High Prevalence of Adverse Social Determinants of Health in Dialysis Access Creation Patients in a Safety-Net Setting.

BACKGROUND: Patients receiving dialysis access surgery are often exposed to adverse social determinants of health (SDH) that negatively impact their care. Our goal was to characterize these factors experienced by our arteriovenous dialysis access patients and identify differences in health outcomes based on their SDH. METHODS: We performed a retrospective cohort study of all patients who underwent dialysis access creation (2017-2021) and were screened for SDH at a clinical visit (using THRIVE survey) implemented at an urban, safety-net hospital institution within 1 year of access creation. Demographics, procedural details, early postoperative outcomes, survey responses, and referral to our hospital's preventive food pantry were recorded. Univariable analysis and multivariable analyses were performed to assess for associations with key health outcomes. RESULTS: There were 190 patients who responded to the survey within 1 year of their operation. At least 1 adverse SDH was identified in 42 (22%) patients. Normalized to number of respondents for each question, adverse SDH identified were difficulty obtaining transportation to medical appointments (18%), food insecurity (16%), difficulty affording utilities (13%), difficulty affording medication (12%), unemployed and seeking employment (9%), unstable housing (7%), difficulty caring for family/friends (6%), and desiring more education (5%). There were 71 (37%) patients who received food pantry referrals. Mean age was 60 years and 38% of patients were female and 64% were Black. More than half of patients (57%) had a tunneled dialysis catheter (TDC) at the time of access creation. Dialysis accesses created were brachiocephalic (39%), brachiobasilic (25%), radiocephalic fistulas (16%), and arteriovenous grafts (14%). Thirty-day emergency department (ED) visits, 30-day readmissions, and 90-day mortality occurred in 23%, 21%, and 2%, respectively. On univariable and multivariable analyses, any adverse SDH determined on survey and food pantry referral were not associated with preoperative dialysis through TDCs, receiving nonautogenous dialysis access, 30-day ED visits and readmissions, or 90-day mortality. CONCLUSION: Nearly a quarter of dialysis access surgery patients at a safety-net hospital experienced adverse SDH and more than one-third received a food pantry referral. Most common difficulties experienced include difficulty obtaining transportation to medical appointments, food insecurity, and difficulty paying for utilities and medication. Although there were no differences in postoperative outcomes, the high prevalence of these adverse SDH warrants prioritization of resources in this population to ensure healthy equity and further investigation into their effects on health outcomes.

Analysis of Early Death after Elective Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: Mortality after open abdominal aortic aneurysm repair is a quality measure and early death may represent a technical complication or poor patient selection. Our objective was to analyze patients who died in the hospital within postoperative day (POD) 0-2 after elective abdominal aortic aneurysm repair. METHODS: The Vascular Quality Initiative was queried from 2003-2019 for elective open abdominal aortic aneurysm repairs. Operations were categorized as in-hospital death on POD 0-2 (POD 0-2 Death), in-hospital death beyond POD 2 (POD ≥3 Death), and those alive at discharge. Univariable and multivariable analyses were performed. RESULTS: There were 7,592 elective open abdominal aortic aneurysm repairs with 61 (0.8%) POD 0-2 Death, 156 (2.1%) POD ≥3 Death, and 7,375 (97.1%) alive at discharge. Overall, median age was 70 years and 73.6% were male. Iliac aneurysm repair and surgical approach (anterior/retroperitoneal) were similar among groups. POD 0-2 Death, compared to POD ≥3 Death and those alive at discharge, had the longest renal/visceral ischemia time, more commonly had proximal clamp placement above both renal arteries, an aortic distal anastomosis, longest operative time, and largest estimated blood loss (all P < 0.05). Postoperative vasopressor usage, myocardial infarction, stroke, and return to the operating room were most frequent in POD 0-2 Death and extubation in the operating room was least frequent (all P < 0.001). Postoperative bowel ischemia and renal failure occurred most commonly among POD ≥3 Death (all P < 0.001).On multivariable analysis, POD 0-2 Death was associated with congestive heart failure, prior peripheral vascular intervention, female sex, preoperative aspirin use, lower center volume quartile, renal/visceral ischemia time, estimated blood loss, and older age (all P < 0.05). CONCLUSIONS: POD 0-2 Death was associated with comorbidities, center volume, renal/visceral ischemia time, and estimated blood loss. Referral to high-volume aortic centers could improve outcomes.

Prevalence of Central Venous Stenosis among Black and White ESKD Patients with Dysfunctional Dialysis Access.

