Development of a comorbidity index for patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) and open surgical repair (OSR) are two modalities to treat patients with abdominal aortic aneurysm (AAA). Alternative to individual comorbidity adjustment, a summary comorbidity index is a weighted composite score of all comorbidities that can be used as standard metric to control for comorbidity burden in clinical studies. This study aimed to develop summary comorbidity indices for patients who underwent AAA repair. METHODS: Patients who went under EVAR or OSR were identified in National Inpatient Sample (NIS) between the last quarter of 2015 to 2020. In each group, patients were randomly sampled into experimental (2/3) and validation (1/3) groups. The weights of Elixhauser comorbidities were determined from a multivariable logistic regression and single comorbidity indices were developed for EVAR and OAR groups, respectively. RESULTS: There were 34,668 patients underwent EVAR (2.19% mortality) and 4792 underwent OSR (10.98% mortality). Both comorbidity indices had moderate discriminative power (EVAR c-statistic, 0.641; 95% confidence interval [CI], 0.616-0.665; OSR c-statistic, 0.600; 95% CI, 0.563-0.630) and good calibration (EVAR Brier score, 0.021; OSR Brier score, 0.096). The indices had significantly better discriminative power (DeLong P <.001) than the Elixhauser Comorbidity Index (ECI) (EVAR c-statistic, 0.572; 95% CI, 0.546-0.597; OSR c-statistic, 0.502; 95% CI, 0.472-0.533). For internal validation, both indices had similar performance compared with individual comorbidity adjustment (EVAR DeLong P = .650; OSR DeLong P = .431). These indices demonstrated good external validation, exhibiting comparable performance to their respective validation groups (EVAR DeLong P = .891; OSR DeLong P = .757). CONCLUSIONS: ECI, the comorbidity index formulated for the general population, exhibited suboptimal performance in patients who underwent AAA repair. In response, we developed summary comorbidity indices for both EVAR and OSR for AAA repair, which were internally and externally validated. The EVAR and OSR comorbidity indices outperformed the ECI in discriminating in-hospital mortality rates. They can standardize comorbidity measurement for clinical studies in AAA repair, especially for studies with small samples such as single-institute data sources to facilitate replication and comparison of results across studies.

Comparative assessment of racial disparity in 30-day outcomes for Asian Americans undergoing carotid endarterectomy.

OBJECTIVE: Carotid endarterectomy (CEA) is an effective treatment for carotid stenosis. All previous studies on racial disparity of CEA outcomes omitted Asian Americans. This study aimed to address this gap by investigating racial disparities in 30-day outcomes following CEA among Asian Americans. METHODS: Asian American and Caucasian patients who underwent CEA were identified in the American College of Surgeons National Surgical Quality Improvement Program targeted database from 2011 to 2021. Patients with age less than 18 years old were excluded. Patients with symptomatic and asymptomatic carotid stenosis were examined separately. A 1:5 propensity-score matching was used to address preoperative differences. Thirty perioperative outcomes were assessed. RESULTS: There were 380 Asian Americans (2.27%) and 13,250 Caucasians (79.18%) with symptomatic carotid stenosis who underwent CEA. Also, 289 Asian Americans (1.40%) and 18,257 Caucasians (88.14%) with asymptomatic carotid stenosis had CEA. Asian Americans undergoing CEA presented with higher comorbid burdens and more severe symptomology. Also, asymptomatic Asian Americans were more likely to undergo surgeries for mild stenosis (<50%), which is not in line with practice guidelines. After 1:5 propensity-matching, all symptomatic Asian Americans were matched to 1550 Caucasian patients, and all asymptomatic Asian Americans were matched to 1445 Caucasians; preoperative differences were addressed. Asian Americans exhibited low overall 30-day mortality (symptomatic, 1.61%; asymptomatic, 0.35%) and stroke (symptomatic, 2.26%; asymptomatic, 0.69%). All perioperative outcomes were comparable to Caucasians, with the exception that Asian Americans experienced longer operation times. CONCLUSIONS: Evidence suggested that Asian Americans with asymptomatic stenosis were underrepresented in CEA. After propensity-score matching, Asian Americans demonstrated comparable 30-day outcomes to Caucasians. These suggest that, when afforded equal access to quality health care, CEA serves as an effective treatment for carotid stenosis among Asian Americans. Therefore, efforts may be aimed at addressing health care access, potentially in the screening for asymptomatic carotid stenosis in Asian Americans. This would ensure they have equitable benefits from CEA. Nevertheless, the exact preoperative differences and long-term CEA outcomes in Asian Americans should warrant further examination in future studies.

Systematic literature review of real-world evidence for treatments in HR+/HER2- second-line LABC/mBC after first-line treatment with CDK4/6i.

BACKGROUND: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC. METHODS: MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens. RESULTS: Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics. CONCLUSIONS: The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.

The 5-Factor Modified Frailty Index is a Concise and Effective Predictor of 30-Day Adverse Outcomes in Carotid Endarterectomy.

