Median Research Articles

High-Frequency Jet Ventilation Versus Spontaneous Respiration for Percutaneous Cryoablation of Lung Tumors: Comparison of Adverse Events and Procedural Efficiency.

BACKGROUND. High-frequency jet ventilation (HFJV) facilitates accurate probe placement in percutaneous ablation of lung tumors but may increase risk for adverse events, including systemic air embolism. OBJECTIVE. The purpose of this study was to compare major adverse events and procedural efficiency of percutaneous lung ablation with HFJV under general anesthesia to spontaneous respiration (SR) under moderate sedation. METHODS. This retrospective study included consecutive adults who underwent CT-guided percutaneous cryoablation of one or more lung tumors with HFJV or SR between January 1, 2017, and May 31, 2023. We compared major adverse events (Common Terminology Criteria for Adverse Events grade ≥ 3) within 30 days postprocedure and hospital length of stay (HLOS) of 2 days or more using logistic regression analysis. We compared procedure time, room time, CT guidance acquisition time, CT guidance radiation dose, total radiation dose, and pneumothorax using generalized estimating equations. RESULTS. Overall, 139 patients (85 women, 54 men; median age, 68 years) with 310 lung tumors (82% metastases) underwent 208 cryoablations (HFJV, n = 129; SR, n = 79). HFJV showed greater rates than SR for the treatment of multiple tumors per session (43% vs 19%, respectively; p = .02) and tumors in a nonperipheral location (48% vs 24%, p < .001). Major adverse event rate was 8% for HFJV and 5% for SR (p = .46). No systemic air embolism occurred. HLOS was 2 days or more in 17% of sessions and did not differ significantly between HFJV and SR (p = .64), including after adjusting for probe number per session, chronic obstructive pulmonary disease, and operator experience (p = .53). Ventilation modalities showed no significant difference in procedure time, CT guidance acquisition time, CT guidance radiation dose, or total radiation dose (all p > .05). Room time was longer for HFJV than SR (median, 154 vs 127 minutes, p < .001). For HFJV, the median anesthesia time was 136 minutes. Ventilation modalities did not differ in the frequencies of pneumothorax or pneumothorax requiring chest tube placement (both p > .05). CONCLUSION. HFJV appears to be as safe as SR but had longer room times. HFJV can be used in complex cases without significantly impacting HLOS of 2 days or more, procedure time, or radiation exposure. CLINICAL IMPACT. Selection of the ventilation modality during percutaneous lung ablation should be based on patient characteristics and anticipated procedural requirements as well as operator preference.

Assessment of drug utilization and potentially inappropriate medications in hemodialysis patients with end-stage renal dysfunction: A study in a tertiary care hospital in Bahrain.

Patients undergoing dialysis pose therapeutic challenges in terms of polypharmacy, administration of potentially inappropriate drugs, and drugs with the potential risk of toxicity. This study evaluated the use of drugs, potentially inappropriate medicines (PIM), drugs with risk of Torsades de Pointes (TdP), and the complexity of the prescribed regimen using the medication regimen complexity index scale in patients undergoing hemodialysis. A retrospective cohort study was carried out amongst patients receiving hemodialysis. Drugs were classified into one of four classes: (i) drugs used in managing renal complications, (ii) cardiovascular drugs, (iii) anti-diabetic drugs, (iv) drugs for symptomatic management, and (v) others. Drugs were considered as PIM according to the Can-SOLVE CKD working group from a network of Canadian nephrology health professionals. The study adhered to the CredibleMeds classification of drugs with known, possible, and conditional risk of TdP and the complexity of prescribed medicines was evaluated based on the pre-validated medication regimen complexity index scale based on form/route, frequency of dosing, and requirement of special instructions. Sixty-three participants were included in the study (49 males and 14 females) with the median (range) age of 45 (21-66) years. Cardiovascular drugs followed by drugs used for managing renal complications were the most common classes administered. Notably, 12 (19.1%) patients received one of the non-steroidal anti-inflammatory drugs, 21 (33.3%) received a proton pump inhibitor, three (4.8%) received pregabalin, two (3.2%) received opioid drugs, and one (1.6%) was administered celecoxib. Atorvastatin, furosemide, omeprazole, and allopurinol were the most common PIM drugs administered to the study participants followed by others. Drugs used for symptomatic management had significantly more PIM compared to other classes (p <0.0001). Six (9.5%) patients received drugs with known TdP risk, one with possible TdP risk, and 61 with conditional risk. Median (range) medical regimen complexity index score was 26.5 (2-62.5). A huge burden of drug therapy was observed in the hemodialysis patients in terms of higher proportions of PIM, complex medical regimen, and prescription of drugs with risk of TdP. Implementation of clinical decision support tools enhancing rational prescription and identification of drugs with TdP risk, introducing antimicrobial stewardship, and stepwise deprescription of the drugs with the least benefit-risk ratio are warranted.

