Citations

Objective: To compare target artery (TA) outcomes after fenestrated or branched endovascular aortic repair (FB-EVAR) versus open surgical repair (OSR) of thoracoabdominal aortic aneurysms (TAAAs). Background: Few studies have compared TA outcomes after endovascular incorporation and open reconstruction. Methods: Among consecutive patients who underwent elective OSR or FB-EVAR of TAAAs (2008–2020), we reviewed those who had postoperative imaging studies evaluating TA. Data of FB-EVAR patients were obtained from a prospectively maintained institutional database. TAs included celiac, superior mesenteric, right, and left renal arteries treated during TAAA repairs. The primary endpoint was TA patency (primary and secondary). Results: There were 131 patients (487 TAs) treated by OSR and 350 (1300 TAs) by FB-EVAR. In the OSR group, 440 TAs (90.3%) were reconstructed by bypasses, and 47 (9.7%) by reimplantation. In the FB-EVAR group, 841 TAs (64.7%) were incorporated by fenestrations and 459 (35.3%) by directional branches. Thirty-day TA primary patency rates were not significantly different between FB-EVAR and OSR (99.4%% vs 99.0%, P = 0.36), but the secondary patency rate was higher after FB-EVAR (99.8% vs 99.0%, P = 0.02). Three-year primary patency rates were 95.9% (95% CI: 94.7%–97.2%) and 94.7% (95% CI: 92.2%–97.2%), respectively; secondary patency rates were 98.5% (95% CI: 97.7%–99.2%) and 94.7% (95% CI: 95.7%–99.2%), respectively. There were no significant differences in late primary patency and secondary patency between groups (each P < 0.05). Conclusions: TA primary and secondary patency rates following elective OSR or FB-EVAR were high. Endovascular repair was not associated with loss of primary patency and late secondary patency.

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility. Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Demographic, preoperative physical examination, and radiographic data were collected from a multicenter national prospective cohort of patients with OCD of the knee. Inclusion criteria included patients <19 years of age and patients with arthroscopically confirmed mobility status based on the Research on Osteochondritis Dissecans of the Knee arthroscopy classification. Multivariable logistic regression analysis using stepwise model selection was used to determine factors associated with the likelihood of a mobile versus an immobile lesion. A 75% partition of the data was used for model training, and 25% was used as a validation cohort. Quantitative model fit statistics were computed using the holdout data, including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), along with the corresponding 95% CI. Results: A total of 407 patients in the prospective cohort met inclusion criteria, and 62% were male. The mean ± SD age was 13.7 ± 2.2 years, height 161.8 ± 5.3 cm, and weight 59.2 ± 42.2 kg. Arthroscopic evaluation yielded 235 immobile and 172 mobile lesions. Multivariable analysis determined that the best model to predict lesion mobility included chronologic age ≥14 years ( P < .001), effusion on physical examination ( P < .001), and any loss of range of motion on physical examination ( P = .07), while controlling for male sex ( P = .38) and weight >54.4 kg ( P = .12). In the 25% holdout validation sample (n = 102), a sensitivity of 83%, a specificity of 82%, and an AUC of 0.89 (95% CI, 0.82-0.95) were achieved with these predictive factors. Conclusion: Age, effusion, and loss of motion can predict knee OCD lesion mobility at the time of arthroscopy. Education about lesion mobility can help with surgical planning and patient and family counseling.

