Diabetes, Hypertension, and Smoking Do Not Affect Outcomes of Iliofemoral Vein Stenting for Chronic Proximal Venous Outflow Obstruction.

BACKGROUND: Diabetes, hypertension, and smoking are well-recognized risk factors for peripheral artery disease (PAD), but little is known of their impact on chronic venous insufficiency (CVI). This study evaluates these factors in patients undergoing iliac vein stenting (IVS) for CVI. METHODS: A registry of 708 patients who underwent IVS from August 2011 to June 2021 was retrospectively analyzed. Symptoms were quantified using venous clinical severity score (VCSS) and CEAP classification. Both major and minor reinterventions were recorded. Logistic regression models were used to determine the unadjusted and adjusted odds ratio of any reintervention. Log-rank test was used to assess differences in reintervention-free survival. RESULTS: The prevalence of hypertension was 51.1% (N = 362), diabetes was 23.0% (N = 163), and smoking was 22.2% (N = 157). Patients with diabetes (3.6 vs. 3.4; P = 0.062), hypertension (3.6 vs. 3.3; P < 0.001), and smoking (3.7 vs. 3.4; P = 0.003) had higher CEAP scores than those without these comorbidities. Improvement in VCSS composite scores showed no differences postoperatively (diabetes: P = 0.513; hypertension: P = 0.053; smoking: P = 0.608), at 1-year follow-up (diabetes: P = 0.666; hypertension: P = 0.681; smoking: P = 0.745), or at 5-year follow-up (diabetes: P = 0.525; hypertension: P = 0.953; smoking: P = 0.146). Diabetes (P = 0.454), smoking (P = 0.355), and hypertension (P = 0.727) were not associated with increased odds of major reintervention. Log-rank test similarly showed no differences in reintervention-free survival for major or minor reoperations between those with and without diabetes (P = 0.79), hypertension (P = 0.14), and smoking (P = 0.80). CONCLUSIONS: Diabetes, hypertension, and smoking were prevalent among CVI patients, but unlike in PAD patients, they had little to no impact on long-term outcomes or reinterventions after IVS.

Gender Differences in Iliofemoral Vein Stenting for Chronic Venous Insufficiency.

INTRODUCTION: Little is known about gender's role in chronic venous insufficiency (CVI). The aim of this study was to evaluate the impact of gender on outcomes of iliac vein stenting(IVS) for CVI. METHODS: 866 patients who underwent vein stenting for CVI at one institution from August 2011 to June 2021 were analyzed via retrospective review. Patients were followed up to 5 years after initial stent placement. Presenting symptoms were quantified using Venous Clinical Severity Score(VCSS), Clinical Assessment Score(CAS), and Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) class. Reoperations after initial IVS were recorded. Major reoperations were defined as iliac interventions using venography. Minor reoperations were defined as thermal ablation. Multivariate logistic regression models were used determine odds of any and major reintervention. RESULTS: Compared to females, males pre-operatively presented with a higher mean CEAP class (3.6 vs .3.3; P < .001), VCSS composite (11.3 vs .9.9; P < .001), and smoking history (134 vs .49; P < .001). The 2 groups were similar in age (P = .125), BMI(P = .898), previous DVT (P = .085), diabetes (P = .386), hypertension (P = 1.0), and CAD (P = .499). Multivariate analyses revealed no association between gender and any reintervention (OR, 1.02; 95%CI, .71-1.46; P = .935) or gender and major reintervention (OR, 1.39; 95% CI, .86-2.23 P = .177). There were no differences in number of stents placed (P = .736) or symptomatic improvement at 1 month (P = .951), 3 months (P = .233), 6 months(P = .068), and greater than 1 year (P = .287). At the 1 year follow-up, the male cohort had higher CAS values than females P = .034). Males had larger reduction in composite VCSS than women at 1 year (5.1 vs. 3.8; P = .003) and 3 years (5.3 vs .3.7; P = .031) of follow-up and similar levels of improvement in post-op (4.0 vs .3.5; P = .059), 2 years (4.3 vs .3.8; P = .295), 4-years (5.1 vs .4.6; P = .529), 5 years (5.6 vs .4.2; P = .174), and 6 years (5.93vs.3.3 P = .089). CONCLUSIONS: In a single site study of IVS in patients with CVI, males tended to present worse symptoms than females. After surgery, however, both cohorts showed improvement, and both seemed to improve to the same degree of residual symptoms.