INTRODUCTION: Frailty is a clinically identifiable condition characterized by heightened vulnerability. The 5-item Modified Frailty Index provides a concise calculation of frailty that has proven effective in predicting adverse perioperative outcomes across a variety of surgical disciplines. However, there is a paucity of research examining the validity of 11-item Modified Frailty Index (mFI-5) in carotid endarterectomy (CEA). This study aimed to investigate the association between mFI-5 and 30-day outcomes of CEA. METHODS: Patients underwent CEA were identified from American College of Surgeons National Surgical Quality Improvement Program targeted database from 2012 to 2021. Patients with age<18 were excluded. Patients were stratified into four cohorts based on their mFI-5 scores: 0, 1, 2, or 3+. Multivariable logistic regression was used to compare 30-day perioperative outcomes adjusting for preoperative variables with P value<0.1. RESULTS: Compared to controls (mFI-5 = 0), patients mFI-5 = 1 had higher risk of stroke (adjusted odds ratio [aOR] = 1.333, P = 0.02), unplanned operation (aOR = 1.38, P < 0.01), and length of stay (LOS) > 7 days (aOR = 0.814, P < 0.01). Patients with mFI-5 = 2 had higher stroke (aOR = 1.719, P < 0.01), major adverse cardiovascular events (MACE) (aOR = 1.315, P = 0.01), sepsis (aOR = 2.243, P = 0.01), discharge not to home (aOR = 1.200, P < 0.01), 30-day readmission (aOR = 1.405, P < 0.01). Compared with controls, patients with mFI-5≥3 had higher mortality (aOR = 1.997 P = 0.02), MACE (aOR = 1.445, P = 0.03), cardiac complications (aOR = 1.901, P < 0.01), pulmonary events (aOR = 2.196, P < 0.01), sepsis (aOR = 3.65, P < 0.01), restenosis (aOR = 2.606, P = 0.02), unplanned operation (aOR = 1.69, P < 0.01), LOS>7 days (aOR = 1.425, P < 0.01), discharge not to home (aOR = 2.127, P < 0.01), and 30-day readmission (aOR = 2.427, P < 0.01). CONCLUSIONS: The mFI-5 is associated with 30-day mortality and complications including stroke, MACE, cardiac complications, pulmonary complications, sepsis, and restenosis. Additionally, elevated mFI-5 scores correlate with an increased likelihood of unplanned operations, extended LOS, discharge to facilities other than home, and 30-day readmissions, all of which could negatively impact long-term prognosis. Therefore, mFI-5 can serve as a concise yet effective metric of frailty in patients undergoing CEA.

The 5-Factor Modified Frailty Index is a Succinct yet Effective Predictor of Adverse Outcomes in Patients Undergoing Open Surgery for Abdominal Aortic Aneurysm.

BACKGROUND: Frailty is an age-related, clinically recognizable state marked by increased susceptibility. The 5-item Modified Frailty Index (mFI-5) offers a concise assessment of frailty and has demonstrated its efficacy in various surgical fields. While the mFI-5 has been validated for endovascular aneurysm repair for abdominal aortic aneurysm (AAA), its applicability in open surgical repair (OSR) for AAA remains largely unexplored. This study sought to evaluate the utility of mFI-5 in predicting 30-day outcomes following OSR for AAA. METHODS: Patients underwent OSR for AAA were identified in American College of Surgeons National Surgical Quality Improvement Program-targeted database from 2012 to 2021. Patients were stratified into 3 cohorts: mFI-5 score of 0 (control), 1, and 2+. Multivariable logistic regression was used to compare 30-day perioperative outcomes between frail patients and controls adjusting preoperative variables with P value <0.1. RESULTS: Of the 5,249 patients who underwent OSR for AAA, 1,043 were controls, 2,938 had an mFI-5 score of 1 and 1,268 had an mFI-5 score of 2+. When compared to the control group, patients with an mFI-5 = 1 were more likely to have pulmonary events (adjusted odds ratio (aOR) = 1.452, P < 0.01), bleeding events (aOR = 1.33, P < 0.01), wound complications (aOR = 2.214, P < 0.01), ischemic colitis (aOR = 1.616, P = 0.01), and unplanned reoperation (aOR = 1.292, P = 0.04). Those with an mFI-5 = 2+ demonstrated higher risks of mortality (aOR = 1.709, P < 0.01), major adverse cardiovascular events (aOR = 1.347, P = 0.04), pulmonary events (aOR = 2.045, P < 0.01), renal dysfunction (aOR = 1.568, P < 0.01), sepsis (aOR = 1.587, P = 0.01), bleeding events (aOR = 1.429, P < 0.01), wound complications (aOR = 2.338, P < 0.01), ischemic colitis (aOR = 1.775, P = 0.01), unplanned reoperation (aOR = 1.445, P = 0.01), operation over 4 hours (aOR = 1.34, P < 0.01), length of stay over 7 days (aOR = 1.324, <0.01), discharge not to home (aOR = 1.547, P < 0.01), 30-day readmission (aOR = 1.657, P = 0.01). CONCLUSIONS: The mFI-5 emerges as a succinct yet effective indicator of frailty for patients undergoing OSR for AAA. Especially, an mFI-5 score of 2+ is linked with increased 30-day mortality and complications. As such, mFI-5 can be used as a valuable screening tool for frailty in patients undergoing OSR for AAA.

Locoregional Anesthesia Has Lower Risks of Cardiac Complications Than General Anesthesia After Prolonged Endovascular Repair of Abdominal Aortic Aneurysms.

