Midterm Outcomes of Antegrade In Situ Laser Fenestration of Polyester Endografts for Urgent Treatment of Aortic Pathologies Involving the Visceral and Renal Arteries.

OBJECTIVE: Aortic endografting and antegrade in situ laser fenestration of visceral arteries (LFEVAR) may be considered as an alternative to open surgery for the emergency repair of complex abdominal aortic aneurysms (AAA) in fragile patients. The aim of this article was to evaluate the midterm results of LFEVAR performed with polyester endografts. METHODS: From August 2015 to December 2020, all consecutive LFEVAR performed for non-deferrable treatment of complex AAA were analysed. Polyester endografts were deployed and subsequently fenestrated using an atherectomy laser probe; the fenestrations were enlarged using cutting and semicompliant balloons before implantation of balloon expandable bridging stents into the target vessels. Prospectively collected midterm survival, patency, and re-intervention rates were analysed. RESULTS: Forty four procedures were performed for 11 type 1a endoleaks, five thoraco-abdominal aneurysms, 20 pararenal aneurysms, four segmental renal artery (RA) preservations, three anastomotic aneurysms, and one aortic dissection. One hundred and eight laser fenestrations were performed (26 for the superior mesenteric artery [SMA], 13 for the coeliac trunk, 33 and 31 for the right and left RA, respectively). The median ischaemia duration was 7, 48, 48, and 45 minutes, respectively. The technical success rate was 97%, with no open surgical conversions. The 30 day mortality was 4.5% (n = 2). No spinal cord ischaemia events were observed nor early stent related complications. Kaplan-Meier overall survival at two years was 73%, the aortic related re-intervention free survival was 70%, and the stent related re-intervention free survival was 90.6%. Four target vessel thromboses were detected, of which three were rescued. Three type IIIc endoleaks, one RA false aneurysm, and one SMA stenosis, required re-intervention during a median follow up of 24.7 months. CONCLUSION: Antegrade LFEVAR is feasible, safe, and provides satisfactory early and midterm outcomes for non-deferrable treatment of aortic pathologies involving the visceral segment. Long term data are mandatory to confirm the usefulness of this promising off label technique.

Five Year Post-Endovascular Aneurysm Repair Aneurysm Sac Evolution in the GREAT Registry: an Insight in Diabetics Using Propensity Matched Controls.

OBJECTIVE: To assess differences in the five year abdominal aortic aneurysm (AAA) sac regression rate after endovascular aneurysm repair (EVAR) in patients with and without diabetes mellitus (DM). METHODS: An international prospective registry (Europe, USA, Brazil, Australia, and New Zealand) of patients treated with the GORE EXCLUDER endograft. All scheduled EVARs for infrarenal AAA between 2014 and 2016 with complete five year imaging follow up were included. Emergency procedures, ancillary proximal procedures, and inflammatory and infectious aetiologies were excluded. Descriptive and inferential statistics, and Cox proportional hazards survival models were used. A control group of patients without DM with similar age and comorbidities was selected using propensity scores, matched in a 1:2 scheme. RESULTS: A total of 2 888 patients (86.1% male; mean age 73.5 ± 8 years) was included, of whom 545 (18.9%) had DM. Patients with DM had higher rates of hypertension (89.2% vs. 78.4%), dyslipidaemia (76.0% vs. 60.7%), coronary artery disease (52.3% vs. 37.9%), and chronic renal impairment (20.9% vs. 14.0%) (all p < .001). The mean pre-procedural AAA diameter was 58.1 ± 10 mm. Five years post-EVAR, the type 1A endoleak rate was 1.1% (0.6% DM vs. 1.2% non-DM), the endograft related re-intervention rate was 7.3% (6.2% vs. 7.6%), the major adverse cardiovascular event (MACE) rate was 1.4% (1.1% vs. 1.5%), and aortic related mortality rate was 1.0% (0.6% vs. 1.2%), without statistically significant differences between groups. The overall five year mortality rate was higher in diabetics (36.3% vs. 30.5%; hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.07 - 1.58; p = .001). No statistically significant differences were found in sac regression rate (≥ 5 mm) between diabetics and non-diabetics 70.0% vs. 73.1%; HR 0.88, 95% CI 0.75-1.04; p = .131. These differences remained statistically non-significant after excluding patients performed out of instructions for use (p = .61) and patients with types 1, 2 or 3 endoleaks (p = .39). CONCLUSION: The paradoxical relationship between DM and AAA does not appear to result in differences in post-EVAR sac regression rates. However, even when controlling for other comorbidities, patients with DM undergoing EVAR may have a higher five year mortality rate.