In the United States, significant racial and ethnic disparities exist in chronic kidney disease (CKD) and its management. Hemodialysis constitutes the main stay of renal replacement therapy for end-stage kidney disease (ESKD), which is initiated using central venous catheters (CVC) in most CKD patients in the United States. Black ESKD patients have higher usage and greater time on CVC for hemodialysis compared to White patients. This trend places Black patients at a potentially higher risk for CVC-related complications such as central venous stenosis (CVS). We posited that Black patients would have a higher prevalence and a greater risk of CVS. A retrospective review was performed of ESKD patients who underwent a fistulogram for dialysis access malfunction. CVS was defined as > 50% stenosis in the central veins. Fistulograms of 428 ESKD patients were adjudicated, and CVS was noted in 167 of these patients. Of the entire cohort, 370 fistulograms belonged to self-reported unique Black and White ESKD patients, of whom 137 patients were noted to have CVS. There was no difference in the of CVS between Black (40%) and White (41%) ESKD patients. However, a higher severity of stenosis (>70%) (P = 0.03) was noted in White ESKD patients. An unadjusted model showed a significant association between CVS and cardiovascular disease and the use of CVCs. The risk-adjusted model showed a significant association between diabetes and CVS. Unlike arterial stenotic lesions, this work for the first time demonstrated higher prevalence of severe venous stenotic lesions in White ESKD patients and linked diabetes to stenotic venous disease. This work paves the way for future studies investigating the risk and influence of race and ethnicity on CVS using a larger and diverse data set.

Access site complications are uncommon with vascular closure devices or manual compression after lower extremity revascularization.

OBJECTIVE: Vascular closure devices (VCDs) and manual compression (MC) are used to achieve hemostasis after peripheral vascular interventions (PVIs). We sought to compare perioperative outcomes between MC and four VCDs after PVI in a multicenter setting. METHODS: The Vascular Quality Initiative was queried for all lower extremity PVIs with common femoral artery access performed from 2010 to 2020. The VCDs included were MynxGrip (Cordis, Santa Clara, CA), StarClose SE (Abbott Vascular, Redwood City, CA), Angio-Seal (Terumo, Somerset, NJ), and Perclose ProGlide (Abbott Vascular). In a blinded fashion, these four VCDs (labeled A, B, C, and D) were compared to MC for baseline characteristics, procedural details, and outcomes (access site hematoma and stenosis/occlusion). Those with a sheath size >8F were excluded. Propensity score matching (1:1) was performed. Univariable and multivariable analyses were completed for unmatched and matched data. RESULTS: A total of 84,172 lower extremity PVIs were identified. Of these, 32,013 (38%) had used MC and 52,159 (62%) had used VCDs (A, 12,675; B, 6224; C, 19,872; D, 13,388). The average age was 68.7 years, and 60.4% of the patients were men. The most common indications for intervention were claudication (43.8%) and tissue loss (40.1%). Compared with MC, VCDs were used more often for patients with obesity, diabetes, and end-stage renal disease (P < .001 for all). VCDs were used less often for patients with hypertension, chronic obstructive pulmonary disease, coronary artery disease, prior percutaneous coronary and extremity interventions, and major amputation (P < .001 for all). VCD use was more common than MC during femoropopliteal (73% vs 63.8%) and tibial (33.8% vs 22.3%) interventions but less common with iliac interventions (20.6% vs 34.7%; P < .001 for all). Protamine was used less often with VCDs (19.1% vs 25.6%; P < .001). Overall, 2003 hematomas had developed (2.4%), of which 278 (13.9%) had required thrombin or surgical intervention. Compared with MC, the use of any VCD had resulted in fewer hematomas (1.7% vs 3.6%; P < .001) and fewer hematomas requiring intervention (0.2% vs 0.5%; P < .001). When divided by hemostatic technique, the rate of the development of any hematoma was as follows: MC, 3.6%; VCD A, 1.4%; VCD B, 1.2%; VCD C, 2.3%; and VCD D, 1.1% (P < .001). The rate of hematomas requiring intervention was as follows: MC, 0.5%; VCD A, 0.2%; VCD B, 0.2%; VCD C, 0.3%; and VCD D, 0.1% (P < .001). Access site stenosis/occlusion was similar between the MC and any VCD groups (0.2% vs 0.2%; P = .12). Multivariable analysis demonstrated that any VCD use and the use of the individual VCDs compared with MC were independently associated with the development of fewer hematomas. The incidence of access site stenosis/occlusion was similar between the use of any VCD and MC. The matched analysis revealed similar findings. CONCLUSIONS: Although the overall rates of hematomas requiring intervention were low regardless of hemostatic technique, VCD use, irrespective of type, compared favorably with MC, with significantly fewer access site complications after PVI.