OBJECTIVES: Although general anesthesia is the primary anesthesia in endovascular aneurysm repair (EVAR), some studies suggest locoregional anesthesia could be a feasible alternative for eligible patients. However, most evidence was from retrospective studies and was subjected to an inherent selection bias that general anesthesia is often chosen for more complex and prolonged cases. To mitigate this selection bias, this study aimed to compare 30-day outcomes of prolonged, nonemergent, intact, infrarenal EVAR in patients undergoing locoregional or general anesthesia. In addition, risk factors associated with prolonged operative time in EVAR were identified. DESIGN: Retrospective large-scale national registry study. SETTING: American College of Surgeons National Surgical Quality Improvement Program targeted database from 2012 to 2022. PARTICIPANTS: A total of 4,075 out of 16,438 patients (24.79%) had prolonged EVAR. Among patients with prolonged EVAR, 324 patients (7.95%) were under locoregional anesthesia. There were 3,751 patients (92.05%) under general anesthesia, and 955 of them were matched to the locoregional anesthesia cohort. INTERVENTIONS: Patients undergoing infrarenal EVAR were included. Exclusion criteria included age <18 years, emergency cases, ruptured abdominal aortic aneurysm, and acute intraoperative conversion to open. Only cases with prolonged operative times (>157 minutes) were selected. A 1:3 propensity-score matching was used to address demographics, baseline characteristics, aneurysm diameter, distant aneurysm extent, and concomitant procedures between patients under locoregional and general anesthesia. Thirty-day postoperative outcomes were assessed. Moreover, factors associated with prolonged EVAR were identified by multivariate logistic regression. MEASUREMENTS AND MAIN RESULTS: Except for general anesthesia contraindications, patients undergoing locoregional or general anesthesia exhibited largely similar preoperative characteristics. After propensity-score matching, patients under locoregional and general anesthesia had a lower risk of myocardial infarction (0.93% v 2.83%, p = 0.04), but comparable 30-day mortality (3.72% v 2.72%, p = 0.35) and other complications. Specific concomitant procedures, aneurysm anatomy, and comorbidities associated with prolonged EVAR were identified. CONCLUSIONS: Locoregional anesthesia can be a safe and effective alternative to general anesthesia, particularly in EVAR cases with anticipated complexity and prolonged operative times, as it offers the potential benefit of reduced cardiac complications. Risk factors associated with prolonged EVAR can aid in preoperative risk stratification and inform the decision-making process regarding anesthesia choice.

Prior abdominal surgery is not associated with 30-day mortality or morbidities after endovascular repair of complex abdominal aortic aneurysm.

BACKGROUND: Prior abdominal surgery (PAS) has the potential to affect outcomes of abdominal aortic aneurysm (AAA) repair. Recently, endovascular aneurysm repair (EVAR) has been expanded among patients with complex AAA, which involves visceral branches in the upper abdominal aortic. However, outcomes of EVAR for complex AAA in patients with PAS have not been examined. This study aimed to investigate the impact of PAS on 30-day outcomes in EVAR for complex AAA. METHODS: Patients who underwent EVAR for complex AAA were identified in ACS-NSQIP targeted database from 2012 to 2022. Complex AAA was defined as juxtarenal, suprarenal, or pararenal proximal extent, Type IV thoracoabdominal aneurysm, or aneurysms treated with Zenith Fenestrated endograft. Patients with age less than 18 years, ruptured AAA with or without hypotension, acute intraoperative conversion to open, and emergency presentation were excluded. Multivariable logistic regression was used to compare 30-day postoperative outcomes of patients with and without PAS. Demographics, baseline characteristics, aneurysm diameter, indication for surgery, proximal and distant aneurysm extent, anesthesia, and concomitant procedures were adjusted. RESULTS: There were 515 (28.34%) and 1302 (71.66%) patients with and without PAS, respectively, who underwent EVAR for complex AAA. Patients with and without PAS had comparable 30-day mortality (3.11% vs 3.00%, aOR = 0.766, 95 CI = 0.407-1.442, p = .41). Organ system complications including cardiac complications, stroke, pulmonary complications, and renal complications were comparable between patients with and without PAS. All other 30-day outcomes were similar between groups. However, patients with PAS had higher 30-day readmission rate (11.65% vs 7.14%, aOR = 1.634, 95 CI = 1.145-2.331, p = .01). CONCLUSION: While PAS has high prevalence among patients undergoing EVAR for complex AAA, it does not impact 30-day mortality and morbidities. Thus, EVAR for complex AAA can be considered safe for patients with PAS in terms of short-term outcomes, despite the long-term prognosis in these patients being needed in further studies.

Risk factors associated with the severity of pericoronitis of mandibular third molar.

PURPOSE: The factors related to pericoronitis severity are unclear, and this study aimed to address this knowledge gap. MATERIALS AND METHODS: In total, 113 patients with pericoronitis were included, and their demographic, clinical, and radiographic characteristics were recorded. The Patient-Clinician Pericoronitis Classification was used to score and categorize the severity of pericoronitis. Statistical analysis was conducted to examine the participants' characteristics, validity of the Patient-Clinician Pericoronitis Classification, and risk factors associated with the severity of pericoronitis. RESULTS: The demographic, clinical, and radiographic characteristics of males and females were similar, except for Winter's classification, pain, and intraoral swelling. The constructive validity of the Patient-Clinician Pericoronitis Classification was confirmed with three latent factors, including infection level, patient discomfort, and social interference. Ordinal logistic multivariate regression analysis revealed that upper respiratory tract infection was the sole risk factor associated with pericoronitis severity in males (odds ratio = 4.838). In females, pericoronitis on the right side (odds ratio = 2.486), distal radiolucency (odds ratio = 5.203), and menstruation (odds ratio = 3.416) were significant risk factors. CONCLUSION: This study demonstrated the constructive validity of the Patient-Clinician Pericoronitis Classification. Among females, pericoronitis in mandibular third molars on the right side with radiolucency in menstruating individuals was more severe. In males, upper respiratory tract infection was the sole risk factor associated with pericoronitis severity. CLINICAL RELEVANCE: Individuals with risk factors should be aware of severe pericoronitis in the coming future.

