Faculty Bibliography

BACKGROUND:CD19-directed chimeric antigen receptor T-cell (CAR T) therapy has significantly improved outcomes for patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) but is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS), a major cause of morbidity and mortality. Preclinical and early phase clinical studies suggest that interleukin-1 blockade with anakinra may mitigate ICANS without impairing CAR T efficacy. However, real-world data evaluating the efficacy and safety of prophylactic anakinra remain limited. OBJECTIVES/OBJECTIVE:We performed a retrospective analysis comparing CAR T toxicities and clinical outcomes among patients treated with prophylactic anakinra versus controls using inverse probability of treatment weighting (IPTW), hypothesizing that anakinra prophylaxis would be associated with decreased severe ICANS. STUDY DESIGN/METHODS:In 2023, our institution implemented a policy for anakinra prophylaxis for high-risk patients based on promising early phase data. We conducted a single-center retrospective cohort study of 176 adult patients with R/R B-NHL who received CD19 CAR T therapy between 2018 and 2025. The analysis was restricted to patients meeting institutional criteria for anakinra prophylaxis (age ≥65 years or receipt of a CD28 costimulatory domain CAR T product), excluding those with baseline ICE score <8. Patients treated with anakinra in the post-policy era were compared with patients treated prior to the implementation of the policy. Inverse probability of treatment weighting (IPTW) was used to balance baseline clinical and disease-related covariates between groups. RESULTS:After IPTW, patients receiving prophylactic anakinra had a higher incidence of any-grade ICANS compared with those who did not (40.0% vs 23.0%, p = 0.03), while rates of grade ≥3 ICANS were similar between groups (p = 0.62). In multivariate regression, anakinra prophylaxis was associated with increased odds of any-grade ICANS (aOR 3.22; 95% CI 1.39-7.46) but not grade ≥3 ICANS (aOR 1.84; 95% CI 0.61-5.5). Rates of all-grade CRS were comparable (p = 0.74); however, in multivariate regression, anakinra prophylaxis was associated with increased odds of grade ≥3 CRS (aOR 17.83; 95% CI 1.30-245.21), though the estimate was imprecise due to sparse events. Grade ≥3 infections were more common in the anakinra cohort (21.5% vs 7.3%; p = 0.01) by day 30 and by day 90 (27.1% vs 10.4%; p = 0.01). Grade ≥3 infections remained associated with use of anakinra in multivariate regression (day 30: aOR 7.08; 95% CI 1.90-26.30, p = 0.004) (day 90: (aOR 5.59; 95% CI 1.83-17.04; p = 0.003). No differences in response rates, event-free or overall survival were observed between groups. CONCLUSION/CONCLUSIONS:In this single-center historical comparison of high-risk patients receiving CD19 CAR T cells, prophylactic anakinra did not reduce severe ICANS and was associated with increased immune-mediated toxicities and infectious complications. Causal inference is limited by policy-driven treatment assignment, residual temporal confounding, and limited practical overlap. These findings suggest the need for caution in routine use of anakinra prophylaxis outside of clinical trials and underscore the importance of prospective studies to better define optimal toxicity mitigation strategies.

[This corrects the article DOI: 10.1016/j.waojou.2021.100613.].

INTRODUCTION/BACKGROUND:Chronic traumatic encephalopathy (CTE) is a tauopathy linked to repetitive head impacts. Factors influencing brain regional susceptibility to tau deposition and spreading remain unclear. METHODS:We used three datasets: [18F]flortaucipir positron emission tomography (PET) in 157 former professional American football players and 53 controls (DIAGNOSE CTE); cortical myelin water fractions (MWF) in 50 healthy individuals (Myelin Water Atlas); and white matter (WM) tract MWF and functional connectivity (FC) in 100 healthy individuals (Human Connectome Project). We tested associations between tau-PET uptake and covariance in football players and typical cortical gray matter (GM) MWF, WM tract MWF, and FC. RESULTS:Cortical regions with lower typical GM MWF showed higher tau-PET uptake (β = -0.399, p = 0.001). WM tracts with lower typical MWF were associated with higher tau-PET covariance (β = -0.238, p < 0.001). Higher typical FC was associated with higher tau-PET covariance (β = 0.447, p < 0.001). DISCUSSION/CONCLUSIONS:In former football players at risk for CTE, regional susceptibility to tau deposition may be driven by low myelin and high FC.

BACKGROUND/UNASSIGNED:Recent observational studies have suggested that early treatment (<12 hours from diagnosis) of intermediate risk pulmonary embolism (PE) with catheter-based therapies may reduce morbidity and mortality. However, the effect of early versus late mechanical thrombectomy on acute pulmonary hemodynamics and right ventricular mechanics is less well defined. METHODS/UNASSIGNED:Patients enrolled in SYMPHONY-PE were divided into one of 2 groups based on the time from baseline CT pulmonary angiography to mechanical thrombectomy: Early <12 hours versus late ≥12 hours. The primary safety end point was the rate of major adverse events within 48 hours, as adjudicated by an academic independent safety board. The primary efficacy end point was the core-lab assessed mean change in right ventricle-to-left ventricle ratio from baseline to 48 hours. RESULTS/UNASSIGNED:=0.431) between groups, and there were no mortalities. The differences in efficacy outcomes were greatest in higher-risk patients per the Composite Pulmonary Embolism Shock score. CONCLUSIONS/UNASSIGNED:Early mechanical thrombectomy was associated with larger reductions in right ventricle-to-left ventricle ratio and mean pulmonary artery pressure, with no significant differences in safety event rates compared with patients who underwent late thrombectomy. Randomized trials are needed to test these associations. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06062329.

