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Abstract TP290: Final Infarct Volume as a Surrogate Endpoint in Anterior-Circulation ICAS-LVO Stroke - Secondary Analysis of the RESCUE-ICAS Registry
No full textIntroduction: Final infarct volume (FIV) on 24-hour MRI is a well-established imaging biomarker linked to functional recovery after ischemic stroke,1-3 yet its prognostic value in ICAS-LVO remains poorly explored. The impact of adjunct intracranial stenting on both infarct size and infarct progression also remains unclear in this population. This study aimed to examine the association between FIV and clinical outcome, evaluate the effect of adjunct stenting on FIV and infarct progression, and assess the relationship between infarct progression and functional independence.
Methods: We conducted a secondary analysis of the RESCUE-ICAS registry,4 only patients with anterior circulation LVO with MRI after thrombectomy were included. Final infarct volume (FIV) was measured on diffusion-weighted MRI performed 24-36 hours post thrombectomy. Infarct progression was defined as the difference between baseline CTP infarct volume (CBF <30%) on presentation and 24-36-hour FIV. The primary outcome was 90-day functional independence (mRS 0-2). Secondary outcomes included the effect of adjunct stenting on FIV and infarct progression. Associations were analyzed using multivariable logistic regression and inverse probability of treatment weighting (IPTW).
Results: Of the 417 patients included in the RESCUE-ICAS registry, 203 had anterior circulation ICAS-LVO and underwent MRI 24-36 hours post-thrombectomy. Among these, 80 patients (39%) received adjunct stenting. FIV was independently associated with 90-day functional independence (adjusted OR per 10 mL increase: 0.8; 95% CI: 0.68-0.94; p = 0.007). Adjunct stenting was associated with smaller FIV (IPTW-adjusted mean difference: -25.07 mL; 95% CI: -40.36 to -9.78; p = 0.001). In 108 patients with baseline CTP data and FIV data, infarct progression was not significantly different between stented and non-stented groups (Δ -9.53 mL; 95% CI: -37.9 to 18.8; p = 0.506), but progression <44.5 mL was strongly associated with favorable outcome.
Conclusion: Among ICAS-LVO patients, 24-36-hour FIV is a strong predictor of functional outcome. Adjunct stenting is associated with smaller FIV. Lower infarct progression was also associated with favorable outcome. These findings highlight FIV as a reliable imaging biomarker and potential surrogate endpoint in future trials
Corrigendum to “Medical treatment of hypercortisolism with relacorilant: Final results of the phase 3 GRACE study” [American Heart Journal 278S (2024) Pages 10-11]
No full textDermatological Complications in Superficial Temporal Artery Embolization: An Illustrative Case and Literature Review
No full textEndovascular embolization is the mainstay of treatment for multiple diseases affecting the superficial temporal artery (STA). However, it is not exempt from complications. While neurologic complications are vastly reported in the literature, dermatological complications are seldom described. Here, we present the case of a 16-year-old female who developed pustules, erythema, trichodynia and regional pain along the facial branch of the STA following endovascular treatment. On trichoscopy follicular crusts with microhemorrhagic areas, erythema, telangiectasia and patchy brown-gray areas were visualized with histopathologic findings compatible with vasculopathy and increased telogen count. Additionally, we performed a literature review of dermatological complications associated with endovascular treatment of the STA. A total of 16 cases were identified, most of which involved trans-arterial embolization (TAE). The most common dermatological complication was scalp necrosis (50%), followed by secondary infection (18.75%) and mass effect (18.75%). The time of presentation varied, from immediately after embolization up to 46 days