There is an accepted grading system for EHIT, but there is no consensus on treatment type, duration, or follow-up. We retrospectively evaluated all cases of EHIT after radiofrequency ablation or endovenous laser ablation at our institution during a 7-year period, focusing on classification, treatment, and outcomes of EHIT. METHODS: The analysis included all patients aged >18 years who underwent radiofrequency ablation or endovenous laser ablation at our institution, Spectrum Health Hospital Vein Solutions (Grand Rapids, Mich), between January 1, 2008, and December 31, 2014. Electronic medical records were queried retrospectively to identify patients with EHIT during the study interval by International Classification of Diseases-Ninth Revision code. Demographic data, including age, gender, comorbidities (eg, history of deep venous thrombosis, hypercoagulable state, family history of blood clots, etc), body mass index, Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, and use of preoperative anticoagulation were collected for each patient in the registry. Each patient had a required postoperative duplex ultrasound (US) examination within 1 to 2 weeks of the procedure. Preoperative and postoperative US imaging data and procedure-specific data were also recorded for each patient. EHIT was graded from 1 to 4 by review of the US studies. Each patient's treatment course was reviewed for type of anticoagulation, duration of treatment, follow-up imaging, and outcome. RESULTS: From 2008 to 2014, 4799 ablations were performed at Spectrum Health Hospital Vein Center, and EHIT was identified in 70 patients. At presentation, 87% of patients were asymptomatic, 10% reported pain, and 2.9% reported swelling. Patients with EHIT grades 1 or 2 were treated with daily aspirin, and most of those with grades 3 or 4 were treated with systemic anticoagulation. Repeat US imaging was performed at 1 to 2 weeks to evaluate progression. Progression was not seen in any patients treated with systemic anticoagulation (grades 3-4). Thrombus progression occurred in two patients with grades 1 or 2 EHIT treated with aspirin. A bleeding complication occurred in one patient. CONCLUSIONS: EHIT after endovenous ablation occurred in ∼1.5% of patients, which is similar to that reported in the literature. Our review shows that systemic anticoagulation is effective in the prevention of progression with a low risk of bleeding complications. Patients with EHIT grades 1 or 2 can be treated with aspirin alone with a low risk of progression (3%).