Self-Made Bovine Pericardial Tube Grafts for the Treatment of Abdominal Aortic Infections.

BACKGROUND: Aortic infections are uncommon but life-threatening diseases. The material of choice for aortic reconstruction is still a matter of debate. The aim of this study is to examine the short- and mid-term outcomes in the treatment of abdominal aortic infections using self-made bovine pericardium tube grafts. METHODS: This retrospective, single-center study collected all patients who underwent in situ abdominal aortic reconstruction using self-made bovine pericardial tube grafts between February 2020 and December 2021 in a tertiary care center. Patient comorbidities, symptoms, radiological, bacteriological, and perioperative findings, as well as postoperative outcomes, were analyzed. RESULTS: Bovine pericardial aortic tube grafts were used in 11 patients (10 males, median age 68.7 years). Two patients presented with a native aortic infection, and 9 had graft infections (4 bypass grafts, 4 endografts, and a plurioperated patient who had undergone both endovascular and open procedures). There were 2 emergent surgeries due to infectious aneurysm ruptures. All patients were symptomatic, and the most frequent clinical finding was lumbar or abdominal pain (36%), followed by wound infection (27%), and fever (18%). Seven bifurcated and 4 straight pericardial tube grafts were needed. Purulent drainage was obtained around the previous graft or in the aneurysmal sac in 7 cases; intraoperative cultures were positive in 6 cases (gram + bacteria). Two patients died in the immediate postoperative period (perioperative mortality 18%; urgent procedures 50%; scheduled procedures 11%). One patient had a major complication due to bilateral severe acute respiratory syndrome coronavirus 2 pneumonia. There was 1 single reintervention to control hemostasis due to bleeding nongraft-related. The median follow-up was 14.1 months (3-24 months). CONCLUSIONS: Our preliminary experience in the treatment of abdominal aortic infections by in situ reconstruction with self-made bovine pericardial tube grafts shows promising results. These should be confirmed in the long term.

Psoas muscle analysis as a surrogate marker of sarcopenia and frailty: A multicenter analysis of predictive capacities over short- and long-term outcomes after abdominal aortic aneurysm repair.

OBJECTIVES: Several predictive models exist for estimating the postoperative risks of abdominal aortic aneurysm (AAA) repair, although no particular tool has seen widespread use. We present the results of a multicenter, historic cohort study comparing the predictive capacity of the psoas muscle area (PMA), radiodensity (PMD), and lean muscle area (LMA) as surrogate markers of sarcopenia, over short- and long-term outcomes after AAA repair, compared to the mFI-5 and American Society of Anesthesiologists (ASA) scales. METHODS: Retrospective review was conducted of all consecutive AAA elective repair cases (open or endovascular) in three tertiary-care centers from 2014 to 2019. Cross-sectional PMA, PMD, and LMA at the mid-body of the L3 vertebra were measured by two independent operators in the preoperative computed tomography. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values. Bivariate analysis, logistic regression, and Cox's proportional hazards models were built to examine the relationship between baseline variables and postoperative mortality, long-term mortality, and complications. RESULTS: 596 patients were included (mean age 72.7 ± 8 years, 95.1% male, 66.9% EVAR). Perioperative mortality was 2.3% (EVAR 1.2% vs open repair 4.6%, p = .015), and no independent predictors could be identified in the multivariate analysis. Conversely, an age over 74 years old (OR 1.84 95%CI 1.25-2.70), previous heart diseases (OR 1.62 95%CI 1.13-2.32), diabetes mellitus (OR 1.61 95%CI 1.13-2.32), and a PMD value over 66 HU (OR 0.58 95%CI 0.39-0.84) acted as independent predictors of long-term mortality in the Cox's proportional hazards model. Heart diseases (congestive heart failure or coronary artery disease), serum creatinine levels over 1.05 mg/dL, and an aneurysm diameter over 60 mm were independent predictors of major complications. CONCLUSION: Surrogate markers of sarcopenia had a poor predictive profile for postoperative mortality after AAA repair in our sample. However, PMD stood out as an independent predictor of long-term mortality. This finding can guide future research and should be confirmed in larger datasets.