Comparative efficacy of sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta-analysis.

AIM: To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). MATERIALS AND METHODS: We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001). Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes. CONCLUSIONS: SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.

Cost-effectiveness of canagliflozin and dapagliflozin for treatment of patients with chronic kidney disease and type 2 diabetes.

AIM: To examine the cost-effectiveness of adding canagliflozin or dapagliflozin to standard of care (SoC) versus SoC alone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). MATERIALS AND METHODS: We used a Markov microsimulation model to assess the cost-effectiveness of canagliflozin plus SoC (canagliflozin + SoC), dapagliflozin plus SoC (dapagliflozin + SoC) and SoC alone. Analyses were conducted from a healthcare system perspective. Costs were measured in 2021 Canadian dollars (C$), and effectiveness was measured in quality-adjusted life-years (QALYs). RESULTS: Over a patient's lifetime, canagliflozin + SoC and dapagliflozin + SoC yielded cost savings of C$33 460 and C$26 764 and generated 1.38 and 1.44 additional QALYs compared with SoC alone, respectively. While QALY gains with dapagliflozin + SoC were higher than those with canagliflozin + SoC, this strategy was also more costly with the incremental cost-effectiveness ratio exceeding the willingness to pay threshold of C$50 000 per QALY. Dapagliflozin + SoC, however, generated cost savings and QALY gains compared with canagliflozin + SoC over shorter time horizons of 5 or 10 years. CONCLUSIONS: Dapagliflozin + SoC was not cost-effective versus canagliflozin + SoC in patients with CKD and T2D over the lifetime horizon. However, adding canagliflozin or dapagliflozin to SoC was less costly and more effective relative to SoC alone for treatment of CKD and T2D.

Comparison of contemporary and historical outcomes of elective and ruptured open abdominal aortic aneurysm repair.

BACKGROUND: Recently, open abdominal aortic aneurysm (AAA) repair (OSR) has become less common and will often be reserved for patients with more complex aortic anatomy. Despite improvements in patient management, the reduced surgical volume has raised concerns for potentially worsened outcomes in the contemporary era (2014-2019) compared with an earlier era in which OSR was more widely practiced (2005-2010). In the present study, we compared the 30-day outcomes of open AAA repair between these two eras. METHODS: The American College of Surgeons National Quality Improvement Program general database was queried for open AAA repair using the Current Procedural Terminology and International Classification of Diseases, 9th and 10th, codes. The cases were stratified into two groups by operation year: 2005 to 2010 (early) and 2014 to 2019 (contemporary). In each era, the cases were further divided into elective and ruptured groups. The 30-day outcomes, including mortality, major morbidity, postoperative sepsis, and unplanned reoperation, were compared between the contemporary and early eras in the elective and ruptured groups. Preoperative variables with a P value <.25 were adjusted for in the multivariate analysis. RESULTS: In the contemporary and early eras, 3749 and 3798 patients had undergone elective OSR and 1148 and 907 had undergone ruptured OSR, respectively. These samples were of similar sizes owing to the National Quality Improvement Program sampling process and our relatively strict inclusion criteria. In the contemporary era, fewer patients were elderly and fewer were smokers or had hypertension or dyspnea in the elective and rupture cohorts. More patients had had American Society of Anesthesiologists class >3 in the elective contemporary era (39% vs 24%; P < .0001). The contemporary elective repair group demonstrated increased 30-day mortality (3.7% vs 3.2%; adjusted odds ratio [aOR], 1.36; P = .006), major adverse cardiac events (5.7% vs 3.4%; aOR, 1.87; P < .0001), and bleeding requiring transfusion (58.5% vs 13.7%; aOR, 8.96; P < .0001). The incidence of pulmonary complications (12.1% vs 15.2%; aOR, 0.80; P = .02) and sepsis (3.7% vs 8.4%; aOR, 0.47; P < .0001) had decreased in the contemporary era, with a similar rate of unplanned reoperations (8.4% vs 7.7%; aOR, 1.16; P = .09). The incidence of renal complications in the contemporary era had increased, with a statistically significant difference. However, the absolute increase of <0.5% was likely not clinically relevant (5.5% vs 5.1%; aOR, 1.23; P = .049). In the ruptured cohort, contemporary repair was associated with increased 30-day mortality (41.4% vs 40%; aOR, 1.53; P < .0001), major adverse cardiac events (25.8% vs 12.8%; aOR, 2.49; P < .0001), and bleeding requiring transfusion (88.2% vs 27%; aOR, 23.03; P < .0001). The incidence of pulmonary complications (36.9% vs 48.1%; aOR, 0.67; P < .0001), sepsis (14.6% vs 23%; aOR, 0.75; P = .03), and unplanned reoperations (18.1% vs 22.7%; aOR, 0.74; P = .008) had decreased in the contemporary OSR group. No differences were detected in the incidence of renal complications. CONCLUSIONS: The 30-day mortality has worsened after open AAA repair in the elective and rupture settings despite the improvements in perioperative management over the years. These complications likely stem from increased bleeding events and major cardiac events, which were increased in the contemporary era.

Dependent functional status rather than age is a better predictor of adverse outcomes after excision of an infected abdominal aortic graft.

