Citations

OBJECTIVE The Woven EndoBridge (WEB) device was approved to treat wide-necked bifurcation aneurysms. The device is designed as an intrasaccular flow disruptor covering aneurysm widths up to 10 mm. Although prior studies combined all aneurysm sizes, it is known that aneurysms behave differently in response to endovascular treatment based on their size. Therefore, the authors’ objective was to identify ideal middle cerebral artery (MCA) aneurysm width and neck sizes most suitable for WEB treatment. METHODS The WorldWideWEB consortium is a large multicenter retrospective database that analyzes intracranial aneurysms treated with the WEB device. In this study, all unruptured MCA bifurcation aneurysms with available measurements were included. Cutoff values based on aneurysm width and neck in relation to aneurysm occlusion status were measured using the receiver operating characteristic (ROC) curve. Propensity score matching (PSM) was then used to compare treatment outcomes between aneurysms smaller and larger than the cutoff value for both width and neck size. RESULTS The ideal cutoff values for MCA bifurcation aneurysm width and neck were 6.1 mm and 4.6 mm, respectively. On PSM, 87 matched pairs were compared based on width size (≤ 6.1 mm and > 6.1 mm), and 77 matched pairs were compared based on neck size (≤ 4.6 mm and > 4.6 mm). There was a significant difference in adequate aneurysm occlusion between aneurysms smaller and larger than those cutoff values for both widths (93% vs 76%, p = 0.0017) and neck sizes (90% vs 70%, p = 0.0026). The retreatment rate was also significantly higher for larger aneurysms in both parameters. CONCLUSIONS This study shows that MCA bifurcation aneurysms ≤ 6.1 mm in width and ≤ 4.6 mm in neck size are significantly better candidates for WEB treatment, leading to improved occlusion status and reduced retreatment rate, which are important considerations when using WEB devices.

Many patients with malignant spinal cord compression (MSCC) who are not candidates for neurosurgery receive radiotherapy alone. This study compared 15 × 2.633 Gy over three weeks to 20 × 2.0 Gy over four weeks in patients with favorable survival prognoses. The outcomes of 34 patients treated with 15 × 2.633 Gy (equivalent dose 41.6 Gy10) in the RAMSES-01 trial were compared to 239 patients from an existing database receiving 20 × 2.0 Gy using propensity-score-adjusted Cox and logistic regression models. All patients had favorable survival prognoses. Endpoints included local progression-free survival (LPFS), improvement of motor function, post-treatment ambulatory status, and overall survival (OS). After propensity score adjustment, the 12-month rates of LPFS and OS were 98.1% (RAMSES-01 cohort) vs. 91.6% (p = 0.265) and 79.1% vs. 82.2% (p = 0.704), respectively. Regarding improvement of motor function, 15 × 2.633 Gy appeared superior (p = 0.073). No significant difference was observed regarding ambulatory status (p = 0.822). The three-week regimen for MSCC has similar outcomes and reduces treatment time when compared to a four-week regimen.

Objectives: Injury to the Medial Ulnar Collateral Ligament (MUCL) is a common setback experienced by many throwing athletes often requiring reconstruction with 12-18 months of rehabilitation. Current reconstructive techniques fail to anatomically restore the MUCL which may contribute to the prolonged course of rehabilitation. In recent years, we described an anatomic MUCL reconstruction with internal brace augmentation which demonstrated improved biomechanical strength when compared to the docking technique in cadaveric specimens. The purpose of this study was to evaluate the postoperative course of both amateur and professional throwing athletes that underwent anatomic MUCL reconstruction with internal brace augmentation. We hypothesized that throwers would return to the same level of play and that return to play (RTP) would be a shorter duration compared to current reported outcomes. Methods: In this surgical technique, the native MUCL is formally repaired. The graft and a suture tape are folded over a suspensory loop and secured in a socket of the medial epicondyle of the humerus to maximize tendon to bone contact. On the ulnar side, the graft and internal brace are secured proximally by two suture anchors on either side of the sublime tubercle and further secured across the sublime tubercle ridge distally to re-create the anatomic triangular insertion of the native ligament. All surgeries were performed by a single surgeon. Patient reported outcomes in addition to date of RTP, level of play, and functional outcomes were retrospectively gathered. All patients initially followed an Accelerated Rehabilitation Protocol and were converted to a Standard Paced protocol if setbacks were encountered. Results: A total of 26 baseball players underwent primary (n=23) or revision (n=3) MUCL reconstruction with the Anatomic Technique. Of these, 15 were professional and 11 were amateur athletes. 92% of throwers returned to play at a mean of 9.9 months following reconstruction. 89% were able to advance through the accelerated postoperative protocol without issues and 85% returned to the same role and level of play. Post injury KJOC scores improved from 41 to 86.9 and SANE scores improved from 32.5 to 95.5. No significant difference was identified in pre-injury versus post-reconstruction throwing velocity, ball spin rate, or horizontal/vertical ball movement. Conclusions: Anatomic reconstruction of the MUCL with internal bracing is a viable option for MUCL injuries. Advantages include increased tendon-bone contact of the reconstruction, multiple fixation points, and anatomic restoration of the MUCL. This technique allowed an expedited return to sport for these baseball athletes.