post-procedure. The most common embolic agent associated with complications was Onyx (50%). According to our review, dermatologic complications seem to arise from multiple mechanisms, including tissue inflammation, cell wall rupture, radiation damage, and infusion rate of the embolic agents. We emphasize the need for greater attention and reporting of these complications, as they can impact cosmetic outcomes and overall quality of life of patients. Physicians should be aware of cutaneous manifestations following STA embolization as early recognition and appropriate management can significantly improve cosmetic outcomes
Single-layer Endoscopic Repair of Anterior Skull Base Defects
No full textThis article reviews contemporary strategies for single-layer endoscopic repair of anterior skull base cerebrospinal fluid leaks, which are important for small defects and when multiple layers using vascularized tissue options are not available. Successful reconstruction requires restoring a watertight barrier between the intracranial compartment and the sinonasal tract, with technique selection guided by defect size, location, flow dynamics, and tissue availability. When appropriately selected, patients undergoing single-layer endoscopic repair achieve closure rates exceeding 90%. The article also discusses factors associated with failure and practical considerations for enhancing durability, highlighting the ongoing relevance of single-layer reconstruction in modern skull base surgery
Serendipity, steroids and science
No full textThe androgen signaling pathway is probably the most important pathway in enabling prostate cancer progression but it also plays essential roles in numerous processes in normal physiology. Both testosterone and dihydrotestosterone are potent androgens that activate the androgen receptor (AR). The essentiality of the androgen pathway in prostate cancer is evidenced in part by the reactivation of AR in prostate cancer that becomes resistant to treatment by gonadal testosterone deprivation. Furthermore, steroid metabolic processes that allow the regeneration of potent androgens in prostate cancer tissues drive this treatment-resistant state, as is made clear by the survival benefit of blocking the synthesis of non-gonadal androgens, e.g., with abiraterone. Here, I narrate and review the process that led to a series of discoveries in androgen metabolism from our group. In this perspective and mechanistic narrative review, I give an honest description of the accidental nature of some of our initial findings, followed by data-driven hypothesis refinement and subsequent studies that illuminate elements of androgen metabolism, with a focus on metabolism of carbon 3, carbon 5 and carbon 17 of the steroid backbone
Biomarker analysis from the phase 2 LITESPARK-013 study of 2 different belzutifan (bel) doses in participants (pts) with advanced clear cell renal cell carcinoma (ccRCC)
No full text545 Background: The LITESPARK-013 study (NCT04489771) showed similar efficacy and safety between 200 mg and 120 mg (approved dose) doses of the HIF-2α inhibitor bel in pts with pretreated advanced ccRCC. We report exploratory biomarker analyses (including HIF-2α IHC, RNAseq, and WES) from this study. Methods: Pts with advanced ccRCC whose disease progressed after 1-3 prior systemic therapies (including an anti–PD-[L]1 therapy) were randomly assigned 1:1 to bel 200 mg or 120 mg QD. Treatment arms were pooled for biomarker analyses. Association of HIF-2α tumor proportion score (TPS; IHC D6T8V) and H-score (sum of each percentage multiplied by its corresponding intensity [0, 1+, 2+, 3+]) with clinical outcomes (ORR, PFS, OS) were tested at prespecified multiplicity-adjusted α = 0.05. Associations of RNAseq-based HIF-2α co-expression and HIF-2α cancer cell scores, glycolysis, angiogenesis, and other HIF-2α–related genes and signatures were tested at prespecified multiplicity-adjusted α = 0.10. Associations for molecular subtypes (Motzer et al. Cancer Cell . 