Postsurgical Outcomes of Mesial Temporal Lobe Epilepsy due to Hippocampal Sclerosis Associated with Calcified Neurocysticercosis.

The aim of this study was to analyze postsurgical outcomes for individuals with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) who underwent anterior temporal lobectomy, based on the presence of calcified neurocysticercosis (cNCC). A retrospective cross-sectional study was conducted on 89 patients with MTLE-HS who underwent anterior temporal lobectomy between January 2012 and December 2020 at a basic epilepsy surgery center located in Lima, Peru. We collected sociodemographic, clinical, and diagnostic information. The postsurgical results were analyzed using bivariate analysis according to the Engel classification. We included 89 individuals with a median age of 28 years (interquartile range [IQR]: 24-37), and more than half (55.1%) were male. Seventeen (19.1%) were diagnosed with cNCC. A greater number of patients with cNCC had lived in rural areas of Peru during their early life compared with those without cNCC (12 [70.6%] versus 26 [36.1%]; P = 0.010). Patients with cNCC exhibited a greater median frequency of focal to bilateral tonic-clonic seizures per month (1 [IQR: 0-2] versus 0 [0-0.5]; P = 0.009). Conversely, a lower proportion of patients with cNCC reported a history of an initial precipitating injury in comparison to the group without cNCC (4 [23.5%] versus 42 [58.3%]; P = 0.014). At the 1-year follow-up, most patients (82.4%) with cNCC were categorized as Engel IA. Similarly, at the 2-year follow-up, nine (75.0%) were classified as Engel IA. Our findings suggest that most patients diagnosed with cNCC exhibit favorable postsurgical outcomes, comparable to those without cNCC. Additionally, it can be postulated that cNCC may play a role as an initial precipitating injury.

Barriers, Facilitators, and Preferences for Mental Health Services Among Patients With Systemic Lupus Erythematosus: A Qualitative Study.

Although patients with systemic lupus erythematosus (SLE) experience high levels of depression and anxiety disorders, evidence concerning patient perceptions of facilitators and barriers to effective uptake of mental health services (eg, referral to therapists and psychiatrists, psychoeducational interventions, or support groups) is limited. We conducted semistructured qualitative interviews with 15 adults with SLE to explore patient experiences and perceptions of mental health services to identify facilitators and barriers to accessing mental health care among patients with SLE. Qualitative interviews were conducted via telephone and audio recorded for transcription and directed content analysis using NVivo software by two coders. The median age of the 15 participants was 48 years, 87% were female, 33% identified as Black or African American, and 33% identified as Hispanic or Latino. Qualitative themes were organized into three domains: barriers, facilitators, and preferences for mental health services. Barriers to the use of mental health services include mental health stigma, sociodemographic factors, lack of autonomy, and time commitment. Facilitators to the use of mental health services included strong relationships with their rheumatologists and mental health care clinician experience with patients with SLE. Preferences for mental health services included education-based formats, mental health providers who work with patients with SLE, peer group formats, demographically and disease-matched psychological resources, and an emphasis on non-disease-related activities. In the setting of persistent unmet psychosocial needs of patients living with SLE, data from this qualitative study will inform the development and refinement of mental health interventions that bolster psychological wellbeing in the SLE population.

Intravenous Tirofiban Versus Alteplase Before Endovascular Treatment in Acute Ischemic Stroke: A Pooled Analysis of the DEVT and RESCUE BT Trials.