Midterm results of endovascular versus open surgical repair for infrarenal abdominal aortic aneurysms in low surgical risk patients.

OBJECTIVE: The objective of this study was to analyze midterm outcomes of endovascular repair (EVAR) versus open repair (OR) for treatment of infrarenal abdominal aortic aneurysms (AAAs) in low surgical risk patients. METHODS: Elective patients with AAAs undergoing treatment from 2003 to 2017 in a single, tertiary-care institution were evaluated. All patients with a low preoperative risk of complications and perioperative mortality (Medicare Aneurysm Scoring System <3) were included, and rates of perioperative and long-term mortality, adverse events, and reintervention were evaluated for EVAR and OR. A propensity score-matched cohort, leveling age, risk factors, and comorbidities was additionally performed. RESULTS: A total of 227 patients were included (EVAR 59.9% and OR 40.1%) and followed for a mean of 80 ± 48 months. Patients undergoing EVAR were older (66.6 ± 5 vs. 64.1 ± 6 years; P <.001), had a higher body mass index (29.6 ± 4 vs 28.1 ± 3 kg/m2; P = .005), a higher prevalence of chronic obstructive pulmonary disease (27.3% vs 9.9%; P = .001), and lower prevalence of dyslipidaemia (46.3% vs 65.9%; P = .004). Patients undergoing OR had a higher rate of major adverse events (19.7% vs 2.6%; P = .001) and 30-day reinterventions (8.8% vs. 1.5%; P = .016), with 30-day mortality being 0% in both groups. The propensity-score matched cohort included 76 matched pairs (1:1), with differences in hospital stay and major complications remaining significant, without affecting mortality. At 5-year follow-up, there were no significant differences in the reintervention rate (EVAR 18.5% vs OR 17.6%; P = .67) or survival (EVAR 85% vs OR 91%; P = .195). CONCLUSIONS: In low surgical risk patients with AAAs, EVAR may offer comparable midterm results to OR, with a lower rate of major adverse events and a shorter in-hospital stay. With the current OR-first paradigm in low-risk patients, several factors should be taken into account for decision-making (anatomic suitability, risk of sexual dysfunction, risk of type 2 endoleaks, and need for follow-up).

Midterm Results of Endovascular Treatment for Complete Iliac Axis Occlusions Using Covered Stents.

BACKGROUND: Endovascular treatment of complex aortoiliac disease is seeing a growing popularity despite the Trans-Atlantic Inter-Society Consensus (TASC) II recommendations for open surgery in this cases. However, the available evidence does not focus particularly on patients with complete unilateral iliac axis obstruction (CIAO) (TASC II D4 group). This study reports mid-term results of endovascular therapy with covered stents for CIAO. METHODS: This is single-center retrospective review of patients with CIAO endovascular treatment from January 2015 to December 2017 (3 years). Two types of covered stents were used, alone or combined: the Viabahn self-expandable stent (W. L. Gore, Flagstaff, AZ) and the Advanta V12 balloon-expandable stent (Atrium-Maquet, Hudson, NH). Thirty-day outcomes, long-term patency (assessed with Kaplan-Meier estimates), in-hospital stay, and limb salvage were analyzed. RESULTS: Thirty-nine patients with CIAO were treated in the period (87.2% male, mean age 64.3 ± 9 years). A majority presented with critical limb ischemia (56.4%, n = 22). Recanalization could be accomplished from an ipsilateral or contralateral femoral access in 82.1% of patients (1 case needed the use of a re-entry device), and from a left brachial access in 17.9%. Technical success was 100%. About 66.7% of cases received an aortic kissing stent technique. Common femoral artery/profundoplasty with prosthetic or bovine patch was associated with 74.3% of cases. Thirty-day mortality was 2.6% (1/39). Primary, assisted, and secondary patency rates at 24 months were all 96.8%. Mean in-hospital stay was 5 days; no limb loss was registered during follow-up. CONCLUSIONS: Endovascular treatment of complete iliac axis occlusions can offer comparable midterm patency rates to open surgery aortoiliac femoral bypass, when an adequate combination of balloon and self-expandable covered stents is used and an appropriate outflow through the common femoral artery is warranted.