OBJECTIVE: The optimal management of infected abdominal aortic grafts is complete surgical excision plus in situ or extra-anatomic revascularization in patients who can tolerate this morbid operation. In addition to using age and the presence of comorbidities for risk assessment, physicians form a global clinical impression when deciding whether to offer excision or to manage conservatively. Functional status is a distinct objective measure that can inform this decision. This study examines the relative impact of age and functional status on outcomes of infected abdominal aortic graft excision to guide surgical decision-making. METHODS: Current Procedural Terminology code 35907 was used to identify patients undergoing excision of infected abdominal aortic graft in the 2005 to 2017 American College of Surgeons - National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified by the upper age quartile (75 years old) as a cutoff, and then by functional status, independent vs dependent (as defined by NSIQIP). The patients were then stratified into four groups: Younger (<75)/Independent, Younger (<75)/Dependent, Older (≥75)/Independent, and Older (≥75)/Dependent. Outcomes measured included 30-day mortality and major organ-system dysfunction. RESULTS: There were 814 patients who underwent infected abdominal aortic graft excision: 508 patients (62%) were Younger/Independent, 89 patients (11%) were Younger/Dependent, 176 patients (22%) were Older/Independent, and 41 patients (5%) were Older/Dependent. There was no statistically significant difference in 30-day mortality for Younger/Dependent (odds ratio [OR], 1.66; 95% confidence interval [CI], 0.90-3.09; P = .536) or Older/Independent (OR, 1.31; 95% CI, 0.78-2.19; P = .311) patients when compared with Younger/Independent patients, which suggests that neither old age nor dependent functional status by itself adversely affects mortality. However, when both factors were present, Older/Dependent patients had three times higher mortality when compared with Younger/Independent patients (41.5% vs 13.4%, respectively; OR, 3.13; 95% CI, 1.46-6.71; P = .003). Furthermore, as long as patients presented with independent functional status, old age by itself did not adversely affect major organ-system dysfunction (ORs for Older/Independent vs Younger/Independent were 0.76 [P = .454], 1.04 [P = .874], and 0.90 [P = .692] for cardiac, pulmonary, and renal complications, respectively). On the contrary, even in younger patients, dependent functional status was significantly associated with higher pulmonary complications (Younger/Dependent vs Younger/Independent: OR, 2.22; 95% CI, 1.33-3.73; P = .002) and higher rates of unplanned reoperation (OR, 2.67; 95% CI, 1.62-4.41; P < .0001). CONCLUSIONS: Dependent functional status has significant association with adverse outcomes after excision of infected abdominal aortic grafts, whereas old age alone does not. Therefore, this procedure could be considered in appropriately selected elderly patients with otherwise good functional status. However, caution should be applied in dependent patients regardless of age due to the risk of pulmonary complications.

Single-Institution Learning Curve for Management of Mega-Fistulae Revision.

BACKGROUND: Mega-fistulae are generalized aneurysmal dilations of a high flow (1500-4000 mL/min) autogenous arteriovenous (AV) access which may result in hemorrhage and/or high-output cardiac failure. Current treatments include ligation, ligation with prosthetic jump graft, and imbrication; however, these may not be suitable for advanced disease, or may result in loss of functioning access, poor cosmesis, or recurrence. We describe our early experience with a technique of complete mega-fistula resection and replacement with an early use prosthetic graft that both maintains existing AV access and eliminates the need for long-term catheter (LTC) placement; including lessons learned. METHODS: A single-center, retrospective review of medical records was conducted from March 2018-February 2021. Outcomes were technical success, LTC use, time to cannulation, and complications. Mega-fistulae were completely resected from the proximal to distal aneurysmal segment, including all pseudoaneurysms, followed by tunneling a prosthetic graft (Propaten later converted to Acuseal; W.L. Gore Assoc.) with an end-to-end anastomosis to the remaining arterial and venous ends of the previous AV access. RESULTS: We had 100% immediate technical success (n=12). Pre-operative long-term catheters were placed in all eight Propaten patients; one was already placed in an Acuseal patient.  Average time to cannulation was six weeks with Propaten and 4.5 days with Acuseal. At 30 days, three Propaten patients developed complications including one instance of skin necrosis, one seroma, and one hematoma. Two Acuseal patients developed complications including one central venous occlusion (CVO) and one graft infection. Of the six patients with long-term follow-up, five continue to use their access, however, two required thrombectomies and central venous angioplasties. One patient required a new contralateral access due to CVO. CONCLUSIONS: Complete mega-fistula resection and replacement with Acuseal graft maintains existing AV access and may eliminate the need for long-term catheter placement. Our early experience with this technique is encouraging, but further follow-up is required to determine the durability of this approach.

A Novel Angiography Scoring System Predicts Improvement After Isolated Common Femoral Endarterectomy With Profundaplasty.

