Preliminary results of the Austrian National Registry regarding the novel iCover bridging stent graft in fenestrated endovascular aortic repair.

OBJECTIVE: Bridging stentgrafts (BSGs) are one of the primary limiting factors regarding long-term results after fenestrated endovascular aortic repair (fEVAR). This study aims to report for the first time the outcome of a novel BSG called iCover from a national, multicentric retrospective database. METHODS: A cohort of 58 patients received 212 BSGs for the renovisceral arteries in fEVAR. Patients were followed-up clinically and with computed-tomography angiography. Study end points were mortality, occurrence of complications, technical success of the BSG implantation, defined as successful deployment with vessel patency and absence of type 1c, 3b, and 3c endoleak, and stability over the follow-up. RESULTS: Three BSG unrelated mortalities (5.1 %), four BSG unrelated major complications (6.8 %) and five minor complications (8.6 %) occurred. The technical success of iCover was 207/212 (97.6 %), target vessel patency was 100 % over a follow-up of 4.0 months, and no late BSG related endoleak was detected. In two cases, the BSG was dislodged from the balloon and could be parked in a safe position without further sequelae (0.9 %). CONCLUSION: The iCover represents a feasible BSG for fEVAR with an excellent safety profile and technical success rate in the early phase. Prudent post-dilatation and monitoring of the proximal and distal stent ends can potentially further improve outcome. Longer follow-up series are necessary.

Early experience with bridging stent graft deployment without sheath support in branched and fenestrated endovascular aortic repair.

OBJECTIVE: To assess the early experience with modified version of simplified bare-wire target vessel (SMART) technique, implying delivery of bridging stent grafts without historically established sheath support, and to compare its outcome to standard endovascular aortic repair procedures with fenestrated/branched devices. METHODS: A retrospective analysis of 102 consecutive patients treated with fenestrated/branched devices from January 2020 to December 2022 was undertaken. The study population was divided into three groups-a sheath group (SG), SMART group, and nonsheath group (NSG). Primary end points were radiation exposure (dose-area product), fluoroscopy time, dose of contrast agent, operation time, and incidence of intraoperative target vessel (TV) complications and additional procedures. Freedom from secondary TV related reinterventions at the three follow-up phases were defined as secondary end points. RESULTS: A total of 183 TVs (38.8% visceral arteries [VA]; 56.3% renal arteries [RA]) in the SG, 36 TVs (44.4% VA, 55.6% RA) in the SMART group, and 168 TVs (47.6% VA; 50% RA) in the NSG were accessed. The mean number of fenestrations and bridging stent grafts was equally distributed in all three groups. The SMART group only included cases treated with fenestrated devices. The dose-area product was significantly lower in the SMART (median, 203 Gy × cm2; interquartile range [IQR], 179-365 Gy × cm2) and NSG (median, 340 Gy × cm2; IQR, 220-651 Gy × cm2) groups vs the SG (median, 464 Gy × cm2; IQR, 267-871 Gy × cm2; P = .007). Operation time was also significantly lower in the NSG (median, 265 minutes; IQR, 221-337 minutes) and SMART (median, 292 minutes; IQR, 234-351 minutes) groups vs the SG (median, 326 minutes; IQR, 277-375 minutes; P = .004), respectively. Intraoperative TV-related complications were most frequently observed in the SG (9/183 TVs; P = .008). CONCLUSIONS: This study reports the outcomes of three currently available TV stenting approaches. Previously reported SMART technique, and its modified version (NSG) proved to be a safe alternative to historically established TV stenting technique with sheath support (SG).

Endovascular repair in type A aortic dissection: Anatomical candidacy for currently manufactured stent grafts and conceptual valve-carrying devices for an Endo-Bentall procedure.