Endovascular Treatment of a Traumatic Axillary Artery Rupture Using the Dual Bull's-Eye Technique.

BACKGROUND: Our purpose is to report a case of an axillary artery rupture treated by endovascular means using the dual bull's-eye technique. An 83-year-old woman with multiple comorbidities was diagnosed with axillary artery rupture after the reduction of a shoulder dislocation. METHODS: An endovascular repair attempt was made, but, despite the use of a double approach (antegrade and retrograde), reconnecting both ends of the severed artery was deemed not possible. 5-mm Amplatz GooseNeck snares were advanced from each access and superposed in a perpendicular plane. A percutaneous infraclavicular puncture with a lumbar needle was made through both snares, and a V14 guidewire was subsequently introduced. The guidewire was recovered through femoral and brachial accesses, and a 7 × 100 mm covered self-expandable stent was deployed. RESULTS: The final angiographic control did not show further hemorrhage, and the patient recovered radial pulse. Follow-up showed complete patency and no complications at 9 months after the procedure. CONCLUSIONS: The dual bull's-eye technique can be used as a resource tool in cases of arterial rupture, when the arterial continuity cannot be re-established by conventional approaches.

Predictive Factors of Aneurysm Sac Growth in Patients with a Type II Endoleak in the First Post-EVAR Control.

BACKGROUND: The objective of this study was to identify predictive factors associated with aneurysm sac growth over time in patients diagnosed with a type II endoleak (TII-EL) in the first postoperative control after endovascular aneurysm repair (EVAR). METHODS: A retrospective analysis of all patients undergoing an elective EVAR procedure from January 2003 to December 2011 (9 years) in a single center was performed. Patients with a TII-EL detected in the first post-EVAR imaging control and with over twelve months of follow-up were included. The primary end point was aneurysm sac growth > 5 mm from the first month computed tomography angiography (CTA) to the last available CTA. Demographic variables, cardiovascular risk factors, comorbidities, aneurysm-related data, and procedural information were collected. Three-dimensional volume rendering with the Mimics ® software (Materialise NV, Leuven, Belgium) was used to measure the endoleak nidus. Descriptive, univariate, and multivariate analyses (Cox proportional hazards model) were performed. RESULTS: In this period, 220 EVAR procedures were performed. 63 TII-ELs (28.7%) were detected in the first CTA control (90.5% male, mean age: 75.7 ± 8 years). After a median follow-up of 54 months (interquartile range [IQR], 56.5), aneurysm sac growth > 5 mm was detected in 19 patients (30.1%). Age (P = 0.02) and dyslipidemia (P = 0.03) were associated with sac growth > 5 mm, whereas the presence of chronic obstructive pulmonary disease (COPD) behaved as a protective factor (P = 0.02). The craniocaudal length of the endoleak nidus (P < 0.01) and the nidus volume (P < 0.001) were the only aneurysm-related variables associated with sac growth. Age (HR: 14.1, 95% CI: 2.1-92.3, P = 0.006) and the presence of COPD (HR: 9.6, 95% CI: 1.4-63.7, P = 0.019) were the only independent predictors in the multivariate analysis. CONCLUSIONS: Reliable predictors of long-term aneurysmal sac growth are lacking, although some variables such as age or nidus volume appear to be associated. Strict surveillance remains mandatory.

Expanded Suitability of Ruptured Abdominal Aortic Aneurysms for Total Endovascular Repair Using the Endurant Endograft and Heli-FX EndoAnchors.