Race differences in iliofemoral vein stenting for chronic venous insufficiency.

INTRODUCTION: Major disparities in outcomes by race are present throughout vascular surgery, yet little has been published on iliac vein stent outcomes by race. This retrospective study assessed iliac vein stent outcomes by patient race. METHODS: Patients who underwent iliac vein stenting at a single institution for chronic venous insufficiency (CVI) from 2011 to 2021 were reviewed. Demographic, preoperative, perioperative, and postoperative data were collected. Self-reported race groups included Asian, Black, Hispanic, and White. Univariate differences were analyzed using χ2 tests for categorical variables and 1-way ANOVA for continuous variables. Outcomes included change in Venous Clinical Severity Score (VCSS) at interval timepoints relative to a preoperative baseline and reinterventions. Logistic regression models were used to determine the unadjusted and adjusted odds ratio (OR) of any minor and major reintervention. Multivariate regression models controlled for demographic and comorbidity characteristics. RESULTS: A total of 827 patients were included. Asian patients were younger and had a greater proportion of male patients, lower Body mass index (BMI), less smoking history, and fewer comorbidities. White patients were more likely to have a history of deep vein thrombosis (DVT). White patients presented with the most severe CVI symptoms as defined by both Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification and preoperative VCSS composite scores. There were no differences in acute DVT, number of stents deployed, and bilateral versus unilateral stent placement. Black patients had the longest average days of follow-up, followed sequentially by Hispanic, White, and Asian. Black patients had the most reinterventions, while Asian patients had the fewest. Asian patients were less likely to have a major reintervention. No differences in VCSS composite or change in VCSS were observed. CONCLUSIONS: In patients with CVI, Asian patients presented younger and healthier, while White patients presented with the most severe symptoms. No differences were observed in VCSS outcomes, though Black patients had the most reinterventions.

Iliac vein stenting outcomes for patients with superficial venous insufficiency concurrent with deep venous disease.

OBJECTIVE: Many patients will present with chronic proximal venous outflow obstruction (PVOO) and superficial venous insufficiency (SVI) at the time of iliac vein stenting. In the present study, we aimed to determine whether differences in outcomes were present for patients receiving an iliac vein stent according to whether concurrent SVI was present. METHODS: A registry of 553 patients who had undergone iliac vein stent placement for chronic PVOO from 2011 to 2021 was retrospectively analyzed. Two groups of patients were followed for ≤6 years after initial vein stent placement: group 1 (n = 178; 32.2%) had not had SVI before or after stent placement and group 2 (n = 375; 67.8%) had had SVI at initial iliac vein stent procedure. The patients' symptoms were evaluated using the venous clinical severity score (VCSS). Postoperative procedures after initial stent placement were recorded. Postoperative procedures included any operation performed after the index iliac vein stent procedure. Endovenous thermal ablation was classified as a minor postoperative procedure, and any intervention with venography was classified as a major postoperative reintervention. Multivariate regression models were used to determine the odds of a major reintervention or minor procedure postoperatively. RESULTS: Across the two groups, the mean age (group 1, 65.3 years; group 2, 59.9 years; P < .001), body mass index (27.6 vs 26.1 kg/m2; P = .004), diabetes (32.6% vs 17.6%; P < .001), arterial hypertension (68.5% vs 42.1%; P < .001), and coronary artery disease (16.9% vs 9.6%; P = .048) differed significantly. The time to follow-up was similar between the two groups (P = .915). Longitudinally, both groups had had similar improvements in the composite VCSSs. After multivariable adjustment, group 2 was more likely than group 1 (odds ratio, 5.26; 95% confidence interval, 3.33-8.59; P < .001) to have required a postoperative minor procedure, but not a major reintervention. Group 2 had also averaged a shorter interval from the index procedure to a postoperative procedure than group 1 (525.7 days vs 258.1 days; P < .001). CONCLUSIONS: Compared with patients without SVI, those with SVI and chronic PVOO were younger, had had fewer comorbidities, and fared similarly in the change in the composite VCSSs but were more likely to have required a minor procedure and less likely to have required a major reintervention after the index iliac vein stent procedure.