OBJECTIVES: Endovascular treatment has been suggested as an alternative for open surgery for type A aortic dissection, but current devices have severe anatomical limitations. This study assesses the computed tomography-based anatomical suitability of currently manufactured stent grafts as well as 2 embodiments of valve-carrying devices. METHODS: In a retrospective single-centre cohort of 200 consecutive ascending/arch operations between 2009 and 2018, a total of 112 patients with type A aortic dissections were identified and evaluated for endovascular candidacy based on the locations of the entries, the landing zone diameters/lengths and the supra-aortic vessel origins according to the anatomical instructions for use criteria of 6 commercially available (tubular, branched or fenestrated) stent grafts. Two suggested valve-carrying devices with inner branches or fenestrations for the coronary arteries and branches for the supra-aortic vessels were also evaluated. RESULTS: The anatomical feasibility for commercial stent grafts ranged from 4% to 21%. The main limitations were proximal landing zone diameter (considering oversizing <15%), length due to dilatation and an entry too close to the sinotubular junction. For the valve-carrying conduits, anatomical feasibility was between 31% and 80%, with the main limiting factors being the diameter of the aortic annulus and its distance to the coronary arteries. CONCLUSIONS: The anatomical applicability of currently manufactured stent grafts for the treatment of type A aortic dissection is limited mainly by the absence of a suitable proximal landing zone in the ascending aorta and might substantially be improved by anchoring in the aortic annulus using a valve-carrying device that uses either fenestrations or branches for the coronary arteries.

Monoplane versus biplane fluoroscopy in patients undergoing fenestrated/branched endovascular aortic repair.

OBJECTIVE: Endovascular aortic repair (EVAR) with fenestrated (F-EVAR) or branched (B-EVAR) endografts represents an indispensable tool of modern patient care in vascular surgery. The purpose of this retrospective study was to evaluate the center's initial experience of F/B-EVAR procedures performed under biplane angiography guidance compared with a historical control group. METHODS: From January 2020 to March 2022, 80 consecutive patients underwent F/B-EVAR under general anesthesia at a single institution. As from January 2021, the deployment of complex stent grafts was performed using an alternative intraoperative imaging modality-a biplane fluoroscopy and angiography. The cohort was divided into monoplane (MPA) and biplane (BPA) groups according to the imaging modality applied. The end points were operation time, fluoroscopy time, radiation exposure, dose of contrast agent, and technical success. RESULTS: The MPA group included 59 patients (78% male; median age; 74 years; interquartile range [IQR], 66-78 years) and the BPA group 21 patients (85.7% males; median age, 75 years; IQR, 69-79 years). Operation time (median, 320 minutes; IQR, 266-376 minutes) versus (median, 275 minutes; IQR, 216-333 minutes) was significantly lower in the BPA group (P = .006). The median fluoroscopy time (median, 82 minutes; IQR, 57-110 minutes vs median, 68 minutes; IQR, 54-92 minutes), contrast agent volume applied (median, 220 mL; IQR, 179-250 mL vs median, 200 mL; IQR, 170-250 mL), and radiation dose (dose-area product, median, 413 Gy × cm2; IQR, 249-736 Gy × cm2; vs median, 542 Gy × cm2; IQR, 196-789 Gy × cm2) were similar in both groups. Technical success of 96.6% (57/59 cases) versus 100% (21/21 cases) could be achieved in MPA and BPA group, respectively. CONCLUSIONS: F/B-EVAR procedures performed under BPA guidance were associated with a significant decrease in operation time.

Cytotoxicity of combinations of the pan-KRAS SOS1 inhibitor BAY-293 against pancreatic cancer cell lines.

