Citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

Objective: To evaluate the efficacy of regional anesthesia (RA) in enabling arteriovenous fistula (AVF) creation in patients with small-caliber veins who would typically receive arteriovenous grafts (AVG), and to compare access outcomes between AVF and AVG cohorts. Methods: We conducted a retrospective analysis of a prospectively maintained database from 2018 through 2024 involving patients with chronic kidney disease (CKD) requiring access creation. Eligible patients were those aged 18 years or older with inadequate veins for AVF creation based on initial ultrasound vein mapping. All patients underwent RA prior to the access creation and had a repeated intraoperative vein mapping at least 30 min after RA. Patients whose veins were sufficiently dilated and met the criteria for AVF creation underwent AVF formation; otherwise, an AVG was created. Outcomes included access maturation, patency rates, access failure, abandonment, and mortality. Statistical analysis was performed using R software, with significance set at p < 0.05. Results: Of the 106 patients, 67 (63.2%) underwent AVF creation post-RA due to sufficient vein dilation, while 39 (36.8%) received AVGs. Baseline vein diameters and comorbidities were comparable between groups. AVF maturation was achieved in 83.6% of AVF patients, with longer times to successful cannulation compared to AVG (median 187.0 vs 80.0 days, p = 0.037). Kaplan-Meier analysis revealed no difference in primary patency ( p = 0.97), but AVF patients had superior primary assisted ( p = 0.015) and secondary patency ( p = 0.033), and lower access failure rates ( p = 0.034) compared to AVG patients. Access abandonment and mortality rates did not differ significantly between groups. Conclusions: RA-induced venodilation enables the use of veins previously deemed inadequate for AVF creation, leading to improved access outcomes compared to AVG placement. Implementing RA may increase AVF utilization and enhance patient outcomes in hemodialysis access surgery.

ABSTRACT Newly diagnosed patients with non‐Hodgkin lymphoma (NHL) often have a history of other diseases, and these comorbidities can impact patient treatment and management options, as well as overall survival (OS). We developed the Lymphoma Epidemiology of Outcomes (LEO) comorbidity index (LCI) as a sum of 10 comorbidities adapted from the Self‐Report‐Generated Charlson Comorbidity Index (SRG‐CCI) for use in the LEO cohort, a national prospective study of newly diagnosed NHL. Of the 5502 participants with self‐reported comorbidity data, 3107 (56.4%) were male and the mean age at diagnosis was 60.9 years (range, 18–99 years). The LCI ranged from 0 to 6, with 48.6% having 0, 30.2% having 1, 21.2% having 2 or more comorbidities. With a median follow‐up of 62.4 months among surviving participants, 2099 patients had an event and 1219 died. Continuous LCI similarly predicted both 1‐year mortality (c‐statistic = 0.654) and OS (c‐statistic = 0.655), while it showed a weaker but still statistically significant predictive ability for lymphoma‐specific (c‐statistics = 0.617) and event‐free (c‐statistic = 0.574) survival. Participants with 1 (HR = 1.21, 95% CI 1.05–1.39) and 2+ (HR = 1.80, 95% CI 1.56–2.08) comorbidities had inferior OS compared to those with no comorbidities after adjustment for age and sex (c‐statistic = 0.654), and performance strengthened after adjustment for the International Prognostic Index (c‐statistic = 0.672). LCI predicted OS most strongly in marginal zone (c‐statistics = 0.748) and weakest in T‐cell (c‐statistic = 0.579) lymphoma. The cumulative incidence of death due to lymphoma, lymphoma treatment, and other causes all increased with increasing comorbidities, with the greatest increase observed for death due to other causes. The LCI performs comparable to other published comorbidity indices, supporting its use in the LEO cohort to better model real‐world outcomes and more generally providing an approach to implementing comorbidity indices in cancer survivorship cohorts.

55 Background: Prior authorization (PA) processes are known to create administrative burdens and delays in care, but little is known about how these challenges impact rural oncology patients and practice settings. Methods: To understand the broad impact of prior authorization on rural oncology patients and practices, we conducted this study across three community oncology practices serving majority rural patient populations with distinct geography, healthcare infrastructure, and models of care. Sites included one critical access hospital system located in a highly-rural community (Lakewood Health System; Staples, Minnesota), a community-based hub-and-spoke hospital system-based practice located in a mid-sized community (Mayo Clinic Health System – Northfield; Northfield, Minnesota), and a standalone referral level III trauma center serving a highly rural patient base (Self Regional Healthcare; Greenwood, South Carolina). This retrospective cohort study examined all intravenous and subcutaneous cancer-directed therapy plans (no oral therapy) that required PA submission at these locations over a three-month period from October 1, 2024 to December 31, 2024. Results: 129 PA submissions were required during the study period. 82 were due to cancer-directed therapy agents (of which 14 were immunotherapy agents), and 47 were due to adjunctive therapies (of which 22, 16, and 9 were due to granulocyte stimulation, bone preservation, and anti-emesis agents, respectively). All 129 PA submissions ultimately resulted in approval of the desired medication or formulary-approved biosimilar. Delays from PA submission to approval ranged from 0 to 18 days. A total of 209 patient-days were delayed due to PA during the study period, which did not ultimately result in change of care or denial of care in any instance. Conclusions: At all sites included in this study, all PA submissions were eventually authorized. The PA process was found to introduce inconsistent and potentially avoidable delays for hundreds of patients and their care teams. These findings highlight the inefficiency of current PA processes among rural cancer populations and the practices that care for them, underscoring the need for ongoing efforts directed at state and federal PA reform.