Importance Vascular injuries require urgent repair to minimize loss of limb and life. Standard revascularization relies on autologous vein or synthetic grafts, but alternative options are needed when adequate vein is not feasible and when clinical conditions preclude safe use of synthetic materials. Objective To evaluate the performance of the acellular tissue engineered vessel (ATEV) in the repair of extremity arterial injuries. Design, Setting, and Participants Two open-label, single-arm, nonrandomized clinical trials, including 1 prospective civilian study (CLN-PRO-V005 [V005]) and 1 retrospective observational study in a war zone (CLN-PRO-V017 [V017]), were conducted from September 2018 to January 2024 (follow-up ongoing) at 19 level 1 trauma centers in the US and Israel and 5 frontline hospitals in Ukraine. Patients had vascular injury, no autologous vein available for emergent revascularization, and risk factors for wound infection. Data include the subset of patients with extremity injuries and were analyzed from September 2023 to January 2024. Intervention The ATEV is a bioengineered vascular conduit grown from human vascular cells, available off the shelf, and implantable without immunosuppression. Main Outcomes and Measures Primary patency at day 30 was the primary outcome. Secondary outcomes included limb salvage, graft infection, and patient survival. A systematic literature review identified synthetic graft benchmarks in the treatment of arterial trauma for the same end points. Results The arterial extremity injury subset included 51 of 69 participants in V005 and 16 of 17 participants in V017. The majority were male (V005, 38 [74.5%]; V017, 16 [100%]), the mean (SD) ages were similar (V005, 33.5 [13.6] years; V017, 34.2 [9.0] years), and the mean (SD) Injury Severity Scores were similar (V005, 20.8 [10.5]; V017, 20.1 [18.9]). Penetrating injuries dominated (V005, 29 patients [56.9%]; V017, 14 patients [87.5%]). At day 30 for the V005 and V017 trials, respectively, ATEV primary patency was 84.3% (95% CI, 72.0%-91.8%) and 93.8% (95% CI, 71.7%-98.9%); secondary patency was 90.2% (95% CI, 79.0%-95.7%) and 93.8% (95% CI, 71.7%-98.9%); amputation rate was 9.8% (95% CI, 4.3%-21.0%) and 0% (95% CI, 0.0%-19.4%); ATEV infection rate was 2.0% (95% CI, 0.4%-10.3%) and 0% (95% CI, 0.0%-19.4%); and death rate was 5.9% (95% CI, 2.0%-15.9%) and 0% (95% CI, 0.0%-19.4%) (no deaths attributed to the ATEV at day 30). Day 30 synthetic graft benchmarks were as follows: secondary patency, 78.9%; amputation, 24.3%; infection, 8.4%; and death, 3.4%. Conclusions and Relevance Results of analysis in the subset of patients with vascular extremity injuries in 2 single-arm trials in civilian and real-world military settings suggest that the ATEV provides benefits in terms of patency, limb salvage, and infection resistance. Comparing ATEV outcomes with synthetic graft benchmarks demonstrated improved outcomes in the treatment of acute vascular injuries of the extremities. The analyses reported herein are limited to the subset of 67 patients with vascular extremity injuries out of 86 patients enrolled in 2 trials and excluded 19 patients with iatrogenic and torso injuries. Had these 19 patients been included in these analyses, the efficacy and safety findings could have been attenuated. Trial Registration ClinicalTrials.gov Identifiers: NCT03005418 , NCT05873959

Abstract Objective An accurate evaluation of behavioral responsiveness during and after seizures in people with epilepsy is critical for diagnosis and management. Current methods for assessing behavioral responsiveness are characterized by substantial variation, subjectivity, and limited reliability and reproducibility in ambulatory and epilepsy monitoring unit settings. In this study, we aimed to develop and implement a novel mobile platform for deployment of automated responsiveness testing in epilepsy—the ARTiE Watch—to facilitate standardized, objective assessments of behavioral responsiveness during and after seizures. Methods We prospectively recruited patients admitted to the epilepsy monitoring units for diagnostic evaluation and long‐term video‐electroencephalographic monitoring at Mayo Clinic and Yale New Haven Hospital. Participants wore the ARTiE Watch, a smartwatch paired with custom smartphone software integrated with cloud infrastructure allowing for remote activation of standardized assessment on the participants' smartwatches. The assessment consisted of 18 command prompts that test behavioral responsiveness across motor, language, and memory domains. Upon visually identifying an electrographic seizure during EMU monitoring, the BrainRISE platform was used to deploy the ARTiE Watch behavioral testing sequence. Responsiveness scoring was conducted on smartwatch files. Results Eighteen of 56 participants had a total of 39 electrographic seizures assessed with the ARTiE Watch. The 18 subjects with ARTiE Watch‐tested seizures had a total of 67 baseline (interictal) ARTiE Watch tests collected for analysis. The analysis showed distinct ARTiE Watch behavioral responsiveness phenotypes: (1) decreased responsiveness across all ARTiE Watch commands during seizure (ictal–postictal) periods compared (to baseline ( p < .0001), (2) decreased responsiveness in bilateral tonic–clonic seizures compared to baseline ( p < .0001) and compared to focal seizures ( p < .0001), and (3) decreased responsiveness during focal impaired awareness seizures compared to baseline ( p < .0001) and compared to focal aware seizures ( p < .001). Significance ARTiE Watch behavioral testing deployed utilizing a mobile cloud‐based platform is feasible and can provide standardized, objective behavioral responsiveness assessments during seizures.

BACKGROUND: In the phase 3 randomized controlled study ATTRibute-CM (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy), acoramidis, a transthyretin stabilizer, demonstrated significant efficacy on the primary end point. Participants with transthyretin amyloid cardiomyopathy who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report the efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE. METHODS: Participants who previously received acoramidis through month 30 in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through month 30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through month 42 included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, serum transthyretin, and Kansas City Cardiomyopathy Questionnaire Overall Summary score. Safety outcomes were analyzed through month 42. RESULTS: Overall, 438 of 632 participants in ATTRibute-CM completed treatment, and 389 enrolled in the ongoing OLE (263 continuous acoramidis and 126 placebo to acoramidis). The hazard ratio for ACM or first CVH was 0.57 (95% CI, 0.46–0.72) at month 42 based on a stratified Cox proportional hazards model ( P <0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with hazard ratios of 0.64 (95% CI, 0.47–0.88) and 0.53 (95% CI, 0.41–0.69), respectively, at month 42. Treatment effects for NT-proBNP and 6-minute walk distance also favored continuous acoramidis. On initiation of open-label acoramidis in the placebo-to-acoramidis arm, there was a prompt increase in serum transthyretin. Quality of life assessed by Kansas City Cardiomyopathy Questionnaire Overall Summary score was well preserved in continuous-acoramidis participants compared with the placebo-to-acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation. CONCLUSIONS: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through month 42 of the ongoing OLE study were associated with sustained clinical benefits in a contemporary transthyretin amyloid cardiomyopathy cohort, with no clinically important safety issues newly identified. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04988386.