KRAS is mutated in approximately 25% of cancer patients and first KRAS G12C-specific inhibitors showed promising responses. Pancreatic cancer has the highest frequency of KRAS mutations but the prevailing KRAS G12D mutation is difficult to target. Inhibition of the GTP exchange factor (GEF) SOS1-KRAS interaction impairs oncogenic signaling independently of the specific KRAS mutations. In general, cell lines exhibiting KRAS mutations show specific alterations in respect to glucose utilization, signal transduction and stress survival. The aim of this investigation was to check the putative synergy of the SOS1 inhibitor BAY-293 with modulators targeting specific vulnerabilities of KRAS-mutated cell lines in vitro. The cytotoxicity of BAY-293 combinations was tested against MIA PaCa-2 (G12C), AsPC1 (G12D) and BxPC3 (KRAS wildtype) cell lines using MTT tests and calculation of the combination indices (CI) according to the Chou-Talalay method. The results show that BAY-293 synergizes with modulators of glucose utilization, inhibitors of the downstream MAPK pathway and several chemotherapeutics in dependence of the specific KRAS status of the cell lines. In particular, divergent responses for BAY-293 combinations between pancreatic and NSCLC cell lines were observed for linsitinib, superior inhibitory effects of trametinib and PD98059 in NSCLC, and lack of activity with doxorubicin in case of the pancreatic cell lines. Phosphoproteome analysis revealed inhibition of distinct signaling pathways by BAY-293 for MIA PaCa-2 on the one hand and for Aspc1 and BH1362 on the other hand. In conclusion, BAY-293 exhibits synergy with drugs in dependence of the tumor type and specific KRAS mutation.

Applicability of endovascular branched and fenestrated aortic arch repair devices to treat residual type A dissection after ascending replacement.

OBJECTIVE: Endovascular repair of post-type A aortic dissection (PTAD) after open ascending replacement has recently been shown as safe and feasible, but with limited anatomic applicability because only one stent graft was evaluated. We assessed anatomic and clinical applicability of six commercially available branched/fenestrated stent grafts for endovascular repair of PTAD. METHODS: On postoperative CT scans of 101 patients, we measured the aortic diameter at the sinutubular junction, supra-aortic vessels, and descending aorta, as well as the distances between these landmarks along the outer curvature of the arch and the diameters of the supra-aortic vessel. Anatomic applicability was evaluated according to the instructions for use, clinical applicability with regard to supra-aortic and iliac arteries. Assessed devices were the Cook aortic double branch, Terumo double branch, Najuta fenestrated, Endospan Nexus, Medtronic Mona LSA, and Gore TAG thoracic branch. RESULTS: Single devices were anatomically and clinically applicable between 19 of 101 (Mona LSA) and 83 of 101 (Najuta) cases. Reasons for rejection varied considerably across devices. With all devices available, anatomic applicability was 97 of 101 and clinical applicability 95 of 101. Combinations of a fenestrated and a branched device showed the most favorable clinical applicability for a pair of two devices, ranging from 86 of 101 to 94 of 101. CONCLUSIONS: Anatomic and clinical applicability of endovascular devices for the repair of PTAD is high for fenestrated and branched devices, and very high for the combination of fenestrated and branched devices. Manufacturers should amend specific device requirements for PTAD. Surgeons should emphasize the need for a sufficiently long and straight graft as a potential landing zone.

Branched versus fenestrated thoracic endovascular aortic repair in the aortic arch: A multicenter comparison.

OBJECTIVE: For thoracic endovascular aortic repair of the arch, branched and fenestrated endografts are available with different limitations regarding anatomy and extent of the pathology. Comparisons are lacking in the literature. The aim of this study was to compare the results of 2 currently commercially available devices for branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair. METHODS: In a retrospective, multicenter cohort study, a consecutive patient series treated with branched thoracic endovascular aortic repair or fenestrated thoracic endovascular aortic repair for aortic arch pathologies was assessed. Baseline characteristics, procedural fenestrated thoracic endovascular aortic repair, and outcome were analyzed. Furthermore, the potential anatomic feasibility of the respective alternate device was assessed on the preoperative computed tomography scans. RESULTS: The branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair cohorts consisted of 20 and 34 patients, respectively, with similar comorbidities; indication was aneurysm in 65% and 79%, penetrating aortic ulcer in 20% and 9%, and dissection in the remaining procedures, respectively. Technical success was achieved in all but 1 patient. Perioperative mortality and major stroke rate were both 10% in branched thoracic endovascular aortic repair and 0% and 3% in fenestrated thoracic endovascular aortic repair, respectively. During follow-up of 31 and 40 months, 1 branch occlusion occurred in the branched thoracic endovascular aortic repair cohort, and 2 late endoleaks occurred in the fenestrated thoracic endovascular aortic repair group. One aortic death occurred. Although 35% of patients undergoing branched thoracic endovascular aortic repair were anatomically suitable for fenestrated thoracic endovascular aortic repair, 91% of those undergoing fenestrated thoracic endovascular aortic repair were suitable for branched thoracic endovascular aortic repair. CONCLUSIONS: Both branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair show excellent technical success and acceptable complication rates, whereas branched thoracic endovascular aortic repair tends toward higher morbidity, especially stroke rates. By offering fenestrated thoracic endovascular aortic repair along with branched thoracic endovascular aortic repair, aortic centers could potentially lower complication rates and simultaneously still treat a wide range of anatomies.