Abstract Disclosure: M. Fleseriu: Consulting Fee; Self; Novo Nordisk, Amryt Pharma Holdings Ltd, Ascend Therapeutics (A Besins Healthcare company). Speaker; Self; Xeris Pharmaceuticals, Inc., RECORDATI_RARE_DISEASES_INC., Ipsen Pharma SAS. S.L. Samson: Advisory Board Member; Self; Amryt. Research Investigator; Self; Amryt. N. Biermasz: Advisory Board Member; Self; Recordati, Pfizer Global R&D. Grant Recipient; Self; Macro Registry Grant, Amryt. C.J. Strasburger: Advisory Board Member; Self; Sandoz, Ipsen, Recordati. Consulting Fee; Self; Ascendis, Amryt, Novo Nordisk, Merck, Sandoz, Recordati. Speaker; Self; Ipsen, Novo Nordisk, HRA-Pharma. S. Fuchs Orenbach: Employee; Self; Chiesi Global Rare Diseases. J.A. Crompton: Employee; Self; Chiesi Global Rare Diseases. S. Melmed: Advisory Board Member; Self; Ionis, Crinetics. Consulting Fee; Self; Ipsen. Grant Recipient; Self; Pfizer. Background: Treatment with oral octreotide capsules (OOC) was evaluated in three phase 3 trials (CH-ACM-01, OPTIMAL, MPOWERED) in patients with acromegaly who previously tolerated and responded to the injectable somatostatin receptor ligands (iSRLs) octreotide and lanreotide. Results demonstrated efficacy and safety despite differences in trial design. Pooling data from all three trials can provide further insight into the biochemical response, symptom improvement, and safety profile of OOC. Objective: Analyze the biochemical changes, symptom control, and safety of OOC through a pooled analysis of phase 3 clinical trial datasets. Methods: Patients included were aged ≥18 years with acromegaly and responded biochemically to iSRL therapy before the initiation of OOC (defined as IGF-I <1.3 × ULN and mean integrated GH <2.5 ng/mL for CH-ACM-01 and MPOWERED, and IGF-I ≤1.0 × ULN for OPTIMAL). Data analyzed were from the following periods: baseline until the end of the double-blind placebo-controlled phase of OPTIMAL (36 weeks); the run-in phase of MPOWERED (26 weeks); end of dose escalation (2-5 months; efficacy data) and end of fixed dose phase (up to 7 months, safety data) for CH-ACM-01. Effect of prior iSRL dose was analyzed using a random effects meta-analysis. Symptom severity was scored using the Acromegaly Index of Severity (AIS) tool. Results: Efficacy, symptom, and safety data were available for 318, 194, and 329 patients, respectively. The overall response rate was 65% with no effect of prior iSRL dose (p>0.05). Mean (SD) IGF-I change from baseline was +0.17 (0.32; n=214), +0.19 (0.39; n=81), and +0.22 (0.57; n=23) for patients with baseline IGF-I levels ≤1 × ULN, 1 to <1.3 × ULN, and ≥1.3 × ULN. Twenty percent (16/81) and 35% (8/23) of patients with baseline IGF-I of 1 to <1.3 x ULN and ≥1.3 x ULN shifted to an improved category of response. There was a median decrease of one symptom per patient (p<0.05) and a mean decrease of 0.8 in AIS (p<0.05). The proportion of OOC responders reporting ≤1, 2, or 3 moderate/severe acromegaly symptoms at baseline and month 6 decreased from 56% to 39%, 32% to 20%, and 20% to 12%. At month 6, improvement was seen for all individual symptoms (joint pain, swelling, sweating, fatigue, headache) of moderate/severe grade and was significant for joint pain (36% to 22%) and swelling (15% to 10%) (p<0.02). Most adverse events (AEs) were gastrointestinal (GI) in nature (54%, n=179/329) with a median onset and duration of 15 and 12 days for first reported GI events. Conclusion: Pooled analysis confirms overall maintenance of biochemical control in patients previously responding to iSRL therapy, with decreased symptom burden in OOC responders. OOC was generally well tolerated with no new safety signals. GI-related AEs were largely transient. These results support OOC as a therapeutic option for treating acromegaly. Presentation: 6/3/2024

Background Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives. Objective To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I–III. Methods This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I–III between January 2010 and December 2023 were included. Results The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03). Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group. Conclusion Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

Abstract Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.