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress ß-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated ß-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute-specific mouse models showed diminished ß-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma's AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/ß-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.

A 41-Year-Old Woman with a Cold Foot.

A 41-Year-Old Woman with a Cold FootA 41-year-old woman presented for evaluation of a painful and cold right foot. How do you approach the evaluation, and what is the diagnosis?

Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.

BACKGROUND: CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury. METHODS: IDO-1 expression in mice and human vessels was examined. IDO-1-/- mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used. RESULTS: Both global IDO-1-/- CKD mice and IDO-1 inhibitor in wild-type CKD mice showed reduced blood Kyn levels, TF expression in their arteries, and thrombogenicity compared with respective controls. Several advanced IDO-1 inhibitors downregulated TF expression in primary human aortic vascular smooth muscle cells specifically in response to uremic serum. Further mechanistic probing of arteries from an IS-specific mouse model, and CKD mice, showed upregulation of IDO-1 protein, which was due to inhibition of its polyubiquitination and degradation by IS in vascular smooth muscle cells. In two cohorts of patients with advanced CKD, blood IDO-1 activity was significantly higher in sera of study participants who subsequently developed thrombosis after endovascular interventions or vascular surgery. CONCLUSION: Leveraging genetic and pharmacologic manipulation in experimental models and data from human studies implicate IS as an inducer of IDO-1 and a perpetuator of the thrombotic milieu and supports IDO-1 as an antithrombotic target in CKD.

The Association of Body Mass Index with Outcomes after Carotid Endarterectomy.

BACKGROUND: Patients who are obese or underweight are traditionally at higher risk for perioperative morbidity and mortality. The effect of body mass index (BMI) on outcomes after carotid endarterectomy (CEA) is unclear. Our goal was to analyze the association of BMI with perioperative and long-term outcomes after elective CEA. METHODS: The Vascular Quality Initiative (VQI) database was queried from 2003-2018 for patients undergoing elective CEAs. Patients were categorized into 5 BMI cohorts - underweight (UW, BMI < 18.5 kg/m2), normal weight (NW, BMI 18.5-24.9 kg/m2), overweight (OW, BMI 25-29.9 kg/m2), obese (OB, BMI 30-39.9 kg/m2), and morbidly obese (MO, BMI ≥ 40 kg/m2). Perioperative and long-term outcomes were assessed with univariable and multivariable analyses. RESULTS: There were 89,079 patients included: 2% UW, 26% NW, 38.4% OW, 29.9% OB, and 3.6% MO. Overall, the mean age was 70.6 years, 60% were male, and 91.8% were of white race. There were significant differences among the BMI cohorts in regards to age, sex, smoking status, and comorbidities (all P < 0.05). For perioperative outcomes, the BMI cohorts differed significantly in reoperation for bleeding and 30-day mortality. On multivariable analysis, BMI was not associated with stroke or perioperative mortality. MO was associated with perioperative cardiac complications (Odds Ratios [OR] 1.26, 95% CI 1-1.57, P = 0.05). UW status was associated with increased return to the operating room (OR 1.89, 95% confidence interval [95% CI] 1.28-2.78, P = 0.001), 30-day mortality (OR 1.68, 95% CI 1-2.86, P =0.05), 1-year mortality (Hazard ratio [HR] 1.37, 95% CI 1.08-1.74, P = 0.01), and 5-year mortality (HR 1.22, 95% CI 1.06-1.41, P =0.005). CONCLUSIONS: BMI status was not associated with perioperative stroke, cranial nerve injury, or surgical site infections. Patients with MO had higher perioperative cardiac complications. UW patients have lower short and long-term survival and should be a focus for long-term targeted risk factor stratification and modification.

Intravenous drug use history is not associated with poorer outcomes after arteriovenous access creation.

