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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: Nurtec, a versatile migraine medication, has gained popularity. However, the awareness of migraine surgery remains uncertain. Methods: Following a descriptive approach, this cross-sectional study used Google Trends data as of December 1, 2023, to analyze internet search patterns. Approval from Vanderbilt University’s institutional review board and adherence to Strengthening the Reporting of Observational Studies in Epidemiology guidelines were confirmed. Monthly relative search volume (RSV) data for “migraine surgery,” “Nurtec,” and “Rimegepant” were collected from January 1, 2004, to November 11, 2023, within the United States. Statistical analysis involved determining mean monthly RSV values and percentage changes for critical periods. Results: For “Nurtec,” a significant surge in RSV occurred from March 2020 to April 2020 (344%). Additional peaks were observed from June 2020 to July 2020 (66%), October 2020 to December 2020 (169%), May 2021 to June 2021 (33%), and May 2023 to June 2023 (14%). “Migraine surgery” exhibited a notable 400% increase in RSV, from March 2005 to May 2005. However, post-2006, RSV for “migraine surgery” consistently remained low without noticeable peaks. Conclusions: The analysis of RSV trends for “Nurtec” and “migraine surgery” from 2004 to 2023 reveals the impact of pivotal events and marketing strategies on public interest. The distinct peaks in “Nurtec” RSV align with Food & Drug Administration approvals and marketing campaigns, highlighting the medication’s accessibility. Conversely, the consistently low RSV for “migraine surgery” indicates limited awareness, emphasizing the need for enhanced promotion and education regarding surgical interventions.

Background There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic–pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. Methods Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. Results This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. Conclusions In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

Abstract Aim We aimed to test the hypothesis that a high‐salt diet (HS) impairs NO signaling in kidney microvascular endothelial cells through a histone deacetylase 1 (HDAC1)‐dependent mechanism. Methods Male Sprague Dawley rats were fed normal salt diet (NS; 0.49% NaCl) or HS (4% NaCl) for 2 weeks. NO signaling was assessed by measuring L‐NAME induced vasoconstriction of the afferent arteriole using the blood perfused juxtamedullary nephron (JMN) preparation. In this preparation, kidneys were perfused with blood from a donor rat on a matching or different diet to that of the kidney donor. Kidney endothelial cells were isolated with magnetic activated cell sorting and HDAC1 activity was measured. Results We found HS‐induced impaired NO signaling in the afferent arteriole. This was restored by inhibition of HDAC1 with MS‐275. Consistent with these findings, HDAC1 activity was increased in kidney endothelial cells. We further found the loss of NO to be dependent upon the diet of the blood donor rather than the diet of the kidney donor and the plasma from HS‐fed rats to be sufficient to induce impaired NO signaling. This indicates the presence of a humoral factor we termed plasma‐derived endothelial dysfunction mediator (PDEM). Pretreatment with the antioxidants, PEG‐SOD and PEG‐catalase, as well as the NOS cofactor, tetrahydrobiopterin, restored NO signaling. Conclusion We conclude that HS activates endothelial HDAC1 through PDEM leading to decreased NO signaling. This study provides novel insights into the molecular mechanisms by which a HS decreases renal microvascular endothelial NO signaling.