ABSTRACTXanthogranulomatous epithelial tumor (XGET)/Keratin‐positive giant cell tumor (KP‐GCT) represents a spectrum of recently described neoplasms characterized by a proliferation of distinctive mononuclear cells expressing keratin within a background of osteoclast‐like giant cells, mixed inflammatory cells, and a variably prominent xanthogranulomatous component. Recent studies demonstrated a recurrent HMGA2::NCOR2 fusion in many cases. We herein describe a case of XGET/KP‐GCT arising in the right femoral head of a 19‐year‐old male harboring a rare novel HMGA2::COL14A1 fusion.

Study Design. Literature review and institutional analysis. Objective. This review examines the potential advantages of awake spinal surgery under neuroaxial anesthesia in minimizing positioning-related complications compared with traditional general anesthesia. Summary of Background Data. Spinal surgeries performed in the prone position under general anesthesia are associated with perioperative complications, such as ocular injury and vision loss, nerve damage, and pressure ulcers. Materials and Methods. A comprehensive literature search was conducted for articles published from 1986 to 2023 focusing on awake spinal surgery and positioning-related complications. In addition, insights from the Mayo Clinic team were incorporated to assess the potential benefits of awake spine surgery. Results. The review identified several positioning-related complications associated with prone positioning during spine surgery, including perioperative visual loss, neuropathies, pressure ulcers, and intra-abdominal hypertension leading to systemic cardiovascular effects and potential organ dysfunction. Advances at the Mayo Clinic have enabled the use of awake spinal surgery under neuroaxial anesthesia for complex procedures such as robotic transforaminal lumbar interbody fusion. The use of awake lumbar spine surgery has demonstrated advantages, including reduced positioning-related complications, immediate patient feedback to avoid harmful maneuvers, shorter operating room times, and improved hemodynamic stability. Conclusions. Awake lumbar spine surgery offers notable advantages in reducing positioning-related complications and presents a promising alternative to general anesthesia.

Background MEDI5395 is a recombinant attenuated Newcastle disease virus engineered to express a human granulocyte-macrophage colony-stimulating factor transgene. Preclinically, MEDI5395 demonstrated broad oncolytic activity, augmented by concomitant programmed cell death-1/programmed cell death ligand-1 (PD-L1) axis blockade. Durvalumab is an anti-PD-L1 immune checkpoint inhibitor approved for the treatment of various solid tumors. We describe the results of the first-in-human study combining intravenous MEDI5395 with durvalumab in patients with advanced solid tumors. Methods This phase I, open-label, multicenter, dose-escalation, dose-expansion study recruited adult patients with advanced solid tumors, who had relapsed or were refractory or intolerant to ≥1 prior line of standard treatment. MEDI5395 was administered intravenously as six doses over 15–18 days. The dose-escalation phase assessed four-dose levels (108, 109, 1010, 1011 focus forming units (FFU)) of MEDI5395, with sequential or delayed durvalumab. Durvalumab 1500 mg was administered intravenously every 4 weeks up to 2 years. The dose-expansion phase was not initiated. The primary objectives were to evaluate safety and tolerability, dose-limiting toxicities (DLTs) and the dose and schedule of MEDI5395 plus durvalumab administration. Secondary objectives included the assessment of the efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MEDI5395. Results 39 patients were treated with MEDI5395; 36 patients also received durvalumab. All 39 patients experienced ≥1 treatment-emergent adverse event (TEAE), most commonly fatigue (61.5%), nausea (53.8%) and chills (51.3%). Grade 3–4 TEAEs occurred in 27 (69.2%) patients; these were deemed MEDI5395-related in 12 (30.8%) patients. Two patients experienced a DLT, and the maximum tolerated dose of MEDI5395 with sequential and delayed durvalumab at study termination was 1011 and 1010 FFU, respectively. Four patients (10.3%) achieved a partial response (PR). Patients with PR or stable disease tended to have higher baseline PD-L1 and CD8+ levels in their tumor tissue. A tendency to dose-dependent pharmacokinetics of the viral genome was observed in whole blood and a tendency to dose-dependent viral shedding was observed in saliva and urine. Neutralizing antibodies were observed in all patients but did not appear to impact efficacy negatively. Conclusion This study demonstrates the feasibility, safety and preliminary efficacy of MEDI5395 with durvalumab in patients with advanced solid tumors. Trial registration number NCT03889275

In this case series study, pulmonary artery systolic, diastolic, and mean pressures of 2 participants with obesity and heart failure with preserved ejection fraction were measured at zero gravity during parabolic flight to assess the effect of external constraint on left ventricular filling pressures.