Background: Charcot-Marie-Tooth (CMT) disease is a progressive inherited neurologic disorder causing muscle weakness and lower extremity deformity. The goal of foot and ankle surgical treatment is to create a stable, plantigrade foot, with the potential elimination of brace-wear for ambulation. The aim of this study was to report baseline CMT patient function and subsequent outcome improvement from surgical treatment, as determined by PROMIS physical function (PF), pain interference (PI), and mental health/depression (D) scores. Methods: Retrospective data were collected on consecutive CMT patients older than 18 years receiving surgical treatment by the senior surgeon at Cedars-Sinai Medical Center from 2018 to 2022 with minimum 1-year follow-up. Each patient prospectively completed PROMIS preoperatively and postoperatively after all planned surgical treatment was completed. Prospective clinical and radiographic data were collected to describe complications and correlation to outcome. Results: Ninety-five feet in 64 patients older than 18 years were included for analysis. Mean follow-up was 21 months (range, 12-31) with 100% minimum 1-year follow-up. CMT patients had worse preoperative and baseline scores in all domains except PROMIS-D compared with population normal PROMIS scores. Significant improvements were identified in all PROMIS domains following surgical treatment. The mean PROMIS-PF score increased (40 to 45, delta = 4.9, P < .001), the mean PROMIS-PI score decreased (59 to 52, delta = 7.1, P < .001), and the mean PROMIS-D score decreased (50 to 47, delta = 3.0, P = .004). Subgroup analysis was performed for patients with severe radiographic deformity and those treated with arthrodesis in an attempt to demonstrate the impact of disease severity on outcome. Subgroup analysis demonstrated that arthrodesis led to worse overall PROMIS-PF outcome with the same change score. Conclusion: Surgical treatment for CMT patients provides significant clinical improvement in all measured outcome domains. CMT patients can be restored to normal population physical function and pain interference outcome scores. Patients with more severe deformity have similar improvement from surgical treatment, although their ultimate functional improvement is blunted due to a lower baseline.

Abstract Objectives There are an increasing number of centres performing research on high-resolution vessel wall magnetic resonance imaging (VW-MRI) in GCA. However, harmonized approaches to VW-MRI in GCA are lacking and are essential to performing multicentre studies. Using a data-driven, consensus-based approach, an international expert group developed a standardized MRI protocol and scoring system to advance multi-centred research in cranial GCA. Methods A targeted literature review of VW-MRI in cranial GCA was conducted. A working group comprised of radiologists, rheumatologists and ophthalmologists with expertise in VW-MRI and GCA reviewed the results of the literature search, presented relevant data and images from their respective centres, and then reached consensus on recommendations related to key MRI structures, MRI sequences, scoring system and other important considerations. Results A total of 21 relevant articles were identified and reviewed. Based on published literature, structures to be evaluated on MRI were categorized based on anatomic location (extradural cranial, intradural cranial and orbits) and prioritization (core vs elective). Essential and elective sequences to comprehensively image cranial and orbital structures while minimizing scan time were determined along with scoring systems to grade contrast enhancement. Conclusion This report describes a standardized approach to facilitate research of VW-MRI in cranial GCA that is the result of a multidisciplinary, international collaboration of experts in VW-MRI and/or GCA.

Renal fusion or ectopia can present formidable challenges during aortic surgery. To evaluate morbidity and define optimal management, the clinical histories of 120 patients with renal fusion or ectopia who underwent 21 aortic procedures at the authors' institution over a 37-year period were reviewed. Indications for surgery included aortic aneurysm in 16 patients (infrarenal in 15 and thoracoabdominal in one) and aortoiliac occlusive disease in five (with renovascular hypertension in two). The abnormal kidney was detected before surgery in 13 patients (65%) by excretory urography, arteriography, computed tomography, or ultrasonography. Arteriography revealed multiple and/or anomalous renal arteries in nine of 12 patients studied. At surgery, 15 patients (75%) were found to have multiple or anomalous renal arteries. Six required renal revascularization (reimplantation four, endarterectomy one, aortorenal bypass one). The renal symphysis was divided in two patients. There were no operative deaths. Six major complications included bleeding requiring reoperation, renal failure requiring short-term dialysis, pancreatitis, gastrointestinal bleeding, pneumonia and thrombophlebitis. Preoperative aortography is recommended in patients with renal fusion or ectopia because of the high incidence of associated renal artery anomalies. The surgeon must be prepared to preserve or revascularize these anomalous renal arteries. Division of the renal symphysis is rarely required. Although perioperative morbidity is raised, aortic reconstruction in patients with renal fusion or ectopia can be safely performed without increased mortality.