OBJECTIVE: Rising intravenous drug use (IVDU) paralleled with an increasing dialysis-dependent end-stage renal disease population may pose a challenge for creating and maintaining arteriovenous (AV) access for hemodialysis. We aimed to elucidate baseline characteristics and outcomes of AV access creation in the IVDU population. METHODS: The Vascular Quality Initiative (2011-2018) was queried for patients undergoing AV access placement. Univariable and multivariable analyses comparing outcomes of patients with and without IVDU history were performed. RESULTS: Of 33,404 patients undergoing AV access creation, 601 (1.8%) had IVDU history (21.8% current and 78.2% past users). IVDU patients receiving AV access were more often younger, male, nonwhite, smokers, homeless, Medicaid recipients, and hospitalized at the time of surgery (P < .001 for all). They exhibited higher rates of congestive heart failure, chronic obstructive pulmonary disease, and human immunodeficiency virus/acquired immunodeficiency syndrome (P < .05 for all). They more frequently had tunneled catheters at the time of access creation (53.6% vs 42%; P < .001) and had a previous AV access (25.3% vs 21.7%; P = .002). IVDU patients more often received prosthetic AV grafts (28.6% vs 18%; P < .001) and more often had anastomoses created to basilic veins (33.1% vs 23.2%; P < .001) but less often to cephalic veins (36.8% vs 57.7%; P < .001). IVDU patients had longer postoperative length of stay (2 ± 6 days vs 0.9 ± 5 days; P < .001) but no significant difference in 30-day mortality (1.7% vs 1.2%; P = .3). Comparing IVDU vs no IVDU cohorts, 1-year access infection-free survival (85.4% vs 86.6%; P = .382), primary patency loss-free survival (39.5% vs 37.9%; P = .335), endovascular/open reintervention-free survival (58% vs 57%; P = .705), and overall survival (89.7% vs 88.9%; P = .635) were similar. On multivariable analysis, IVDU was independently associated with postoperative length of stay (odds ratio, 1.64; 95% confidence interval, 1.35-2; P < .001) but not with 30-day mortality or 1-year infection-free survival, primary patency loss-free survival, reintervention-free survival, and all-cause mortality. The null results were confirmed in a propensity score-matched cohort. CONCLUSIONS: IVDU history was uncommon among patients undergoing AV access creation at Vascular Quality Initiative centers and was not independently associated with major morbidity or mortality postoperatively. IVDU patients more often received grafts or autogenous access with anastomoses to basilic veins. Although these patients frequently have more comorbidities, IVDU should not deter AV access creation.

Periprocedural Outcomes in Patients on Chronic Anticoagulation Undergoing Fistulograms.

BACKGROUND: Management of antithrombotic therapy with warfarin in patients undergoing fistulograms and possible interventions is controversial and difficult because of lack of adequate outpatient bridging options. Our goal was to assess periprocedural outcomes in patients managed using different anticoagulation strategies. METHODS: A retrospective, single-institution analysis of all patients on chronic anticoagulation with warfarin undergoing fistulograms from 2011 to 2017 was performed. Anticoagulation management strategies were classified as suspended warfarin (SW), continued warfarin (CW), and a heparin bridge with suspended warfarin (HB). Periprocedural outcomes were analyzed. RESULTS: There were 87 patients on chronic anticoagulation with warfarin who underwent 175 fistulograms. Median age was 63 years, and 43.4% were women. Indications for warfarin included atrial fibrillation (53%), prior pulmonary embolism/deep vein thrombosis (29%), and hypercoagulable state (14%). Distribution was SW (60%), CW (26%), and HB (14%). Approximately half (53%) were same-day procedures, 30% occurred during access-related admissions, and 14% were performed during nonaccess-related admissions. Common indications for a fistulogram included difficulty with dialysis (63.4%), access thrombosis (20.6%), and poor maturation (10.3%). Interventions included angioplasty (82.9%), thrombectomy/embolectomy (20.6%), and stenting (8.6%). Thirty-day outcomes for SW versus CW versus HB were similar for bleeding complications (5.7%, 6.5%, 8.3%; P = 0.89), systemic thrombotic complications (3.8%, 2.2%, 0%; P = 0.569), access rethrombosis (7.6%, 13%, 12.5%; P = 0.517), and tunneled dialysis catheter placement (11.4%, 13%, 12.5%; P = 0.958). After excluding procedures performed during a nonaccess-related admission, length of stay (LOS) was highest among HB (9.6 ± 7.8 days) compared with SW (2.6 ± 5.9 days) and CW (1 ± 2.8 days), (P < 0.0001). CONCLUSIONS: CW therapy in patients undergoing fistulograms was not associated with increased morbidity and was associated with shorter LOS. Bridging with heparin is not associated with improved outcomes, warranting a thorough consideration of continuing warfarin is safe and may streamline preservation of dialysis accesses without significantly increasing resource utilization.

Association of Anesthesia Type with Outcomes after Outpatient Brachiocephalic Arteriovenous Fistula Creation.