Importance Annual rates of first intracranial hemorrhage (ICH) from unruptured brain arteriovenous malformations (AVMs) are often quoted as 2% to 4% in clinical practice. Precise estimates and risk factors are unavailable to inform treatment decisions. Objective To provide estimates of rates and risk factors for first ICH in a large cohort study of unruptured brain AVMs. Design, Setting, and Participants The Multicenter Arteriovenous Malformation Research Study (MARS) included data from 9 cohorts, each contributing 100 or more unruptured brain AVMs. The study was conducted from 2017 to 2023 with retrospective and prospective data collection for existing cohorts and/or new recruitment. This was an international study (2 population-based and 7 referral-based cohorts) that included participants diagnosed with an unruptured brain AVM. Exposures Demographic, clinical, and angiographic characteristics. Main Outcome and Measure The primary outcome was time to first ICH after diagnosis of unruptured brain AVM. Data were collected using standardized definitions; missing data were imputed. Cox regression analysis was performed, censoring at first brain AVM treatment, death, or last visit, and allowing baseline hazards to vary by cohort. Results A total of 3225 individuals were eligible for participation in this study. After 195 exclusions, 3030 participants (median [IQR] age, 38 [25-50] years; 1524 female [50.3%]) were included. Among 2989 participants with unruptured brain AVMs, 1333 (45%) presented with seizure. The median (IQR) maximal brain AVM diameter was 3.1 (2.2-4.4) cm, 248 of 2466 AVMs (10%) had exclusively deep venous drainage, 297 of 2690 (11%) were in supratentorial deep or cerebellar locations, and 457 of 2440 (19%) had associated arterial aneurysms. First ICH occurred in 159 participants over 11 339 person-years of follow-up for an ICH rate of 1.40 (95% CI, 1.20-1.64) per 100 person-years. Significant independent risk factors included (1) increasing age category at diagnosis (hazard ratio [HR], 0.87; 95% CI, 0.53-1.41 for those aged 20 to 39 years; HR, 1.23; 95% CI, 0.74-2.04 for those aged 40 to 59 years; and HR, 2.01; 95% CI, 1.14-3.57 for those aged 60 years vs younger than 20 years; P = .008), (2) presence of associated aneurysms (HR, 1.66; 95% CI, 1.06-2.59; P = .03), and (3) cerebellar or supratentorial deep location (HR, 1.87; 95% CI, 1.16-3.00; P = .01). Conclusions and Relevance The annual ICH rate from unruptured brain AVM was lower than that commonly cited in clinical practice. Increasing age, associated arterial aneurysms, and cerebellar or supratentorial deep brain AVM location were associated with risk of first ICH. These results may be used to counsel patients about the natural history of unruptured brain AVMs.

BACKGROUND: Acute mesenteric ischemia (AMI) is a vascular emergency where delays in diagnosis or treatment can lead to irreversible bowel injury and death. Many patients initially present to hospitals without surgical or vascular capabilities and require interhospital transfer. The clinical impact of such transfers on treatment and outcomes in AMI remains poorly defined. STUDY DESIGN: We performed a retrospective cohort study using the National Inpatient Sample (2019 to 2021) to evaluate the association between interhospital transfer and outcomes in patients with AMI. Adult patients with a primary diagnosis of AMI were identified using ICD-10 codes. Patients were categorized by transfer status. Multivariable logistic regression was used to evaluate associations with in-hospital mortality and procedural interventions, adjusting for age and comorbidity burden. RESULTS: Of 39,690 hospitalizations for AMI, 14.6% involved interhospital transfer. Transferred patients had a higher comorbidity burden and were more often treated at rural or micropolitan hospitals. They were significantly more likely to undergo major surgical and vascular procedures, including bowel resection (odds ratio [OR] 3.48), mesenteric bypass (OR 3.32), and angioplasty (OR 2.66; all p < 0.0001). Markers of critical illness, such as intubation (OR 2.15) and dialysis (OR 1.30), were also more frequent in this group. In-hospital mortality was significantly higher among transferred patients (OR 2.05), and transfer remained independently associated with increased mortality after adjusting for age and comorbidity burden (adjusted OR 1.67, 95% CI 1.32 to 2.10). CONCLUSIONS: Interhospital transfer in AMI is strongly associated with increased clinical severity and in-hospital mortality. These findings emphasize the urgency of early diagnosis, rapid triage, and timely access to definitive care, supporting the need for structured regional systems and transfer protocols for AMI.

