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OBJECTIVE Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients. METHODS TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding. RESULTS From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1–2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7–1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2–1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4–13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1–7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4–7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9–3.6] per 100 patient-years; 2.0 [95% CI 1.3–2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6–2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1–8.9], p < 0.001), large (HR 2.6 [95% CI 1.1–6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2–5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1–4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7–4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0–4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0–3.2) per 100 patient-years. CONCLUSIONS Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.

BACKGROUND AND OBJECTIVES: Awake minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) generates minimal surrounding tissue damage and has been shown to be a safe, time-effective, and cost-reductive technique in single-level procedures. The purpose of this study was to advocate for the utilization of multilevel MIS-TLIF even in challenging cases as it has demonstrated positive outcomes. METHODS: Chart review was conducted for consecutive patients undergoing awake multilevel MIS-TLIF from 2020 to 2023. Various demographic, preoperative, and postoperative variables were collected and descriptively analyzed. RESULTS: Sixteen patients underwent multilevel awake MIS-TLIF at our institution during the specified period. Among them, 87.5% underwent a two-level procedure and 12.5% a three-level procedure. The median age ± IQR was 69.5 ± 11 years, with a slight male predominance (56.25%). Common comorbidities included hypertension (56.25%), obesity (37.5%), sleep apnea (25%), and type 2 diabetes (18.75%). The American Society of Anesthesiologists risk was 2 in 43.75% of patients and 3 in 56.25%. All patients presented pain, and 12.5% showed motor deficit. Intraoperative data showed a median of 196 minutes in the operating room where 156 ± 27.75 minutes corresponded to actual procedure time. The median estimated blood loss was 50 ± 70 cc. In the immediate postoperative period, 1 patient had nausea and emesis, and 1 reported fatigue. The median pain score during this period was 4.6 ± 2.03. Pain control medications were required for various patients, with methocarbamol (50%), hydromorphone (37.5%), and oxycodone (25%) being the most commonly prescribed in the postanesthesia care unit. No patient had new neurological deficits after the surgical intervention. The median length of stay was 2 days ±1.25. All patients were discharged with no complications. CONCLUSION: Multilevel awake MIS-TLIF emerges as a safe and effective technique for complex cases, enhancing patient quality of life with minimal blood loss and postoperative pain.

Abstract Objective The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P &lt; 0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P &lt; 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P &lt; 0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P &lt; 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P &lt; 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

ImportancePatients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT.ObjectiveTo compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT.Design, Setting, and ParticipantsThis cohort study was a propensity score–matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score–matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score.ExposureLeft atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group).Main Outcomes and MeasuresThe primary outcome was time to first ischemic stroke.ResultsFour hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P &amp;lt; .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy.Conclusions and RelevanceIn patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

ObjectiveAvacopan, an activated complement factor 5 receptor antagonist, has been approved as adjunct therapy for severe active antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Current evidence supports the management of AAV presenting with diffuse alveolar hemorrhage (DAH) by administering glucocorticoids combined with either rituximab or cyclophosphamide in addition to supportive care. The role of avacopan in patients with DAH as a primary severe disease manifestation of AAV has not been well established. Furthermore, concerns remain regarding timely access to avacopan, the best glucocorticoid tapering regimen, and long‐term efficacy and safety of the drug. We sought to identify clinical features and outcomes of patients presenting with DAH secondary to AAV who received avacopan in addition to glucocorticoids and rituximab or cyclophosphamide.MethodsWe performed a retrospective cohort study of all consecutive patients presenting with DAH as part of active severe granulomatosis with polyangiitis or microscopic polyangiitis. Demographic and clinical characteristics were collected at presentation and follow‐up.ResultsFifteen patients met inclusion criteria and were observed for a median time of 17 weeks (interquartile range [IQR] 6–37 weeks) after initiation of avacopan. Patients were predominantly female and White, had never smoked, and were a median age of 66 years (IQR 52–72 years) at diagnosis. The majority had newly diagnosed severe AAV with renal involvement. Three patients progressed to respiratory failure. The timing of avacopan introduction and patterns of glucocorticoid tapers varied widely in this cohort. Two serious adverse events related to infection were observed, including one opportunistic infection leading to the patient's death, although neither was directly attributed to avacopan administration.ConclusionWe describe the clinical course of patients who presented with the severe AAV disease manifestation of DAH and received avacopan as adjunct therapy. Most patients achieved remission during follow‐up, and adverse events, including infection, were observed.

Background Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. Objectives To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. Methods An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. Results Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. Conclusion Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.