Use of a Steerable Sheath for Completely Femoral Access in Branched Endovascular Aortic Repair Compared to Upper Extremity Access.

PURPOSE: To compare bridging stent graft (BSG) implantation in downward oriented branches in branched endovascular aortic repair (bEVAR), using a commercially available steerable sheath from an exclusively femoral access (TFA) with traditional upper extremity access (UEA). METHODS: In a retrospective cohort study, 7 patients with 19 branches in the TFA cohort received BSG insertion using the Medtronic Heli FX steerable sheath from a femoral access, and 10 patients with 32 branches in the UEA cohort from a brachial approach. Technical success, total intervention time, fluoroscopy time, branch cannulation time, and complication rate were recorded. RESULTS: Technical success was 19/19 branches in the TFA and 31/32 in the UEA cohort. The mean branch cannulation time was considerably shorter in the TFA group (17 vs. 29 min, p = 0.003), and total intervention time tended to be shorter (169 vs. 217 min, p = 0.176). CONCLUSION: Using a commercially available steerable sheath allowed successful cannulation of all branches in this cohort and was associated with significantly shorter branch cannulation times. Potentially, this technique can lower the stroke and brachial puncture site complication risk as well as reduce total intervention time and radiation dose. LEVEL OF EVIDENCE: 2b, retrospective cohort study.

Structural failure in bridging stentgrafts for branched endovascular aneurysm repair: a case-control study.

OBJECTIVE: To present a case series of spontaneous structural failure of bridging stentgrafts (BSGs) after branched endovascular aortic repair (bEVAR), as well as their failure types and their detection. While bEVAR is a safe and effective procedure, one main limitation is the reintervention rate associated with the BSGs. Structural failure of BSGs, defined as fabric disruption, stent fracture with leak or complete separation is a major cause for reinterventions and difficult to detect in computed tomography angiography (CTA). METHODS: From a multicenter bEVAR complication database, structural BSG failures were identified. Patient and BSG characteristics, detection mode, failure type, treatment and outcome were recorded and compared with bEVAR patients with intact BSGs. RESULTS: Twenty-three BSG failures were detected in 12 patients with only 43% directly identified in CTA, after a mean of 21.4 months after implantation. The BSGs were Advanta (n = 4), E-Ventus (n = 16) and BeGraft (n = 3) in 10 renal, 9 superior mesenteric, and 4 celiac branches. Religning with another BSG was successful in 20/22 cases, one BSG failure necessitated renal branch embolization (organ loss), and one mesenteric bypass surgery. Two reintervention-related mortalities occurred. CONCLUSION: Structural failure of BSGs is a serious limitation for bEVAR, which can result in high reintervention rates and serious complications. BSG failure typically occurs in single-layer types and events are clustered in patients. The necessary reinterventions carry serious morbidity and mortality. Since the use as BSG in bEVAR is off-label with all current BSG manufacturers, caution is advised regarding patient-informed consent.

Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer.

In the absence of suitable molecular markers, non-small cell lung cancer (NSCLC) patients have to be treated with chemotherapy with poor results at advanced stages. Therefore, the activity of the anticancer marine drug fascaplysin was tested against primary NSCLC cell lines established from pleural effusions. Cytotoxicity of the drug or combinations were determined using MTT assays and changes in intracellular phosphorylation by Western blot arrays. Fascaplysin revealed high cytotoxicity against NSCLC cells and exhibit an activity pattern different of the standard drug cisplatin. Furthermore, fascaplysin synergizes with the EGFR tyrosine kinase inhibitor (TKI) afatinib to yield a twofold increased antitumor effect. Interaction with the Chk1/2 inhibitor AZD7762 confirm the differential effects of fascplysin and cisplatin. Protein phosphorylation assays showed hypophosphorylation of Akt1/2/3 and ERK1/2 as well as hyperphosphorylation of stress response mediators of H1299 NSCLC cells. In conclusion, fascaplysin shows high cytotoxicity against pleural primary NSCLC lines that could be further boosted when combined with the EGFR TKI afatinib.