Abstract BACKGROUND Glioblastoma (GBM) is highly aggressive with poor prognosis, especially in recurrent cases where treatments are limited. Intra-arterial (IA) Yttrium-90 (Y90) microsphere therapy, CE-marked for hepatic neoplasia, offers the potential for targeted high-dose beta radiation in GBM by leveraging tumor hypervascularity. The FRONTIER trial evaluated the safety and feasibility of IA Y90-glass microsphere treatment for recurrent GBM. MATERIAL AND METHODS FRONTIER is a prospective, single-arm, multi-center study with Investigational Device Exemption approval from the US FDA. This initial cohort included patients with recurrent GBM in non-dominant, non-eloquent regions after 1-2 lines of prior therapy. The primary endpoint was the 30-day incidence of treatment-related toxicities (primarily ≥grade 3 non-hematologic, with exclusions). Secondary endpoints included overall treatment-related adverse events (AE), neurological function changes, technical success, and efficacy measures. Treatment regions, defined via cerebral angiography-MRI fusion to cover the recurrent lesion were targeted with 40±4Gy. Post-treatment evaluations included MRI, Y90-PET for absorbed dose distribution, and serial neurological assessments. Changes in post-contrast T1-enhancing tissue volume (T1C-vol) were tracked longitudinally. RESULTS Twelve subjects (67% male; average age 57 years) were treated. The procedure was well-tolerated with no limiting toxicities reported or device-related AEs reported. Five patients experienced 8 procedure-related AEs (6 Grade 1, 2 Grade 3). At discharge one day after treatment, there was no decline in neurologic status per NIHSS. Technical success was 100%, with post-treatment Y90-PET showing a median absorbed dose of 41.5 Gy (range 39.2-45.4) to the treatment region (median volume 80.3 cc [40.9-118.5]). The median tumor absorbed dose was significantly higher at 124.2 Gy (range 58.5-508.5) within a median tumor volume of 5.8 cc (range 0.5-55.4), indicating preferential tumor perfusion. At 1 month, the best response was partial response in 17% (2/12), stable disease (SD) in 67% (8/12), and progressive disease in 17% (2/12). At 2 months, 73% (8/11 evaluable) had SD, and 33% (4/12) showed reduced T1C-vol within the treated area. Median progression-free survival was 3.0 (95% CI 1.1-3.7) and median overall survival (OS) was 9.3 months (95% CI 5.0-NE) from Y90 treatment. Exploratory analysis revealed a significant OS benefit for patients receiving a tumor absorbed dose above the median (&gt;124 Gy) compared to those below (13.1 vs 5.8 months, p=0.0054). CONCLUSION Results from this initial cohort of the FRONTIER trial suggest IA Y90 glass microsphere therapy is technically feasible and well-tolerated in patients with recurrent GBM. The observed dose-response relationship warrants further investigation of this modality as a potential treatment option.

Abstract Perioperative low cardiac output syndrome (LCOS) remains a significant complication in adult cardiac surgery, contributing to substantial morbidity, prolonged intensive care, and increased mortality. Its incidence is expected to rise further due to the evolving complexity of referred surgical patients, often characterised by advanced age, multiple comorbidities, challenging anatomy, and impaired haemodynamics. Despite advances in pharmacological and perioperative care, outcomes for high-risk patients have not shown significant improvement, prompting interest in temporary mechanical circulatory support (tMCS) as a proactive strategy. This Expert Consensus Document from the European Association for Cardio-Thoracic Surgery (EACTS) presents the first dedicated guidance on the pre-emptive use of tMCS in high-risk adult cardiac surgical patients. Developed by a multidisciplinary task force, it emphasises structured risk stratification, early initiation, and individualised device management informed by interdisciplinary Heart Team discussions. The document proposes clinical pathways for patient selection, defines criteria for tMCS initiation, and provides practical algorithms for various scenarios, including advanced heart failure, cardiogenic shock, and post-cardiotomy LCOS. It reviews the current evidence on available tMCS devices, such as intra-aortic balloon pumps, microaxial flow pumps, veno-arterial extracorporeal life support and hybrid strategies, and addresses perioperative care, intensive care unit protocols, ethical considerations, as well as informed consent and support withdrawal. Despite promising results, substantial knowledge gaps remain, including long-term outcome data, device selection criteria, and cost-effectiveness analyses. This consensus aims to support clinical decision-making, standardise practice, and stimulate research to improve outcomes in a growing population of high-risk surgical patients.