PURPOSE: To assess if the suitability of endovascular aneurysm repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs) can be expanded by combining the Endurant stent-graft with the Heli-FX EndoAnchors. MATERIALS AND METHODS: Contrast-enhanced computed tomography (CT) scans of 90 patients (mean age 73.2±9 years; 87 men) with RAAA admitted between January 2014 and January 2018 in 2 tertiary care centers were analyzed in a 3-dimensional workstation. Anatomical features of the aneurysms according to the instructions for use (IFU) for the Endurant endograft were evaluated and expansion of treatment with Heli-FX EndoAnchors was assessed. RESULTS: Neck length <10 mm was present in 41 (45.6%) patients; 5 had neck diameters outside the IFU and 45 (50.0%) had conical necks. Thrombus and calcium were absent in 63 (70.0%) and 73 (81.1%), respectively. In the study cohort, 44 (48.9%) patients met all the neck criteria, although overall IFU compliance was found in only 35 (38.9%) patients due to iliac-related issues in 21 patients. The adjunctive use of EndoAnchors in the entire study group would enhance the therapeutic range to an additional 24 patients, 8 of whom would need an associated iliac procedure. This represents an expansion of the total EVAR approach from 48.9% to 75.6% of cases if some iliac issues are overcome and from 38.9% to 56.7% without correcting iliac deficiencies. CONCLUSION: The main reason of being unfit for endovascular treatment in this series was neck length <10 mm. Based on this analysis, nearly 40% of RAAA patients would have been candidates for EVAR based on the IFU neck criteria for the Endurant stent-graft. This suitability could be nearly doubled with the use of EndoAnchors and correction of unsuitable iliac anatomy. The use of EndoAnchors has the potential to offer a significant benefit in the endovascular treatment of RAAA patients.

Multicenter Registry about the Use of EndoAnchors in the Endovascular Repair of Abdominal Aortic Aneurysms with Hostile Neck Showed Successful but Delayed Endograft Sealing within Intraoperative Type Ia Endoleak Cases.

BACKGROUND: The durability of endovascular aortic aneurysms repair (EVAR) is highly related to several anatomical constraints. The term "hostile neck" describes several anatomical features that usually make EVAR treatment technically demanding despite having higher risk of failure. The aim of the study was to describe a multicenter experience with EVAR and an adjunctive use of EndoAnchors in hostile neck anatomies. METHODS: Data were prospectively collected from 4 academic vascular centers including 46 patients with a hostile neck treated by standard EVAR with the adjunctive use of EndoAnchors. Twenty-two of them (47.8%, group A) had an intraoperative type Ia endoleak, and 24 (52.2%) patients were treated in a preventive manner (group B). Primary endpoints were technical and procedural success. Secondary endpoints were regression of the aneurysm sac, freedom from type Ia endoleak, and reinterventions. RESULTS: Neck length and diameter showed no statistical difference in preoperative measures, 9.1 ± 6.9 mm and 8.6 ± 2.8 mm and 25.4 ± 4.7 mm and 27.3 ± 4.7 mm, in group A and B, respectively. Aneurysm sac diameter decreased from 58.2 ± 8 mm and 57.9 ± 9.8 mm to 55.7 ± 8.5 mm and 53.8 ± 10.4 mm in group A and B; respectively, at the last computed tomography scan. Technical and procedural success was 97.8% and 100%, respectively, for group B. Group A showed persistence of type Ia endoleak at completion angiogram in 9 (40.9%) patients. Five of them showed early spontaneous sealing at the first (30 days) computed tomography angiography (CTA), and in the remaining 4, a delayed spontaneous sealing was diagnosed at 12-month CTA. No neck-related secondary procedures were performed. Overall survival was 91%. CONCLUSIONS: Our study shows that additional use of EndoAnchors can successfully improve the sealing of abdominal endografts in case of intraoperative type Ia endoleaks in hostile neck anatomies, representing a safe and effective endovascular alternative in our armamentarium. However, meticulous radiological follow-up is necessary because complete resolution of all observed intraoperative type Ia endoleaks was not observed until the 12-month CTA follow-up.

Effect of antiplatelet therapy on aneurysmal sac expansion associated with type II endoleaks after endovascular aneurysm repair.