2020;38:803) were tested at nominal α = 0.05. DNA mutations were evaluated by WES. Results: Of 154 pts, HIF-2α IHC was evaluable in 136, RNAseq in 109, and WES in 113 pts. HIF-2α TPS and H-score were positively associated with PFS ( P = 0.016 and 0.012, respectively), but not ORR or OS. HIF-2α cancer cell score was positively associated with ORR ( P = 0.085), but not PFS or OS. No associations with clinical outcome were observed for HIF-2α co-expression score. Glycolysis and angiogenesis were positively associated with ORR ( P = 0.036) and PFS ( P = 0.070), respectively, but these were no longer significant after adjustment of other signatures. ORR was consistent across molecular subtypes and by DNA mutation status (Table), with notably higher ORR in the BAP1 mutant vs wild-type group. Conclusions: In this first RNA and WES biomarker analysis of bel, HIF-2α TPS and H-score were potentially associated with PFS, and BAP1 mutation was potentially predictive of improved ORR in pts with RCC. Molecular subtypes, other RCC-related signatures, and VHL mutation showed no associations or trends with ORR, PFS, or OS. Prospective biomarker evaluations are needed to confirm these findings. Clinical trial information: NCT02853344 . n ORR, % (95% CI) All RNAseq evaluable 109 26.6 (18.6-35.9) Molecular subtypes Angiogenic 12 33.3 (9.9-65.1) Angiogenic/stromal 24 25.0 (9.8, 46.7) Immune/proliferative 22 27.3 (10.7-50.2) Stromal/proliferative 17 23.5 (6.8-49.9) Proliferative 17 23.5 (6.8-49.9) Other (unassignable to a subtype) 17 29.4 (10.3-56.0) VHL Mut 80 25.0 (16.0-35.9) WT 33 24.2 (11.1-42.3) PBRM1 Mut 59 23.7 (13.6-36.3) WT 54 25.9 (15.0-39.7) SETD2 Mut 48 25.0 (13.6-39.6) WT 65 24.6 (14.8-36.9) BAP1 Mut 22 45.5 (24.4-67.8) WT 91 19.8 (12.2-29.4) TP53 Mut 23 26.1 (10.2-48.4) WT 90 24.4 (16.0-34.6) Chr3p loss Yes 87 24.1 (15.6-34.5) No 25 28.0 (12.1-49.4
Radiofrequency Ablation for the Treatment of Pain Related to Bertolotti's Syndrome: A Case Report
No full textBertolotti's syndrome is a congenital spinal disorder marked by back pain due to a lumbosacral transitional vertebra, often presenting with sacroiliac joint, groin, and hip pain. This condition results from the articulation of the lumbar 5 vertebra transverse processes with the sacrum, causing both radicular and pseudoradicular pain.
This is a case report of a patient with bilateral axial low back pain related to bilateral Bertolotti joints who received sustained pain relief after a radiofrequency ablation (RFA) targeting the bilateral L4 medial branch, L5 dorsal ramus, and S1 lateral branch.
Our case report demonstrates the complete resolution of chronic low back pain in a patient with bilateral Bertolotti's syndrome after an RFA targeting the L4 medial branch, L5 dorsal ramus, and S1 lateral branch
A brief, clinically feasible alternative to evaluate response to exercise following sport-related concussion: initial validation of the 10-M in male healthy controls
No full textWe aimed to compare physiological responses, concussion symptoms, and rating of perceived exertion between the 10-M and treadmill protocols for the aerobic component of the dynamic exertion test (EXiT). We hypothesized that these outcomes would be similar between protocols and have moderate-to-strong agreement.
We conducted a within subject, cross-over study design comprised of fourteen healthy and physically active male adults. Participants performed the treadmill and the 10-M protocols in a randomized order separated by a 30-minute rest period. Pre- and postexercise resting heart rate (HR), and systolic and diastolic blood pressure (BP) were measured. Symptoms (headache, dizziness, and nausea), and RPE were recorded. Intraclass correlation coefficients (ICCs) were conducted for HR and BP, and Cronbach's alpha for symptoms and RPE.
There was moderate agreement for HR across minutes 6-12 (ICC>0.723, P0.05). Concussion symptoms and RPE were equivocal (Cronbach's alpha = 0.955, P<0.001).