Patients with active venous leg ulcers at the time of iliac vein stenting require more reoperations.

OBJECTIVE: An active venous leg ulcer (VLU) caused by lower extremity venous insufficiency is challenging to treat and will often recur after initially healing. In the present study, we compared the symptomatic outcomes and need for reoperation after iliac vein stenting (IVS) in patients with an active VLU (VLU+) and those without an active VLU (VLU-). METHODS: A single-institution database of patients with chronic venous outflow obstruction who underwent IVS from August 2011 to June 2021 was analyzed. Symptoms were quantified using the venous clinical severity score. The patients were divided into two cohorts: those with (VLU+) and without (VLU-) VLUs. RESULTS: A total of 872 patients (71 VLU+ and 801 VLU-) were identified. Many of the demographics and comorbidities differed between the two cohorts, and these variables were included in the multivariable analysis. On univariate analysis, the VLU+ cohort was more likely to need a major reoperation (odds ratio, 1.94; 95% confidence interval, 1.01-3.52; P = .036). However, on multivariable analysis, the difference was not statistically significant (odds ratio, 1.17; 95% confidence interval, 0.55-2.40; P = .667). Additionally, the VLU+ cohort required a significantly greater mean total of reoperations (1.4 vs 1.0; P = .006) than the VLU- cohort. Comparatively, for patients who underwent at least one reoperation, the difference in the mean total number of reoperations was even greater for the VLU+ cohort (2.6 vs 1.8; P = .001). The results from the Kaplan-Meier log-rank test revealed no differences in the reintervention-free survival time (P = .980). Both cohorts experienced a durable mean reduction in the venous clinical severity score. The ulcer healing rates for the VLU+ cohort at 6, 12, 24, and 36 months were 38%, 47%, 52%, and 59%, respectively. The ulcer recurrence rates for the VLU+ cohort were 4%, 10%, 19%, and 30% at 6, 12, 24, and 36 months, respectively, with a median time to recurrence of 1.2 years. CONCLUSIONS: Patients with active VLUs who underwent a first reintervention after initial IVS, on average, required an additional reintervention.

Symptom Relief and Reintervention after Iliac Vein Stenting Stratified by CEAP Clinical Classification.

BACKGROUND: This study sought to evaluate long-term symptom relief and reintervention rates after iliac vein stenting (IVS) in patients with chronic venous outflow obstruction. METHODS: A single-institution database of patients undergoing IVS from August 2011 to June 2021 was analyzed. Patients were stratified into three cohorts based on the clinical component of the clinical, etiology, anatomical, and pathophysiology (CEAP) classification: C3, C4, and C5/6. Symptoms were quantified using the venous clinical severity score (VCSS). Reintervention was defined as any procedure using venography. Edema, pigmentation, and ulceration progression-free survival as well as reintervention-free survival were assessed with Kaplan Meier analysis. RESULTS: Among 737 total patients, there were 435 C3, 206 C4, and 96 C5/6 patients. The C5/6 cohort had the highest percentage of patients undergo reoperation (36.4%). C5/6 patients yielded the poorest ulceration progression-free survival (P < 0.001) while C3 patients had the poorest skin pigmentation progression-free survival (P = 0.009). On adjusted analysis there was no significant difference in odds of reintervention between study cohorts. Mean composite VCSS scores were significantly different at each yearly post-operative follow-up visit up to 6 years. CONCLUSIONS: The present study is one of the largest investigations of long-term outcomes in IVS patients. Most patients with long-term follow-up experienced an improvement in their composite VCSS. CEAP clinical classification at the time of IVS had a significant influence on the likelihood and quantity of reintervention.