Growth prediction model for abdominal aortic aneurysms.

BACKGROUND: The most relevant determinant in scheduling monitoring intervals for abdominal aortic aneurysms (AAAs) is maximum diameter. The aim of the study was to develop a statistical model that takes into account specific characteristics of AAA growth distributions such as between-patient variability as well as within-patient variability across time, and allows probabilistic statements to be made regarding expected AAA growth. METHODS: CT angiography (CTA) data from patients monitored at 6-month intervals with maximum AAA diameters at baseline between 30 and 66 mm were used to develop the model. By extending the model of geometric Brownian motion with a log-normal random effect, a stochastic growth model was developed. An additional set of ultrasound-based growth data was used for external validation. RESULTS: The study data included 363 CTAs from 87 patients, and the external validation set comprised 390 patients. Internal and external cross-validation showed that the stochastic growth model allowed accurate description of the distribution of aneurysm growth. Median relative growth within 1 year was 4.1 (5-95 per cent quantile 0.5-13.3) per cent. Model calculations further resulted in relative 1-year growth of 7.0 (1.0-16.4) per cent for patients with previously observed rapid 1-year growth of 10 per cent, and 2.6 (0.3-8.3) per cent for those with previously observed slow growth of 1 per cent. The probability of exceeding a threshold of 55 mm was calculated to be 1.78 per cent at most when adhering to the current RESCAN guidelines for rescreening intervals. An online calculator based on the fitted model was made available. CONCLUSION: The stochastic growth model was found to provide a reliable tool for predicting AAA growth.

Cytotoxicity of combinations of the pan-KRAS inhibitor BAY-293 against primary non-small lung cancer cells.

KRAS is mutated in approximately 25% of Non-small Cell Lung Cancer (NSCLC) patients and first specific inhibitors showed promising responses that may be improved by concurrent interference with downstream signaling pathways. Cell lines exhibiting KRAS mutations show specific sensitivities to modulators affecting glucose utilization, signal transduction and cell survival. Novel SOS1-directed inhibitors with a broader anticancer coverage such as BAY-293 and BI-3406 inhibit KRAS through the hindrance of SOS1-KRAS interactions. The aim of this study was to check the putative synergy of BAY-293 with modulators having revealed specific vulnerabilities of KRAS-mutated cell lines. The present investigation tested the cytotoxicity of BAY-293 combinations against a series of Osimertinib-resistant primary NSCLC cell lines using MTT tests and calculation of combination indices according to the Chou-Talalay method. The results show that BAY-293 synergizes with modulators of glucose metabolism, inhibitors of cellular proliferation, several chemotherapeutics and a range of diverse modulators, thus corroborating the chemosensitivities of cells expressing mutated KRAS. In conclusion, BAY-293 exerts cytotoxicity with a wide range of drugs against Osimertinib-resistant primary NSCLC cell lines. The administration of pan-KRAS inhibitors alone may be limited in vivo by toxicity to normal tissues but made feasible by its use as part of suitable drug combinations. This study shows that BAY-293 combinations are active against NSCLC cells not further amenable to mutated EGFR-directed targeted therapy and results likewise hold relevance for pancreatic and colon cancer.

Novel prefabricated bovine pericardial grafts as alternate conduit for septic aortoiliac reconstruction.