OBJECTIVE: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) has gained widespread use through a solid reputation of safety and effectiveness. However, some issues, such as endoleaks and sac growth over time, still arise as important concerns. Antiplatelet therapy, mandatory as secondary prevention of cardiovascular disease, may play a role in both phenomena by interfering with blood clotting properties and the inflammatory process associated with AAA. We analyzed whether different antiplatelet therapies were independent risk factors for type II endoleak (T2E) persistence and midterm sac growth after EVAR. METHODS: All patients with T2E detected in the first post-EVAR control were included, except those without at least 1 year of complete follow-up. Data for demographics, clinical comorbidities, EVAR devices, and antiplatelet therapies were recorded. All patients underwent routine follow-up with contrast-enhanced tomography at 1 month, 6 months, 12 months, and annually thereafter. A three-dimensional rendering of each endoleak was performed for detailed volumetry. Main outcomes were endoleak persistence at 6 months and sac growth >5 mm at end of follow-up. RESULTS: During a 9-year period, 87 patients with initial T2E were monitored for a mean of 41.5 months. On discharge, salicylates were prescribed to 50, clopidogrel to 16, and multiagent therapy or anticoagulation to 9; no therapy was given to 12. No significant differences in comorbidities or baseline AAA characteristics were found between groups. At 6 months thereafter, 59% (n = 51) of the initial T2Es persisted. At end of follow-up, 32 patients had sac growth >5 mm (37%). Sac growth was significantly less frequent in the group treated with salicylates (26% vs 60%; P = .004). Cox proportional hazards model reinforced the role of salicylates as protectors for sac growth over time (hazard ratio, 0.34; 95% confidence interval, 0.13-0.87; P = .024), whereas T2E nidus volume and endoleak complexity behaved like independent risk factors. CONCLUSIONS: Antiplatelet therapy with salicylates appears to be linked to a decreased risk of sac growth >5 mm over time in patients with T2Es detected right after EVAR. Population-based cohort studies are mandatory to confirm this finding and to guide a potential recommendation.

Failed Minimally Invasive Staged Treatment of a Giant Symptomatic Aortic Perigraft Hygroma after Open Aortic Repair.

BACKGROUND: Perigraft hygromas or seromas are an unusual finding and/or complication after open aortic repair. METHODS AND RESULTS: We present a case of an 82-year-old man with a previous urgent aortic bifurcated graft for abdominal aortic aneurysm rupture. He received several treatments due to abdominal compartment syndrome, requiring a Bogota Bag and colostomy derivation. He was finally discharged home and lost on follow-up. Eight years after this procedure, he presented to the urgency department with an abdominal mass and pain. Urgent computed tomography (CT) scan revealed a giant bilobed aortic sac, corresponding with a huge hygroma. A 3-stage minimally invasive procedure was scheduled due to hostile abdomen. Six months after successful treatment, patient came with fever and abdominal pain. He was diagnosed with graft infection and aortoenteric fistula and was treated with explantation and silver in situ repair. CONCLUSIONS: Aortic hygroma or seromas after open repair should be treated by open means whenever possible. Endovascular techniques could be a valid option in selected patients; however, further evidence is needed.

A Word of Caution for Extra Large Self-expandable Nitinol Stents.

BACKGROUND: To report an unsuccessful use of large nitinol stent to prevent proximal endoleak in endograft treatment for juxtarenal aortic aneurysm. CASE REPORT: An 82-year-old male presented coronary disease and severe chronic obstructive pulmonary disease requiring oxygen support. A large 80-mm juxtarenal aneurysm was found on routine urological examination. Neck features were as follows: 7 mm and high anterior-posterior angulation. ASA risk score IV was given. Patient wanted to be treated. We decided a 1-shot intervention based on self-expandable suprarenal fixation endograft with adjunctive extra large self-expandable (high radial force) nitinol stent. Control computed tomography scan demonstrates nitinol stent severe infolding and a possible perforation of the primary endograft. At 6-month follow-up, sac reveals enlargement of 5 mm and 6% volume increase. Patient does not want further treatments due to high risk of procedures. CONCLUSIONS: Extreme caution should be taken when using self-expandable extra large nitinol stents for preventive matters. Oversizing should be carefully considered, not necessarily reaching the endograft chosen size. When short and angulated neck morphology co-exists, other devices or procedures may be a better option.

"Lower limbs revascularization from supraceliac and thoracic aorta".

Revascularization of femoral arteries from descending thoracic or supraceliac aorta is an uncommon procedure, in part because of the popularization of the technically easier extra-anatomic bypasses. However, using those aortic levels as the source of the bypass inflow is a useful alternative in selected patients with aortoiliac disease, with excellent results. We report long-term results in 4 patients with revascularization from thoracic aorta and another 2 cases from aorta at supraceliac level. This technique should be considered as a good alternative in patients with adverse abdominal conditions or with a severely diseased infrarenal aorta due to heavy calcification.