BACKGROUND: Brachiocephalic arteriovenous fistulas (BCFs) are commonly placed in outpatient settings. The impact of general anesthesia (GA), regional anesthesia (RA), or local anesthesia (LA) on perioperative recovery and fistula maturation/patency after outpatient BCF creations is unknown. We evaluated whether outcomes of outpatient BCF creations vary based on anesthesia modality. METHODS: The Vascular Quality Initiative (2011-2018) national database was queried for outpatient BCF creations. Anesthesia modalities included GA, RA, and LA. Perioperative, 3-month, and 1-year outcomes were compared between GA versus RA/LA anesthesia types. RESULTS: Among 3,527 outpatient BCF creations, anesthesia types were GA in 1,043 (29.6%), RA in 1,150 (32.6%), and LA in 1,334 (37.8%). Patients receiving GA were more often younger, obese, Medicaid recipients, without coronary artery disease, and treated in non-office-based settings (P < 0.05 for all). GA compared with RA/LA cohorts were more often admitted postoperatively (5.3% vs. 2.4%, P < 0.001) but had similar rates of thirty-day mortality (0.9 vs. 0.6%, P = 0.39). 3-month access utilization for hemodialysis was lower in GA than in RA/LA cohorts (12.6% vs. 23.6%, P < 0.001). The Kaplan-Meier analysis showed that GA and RA/LA cohorts had similar 1-year primary access occlusion-free survival (43.6% vs. 47.1%, P = 0.24) and endovascular/open reintervention-free survival (57.2% vs. 57.6%, P = 0.98). On multivariable analysis, GA compared with RA/LA use was independently associated with increased postoperative admission (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.08-2.67, P = 0.02) and decreased 3-month access utilization (OR: 0.39, 95% CI: 0.25-0.61, P < 0.001) but had similar 1-year access occlusion (hazard ratio [HR]: 1.09, 95% CI: 0.9-1.32, P = 0.36) and reintervention (HR: 1.02, 95% CI: 0.82-1.26, P = 0.88). On subgroup analysis of the RA/LA cohort, RA compared with LA was associated with increased 3-month access utilization (OR: 1.6, 95% CI: 1.01-2.5; P = 0.04) and 1-year access reintervention (HR: 1.46, 95% CI: 1.12-1.89), but had similar 1-year access occlusion (HR: 1.2, 95% CI: 0.95-1.51, P = 0.13). CONCLUSIONS: Compared with RA/LA use, GA use in patients undergoing outpatient BCF creations was associated with increased hospital admissions, decreased access utilization at 3 months, and similar 1-year access occlusion and reintervention. RA/LA is preferable to expedite recovery and access utilization.

Perioperative and long-term outcomes after percutaneous thrombectomy of arteriovenous dialysis access grafts.

OBJECTIVE: Maintenance of functional arteriovenous grafts (AVGs) for dialysis is difficult secondary to low primary patency, need for reinterventions, and limited alternative dialysis access options. We assessed our experience with percutaneous thrombectomy for treatment of occluded AVGs. METHODS: We performed a retrospective analysis of all percutaneous thrombectomies for AVGs from 2015 to 2017. These were generally performed using mechanical thrombectomy and occasional chemical tissue plasminogen activator thrombolysis, over-the-wire balloon embolectomy for inflow, and adjunctive inflow and outflow interventions as necessary. Perioperative outcomes, long-term patency, reinterventions, and need for new permanent access placement were analyzed. RESULTS: There were 218 percutaneous thrombectomies performed on 86 AVGs in 77 patients. Approximately half (53.2%) of the patients were male and 68.8% were black. Mean age was 61.1 ± 13.0 years. At the time of thrombectomy, 73.8% underwent venous outflow interventions and 4.5% underwent arterial inflow interventions. Within 30 days, 24.8% of declotted grafts underwent repeated percutaneous thrombectomy, 14.3% required tunneled dialysis catheter placement, 4% developed minor access site or graft infections, and one patient underwent surgical arterial thrombectomy for arm ischemia. There were no venous thromboembolic, cardiopulmonary, or cerebrovascular complications or clinically significant pulmonary embolism. At 1 year and 3 years after percutaneous thrombectomy, freedom from repeated thrombosis was 37% and 18%, respectively, and freedom from new dialysis access placement was 66% and 51%, respectively. Overall patient survival was 82% at 3 years. CONCLUSIONS: Percutaneous thrombectomy of AVGs is safe and is associated with acceptable patency rates. This minimally invasive method extends AVG use for these high-risk patients with limited dialysis access options.

Haploinsufficiency of Casitas B-Lineage Lymphoma Augments the Progression of Colon Cancer in the Background of Adenomatous Polyposis Coli Inactivation.