The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion. This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed. One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P=0.51) and mortality (17.8% versus 19.4%; P=0.76). The propensity score overlap weighting analyses showed consistent outcomes. Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial. URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Safety and Feasibility of JAK Inhibitor Ruxolitinib in Newly-Diagnosed High-Grade Gliomas (CRUX): Final Trial Report

INTRODUCTION: Dysregulation of the JAK/STAT pathway in newly-diagnosed high-grade gliomas (nHGG) is linked to enhanced survival and proliferation of tumor cells. Ruxolitinib, a small molecule inhibitor of JAK1, JAK2, and JAK3, limits glioma growth in preclinical models. METHODS: This non-randomized prospective study included 60 WHO Grade 3-4 nHGG patients who received standard of care (SOC) therapy along with ruxolitinib in a 3 + 3 dose-escalation design; level 1 of 10 mg BID, level 2 of 15 mg BID, level 3 of 20 mg BID, level -1 of 5 mg BID. Primary study objective was determination of maximum tolerated dose (MTD) of ruxolitinib in combination with chemoradiation. Secondary objective was the determination of safety as assessed using NIH CTCAE scale, overall survival (OS), and progression-free survival (PFS). Exploratory aims were to investigate relationships between clinical outcomes and genomic signatures. RESULTS: 60 patients were enrolled, with median age 60.5 years (range 22-78), 23 (38%) female, and 37 (62%) were male. Amongst 59 evaluable patients, 29 (49%) were MGMT unmethylated and received ruxolitinib with 60Gy radiation over 6 weeks, while 30 (51%) patients were MGMT methylated and received ruxolitinib with 75mg/m2 of temozolomide (TMZ) with 60Gy radiation over 6 weeks. MTD for both cohorts was 20 mg BID. No dose-limiting toxicities were observed. Toxicities attributable to study medications included four grade 4 AEs including seizure, respiratory distress, somnolence, and thromboembolic event along with 14 grade 3 adverse events (AEs), including respiratory distress, seizure, gait disturbance, weakness, thrombocytopenia, cognitive disturbance, urinary retention, and meningitis. Median follow-up of patients alive was 34.2 months (range 18-52.2) with outcomes. CONCLUSIONS: Ruxolitinib therapy is safe and therapeutically feasible in combination with TMZ and radiation. A randomized phase 2 trial is planned.

Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke.

Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM). We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS2 score. Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5-76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397-827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend P<0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24-3.58) and 3.23 (95% CI, 2.07-5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14-5.74) and 4.25 (2.14-8.47), respectively. The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke.

Implementation of Best Practices in Pancreatic Cancer Care in the Netherlands: A Stepped-Wedge Randomized Clinical Trial.

Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score). Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, -1.09, 95% CI, -3.05 to 0.94). In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. ClinicalTrials.gov Identifier: NCT03513705.

Targeted DNA Sequencing Reveals Molecular Factors Associated with Clinical Outcomes in Recurrent Glioblastoma

INTRODUCTION: The prognostic significance of molecular alterations in recurrent glioblastoma (rGBM) remains unclear. METHODS: 121 consecutive glioblastoma (GBM) patients who underwent re-resection at a single institution from 2016-2021 were retrospectively reviewed. All patients underwent maximal safe resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ) at time of initial diagnosis. DNA mutations from re-resection samples were assessed with a CLIA certified next-generation targeted DNA sequencing assay. Overall (OS) and progression-free survival (PFS) from re-resection were analyzed with the Kaplan-Meier method and Cox regression analyses. RESULTS: Median age at first recurrence was 57 years (range, 27-78), and median follow up from re-resection was 11 months. Salvage therapy comprised re-irradiation (n = 52, 43%), temozolomide (TMZ) (n = 39, 32%), lomustine (n = 47, 39%), and/or bevacizumab (n = 22, 18%). Median OS and PFS times were 12.1 and 4.4 months, respectively. Median tumor mutation burden (TMB) was 4 mut/Mb (range, 1-650), microsatellite instability (MSI) was 1.16% (range, 0-20), and MGMT methylation was present in 71 (59%) patients. Longer OS was found after postoperative TMZ (19.1 vs. 9.1), KPS &gt;70 (13.6 vs. 11.1), and/or re-irradiation (12.6 vs. 8.4) (p &lt; .05 for each). On multivariate analysis, TMZ (HR 0.2, 0.079-0.48), re-irradiation (HR 0.27, 0.12-0.58), and mutations in the PDGFRA (HR 0.24, 0.067-0.83) or PTEN (HR 2.3, 1.1-4.8) genes on targeted sequencing were associated with longer OS after re-resection (p &lt; .05). Multivariate predictors of re-irradiation response included MSI &gt; 1.16 (HR 0.25, 0.084-0.75), and mutations in PDGFRA (HR 0.04, 0.005-0.33), TERT (HR 0.16, 0.033-0.78), or PIK3R1 (HR 0.18, 0.041-0.8) genes. In the 46 matched primary/recurrent tumors, 40 (46%) had a longitudinal change in a mutation and 9 (24%) demonstrated hypermutation, of which 4 (57%) had simultaneous mismatch repair deficiencies. CONCLUSIONS: Our study identifies molecular factors associated with survival and response to re-irradiation in rGBM.