OBJECTIVE: Infection of prosthetic aortic grafts represents a serious complication with high morbidity and mortality. Replacement with autologous material is recommended; however, in its absence, biological material should be favored. In the present retrospective cohort study, we evaluated the short- and midterm results with the use of commercially available prefabricated bovine pericardium grafts (BPGs) used for the management of aortic graft infection or aortic reconstructive surgery in the presence of systemic infection. METHODS: We performed a retrospective analysis of patients in whom BPGs had been used for aortic reconstruction at two vascular centers. Prefabricated vascular pericardium grafts were preferred over other biological reconstruction techniques for selected cases. Comorbidities, procedure-related details, perioperative morbidity, clinical outcomes, and mortality were analyzed. RESULTS: From 2014 to 2019, 21 patients had received BPGs at two Austrian vascular centers. Their median age was 63 years (interquartile range [IQR], 55-71 years), the patients were predominantly male (76%), and the median body mass index was 25.3 kg/m2 (IQR, 21.7-27.3 kg/m2). The major comorbidities included arterial hypertension, peripheral artery disease, smoking, and chronic pulmonary disease. The indications for surgery were vascular graft or endograft infection in 62% and aortic reconstruction in the presence of systemic infection in 38%. Three patients (14%) had aortoenteric fistulas. Surgery was technically successful in all cases. The median follow-up was 21.6 months (IQR, 6.0-34.6 months). The 30-day mortality was 9.5%. The 1- and 2-year overall survival was 84% and 75%, respectively. Of the 21 patients, 89% had remained free of recurrent infection. One of the two reinfections had resolved after treatment of the underlying focus. At 2 years, the primary and assisted primary patency rates were 86% and 94%, respectively. No limbs were lost during follow-up. CONCLUSIONS: Prefabricated BPGs represent a promising alternative for the management of aortic graft infections and aortoiliac reconstruction in the presence of systemic infection.

Signet Ring Cell Carcinoma of the Lung: A Diagnostic Pitfall in Pregnancy.

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the 22nd week of gestation.

Thoracic endovascular repair for acute complicated type B aortic dissections.

OBJECTIVE: This study retrospectively assessed in-hospital mortality and long-term results of emergency thoracic endovascular aortic repair (TEVAR) for patients with life-threatening acute complicated type B aortic dissection (acTBD). METHODS: Between March 2001 and December 2016, there were 55 patients (40 male; median age, 52 ± 13 years) with an acTBD who were treated with TEVAR for malperfusion (58%), aortic rupture (18%), or persistent untreatable pain with true lumen reduction or rapid aortic diameter enlargement (24%) as a sign of disease progression. The patients were categorized according to clinical appearance into two groups: group A, malperfusion, pending rupture, or rupture; and group B, persistent ongoing pain, rapid enlargement of aortic diameter, or significant changes in the true to false lumen ratio. Four patients (7%) had undergone previous aortic surgery. RESULTS: Technical success (coverage of the primary intimal tear) was achieved in 50 patients (91%). The overall in-hospital mortality rate was 9% (n = 5), and there was a statistically significant difference in early mortality between group A and group B (7% vs 2%; P < .02). Causes of in-hospital death were all aorta related, including a rupture during the procedure and on the first postinterventional day in two patients and redissection (ascending aorta, n = 2; descending aorta, n = 1) with a consequent aortic rupture after TEVAR in the remaining three. Permanent neurologic dysfunction occurred in five patients (stroke, n = 2; paraplegia, n = 3). Overall, 19 patients (34%) developed early endoleaks (type IA, n = 5; type IB, n = 11; type II, n = 2; type IB plus type II, n = 1). Therefore, 5 patients needed early (within 30 days) endovascular intervention because of a type IA (n = 2), type IB (n = 3), or type II endoleak (n = 1) and the rapid progression of aortic diameter, persistent signs of ischemia (n = 2), or rupture (n = 1), whereas the remaining 14 patients were treated conservatively and followed up by computed tomography angiography. Seven patients with early endoleaks needed an endovascular intervention (n = 3) or conventional surgery (n = 4) because of aortic progression in the follow-up period (mean interval after procedure, 92 ± 56 months). The actual survival rates were 87%, 85%, and 75% at 1 year, 2 years, and 5 years, respectively, and freedom from aorta-related death was 87%, 87%, and 77% at 1 year, 2 years, and 5 years, respectively. Freedom from reintervention for any cause using a Kaplan-Meier analysis was 70%, 68%, 68%, and 63% at 6 months, 1 year, 2 years, and 5 years, respectively. CONCLUSIONS: TEVAR of acTBD has been proven to be an excellent treatment modality in this cohort of high-risk patients, with promising midterm and long-term results.