Casitas B-lineage lymphoma (c-Cbl) is a recently identified ubiquitin ligase of nuclear ß-catenin and a suppressor of colorectal cancer (CRC) growth in cell culture and mouse tumor xenografts. We hypothesized that reduction in c-Cbl in colonic epithelium is likely to increase the levels of nuclear ß-catenin in the intestinal crypt, augmenting CRC tumorigenesis in an adenomatous polyposis coli (APCΔ14/+) mouse model. Haploinsufficient c-Cbl mice (APCΔ14/+ c-Cbl+/-) displayed a significant (threefold) increase in atypical hyperplasia and adenocarcinomas in the small and large intestines; however, no differences were noted in the adenoma frequency. In contrast to the APCΔ14/+ c-Cbl+/+ mice, APCΔ14/+ c-Cbl+/- crypts showed nuclear ß-catenin throughout the length of the crypts and up-regulation of Axin2, a canonical Wnt target gene, and SRY-box transcription factor 9, a marker of intestinal stem cells. In contrast, haploinsufficiency of c-Cbl+/- alone was insufficient to induce tumorigenesis regardless of an increase in the number of intestinal epithelial cells with nuclear ß-catenin and SRY-box transcription factor 9 in APC+/+ c-Cbl+/- mice. This study demonstrates that haploinsufficiency of c-Cbl results in Wnt hyperactivation in intestinal crypts and accelerates CRC progression to adenocarcinoma in the milieu of APCΔ14/+, a phenomenon not found with wild-type APC. While emphasizing the role of APC as a gatekeeper in CRC, this study also demonstrates that combined partial loss of c-Cbl and inactivation of APC significantly contribute to CRC tumorigenesis.

Shunt intention during carotid endarterectomy in the early symptomatic period and perioperative stroke risk.

OBJECTIVE: Whether recent stroke mandates planned shunting during carotid endarterectomy (CEA) is controversial. Our goal was to determine associations of various shunting practices with postoperative outcomes of CEAs performed after acute stroke. METHODS: The Vascular Quality Initiative database (2010-2018) was queried for CEAs performed within 14 days of an ipsilateral stroke. Surgeons who prospectively planned to shunt either shunted routinely per their usual practice or shunted selectively for preoperative indications. Surgeons who prospectively planned not to shunt either shunted selectively for intraoperative indications or did not shunt. Univariable and multivariable analyses compared shunting approaches. RESULTS: There were 5683 CEAs performed after acute ipsilateral stroke. Surgeons planned to shunt in 56.1% of cases. Patients whose surgeons planned to shunt vs planned not to shunt were more likely to have severe contralateral stenosis (8.8% vs 6.9%; P = .008), to receive general anesthesia (97.5% vs 89.1%; P < .001), and to undergo conventional CEA (94% vs 81.8%; P < .001). Unadjusted outcomes were similar between the cohorts for operative duration (124.3 ± 48.1 minutes vs 123.6 ± 47 minutes; P = .572) and 30-day stroke (3.4% vs 3%; P = .457), myocardial infarction (1.1% vs 0.8%; P = .16), and mortality (1.6% vs 1.3%; P = .28). On multivariable analysis, planning to shunt vs planning not to shunt was associated with similar risk of 30-day stroke (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.82-1.67; P = .402). On subgroup analysis, in 38.4% patients, no shunt was placed, whereas the remainder received routine shunts (44.4%), preoperatively indicated shunts (11.6%), and intraoperatively indicated shunts (5.5%). Compared with no shunting, shunting by surgeons who routinely shunt was associated with a similar stroke risk (OR, 1.39; 95% CI, 0.91-2.13; P = .129), but shunting by surgeons who selectively shunt on the basis of preoperative indications (OR, 2.11; 95% CI, 1.22-3.63; P = .007) or intraoperative indications (OR, 3.34; 95% CI, 1.86-6.01; P < .001) was associated with increased stroke risk. Prior coronary revascularization independently predicted increased intraoperatively indicated shunting (OR, 1.37; 95% CI, 1.05-1.8; P = .022). CONCLUSIONS: In CEAs performed after acute ipsilateral stroke, there is no difference in postoperative stroke risk when surgeons prospectively plan to shunt or not to shunt. Shunting is often not necessary; however, when shunting is performed, routine shunters achieve better outcomes.

Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease.