PCV Adjuvant Therapy as a Preferred Treatment Option for Oligodendroglioma Patients: A Comparative Study With Temozolomide and Concurrent Radiotherapy

INTRODUCTION: When treating oligodendroglioma patients, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life. METHODS: 87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis. RESULTS: The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in terms of age, tumor genetic profiling, extent of resection, or KPS score, however, the TMZ-based group had more patients receiving concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer for those receiving PCV-based treatment compared to TMZ-based treatment. After adjusting for factors mentioned above, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p &gt; 0.99). CONCLUSIONS: PCV confers improved progression-free survival than TMZ-based treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. As we anticipate the results of the CODEL trial, our findings suggest PCV-based therapy warrants consideration as a preferred therapeutic option for oligodendroglioma patients.

Simulation-based training of endoscopic hemostasis for Japanese pediatric endoscopy learners: a pilot program

Background and AimsEndoscopic hemostasis training, often in emergencies, can be challenging for pediatric endoscopists. This study aimed to establish hands-on seminar sessions using the novel clip hemostasis simulator, and to explore the underlying concerns about endoscopic hemostasis among pediatric endoscopists and the potential of simulator-based training (SBT). MethodsA SBT course was incorporated into seminars by the Japanese Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Surveys with Visual Analog Scale (VAS, 0-100) completed by consenting pediatricians during four seminars from October 2021 to March 2023, were compared with the responses of adult gastrointestinal (GI) residents and junior residents. ResultsFifty-two pediatric endoscopists (median age 31, PGY 7) were enrolled. A median VAS score of 47 (IQR 23.5-65) for understanding endoscopic hemostasis, significantly lower than adult GI residents (median 76, IQR 58-82, P<0.001) and comparable to junior residents (median 54, IQR 50-65). Pediatric endoscopists' confidence in independently performing hemostasis was low, with a median score of 0 (IQR 0-16.5), below adult GI residents (median 67, IQR 49-77, P<0.001) and junior residents (median 11.5, IQR 10-39, P=0.014). Regarding skill enhancement by SBT, a median score of 94.5 showed high and no significant difference from junior residents and adult GI residents. All pediatric endoscopists expressed interest in repeated SBT sessions. Discussion and Future ProspectsPediatric endoscopists were concerned about their competence in endoscopic hemostasis. The simplified SBT programs with the simulator, may potentially improve their skills and confidence.

Longitudinal treatment outcomes of recurrent clival chordomas: a single-center retrospective study.

The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors' institution between 1990 and 2022. A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18-79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36-62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1-8), and the median (IQR) time to the first recurrence was 29 (9-51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0-245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54-82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038-0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01-1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11-51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

Combinatorial Checkpoint Blockade and Laser Interstitial Thermal Therapy: A Single Center Study