Long-Term Course of Shoulders After Ultrasound Therapy for Calcific Tendinitis: Results of the 10-Year Follow-Up of a Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to follow both the structure- and function-related long-term course of shoulders that had been treated with therapeutic ultrasound for symptomatic calcific tendinitis. DESIGN: This is a long-term follow-up of 45 shoulders (37 patients) that had been treated for symptomatic calcific tendinitis with either a series of ultrasound or sham ultrasound 10 yrs ago. The main outcome variables were presence of calcium deposits and subacromial impingement on standardized x-ray imaging, shoulder symptoms (Binder score), and function (Constant score). RESULTS: At 10 yrs, a similar proportion of calcium deposits had resolved in 78% of the originally ultrasound treated compared with 83% of sham-treated shoulders, whereas at 9 mos, significantly more calcium deposits had been resolved in the ultrasound group (P = 0.045). Relative to baseline, shoulder symptoms and function had significantly improved at both the 10-yr and 9-mo follow-up examinations with no significant differences between groups. Regular sports performance at baseline predicted a favorable long-term outcome. CONCLUSIONS: Symptomatic calcific tendinitis of the shoulder has a good likelihood to completely resolve in the long term. Treating the calcium deposit effectively, however, may not be causal to the recovery from symptoms and function in calcific tendinitis.

Successful Treatment of a Ruptured Extracranial Vertebral Artery Aneurysm with Onyx Instillation.

The rupture of an extracranial vertebral artery aneurysm has only been rarely described in the literature and treatment options are therefore not standardized. Here we report the successful endovascular repair of a spontaneously ruptured extracranial left vertebral artery aneurysm using Onyx instillation. A 48-year-old woman was transferred to our clinic after having been intubated due to a massive hematoma of the left neck. A contrast-enhanced computed tomography (CT) showed a rupture of the left extracranial vertebral artery. Several issues complicated the therapeutic decision making in this rare case: first, the patient showed multiple aneurysms in CT angiography; therefore a connective tissue disease could not be excluded. Furthermore, as anamnestic work-up revealed that several episodes of postoperative bleeding and open surgery at this anatomic location are rarely performed, risks for postoperative complications were high. Therefore, the patient was hemodynamically stabilized and the ruptured aneurysm was treated in an endovascular approach with Onyx instillation and coil embolization. Complete exclusion of the aneurysm was achieved without periprocedural or neurological complications. Successful repair was confirmed by CT angiography on the first postoperative day as well as 12 months after the intervention. In conclusion, this case shows that endovascular Onyx embolization of ruptured vertebral aneurysms is a save and feasible method.

Worldwide results from the RESTORE II on elective endografting of thoracic aneurysms and dissections.