BACKGROUND: Numerous angiography-based peripheral arterial disease classification schemes have been developed to stratify severity of preoperative patient disease, but few studies have correlated angiography-based anatomic classification schemes to postoperative outcomes. This study examined whether a proposed pre-operative angiography scoring system was predictive of outcomes after isolated common femoral endarterectomy with profundaplasty (CFEP). METHODS: A retrospective review was conducted of patients treated with isolated CFEP for claudication and/or rest pain at a single institution from 2016-19. Pre-operative angiograms were assessed quantitatively by 4 blinded surgeons across 3 domains: profunda stenosis, profunda disease length, and outflow disease severity. Table I describes the proposed angiography scoring system. Internal consistency reliability of rater scores was calculated using Cronbach alpha. Outcomes included clinical improvement, further interventions, major amputations, mortality, and mean increase in ankle-brachial index (ABI) at 30 days, and 6 months. McNemar tests, between-group t-tests, Pearson correlations, and linear regression were used. RESULTS: Clinical Outcomes 88% of patients (n = 22) had clinical improvement at 30 days; the remaining 12% of patients (n = 3) required further interventions. One patient (4%) required major amputation between 30 days and 6 months for recurrence of rest pain that had initially resolved after isolated CFEP. There was 0% mortality during the study period. Mean ABI increased by 0.15 ± 0.21 at 30 days, and by 0.06 ± 0.21 at 6 months. Angiography Scoring System Profunda stenosis score was associated with clinical improvement at 6 months (P = 0.04). A profunda stenosis score of ≥2.6 was strongly associated with 6-month clinical improvement (64% of those ≥ 2.6 improved, versus 15% of those <2.6, P = 0.15). Profunda stenosis score was associated with ABI improvement at 30 days (r = 0.73, P = 0.01) and 6 months (r = 0.82, P = 0.007). Profunda disease length score was associated with clinical improvement at 30 days (P = 0.002). 100% of patients with a profunda disease length score of ≥1.5 clinically improved at 30 days, versus 67% of those with <1.5 (P = 0.04). Angiography scores were not found to be associated with further intervention, major amputation, or mortality. Cronbach alpha for profunda stenosis, profunda disease length, and outflow severity scores were 0.90, 0.90, and 0.79, respectively, indicating strong internal consistency. CONCLUSIONS: This institutional angiography scoring system successfully predicts clinical improvement following CFEP.  Higher profunda stenosis and profunda disease length scores were most predictive of operative success within 6 months. Future validation studies will investigate these outcomes in a larger population, and over a longer period.

Six New Polyoxygenated Xanthones from Garcinia cowa and Their Neuroprotective Effects on Glutamate-Mediated Hippocampal Neuronal HT22 Cell Death.

Six new polyoxygenated xanthones, garcicowanones F-H (1-3), norcowanol A-B (4-5), and garcinone F (6) along with twelve known compounds 7-18 were obtained from the latex of Garcinia cowa Roxb. ex Choisy. All new compounds have a 1,3,7-trioxygenated or 1,3,6,7-tetraoxygenated xanthone nucleus and differ from majority of xanthones from G. cowa by hydrated side chains. Compounds 1, 7, 8 and 18 exhibited significant neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death. In particular, compound 1 exhibited the most potent neuroprotective effect with >80 % cell viability in the concentration range of 2.9-115 µM. Further studies on compound 1 showed that it decreased cellular Ca2+ influx and inhibits cellular reactive oxygen species generation in HT22 cells. A Western blot analysis showed that MAPK phosphorylation, Bax, and AIF translocation dramatically increased upon treatment with 5 mM glutamate and decreased upon a co-treatment with compound 1.

Mutated CEACAMs Disrupt Transforming Growth Factor Beta Signaling and Alter the Intestinal Microbiome to Promote Colorectal Carcinogenesis.

BACKGROUND & AIMS: We studied interactions among proteins of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, which interact with microbes, and transforming growth factor beta (TGFB) signaling pathway, which is often altered in colorectal cancer cells. We investigated mechanisms by which CEACAM proteins inhibit TGFB signaling and alter the intestinal microbiome to promote colorectal carcinogenesis. METHODS: We collected data on DNA sequences, messenger RNA expression levels, and patient survival times from 456 colorectal adenocarcinoma cases, and a separate set of 594 samples of colorectal adenocarcinomas, in The Cancer Genome Atlas. We performed shotgun metagenomic sequencing analyses of feces from wild-type mice and mice with defects in TGFB signaling (Sptbn1+/- and Smad4+/-/Sptbn1+/-) to identify changes in microbiota composition before development of colon tumors. CEACAM protein and its mutants were overexpressed in SW480 and HCT116 colorectal cancer cell lines, which were analyzed by immunoblotting and proliferation and colony formation assays. RESULTS: In colorectal adenocarcinomas, high expression levels of genes encoding CEACAM proteins, especially CEACAM5, were associated with reduced survival times of patients. There was an inverse correlation between expression of CEACAM genes and expression of TGFB pathway genes (TGFBR1, TGFBR2, and SMAD3). In colorectal adenocarcinomas, we also found an inverse correlation between expression of genes in the TGFB signaling pathway and genes that regulate stem cell features of cells. We found mutations encoding L640I and A643T in the B3 domain of human CEACAM5 in colorectal adenocarcinomas; structural studies indicated that these mutations would alter the interaction between CEACAM5 and TGFBR1. Overexpression of these mutants in SW480 and HCT116 colorectal cancer cell lines increased their anchorage-independent growth and inhibited TGFB signaling to a greater extent than overexpression of wild-type CEACAM5, indicating that they are gain-of-function mutations. Compared with feces from wild-type mice, feces from mice with defects in TGFB signaling had increased abundance of bacterial species that have been associated with the development of colon tumors, including Clostridium septicum, and decreased amounts of beneficial bacteria, such as Bacteroides vulgatus and Parabacteroides distasonis. CONCLUSION: We found expression of CEACAMs and genes that regulate stem cell features of cells to be increased in colorectal adenocarcinomas and inversely correlated with expression of TGFB pathway genes. We found colorectal adenocarcinomas to express mutant forms of CEACAM5 that inhibit TGFB signaling and increase proliferation and colony formation. We propose that CEACAM proteins disrupt TGFB signaling, which alters the composition of the intestinal microbiome to promote colorectal carcinogenesis.