INTRODUCTION: Immune checkpoint blockade (ICB) has gained acceptance as a life-extending therapy in a variety of solid tumor types. For patients with brain metastases, combination stereotactic radiosurgery (SRS) and ICB remains an area of clinical equipoise. Similarly, for recurrent or difficult-to-access intracranial lesions, safety and synergy of laser interstitial thermal therapy (LITT) and ICB has yet to be explored. METHODS: In accordance with an IRB-approved protocol, all patients undergoing LITT at a tertiary center from 2015-2022 were retrospectively reviewed. Patients who received ICB within 6 weeks of LITT were included in the LITT + ICB cohort. Demographic, clinical, and survival data were collected. RESULTS: Combination LITT and ICB occurred in 25 patients with clinically recurrent tumors. The median cohort age was 62 (40-78) and 12 (48%) were female. The median KPS was 80 (50-100). The most common primary pathology was non-small cell lung cancer (NSCLC) in 15 patients (60%), followed by melanoma in 3 (12%); two high-grade gliomas were additionally treated. The majority of the cohort (24 patients, 96%) recieved single agent ICB in combination with LITT, with pembrolizumab (12, 48%) and nivolumab (6, 24%) most common. Median duration between ICB dosing and LITT was 2.85 (0.85-5.84) weeks. Ten patients (40%) had evidence of immune-related adverse events attributable to ICB, with only 1 event &gt; grade 3 according to Common Terminology Criteria; 17 (68%) had a pre-LITT steroid requirement. Intracranial adverse events related to LITT were rare, with median overall survival for the cohort of 8.6 months (1.4-26.4 months). CONCLUSIONS: Combination LITT and ICB appears safe and feasible. No prospective studies have compared cytoreduction with LITT to LITT + ICB; construction of a matched NSCLC cohort is ongoing. Exploration of the immune consequences of LITT + ICB is needed.

Predictors of Success of Endonasal Septal Perforation Repair: A 10-Year Experience.

Background: There is no consensus on optimal repair technique for nasal septal perforations (NSPs). Objective: To measure success rate and evaluate predictors of success for NSP repair. Methods: Medical records of patients who underwent NSP repair from 2010 to 2020 were reviewed. Included patients had at least 60 days of postsurgical follow-up. Surgical technique involves an endonasal approach; subperichondrial dissection with local flap mobilization; and multilayer closure using cartilage interposition graft, fascia graft, and mucoperichondrial flaps. A chi-squared test or Fisher exact test was used for statistical analysis. Results: Eighty-one repairs were performed with a closure rate of 86%. The median patient age was 46 years (range 13-77); 34.6% of perforations were ≥2 cm. Conchal (77.8%), rib (7.4%), or septal (7.4%) cartilage was used as graft material. A complication rate of 8.6% was reported. Perforation size or graft material had no impact on successful closure rate. Of patients with failed repairs, 55% had perioperative complications or conditions associated with poor healing. Conclusion: An endonasal approach for NSP repair showed a high success rate across diverse presentations; however, NSP repair was significantly more likely to be successful in patients without perioperative complications or pre-existing conditions associated with poor wound healing.

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.

Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases. In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging score in the PC. Thirty-five children with a median age of 6.3 (interquartile range, 2.7-8.2 [95% CI, 0.9-15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11-0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75-21.0) compared with 4.5 (interquartile range, 2.0-8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54). FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.

The Effect of Social Isolation on 1-Year Outcomes After Surgical Repair of Low-Energy Hip Fracture.

To evaluate whether social isolation or loneliness is associated with outcomes 1 year after low-energy hip fracture. Prospective inception cohort study. Academic level I trauma center. Participants were 65 years or older and enrolled 2-4 days after surgery for a first low-energy hip fracture. Exclusion criteria were bilateral or periprosthetic hip fracture, previous hip fracture, non-English speaking, international address, active cancer, stage 4 cancer in the past 5 years, radiation to the hip region, and cognitive impairment. Participants were followed longitudinally for 1 year. The patient-reported outcomes measurement information system (PROMIS)-29 was elicited 2-4 days postoperatively and 1 year later. Patient-reported risk factors included the Lubben Social Networks Scale and the University of California, Los Angeles Loneliness Scale, which were compared with the lower extremity activity scale and PROMIS-29 domains. Three hundred and twenty-five patients were enrolled. Participants had a median age of 81.7 years, were 70.9% female, and were 85.9% White. In total, 31.6% of patients were socially isolated at the time of fracture. At 1 year, 222 of the 291 subjects who were confirmed alive at 1 year provided data. Multivariable linear models were performed separately for each outcome, including lower extremity activity scale and PROMIS-29 domains. Controlling for age, sex, education, and body mass index, those who were socially isolated at the time of fracture had worse PROMIS-29 function (β = -3.83; P = 0.02) and ability to participate in social roles (β = -4.17; P = 0.01) at 1 year. Secondary analyses found that prefracture loneliness was associated with clinically meaningfully worse function, anxiety, depression, fatigue, sleep, pain, and ability to participate in social roles at 1 year (all P < 0.01). Prefracture social isolation was associated with worse outcomes 1 year after surgical repair of low-energy hip fracture. These data suggest loneliness may be more strongly associated with important patient-centric metrics than prefracture social isolation. Given the dearth of modifiable risk factors in this population, future studies are needed to evaluate whether improving social connections could affect outcomes in this rapidly growing demographic. Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