601 Background: EOP is an I-SPY2 neoadjuvant sub-study designed to test the tolerability and impact of novel endocrine-based strategies in stage 2/3 BC pts predicted to have lower benefit from chemotherapy. Amcenestrant (A) is an oral selective estrogen receptor degrader (SERD) with activity in hormone receptor positive (HR+) HER2- metastatic BC. Methods: EOP eligibility included pts screened for the main I-SPY2 trial with HR+ HER2-, MammaPrint (MP) low risk Stage 2/3 BC. Pts with MP High risk tumor signatures were eligible if clinically node-negative (cN-). Pts were stratified by SET index and menopausal status. Pts were randomized to 3 arms: A 200 mg qd (A), A + abemaciclib 150 mg bid (AA), A + letrozole 2.5 mg qd (AL). Premenopausal pts received concurrent ovarian function suppression. Treatment was for 6 mos followed by surgery. Baseline (BL) and 3-wk biopsies were performed. Breast MRIs were conducted at BL (T0), 3 wks (T1), 12 wks (T2), 6 mos (T3). The primary endpoint was feasibility, defined as >75% of pts completing >75% study therapy. Results: Between May 2021 and Aug 2022, 74 pts were randomized: 31 A, 21 AA, 22 AL. Median age 50 years, 54% premenopausal, 38% clinically node-positive (cN+). 41% pts had ductal, 38% lobular, 11% mixed ductal/lobular histology. Mean BL tumor Ki67 (central testing) was 16.9%, 88% MP low, 76% SET index Hi. Pt and tumor characteristics were balanced across the 3 arms. Treatment in all 3 arms was feasible with 95% of pts completing >75% study therapy. Most common AEs include grade 1-2 hot flashes (69%) and fatigue (66%). Grade 3 AEs include neutropenia (2 pts) and diarrhea (1 pt) in AA. Table summarizes key response endpoints, which were similar between pre- and postmenopausal pts. Of 28 cN+ pts, 2 (7%) were pathologically node-negative (pN-). Mean MRI Functional Tumor Volume (cc) change between T0->T1, T1->T2, T2->T3, T0->T3 was -6.06 (-34.2%), -3.55 (-29.2%), -0.829 (-20.1%), -11.3 (-68.4%), respectively, similar across arms (p=0.396).ctDNA was detected in 10/59 (17%) pts at T0. ctDNA became undetectable in 6 pts, decreased in 4 pts, and went from ctDNA undetectable at baseline to detectable at T3 in 2 pts. Conclusions: Six months of neoadjuvant endocrine therapy (NET) with the oral SERD amcenestrant is feasible, well-tolerated, and demonstrates anti-proliferative and anti-tumor activity in pre- and postmenopausal pts. NET provides a rich platform for biomarker discovery and investigating response to endocrine therapy. Clinical trial information: NCT01042379 . [Table: see text]

BACKGROUND: Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used as a minimally invasive alternative to open surgical repair to treat patients with thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to evaluate aortic-related mortality (ARM) and aortic aneurysm rupture after FB-EVAR of TAAAs. METHODS: Patients enrolled in 8 prospective, nonrandomized, physician-sponsored investigational device exemption studies between 2005 and 2020 who underwent elective FB-EVAR of asymptomatic intact TAAAs were analyzed. Primary end points were ARM, defined as any early mortality (30 days or in hospital) or late mortality from aortic rupture, dissection, organ or limb malperfusion attributable to aortic disease, complications of reinterventions, or aortic rupture. Secondary end points were early major adverse events, TAAA life-altering events (defined as death, permanent spinal cord injury, permanent dialysis, or stroke), all-cause mortality, and secondary interventions. RESULTS: A total of 1109 patients were analyzed; 589 (53.1%) had extent I–III and 520 (46.9%) had extent IV TAAAs. Median age was 73.4 years (interquartile range, 68.1–78.3 years); 368 (33.2%) were women. Early mortality was 2.7% (n=30); congestive heart failure was associated with early mortality (odds ratio, 3.30 [95% CI, 1.22–8.02]; P =0.01). Incidence of early aortic rupture was 0.4% (n=4). Incidence of early major adverse events and TAAA life-altering events was 20.4% (n=226) and 7.7% (n=85), respectively. There were 30 late ARMs; 5-year cumulative incidence was 3.8% (95% CI, 2.6%–5.4%); older age and extent I–III TAAAs were independently associated with late ARM (each P <0.05). Fourteen late aortic ruptures occurred; 5-year cumulative incidence was 2.7% (95% CI, 1.2%–4.3%); extent I–III TAAAs were associated with late aortic rupture (hazard ratio, 5.85 [95% CI, 1.31–26.2]; P =0.02). Five-year all-cause mortality was 45.7% (95% CI, 41.7%–49.4%). Five-year cumulative incidence of secondary intervention was 40.3% (95% CI, 35.8%–44.5%). CONCLUSIONS: ARM and aortic rupture are uncommon after elective FB-EVAR of asymptomatic intact TAAAs. Half of the ARMs occurred early, and most of the late deaths were not aortic related. Late all-cause mortality rate and the need for secondary interventions were 46% and 40%, respectively, 5 years after FB-EVAR. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02089607, NCT02050113, NCT02266719, NCT02323581, NCT00583817, NCT01654133, NCT00483249, NCT02043691, and NCT01874197.