Compression Stocking Compliance Does Not Impact Reintervention or Symptom Change after Iliac Vein Stenting in Patients with Moderate to Severe Lower Extremity Edema.

BACKGROUND: Medical compression stocking (MCS) therapy remains a core treatment for chronic venous disease, particularly in patients with lower extremity edema. This study investigated the impact of postoperative MCS adherence on patients with moderate to severe edema who underwent iliac vein stenting (IVS). METHODS: Patients at a large tertiary care center who underwent IVS from August 2011 to June 2021 were analyzed. Symptoms were quantified using the venous clinical severity score (VCSS) and clinical assessment score (CAS). The criterion for inclusion was moderate or severe lower extremity edema at the time of IVS. Patients were stratified into two cohorts: complete postoperative compression therapy compliance (MCS+) and no postoperative compression therapy use (MCS-). RESULTS: Among 376 patients fitting our study criteria, we identified 168 MCS+ and 208 MCS- patients. The VCSS edema score did not significantly differ between groups (P = 0.179). Postoperatively, the mean changes in VCSS edema at the first postoperative visit, the one-year follow-up, and the two-year follow-up were not significantly different between the MCS+ and MCS- cohorts (P = 0.123, 0.296, and 0.534, respectively). An analysis of CAS for edema revealed that the MCS+ cohort had a modestly better improvement in edema at the 90-day follow-up visit versus the MCS- cohort (P = 0.018), but this difference was not observed in the 30-day (P = 0.834) or six-month follow-up visit (P = 0.755). A multivariate analysis revealed no difference in the need for major intervention (OR 0.93, 95% CI 0.44 to 1.50, P = 0.504). A Kaplan-Meier analysis via log-rank test revealed no difference in reintervention-free survival between groups (P = 0.77). CONCLUSIONS: Many patients with moderate to severe lower extremity edema experience a reduction in their edema after IVS. In our study, compression stocking compliance after surgery had a little impact on edema relief in this population.

Enhanced Prefrontal Neuronal Activity and Social Dominance Behavior in Postnatal Forebrain Excitatory Neuron-Specific Cyfip2 Knock-Out Mice.

The cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2) gene is associated with epilepsy, intellectual disability (ID), and developmental delay, suggesting its critical role in proper neuronal development and function. CYFIP2 is involved in regulating cellular actin dynamics and also interacts with RNA-binding proteins. However, the adult brain function of CYFIP2 remains unclear because investigations thus far are limited to Cyfip2 heterozygous (Cyfip2+/- ) mice owing to the perinatal lethality of Cyfip2-null mice. Therefore, we generated Cyfip2 conditional knock-out (cKO) mice with reduced CYFIP2 expression in postnatal forebrain excitatory neurons (CaMKIIα-Cre). We found that in the medial prefrontal cortex (mPFC) of adult Cyfip2 cKO mice, CYFIP2 expression was decreased in both layer 2/3 (L2/3) and layer 5 (L5) neurons, unlike the L5-specific CYFIP2 reduction observed in adult Cyfip2+/- mice. Nevertheless, filamentous actin (F-actin) levels were increased only in L5 of Cyfip2 cKO mPFC possibly because of a compensatory increase in CYFIP1, the other member of CYFIP family, in L2/3 neurons. Abnormal dendritic spines on basal, but not on apical, dendrites were consistently observed in L5 neurons of Cyfip2 cKO mPFC. Meanwhile, neuronal excitability and activity were enhanced in both L2/3 and L5 neurons of Cyfip2 cKO mPFC, suggesting that CYFIP2 functions of regulating F-actin and excitability/activity may be mediated through independent mechanisms. Unexpectedly, adult Cyfip2 cKO mice did not display locomotor hyperactivity or reduced anxiety observed in Cyfip2+/- mice. Instead, both exhibited enhanced social dominance accessed by the tube test. Together, these results provide additional insights into the functions of CYFIP2 in the adult brain.