501 Systemic Immunological Suppression in Glioblastoma Is Targeted by Concurrent VEGF and PD-1 Inhibition in a Dose-Dependent Manner: Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) From a Randomized Controlled Trial

INTRODUCTION: Anti-PD1 blockade has had poor efficacy in recurrent glioblastoma (rGBM) across three RCTs. VEGF, a proangiogenic factor that is upregulated in rGBM, contributes to tumor-associated immunosuppression and is widely targeted through bevacizumab. Preclinical data indicate a potential dose-dependent effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD-1 and anti-VEGF agents is a promising approach for rGBM, for which an RCT was conducted. METHODS: Patients with rGBM were administered nivolumab (240mg IV q2weeks) plus either standard dose bevacizumab (10mg/kg) or low dose bevacizumab (3mg/kg) IV q2weeks, with 1:1 randomization. Stratification factors were age, performance status, extent of resection, and MGMT methylation status. Primary endpoint was overall survival (OS) at 12 months. CITE-Seq was performed on 16 patients across trial arms, both pre- and on-therapy, yielding total 32 immunological profiles. For control, CITE-seq was done on three patients receiving anti-VEGF therapy alone. RESULTS: 90 patients were enrolled with median age of 60.6 years and 45 patients per arm. Both arms had similar OS at 12 months (P = 0.14). Significantly higher OS was found in posthoc analysis for patients aged = 60 years with standard dose. Distinct immune cell populations were identified and differential changes in myeloid-derived suppressor cells (MDSCs) found across trial arms on-therapy. Network medicine approach identified VEGF as target to reduce MDSCs, with VEGF primarily expressed by responders’ MDSCs. Differential gene expression analysis identified increased pro-inflammatory signatures in standard dose arm. CONCLUSIONS: Standard dose bevacizumab was associated with increased inflammatory response and reduction of immunosuppressive MDSC. These mechanistic insights potentially explain survival benefit seen with concurrent VEGF and PD-1 inhibition in elderly rGBM patients.

Flow diverters versus stent-assisted coiling in unruptured intracranial vertebral artery dissecting aneurysms.

Flow diverters (FDs) have been used in unruptured intracranial vertebral artery dissecting aneurysms (IVADAs) with seemingly more favorable outcomes compared with stent-assisted coiling (SAC). However, the benefits of FDs over SAC in unruptured IVADAs need further evaluation. This was a propensity score-matched, retrospective cohort study. Consecutive patients with unruptured IVADAs treated with FDs or SAC at the authors' hospital between January 2016 and December 2020 were reviewed. Propensity score matching at 1:1 was based on age, significant stenosis adjacent to aneurysmal dilatation, maximum diameter, and posterior inferior cerebellar artery involvement. Periprocedural cerebrovascular complications and angiographic and clinical outcomes were compared between the two matched groups. A total of 124 unruptured IVADAs in 123 patients (median age 53 [interquartile range 47-59] years; 101 men) were included. The FD and SAC groups included 65 and 59 IVADAs, respectively. Propensity score matching resulted in 47 matched pairs. The rates of immediate complete occlusion were significantly lower in the matched FD group than in the matched SAC group (6.4% vs 68.1%, p < 0.001). The rates of periprocedural cerebrovascular complications were comparable between the two matched groups (6.4% vs 6.4%, p > 0.99). At last follow-up, the rates of complete occlusion (89.4% vs 80.9%, p = 0.39) and favorable clinical outcomes (100.0% vs 97.9%, p > 0.99) were comparable, whereas the rate of recanalization was significantly lower in the matched FD group than in the matched SAC group (0.0% vs 12.8%, p = 0.03). Although the difference between the rates of in-stent stenosis was not statistically significant (17.0% vs 6.4%, p = 0.18), the difference in the effect measures was considerable. In unruptured IVADAs and compared with SAC, FDs provide comparable rates of periprocedural cerebrovascular complications, favorable clinical outcomes, and follow-up complete occlusion, lower rates of immediate complete occlusion and follow-up recanalization, and likely higher rates of in-stent stenosis.