AbstractBackgroundThis was a single‐arm, phase 2 clinical trial of Bavarian Nordic (BN)‐Brachyury vaccine plus radiotherapy (RT) designed to determine the objective response rate (ORR), progression‐free survival (PFS), and safety of the combination in chordoma.MethodsA total of 29 adult patients with advanced chordoma were treated with two subcutaneous priming vaccine doses of modified vaccinia Ankara‐Bavarian Nordic (MVA‐BN)‐Brachyury and one vaccine dose of fowlpox virus (FPV)‐Brachyury before RT. After RT, booster vaccinations were given with FPV‐Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). A minimum RT dose of >8 Gy in one fraction for each target was required. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients.ResultsTwo of 26 evaluable patients experienced durable partial response (PR) (ORR of 7.7%; 90% confidence interval [CI], 2.6–20.8]) by mRECIST 1.1. A total of 21 patients (80.8%; 90% CI, 65.4–90.3) had stable disease, and three patients (11.5%; 90% CI, 4.7–25.6) had progressive disease as best response per mRECIST 1.1. Median PFS was not reached during the study.ConclusionsThis trial confirms the safety of BN‐Brachyury and RT. Although the study did not meet the predefined study goal of four responses in 29 patients, we did observe two PRs and a PFS of greater than 2 years. For a vaccine‐based study in chordoma, an ultra‐rare disease where response rates are low, a randomized study or novel trial designs may be required to confirm activity.

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OBJECTIVE The purpose of this study was to determine the effect of osteoporosis medications on opportunistic CT-based Hounsfield units (HU). METHODS Spine and nonspine surgery patients were retrospectively identified who had been treated with romosozumab for 3 to 12 months, teriparatide for 3 to 12 months, teriparatide for > 12 months, denosumab for > 12 months, or alendronate for > 12 months. HU were measured in the L1–4 vertebral bodies. One-way ANOVA was used to compare the mean change in HU among the five treatment regimens. RESULTS In total, 318 patients (70% women) were included, with a mean age of 69 years and mean BMI of 27 kg/m 2 . There was a significant difference in mean HU improvement (p < 0.001) following treatment with romosozumab for 3 to 12 months (n = 32), teriparatide for 3 to 12 months (n = 30), teriparatide for > 12 months (n = 44), denosumab for > 12 months (n = 123), and alendronate for > 12 months (n = 100). Treatment with romosozumab for a mean of 10.5 months significantly increased the mean HU by 26%, from a baseline of 85 to 107 (p = 0.012). Patients treated with teriparatide for > 12 months (mean 23 months) experienced a mean HU improvement of 25%, from 106 to 132 (p = 0.039). Compared with the mean baseline HU, there was no significant difference after treatment with teriparatide for 3 to 12 months (110 to 119, p = 0.48), denosumab for > 12 months (105 to 107, p = 0.68), or alendronate for > 12 months (111 to 113, p = 0.80). CONCLUSIONS Patients treated with romosozumab for a mean of 10.5 months and teriparatide for a mean of 23 months experienced improved spinal bone mineral density as estimated by CT-based opportunistic HU. Given the shorter duration of effective treatment, romosozumab may be the preferred medication for optimization of osteoporotic patients in preparation for elective spine fusion surgery.