OBJECTIVE: To assess safety, performance, and efficacy of the RELAY thoracic stent graft (Bolton Medical, Barcelona, Spain) in the treatment of patients who require elective thoracic endovascular aortic repair including aneurysms and dissections. METHODS: The RELAY Endovascular Registry for Thoracic Disease II (RESTORE II) is a multicenter, prospective, international cohort study involving 21 centers in 12 countries worldwide. All consecutively included patients underwent elective thoracic endovascular aortic repair with a RELAY or RELAY NBS stent graft (including off the shelf and custom-made devices) to repair thoracic aortic aneurysms or dissections. Demographic, clinical, and aortic parameters were Web-based registers. Safety and efficacy data were collected for a follow-up period of 24 months. RESTORE was a precedent registry involving European sites that used RELAY first-generation devices. RESULTS: A total of 173 patients were enrolled in the registry from October 2010 to September 2014 (aneurysm [n = 99]/dissection [n = 74]). Overall technical success of the intervention reached 97.1% irrespective of the etiology and geographic origin of patients. Baseline clinical heterogeneity was observed between devices concerning the etiology of the disease and certain comorbidities and/or risk factor distribution (diabetes, hypertension, myocardial infarction, angina pectoris). An average of 1.36 stent graft components were used per patient, with mean intended treatment length of 197.0 ± 87.7/188.7 ± 103.1 mm and mean access site diameter of 10.3 ± 8.2/9.7 ± 1.7 mm in aneurysms/dissections, respectively. The rate of all-cause 30-day mortality was lower than in the RESTORE registry (4.0% vs 7.2%). Perioperative neurologic complications were infrequent: paraplegia/paraparesis (2.9%) and stroke (0.6%) (vs 2.0% and 1.6% in the RESTORE registry). Freedom from all-cause mortality at 2 years was 93.6%. At the final completion angiography, device-associated complications were detected in 4.6% of the patients (vs 5.3% in the RESTORE) and endoleak rate was 6.4% (type I 5.8% and type II 1.7%). CONCLUSIONS: The worldwide results of the RESTORE II registry show the safety and effectiveness of RELAY and RELAY NBS stent grafts for elective endovascular thoracic aortic repair. Compared with the RESTORE registry, the device presents a lower rate of perioperative complications.

Nucleophilic cross-linked, dextran coated iron oxide nanoparticles as basis for molecular imaging: synthesis, characterization, visualization and comparison with previous product.

We present a new synthesis protocol for a multivalent, multimodality, nucleophilic nanoparticle ideal for in vivo imaging. Stability requirements necessitated covalent cross-linking of the carbohydrate cage, easy functionalization the introduction of sterically accessible amine groups. The new protocol aimed at more uniform particle size, less clustering and superior magnetic properties compared with commercial nanoparticles. Particles were precipitated from Fe(2+) and Fe(3+) in the presence of 10 kDa dextran monodispersed from the aerosol phase. Cross-linking was achieved with epichlorhydrin, nuclophilication with NH3, purification with ultrafiltration and dialysis. Particles and a commercial product (Rienso®, Takeda Pharma) underwent physicochemical characterizations. Biocompatibility was assessed by Resazurin on LLC-PK1 cells; the internalization rate was measured for three cell lines (HAEC, HASMC, HT29). Core size was 5.61 ± 1.25 nm; hydrodynamic size was 49.56 ± 11.73 nm. The number of sterically accessible amine groups averaged 9.9. The cores showed cubic magnetite structure. Values of r1 and r2 were 10.9 and 148.17 mM(-1) s(-1). Cellular viability was unchanged after incubation. Introduction of aerosol phase dextran resulted in a reduction of the overall hydrodynamic diameter and a narrower size distribution of the synthesized particles. Electron tomography visualized for the first time the postulated 'hairy layer' of the dextran coating and enabled the measurement of the overall diameter of 100.2 ± 7.92 nm. The resulting nanoparticle is biocompatible, functionalizable and detectable at nanomolar concentrations with MRI and optical imaging. It can potentially serve as a platform for multimodal molecular imaging and targeted therapy approaches.

Secondary modification into aortouniiliac configuration to salvage failed endovascular aneurysm repair is safe and effective but not associated with higher intervention rates during long-term follow-up.

BACKGROUND: Reports of secondary modifications into aortouniiliac configuration to salvage-failed endovascular aneurysm repair (EVAR) are limited. We evaluated long-term results after these procedures and compared them with those after primary aortouniiliac endografting (AUE). METHODS: A retrospective review of all EVAR performed from March 1995 until July 2011 was conducted. Patients were included when primary AUE (group I) or modification into aortouniiliac configuration (group II) was done. RESULTS: Data analysis obtained 27 group I and 23 group II patients. Salvage of failed EVAR could be achieved in 96% of group II patients, and mortality was zero. Frequency of adverse events and amount of interventions to maintain aneurysm exclusion were not increased after secondary AUE. Kaplan-Meier estimates for long-term survival between groups were comparable (P = .36). CONCLUSIONS: Secondary AUE allows correction of graft-related endoleaks potentially leading to late aneurysm rupture. Complications and adverse events throughout long-term follow-up were not necessarily increased when compared with primary AUE.