Comparative Analysis of Single Versus Dual Anti-Epileptic Drugs for Controlling Intra-Operative and Early Postoperative Seizure in Glioma Patients Undergoing an Awake Craniotomy; A Retrospective Study

INTRODUCTION: Awake craniotomy (AC) is the standard approach for tumors of eloquent areas. However, concerns remain regarding the perioperative seizure risks and complications requiring general anesthesia (GA) or termination. METHODS: This retrospective cohort study included patients who underwent awake craniotomy for Glioma resection. Patients were divided into two groups based on their seizure control medication: Group S (N = 29) received one AED, while Group D (N = 26) received dual AEDs. We compared intraoperative seizures (IOS) and post-operative seizures (POS) rates between Groups S and D. Additionally, we evaluated the risk factors associated with POS and the 1-month post-operative Karnofsky Performance Scale (1M-KPS). RESULTS: This study considered a power of 0.9 so the effect size obtained was 0.866. 55 patients (41.8% female) with a median age of 39.0 (IQR 33.0-51.0) entered. The rate of IOS was 8 (27.6%) in Group S and 3 (11.5%) in Group D, with no statistically significant difference. (p = 0.137) POS occurred in 7 (24.1%) patients in group S and 2 (7.7%) patients in group D, (p = 0.100) pointing out no significant difference. The length of hospital stay (p = 0.606) and the length of ICU stay (p = 0.141), Post-op KPS, and 1M-KPS were not significantly different between the two cohorts (p = 0.131 and p = 0.217, respectively). The occurrence of POS was influenced neither by adjuvant therapy nor IDH1 mutation. The univariate and multivariate regression models showed pre-op KPS and the extent of resection had a significant effect on 1M-KPS. CONCLUSIONS: The addition of a second AED did not significantly affect POS prevention, IOS rate, or 1M-KPS improvement. Further research is needed for optimized strategies and improved patient outcomes.

Validation of the Portuguese Version of the Perceived Physical Literacy Instrument.

The Perceived Physical Literacy Instrument (PPLI) has been the most adopted physical literacy instrument designed for adults to date, having been already translated to 5 languages. Still, despite its popularity, there is limited evidence of its psychometric properties. The aim of this study was to translate and adapt cross-culturally the PPLI to the Portuguese language and to analyze the psychometric properties of the Portuguese version in a sample of Portuguese-speaking adults. The study sample was composed of 434 participants (70% females) with a median age of 25 (18-39)years. Confirmatory factor analysis was used to assess psychometric properties of the scale. In addition, instrument assumptions between sexes through invariance testing were examined. Finally, concurrent validity, test-retest reliability, and test-retest agreement analyses were performed to gather additional evidence. The results of the present study generally supported the measurement model. The 9-item, 3-factor model presented a good fit to the data and adequate construct validity (χ2 = 82.859 [24], P < .001, comparative-fit index = .948, Tucker-Lewis index = .922, standardized root mean square residual = .049, root mean square error of approximation = .075). In addition, the scale presented concurrent validity. Some issues arose with measurement invariance and overtime consistency. Considering the lack of validated instruments, we suggest a fair use of Portuguese version of PPLI to access physical literacy in adults. This study contributes to the validation of the PPLI by providing evidence of its psychometric properties in the Portuguese-speaking adult population and facilitates comparative analysis with previous and future studies utilizing the PPLI instrument.