Abstract Background The diagnosis of monoclonal gammopathies relies on the detection of monoclonal immunoglobulins (M-proteins) in serum or urine. Mass-Fix utilizes matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to detect and quantify M-proteins. This method employs immunoaffinity enrichment using antibodies against heavy chains (HC) and light chains (LC), followed by MS analysis to determine M-protein isotypes. Mass-Fix has also revealed novel M-protein characteristics, including LC glycosylation and fragmentation, facilitated by measuring the mass of LC. LC glycosylation is as an independent risk factor for disease progression of monoclonal gammopathy of undetermined significance (MGUS), while light chain fragments have been postulated as the origin of amyloid light chain (AL) plaques. Since Mass-Fix enriches intact immunoglobulins before dissociating LCs, it potentially enhances fragment detection. However, the precise nature and clinical significance of these fragments remain to be fully elucidated. Methods Mass-Fix serum results from Mayo Clinic patients tested from September 10, 2018, to October 1, 2024, were reviewed for the presence of M-protein and LC fragments. The frequency and the isotype of fragment LC fragments was determined in the M-protein positive cohort (n=15410). Patients diagnosed with either MGUS (n=6996), AL amyloidosis (n=315), or both (n=32) who had positive M-protein results on Mass-Fix, either prior to or within one month after the diagnosis, were included for a retrospective clinical association study of LC fragments and disease. To validate that these fragments were not artifacts of MS analysis, PAGE gel analysis and Western blots were performed using clinical residual serum from 9 patients: 2 IgG/kappa and 3 IgG/lambda patients with detectable LC fragments and 2 IgG/kappa and 2 IgG/lambda patients without fragments. Samples were purified using antibodies against gamma heavy chains and reduced with TCEP prior to gel electrophoresis and Western blot. Results Of the 15410 patients with monoclonal proteins detected by Mass-Fix, 2896 (18.7%) had detectable LC fragments; kappa fragments in 1533 and lambda fragments in 1363. Most often, the fragments were observed in pairs, with combined molecular weight typically equaled that of the full-length monoclonal LC present in the same sample. LC fragments were observed more frequently among patients diagnosed with AL amyloidosis (118/347=34%) compared to those without the diagnosis (685/6996=10%), with an odds ratio of 4.75 (95% CI, 3.75-6.01). PAGE with Coomassie blue staining revealed bands with sizes representing LC fragments in the five M-protein samples with detectable LC fragments on Mass-Fix, while no such bands observed in those without LC fragments. Western blot using anti-kappa or anti-lambda antibodies confirmed the identity of the bands with higher molecular weight as a fragment of LC in each of the IgG/kappa and IgG/lambda samples. Conclusion Mass-Fix is able to discriminate LC fragments from intact LC based on their sizes. The detection of LC fragments with Western blot without ionization suggests a biological origin rather than analytical artifacts from MS. The clinical association study suggests that LC fragments may have utility in increasing the suspicion of AL amyloidosis in M-protein positive patients with LC fragments, potentially facilitating earlier intervention and improving patient outcomes.

Abstract INTRODUCTION In multicenter Alzheimer's disease studies, amyloid positron emission tomography (PET) visual reads are typically performed centrally by a few experts. Incorporating a broader reader network enhances scalability and generalizability. METHODS Ten neuroimaging experts from eight Alzheimer's Disease Research Centers (ADRCs) visually read 180 amyloid PET scans (30 scans and 15 duplicate scans for each of four tracers, imaged across a wide variety of scanners), using preferred reading software without anatomical imaging or quantitation. Scans were classified as elevated or non‐elevated per tracer‐specific criteria. Inter‐ and intra‐rater agreement was assessed. RESULTS Inter‐rater agreement was substantial (Fleiss’ κ = 0.78), with full consensus on 69% of scans. Inter‐rater reliability was substantial to perfect across tracers (Fleiss’ κ = 0.70–0.87). Intra‐rater agreement was substantial to perfect (Cohen's κ = 0.79‐1). Scans with intermediate (10–40 Centiloid) quantitation had lower reader agreement. DISCUSSION A multicenter expert network achieved substantial agreement classifying amyloid PET scans. These scans provide a standard for reader training and reliability assurance in future studies. Highlights Calibration methods ensure reliable amyloid positron emission tomography (PET) visual reads across multiple raters. Substantial agreement is possible across readers using their preferred tools. Agreement is also substantial regardless of the amyloid PET tracer used. Scans with intermediate (10–40 Centiloid) quantitation have lower reader agreement. The calibration set will become a training tool for amyloid PET visual read studies.