Emerging evidence in animal models of chronic kidney disease (CKD) implicates Aryl Hydrocarbon Receptor (AHR) signaling as a mediator of uremic toxicity. However, details about its tissue-specific and time-dependent activation in response to various renal pathologies remain poorly defined. Here, a comprehensive analysis of AHR induction was conducted in response to discrete models of kidney diseases using a transgenic mouse line expressing the AHR responsive-promoter tethered to a ß-galactosidase reporter gene. Following validation using a canonical AHR ligand (a dioxin derivative), the transgenic mice were subjected to adenine-induced and ischemia/reperfusion-induced injury models representing CKD and acute kidney injury (AKI), respectively, in humans. Indoxyl sulfate was artificially increased in mice through the drinking water and by inhibiting its excretion into the urine. Adenine-fed mice showed a distinct and significant increase in ß-galactosidase in the proximal and distal renal tubules, cardiac myocytes, hepatocytes, and microvasculature in the cerebral cortex. The pattern of ß-galactosidase increase coincided with the changes in serum indoxyl sulfate levels. Machine-learning-based image quantification revealed positive correlations between indoxyl sulfate levels and ß-galactosidase expression in various tissues. This pattern of ß-galactosidase expression was recapitulated in the indoxyl sulfate-specific model. The ischemia/reperfusion injury model showed increase in ß-galactosidase in renal tubules that persisted despite reduction in serum indoxyl sulfate and blood urea nitrogen levels. Thus, our results demonstrate a relationship between AHR activation in various tissues of mice with CKD or AKI and the levels of indoxyl sulfate. This study demonstrates the use of a reporter gene mouse to probe tissue-specific manifestations of uremia in translationally relevant animal models and provide hypothesis-generating insights into the mechanism of uremic toxicity that warrant further investigation.

Implementing and Evaluating a Multihospital Standardized Opioid Curriculum for Surgical Providers.

OBJECTIVE: (1) To identify gaps in providers knowledge on opioid medication and dosing, patient-specific characteristics that require alterations in dosing, and patient monitoring and treatment adjustments. (2) To evaluate an educational intervention aimed at minimizing these deficits. DESIGN: Observational prospective study. Providers took an anonymous paired pre-and posteducation knowledge assessment before and after participating in a 75-minute educational session. Results before and after the educational session were compared. SETTING: Surgical providers included nurse practitioners, physician assistants, preinterns, and general surgery residents across 4 quaternary care hospitals in Boston. Participants There were 194 participants and 174 completed both pre- and posteducation knowledge assessments. RESULTS: Average scores on the educational assessment increased from 59% before the course to 68% after the session. Posteducation, providers reported increased comfort in prescribing and 95% stated that the curriculum would impact their practice. CONCLUSIONS: Surgical providers at multiple hospitals have significant gaps in knowledge for optimal prescribing and management of opioid prescriptions. A 75-minute opioid education session increased prescriber knowledge as well as comfort in prescribing. This multicenter study demonstrates how an educational initiative can be implemented broadly and result in decreased knowledge gaps.

Risk assessment of significant upper extremity arteriovenous graft infection in the Vascular Quality Initiative.

OBJECTIVE: Infectious complications of arteriovenous grafts (AVGs) are a major source of morbidity. Our aim was to characterize contemporary risk factors for upper extremity AVG infection. METHODS: The Vascular Quality Initiative (2011-2018) was queried for all patients undergoing upper extremity AVG creation. AVG infection was classified as an infection treated with antibiotics, incision and drainage, or graft removal. Multivariable analyses were used to evaluate risk factors for short- and long-term AVG infection. RESULTS: Of 1758 upper extremity AVGs, 49 (2.8%) developed significant infection within 3 months, resulting in incision and drainage in 24% and graft removal in 76% of cases. None were managed with antibiotics alone in the study sample. Patients with significant AVG infection were more likely to be white, to be insured, to have a history of coronary artery bypass graft and intravenous (IV) drug use, to be undergoing a concomitant vascular procedure, and to be discharged on an anticoagulant. In multivariable analysis, significant AVG infection within 3 months was associated with IV drug use history (odds ratio [OR], 5; 95% confidence interval [CI], 1.75-14.3; P = .003), discharge to a health care facility (OR, 2.66; 95% CI, 1.07-6.63; P = .035), discharge on an anticoagulant (OR, 2.31; 95% CI, 1.13-4.72; P = .021), white race (OR, 2.3; 95% CI, 1.21-4.34; P = .011), and female sex (OR, 2.02; 95% CI, 1.06-3.85; P = .033). Kaplan-Meier analysis showed that freedom from graft site infection at 1 year was 96.4%. Longer term graft infection at 1 year was independently associated with IV drug use history (hazard ratio [HR], 1.98; 95% CI, 1.06-3.68; P = .032), initial discharge to a health care facility (HR, 1.88; 95% CI, 1.19-2.97; P = .007), and white race (HR, 1.64; 95% CI, 1.23-2.19; P = .001). CONCLUSIONS: Although significant AVG infection was uncommon in the Vascular Quality Initiative, the majority were treated with graft removal. In select high-risk patients, extra care should be taken and alternative forms of arteriovenous access may be considered.