Open surgical repair of juxtarenal abdominal aortic aneurysms in the elderly is not associated with increased thirty-day mortality compared with fenestrated endovascular grafting.

OBJECTIVE: Endovascular repair of juxtarenal abdominal aortic aneurysms (JAAAs) with fenestrated grafts (fenestrated endovascular aneurysm repair [FEVAR]) has been reported to decrease operative mortality and morbidity compared with open surgical repair (OSR). However, previous comparisons of OSR and FEVAR have not necessarily included patients with comparable clinical profiles and aneurysm extent. Although FEVAR has often been chosen as the first-line therapy for high-risk patients such as the elderly, many patients will not have anatomy favorable for FEVAR. At present, a paucity of data has examined the operative outcomes of OSR in elderly patients for JAAAs relative to FEVAR. Therefore, we chose to perform a propensity-matched comparison of OSR and FEVAR for JAAA repair in patients aged ≥70 years. METHODS: Patients aged ≥70 years who had undergone elective nonruptured JAAA repairs from 2012 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted endovascular aneurysm repair (EVAR) and AAA databases. Patients who had undergone FEVAR were identified in the targeted EVAR database as those who had received the Cook Zenith Fenestrated endograft (Cook Medical, Bloomington, Ind). Because our study specifically examined JAAAs, those patients who had undergone OSR with supraceliac proximal clamping or concomitant renal/visceral revascularization were excluded. A 1:1 propensity-match algorithm matched the OSR and FEVAR patients by preoperative clinical and demographic characteristics, operative indications, and aneurysm extent. The 30-day outcomes, including mortality, major adverse cardiovascular events, and pulmonary and renal complications, were compared between the propensity-matched OSR and FEVAR groups. RESULTS: A 1:1 propensity match was achieved, and the final analysis included 136 OSR patients and 136 FEVAR patients. No significant differences were found in 30-day mortality (4.4% vs 3.7%; odds ratio [OR], 1.21; 95% confidence interval [CI], 0.36-4.06; P = .759) between the OSR and FEVAR groups. OSR was associated with a higher incidence of major adverse cardiovascular events compared with FEVAR; however, the trend was not statistically significant (8.1% vs 3.7%; OR, 2.31; 95% CI, 0.78-6.82; P = .131). Compared with FEVAR, the OSR group had significantly greater rates of pulmonary complications (19.1% vs 3.7%; OR, 6.19; 95% CI, 2.30-16.67; P < .001) and renal complications (8.1% vs 2.2%; OR, 3.90; 95% CI, 1.06-14.31; P = .040). CONCLUSIONS: In the samples assessed in the present study, the results with OSR of JAAAs in the elderly did not differ from those of FEVAR with respect to 30-day mortality despite a greater incidence of pulmonary and renal complications. Although FEVAR should remain the first-line therapy for JAAAs in elderly patients, OSR might be an acceptable alternative for select patients with anatomy unfavorable for FEVAR.

Thirty-day outcomes of open abdominal aortic aneurysm repair by proximal clamp level in patients with normal and impaired renal function.

OBJECTIVE: Open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) has often been reserved in contemporary practice for complex aneurysms requiring a suprarenal or supraceliac proximal clamp level. The present study investigated the associated 30-day outcomes of different proximal clamp levels in OSR of complex infrarenal/juxtarenal AAA in patients with normal renal function and those with chronic renal insufficiency (CRI). METHODS: All patients undergoing elective OSR of infrarenal and juxtarenal AAA were identified in the American College of Surgeons National Surgical Quality Improvement Program-targeted AAA database from 2012 to 2018. The patients were stratified into two cohorts (normal renal function [estimated glomerular filtration rate, ≥60 mL/min] and CRI [estimated glomerular filtration rate, <60 mL/min and no dialysis]) before further substratification into groups by the proximal clamp level (infrarenal, inter-renal, suprarenal, and supraceliac). The 30-day outcomes, including mortality, renal and pulmonary complications, and major adverse cardiovascular event rates, were compared within each renal function cohort between proximal clamp level groups using the infrarenal clamp group as the reference. Supraceliac clamping was also compared with suprarenal clamping. RESULTS: A total of 1284 patients with normal renal function and 524 with CRI were included in the present study. The proximal clamp levels for the 1808 patients were infrarenal for 1080 (59.7%), inter-renal for 337 (18.6%), suprarenal for 279 (15.4%), and supraceliac for 112 (6.2%). In the normal renal function cohort, no difference was found in 30-day mortality with any clamp level. Increased 30-day acute renal failure was only observed in the supraceliac vs infrarenal clamp level comparison (5.9% vs 1.5%; adjusted odds ratio [aOR], 3.97; 95% confidence interval [CI], 1.04-5.18; P = .044). In the CRI cohort, supraceliac clamping was associated with an increased rate of renal composite complications (22.7% vs 5.6%; aOR, 8.81; 95% CI, 3.17-24.46; P < .001) and ischemic colitis (13.6% vs 3.0%; aOR, 4.78; 95% CI, 1.38-16.62; P = .014) compared with infrarenal clamping and greater 30-day mortality (13.6% vs 2.4%; aOR, 6.00; 95% CI, 1.14-31.55; P = .034) and renal composite complications (22.7% vs 10.8%; aOR, 2.87; 95% CI, 1.02-8.13; P = .047) compared with suprarenal clamping. Suprarenal clamping was associated with greater renal dysfunction (10.8% vs 5.6%; aOR, 2.77; 95% CI, 1.08-7.13; P = .035) compared with infrarenal clamping, with no differences in mortality. No differences were found in 30-day mortality or morbidity for inter-renal clamping compared with infrarenal clamping in either cohort. No differences were found in major adverse cardiovascular events with higher clamp levels in either cohort. CONCLUSIONS: In elective OSR of infrarenal and juxtarenal AAAs for patients with CRI, this study found a heightened mortality risk with supraceliac clamping and increased renal morbidity with suprarenal clamping, though these effects were not present for patients with normal renal function. Every effort should be made to keep the proximal clamp level as low as possible, especially in patients with CRI.