Background: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. Methods: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. Results: Group A (“Advanced”) included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group A T ). Group M (“Mild”) included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6–13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group A T patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. Conclusions: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

e19008 Background: Bispecific antibodies (BsAb) have emerged as a new treatment modality for relapsed/refractory non-Hodgkin lymphomas (R/R NHL). They exert their effect by binding to CD3 on T-cells and CD19 or CD20 on lymphoma cells, activating the T-cell to exert cytotoxic effects against the tumor and normal B-cells. Treatment related adverse events (TRAE) include infections, cytokine release syndrome (CRS), neurotoxicity (ICANS). This meta-analysis was conducted to assess prevalence of TRAEs from prospective clinical trials that evaluated BsAb in R/R NHL. Methods: A systematic review was conducted through PubMed, Embase, Scopus, Web of Science, and Cochrane to identify BsAb clinical trials in NHL through October 2023. Eligible studies included phase I-III trials evaluating BsAb in any type of NHL, either as monotherapy or combination therapy irrespective of prior lines of treatment. Primary outcomes of interest include infection, neutropenia, CRS, and ICANS. All studies were weighted equally. Pooled prevalence estimates of TRAE were calculated using common and random effects models. Heterogeneity tests were performed using Cochran’s Q test. Subgroup analysis examined infection rates in monotherapy versus combination therapy cohorts. Results: After screening 1039 studies, 36 clinical trials with 2162 patients were included. The lymphoma subtypes were diffuse-large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. The BsAbs included mosunetuzumab (13 studies), epcoritamab (10 studies), blinatumomab (5 studies), glofitamab (5 studies), odronextamab (2 studies), and AFM11 (1 study). The median age of patients was 66 years, and patients had received a median of two prior lines of therapy. Median follow-up duration was 9.1 months. The prevalence of all-grade infections was 35% (95% CI: 0.33-0.38; I2 = 79%). For grade ≥3 infections, the prevalence was 16% (95% CI: 0.14-0.18, (I2 = 77%). There were higher rates of all-grade infections in the combination therapy cohort (41%, 95% CI: 0.36-0.47) compared with the monotherapy cohort (33%, 95% CI: 0.30-0.36). All-grade and grade ≥3 neutropenia occurred in 31% (95% CI: 0.29-0.34; I2 = 80%) and 22% (95% CI: 0.20-0.24, I2 = 61%) of patients. CRS was observed in 45% of patients (95% CI: 0.43-0.48, I2 = 85%). Grade ≥3 CRS occurred in only 2% of patients (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). ICANS occurred in 12% (95% CI: 0.10-0.14, I2 = 90%) while grade ≥3 ICANS was rare, at 3% (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). Conclusions: BsAb is associated with nontrivial rates of infections and neutropenia. The rates of high grade CRS and ICANS are low. The heterogeneity of the findings could be attributed by an underreporting of TRAE and small sample sizes from various studies. These results highlight the need for vigilant practices to diagnose and treat infections early and consideration for antibacterial prophylaxis in this immunocompromised population.

Objective: To investigate the longitudinal effects of COVID-19 on major vascular structures and parameters and clinical outcomes. Design: Observational prospective trial. Setting: Post-COVID-19 research clinic established by University of Louisville Division of Infectious Diseases. Participants: The study population consisted of 72 post-COVID-19 individuals and 11 non-COVID-19 infected participants in the control group. The participants were recruited from adult hospitals and from the community. The enrollment started in October 2020 and follow-up periods were at 3, 6, and 12 months from their initial COVID-19 diagnosis. Interventions: The participants were interviewed for medical and COVID-19 infection history. Samples of white blood cell (WBC), C-reactive protein (CRP), and D-dimer were taken at each visit. Certified sonographers performed vascular ultrasound on the study participants. Measurements and Main Results: Median intima-media thickness (IMT) was increased in mild/asymptomatic (0.80 mm) and severe/critical (0.90 mm) groups when compared with controls (0.60 mm; P < .001 for both groups). In the asymptomatic/mild group, 6-month median IMT (0.88 mm) was increased, compared with the 3-month group (0.75 mm), with P = .026. Increased age was associated with decreased mean arterial blood velocities (cm/s): common carotid ( r = −0.236, P = .032), internal carotid ( r = −0.208, P = .048), and subclavian artery mean velocity ( r = −0.357, P = .003). We did not find any instance of deep vein thrombosis. Median D-dimer, CRP, and WBC in the control group differed from asymptomatic/mild COVID-19 group ( P = .026, .011, and .003, respectively). Moreover, WBC in the asymptomatic/mild group and moderate COVID-19 group differed from severe/critical group ( P = .025 and P = .027, respectively); CRP also differed between asymptomatic/mild group and severe/critical group ( P = .014). Conclusions: There were differences in intima-media lumen thickness (IMT), arterial velocities, and inflammatory markers in post-COVID-19 patients. There was no instance of deep vein thrombosis in this post-COVID-19 study cohort. The increased IMT might infer atherosclerosis, which has shown to increase cardiovascular risks. It is not yet known whether the increase in IMT due to COVID should be treated in the same way as non-COVID-19 atherosclerosis—through statins, for example—or whether regular cardiovascular risk reduction would be useful. Clinical trial and mechanistic studies should be performed to further our understanding of COVID-19-related vascular pathologies.