Perioperative outcomes after lower extremity bypass and peripheral vascular interventions in patients with morbid obesity and superobesity.

OBJECTIVE: Although the effect of body mass index (BMI) on the treatment of infrainguinal peripheral artery disease has been reported, outcomes of patients on the upper end of the obesity spectrum, including morbid obesity (MO) and superobesity (SO), are unclear. Our goal was to analyze perioperative outcomes after lower extremity bypass (LEB) and peripheral vascular interventions (PVIs) in this population of patients. METHODS: The Vascular Quality Initiative was reviewed for all infrainguinal peripheral artery disease interventions from 2010 to 2017. All patients were categorized into four groups: nonobese (BMI 18.5-29.9 kg/m2), obese (BMI 30-39.9 kg/m2), morbidly obese (BMI 40-49.9 kg/m2), and superobese (BMI ≥50 kg/m2). Patient and case details were recorded. Multivariable analysis was used to analyze outcomes. For statistical analysis, MO and SO groups were combined. RESULTS: We identified 29,138 LEB cases (68.5% nonobese, 28.3% obese, 2.9% morbidly obese, 0.3% superobese) and 81,405 PVI cases (66.6% nonobese, 29.2% obese, 3.6% morbidly obese, 0.5% superobese). For both LEB and PVI, patients with MO and SO were more likely to be younger, female, nonsmokers, and ambulatory (P < .05). They also more often had diabetes, end-stage renal disease, congestive heart failure, and fewer previous inflow procedures (P < .05). LEB and PVI interventions in patients with MO and SO were less often elective and more often performed for tissue loss. Multivariable analysis showed that LEB in patients with MO and SO was not significantly associated with increased perioperative cardiac complications, return to the operating room, or mortality. Patients with MO and SO were significantly associated with increased surgical site infection (odds ratio, 1.43; 95% confidence interval, 1.02-1.98; P = .03) and increased respiratory complications (odds ratio, 1.6; 95% confidence interval, 1.11-2.31; P = .01). Multivariable analysis showed that MO and SO were not significantly associated with periprocedural access site hematoma, access site stenosis or occlusion, or mortality after PVI. CONCLUSIONS: MO and SO were significantly associated with increased incidence of wound infections and respiratory complications after LEB but were not significantly associated with increased incidence after PVI. Overall, patients with MO and SO have more comorbidities and more advanced presentation of vascular disease at the time of intervention, but MO and SO alone should not deter necessary and appropriate revascularization.

Lower extremity critical limb ischemia: A review of clinical features and management.

Lower extremity critical limb ischemia (CLI) represents symptoms related to end-stage atherosclerotic peripheral arterial disease manifested by rest pain and tissue loss. It is associated with increased risk of limb amputation and cardiovascular-related mortality. The prevalence and cost of CLI are expected to increase with both the aging of the U.S. population and continued influence of smoking and diabetes. Treatments encompass measures to reduce cardiovascular risk and preserve limb viability. Despite increasing popularity of endovascular modalities, revascularization with either surgical bypass or endovascular intervention is the cornerstone of therapy. Adequate Level I data to guide decisions regarding optimal strategies to treat CLI, particularly in patients who are candidates for both open and percutaneous approaches, are currently lacking. Ongoing randomized controlled trials aim to resolve the clinical equipoise.

Resident involvement in minimally-invasive vs. open procedures.

BACKGROUND: The objective of this study was to evaluate the impact of resident involvement on surgical outcomes in laparoscopic compared to open procedures. METHODS: The American College of Surgeons National Surgical Quality Improvement Program 2007-2012 was queried for open and laparoscopic ventral hernia repair (VHR), inguinal hernia repair (IHR), splenectomy, colectomy, or cholecystectomy (CCY). Multivariable regression analyses were performed to assess the impact of resident involvement on surgical outcomes. RESULTS: In total, 88,337 VHR, 20,586 IHR, 59,254 colectomies, 3301 splenectomies, and 95,900 CCY were identified. Resident involvement was predictive for major complication during open VHR (AOR, 1.29; p < 0.001), but not during any other procedure. Resident participation significantly prolonged operative time for open, as well as laparoscopic VHR, IHR, colectomy, splenectomy, and CCY (all p < 0.01). CONCLUSIONS: The results of this study suggest that resident participation has a similar impact on surgical outcomes during laparoscopic and open surgery, and is generally safe.