Physiological and clinical responses between 10-M and treadmill conditions for the aerobic component of EXiT were comparable; the 10-M protocol may be an alternative approach to implement the aerobic component of EXiT
Potential Predictors of Pain and Stiffness Response Following Genicular Artery Embolization for Knee Osteoarthritis
No full textBackground/Objectives: Patient-level predictors of treatment response after genicular artery embolization (GAE) for knee osteoarthritis (OA) are poorly understood. We evaluated clinical, serum, and imaging biomarkers for their ability to predict achievement of the minimally clinically important difference (MCID) for WOMAC pain and stiffness subscales following GAE. Methods: Data from a prospective single-arm clinical trial of 25 patients who underwent GAE for symptomatic knee OA was retrospectively analyzed. Candidate predictors included sex, age, BMI, contralateral Kellgren–Lawrence (KL) scores, and baseline values for serum IL-1Ra, serum VEGF, and total bone marrow edema scores on MRI using the MOAKS methodology. The primary outcomes were the frequency of achieving the MCID in WOMAC pain and WOMAC stiffness at 1, 3, and 12 months, modeled as an ordinal outcome (0–3). Ordinal logistic regression models were constructed. Variance inflation factors (VIFs) were assessed to detect multicollinearity, and leave-one-out cross-validation was performed to evaluate model robustness. Results: All candidate predictors were successfully incorporated into regression models, with no evidence of multicollinearity by VIF analysis. Lower contralateral KL scores (OR: 0.087 [0.012–0.618], p = 0.0146) and higher BMI (OR: 1.383 [1.001–1.910], p = 0.049) were significantly associated with achievement of the MCID for WOMAC pain, although significance for BMI was borderline. Lower baseline serum IL-1Ra levels (OR: 0.122 [0.018–0.816], p = 0.030) were significantly associated with achievement of the MCID for WOMAC stiffness. The remaining clinical, serum, and imaging biomarkers were not significantly associated with MCID achievement. Conclusions: In this exploratory analysis, specific baseline clinical and serum factors were associated with achievement of clinically meaningful improvements in pain and stiffness. Analysis of larger cohorts will help clarify ideal demographic-, biomarker- and imaging-based patient selection strategies that can improve prediction of treatment response and guide clinical decision-making in GAE for knee OA
Examining Aerosol Vertical Transport and Removal during Deep Convective Events
No full textAtmospheric aerosols affect the global energy budget by scattering and absorbing sunlight (direct effects) and by changing the microphysical structure, lifetime, and coverage of clouds (indirect effects). Globally, the free troposphere is a major source of nucleation- and Aitken-mode aerosols due to the enhanced new particle formation rates at high altitudes. Recent studies have shown deep convective systems are capable of transporting these small aerosols from the free troposphere to the boundary layer by strong convective downdrafts and weaker downward motions in the stratiform regions. These vertically transported aerosols can grow into cloud condensation nuclei (CCN) and play a significant role in the global climate. During the deep convective processes, existing accumulation-mode aerosols that act as coagulation sinks of smaller particles are also removed by wet scavenging. Compared to the vertical transport of these particles by entrainment mixing, which is slower but more prevalent, the deep convective downdraft processes may be more rapid and efficient in the vertical transport of aerosols. However, most of the current climate models do not include this mechanism as a source of CCN, mainly because the frequency of deep convective events varies significantly with geographic location and thus their contributions to CCN are unpredictable. We target this critical gap in understanding the vertical transport and removal of aerosols by deep convections. We proposed to analyze a multi-year, multi-site measurement record available from the U.S. Department of Energy (DOE) ARM program, including the observations from the 2014/15 Observations and Modeling of the Green Ocean Amazon (GoAmazon) field campaign, the 2017/18 Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE-ENA) field campaign, the 2018/19 Cloud, Aerosol, and Complex Terrain Interactions (CACTI) field campaign, the 2021/22 Tracking Aerosol Convection Interactions Experiment (TRACER) field campaign, and the long-term measurements collected at the Southern Great Plains (SGP) atmospheric observatory, where deep convective clouds were frequently observed. This project is aimed at the following three objectives: (1) Gaining a detailed and quantitative understanding of the aerosols transported by a convective downdraft and their evolution in the atmosphere; (2) Examining the wet scavenging mechanisms and efficiencies of aerosols at altitudes of deep convective systems based on ground and aircraft measurements; (3) Evaluating the contribution of deep convective systems to CCN as both a source and a sink of atmospheric aerosols and its seasonal variabilities