Failed Prior Endovascular Interventions Do Not Affect 30-day Cardiovascular or Limb-related Outcomes of Infrainguinal Bypasses for Chronic Limb Threatening Ischemia.

BACKGROUND: It is often hypothesized that failed prior endovascular intervention could adversely affect the outcome of subsequent infrainguinal bypass in the corresponding limb. However, this perception is not well supported in the literature because of conflicting data. The aim of this study is to address this controversial issue via analysis of a multicenter prospectively collected database. METHODS: Patients who underwent infrainguinal bypass for chronic limb threatening ischemia (CLTI) were identified in the targeted American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2017. These patients were stratified into 4 groups: first time femoral-popliteal bypass, femoral-popliteal bypass after failed prior endovascular revascularization, first time femoral-tibial bypass, and femoral-tibial bypass after failed prior endovascular revascularization. Thirty-day outcomes including mortality, graft patency, major amputations, and major organ dysfunction were measured. RESULTS: We identified 7,044 patients who underwent surgical bypasses for CLTI. Patients were mostly well matched among the 4 groups except for differences in sex, hypertension, and preoperative renal function. In terms of major adverse cardiovascular events and major adverse limb events, femoral-popliteal or femoral-tibial bypasses after failed prior endovascular intervention had comparable 30-day outcomes to first-time bypasses. However, patients with failed prior endovascular intervention had increased rates of postoperative wound infection, required significantly more blood transfusions, and had longer operative time. CONCLUSIONS: Failed prior endovascular intervention does not adversely affect 30-day outcomes of subsequent infrainguinal bypass surgery in mortality, limb salvage, or other major cardiovascular complications.

Fenestrated Endovascular Aneurysm Repair Affords Fewer Renal Complications than Open Surgical Repair for Juxtarenal Abdominal Aortic Aneurysms in Patients with Chronic Renal Insufficiency.

OBJECTIVE: Although fenestrated endovascular aneurysm repair (FEVAR) has been associated with lower morbidity and mortality than open surgical repair (OSR) in juxtarenal aneurysms (JAAA), there is a paucity of data in the literature comparing outcomes of the approaches specifically in patients with chronic renal insufficiency (CRI). We hypothesized that benefits of FEVAR over OSR observed in the general patient population may be diminished in CRI patients due to their heightened vulnerability to renal dysfunction stemming from contrast-induced nephropathy. This study compares 30-day outcomes between FEVAR and OSR for JAAA in patients with non-dialysis dependent CRI. METHODS: All adults with estimated glomerular filtration rate (eGFR) < 60 mL/min (but not requiring dialysis) undergoing elective, non-ruptured JAAA repairs were identified in the American College of Surgeons - National Surgical Quality Improvement (ACS-NSQIP) Targeted EVAR and AAA databases from 2012-2018. JAAA were identified by recorded proximal aneurysm extent. FEVAR patients were identified in the Targeted EVAR database as those receiving the "Cook Zenith Fenestrated" endograft. OSR cases were defined as those that required proximal clamp positions "above one renal" or "between SMA & renals." Infra-renal or supra-celiac proximal clamp placement, or cases involving concomitant renal/visceral revascularization were excluded. Thirty-day outcomes including mortality, major adverse cardiovascular events (MACE), pulmonary, and renal complications were compared between FEVAR and OSR groups. RESULTS: There were 284 patients with CRI who underwent elective repair of JAAA (FEVAR: 89; OSR: 195). FEVAR patients were significantly older than those undergoing OSR (77.3±7.2 vs. 74.2±7.7, P=0.001) and less likely to be smokers (25.8% vs 42.1%; P = 0.009). Other baseline demographic and pre-operative parameters were comparable between the two groups.Multivariable analysis revealed no significant difference between FEVAR and OSR in 30-day mortality (4.5% vs 4.6%; OR=1.22; 95% CI=0.35 - 4.22; P=0.753) or unplanned re-operation (4.5% vs 5.1%; OR=0.78; 95% CI=0.22 - 2.70; P=0.693). Patients undergoing FEVAR had significantly fewer pulmonary complications (3.4% vs 18.5%; OR=0.12; 95% CI=0.03 - 0.42; P<0.001) and renal dysfunction (3.4% vs 11.8%; OR 0.24 95% CI=0.07 - 0.86; P=0.029) compared to OSR. FEVAR was also associated with significantly shorter ICU and hospital lengths of stay (ICU stay: 0 days vs 3 days, P<0.0001; hospital stay: 3 days vs 8 days, P<0.0001). CONCLUSION: For patients with chronic renal insufficiency, FEVAR offered improved perioperative renal morbidity compared to OSR without a corresponding mortality benefit. Future studies will be required to determine long term outcomes of this procedure in this vulnerable population.