The Yazidi community endured an unprecedented genocide by the Islamic State (ISIS) in August 2014, resulting in mass killings, kinocide, abductions, ongoing disappearances, and sexual enslavement. The intense trauma led to high prevalence rates of posttraumatic stress disorder (PTSD), depression, anxiety, and profound sleep disturbances. This comprehensive article integrates epidemiological data, neurobiological mechanisms, and clinical case reports to elucidate sleep disorders among Yazidi survivors. We detail the historical context, transgenerational trauma, specific sleep-related pathologies (insomnia, nightmares, parasomnias, and disrupted circadian rhythms), neurobiological underpinnings, cultural factors, and evidence-based interventions (e.g., Narrative Exposure Therapy (NET); Cognitive Behavioral Therapy for Insomnia (CBT-I)). Furthermore, we discuss the establishment and role of the Institute for Psychotherapy and Psychotraumatology (IPP) at the University of Duhok, outline barriers to care, and propose future research directions and policy recommendations.

AIMS/OBJECTIVE:We aimed to develop a multistage schema to stratify diabetes risk using continuous plasma glucose (PG) values (fasting and 1 h) in combination with clinical variables. METHODS:In 962 Brazilian adults, we initially estimated the probability of developing diabetes with the Finnish Diabetes Risk Score (FINDRISC). We then stratified participants with a FINDRISC score of 9 or higher into three progressive high-risk stages based on their probability of developing diabetes. We evaluated the schemás ability to predict the incidence of diabetes using robust Poisson regression with a time offset, employing bootstrap resampling for internal validation. RESULTS:to scores produced little change. CONCLUSIONS:A staging schema based on scores derived from continuous FPG and 1 h PG values along with clinical variables, applied after a FINDRISC screening, offers a nuanced and practical approach to identifying individuals for diabetes prevention.

PURPOSE/OBJECTIVE:This study evaluates radiographic outcomes and reoperations in patients undergoing anterior vertebral body tethering (VBT) of the lumbar spine. METHODS:A retrospective review of an EOS database identified pediatric patients who underwent lumbar VBT. Demographic and surgical data were collected, as well as radiographic and clinical outcomes including complications, reoperations, and conversion to posterior spinal fusion (PSIF). Analyses included paired t-tests, Wilcoxon signed-rank tests and chi-square. RESULTS:Thirty-two patients with idiopathic scoliosis who underwent thoracolumbar VBT with 2-year follow-up were included. Mean age at surgery was 13.7 ± 1.8 years (mean follow-up 2.0 ± 0.2 years); median Sanders score was 3 (50% ≤ 3). Lumbar Cobb decreased from 48° ± 12 to 20° ± 10 postoperatively (p < 0.001) with correction loss to 29° ± 12 at 2 years (p < 0.001). Tethered Cobb decreased from 46° ± 8 to 13° ± 9 postoperatively (p < 0.001), with correction loss to 17° ± 12 at 2 years (p = 0.284). At 2 years, 31% had > 5° of correction loss and 84% had a tethered Cobb < 30°. Correction loss did not differ by Sanders stage (p = 0.92). Seven patients (23.3%) demonstrated > 5° of additional curve correction postoperatively. Four patients (12.5%) had unplanned reoperation and five others (15.6%) required PSIF: 28.1% total reoperation rate. CONCLUSIONS:Lumbar VBT provided substantial initial correction with maintenance of correction across the tethered levels at 2-year follow-up. While most patients maintained a tethered Cobb angle < 30° at 2 years, 28.1% of patients underwent reoperation (12.5% UPROR; 15.6% PSIF conversion). Longer follow-up in larger multicenter cohorts is required to more accurately define lumbar VBT durability and conversion-to-fusion risk. LEVEL OF EVIDENCE/METHODS:IV.

PURPOSE/OBJECTIVE:To report perioperative and short-term outcomes of single-port (SP) robotic vascular-preserving (non-transecting) Y-V flap pyeloplasty with stricturoplasty for ureteropelvic junction obstruction (UPJO). The most commonly performed pyeloplasty technique is the dismembered Anderson-Hynes technique; however, transection of the ureter compromises its blood supply and makes revision surgery more complex. Non-transecting pyeloplasty preserves the longitudinal ureteral blood supply and serves as an alternative to transecting techniques. METHODS:All patients who underwent SP robotic-assisted non-transecting Y-V flap pyeloplasty with stricturoplasty for primary UPJO between December 2020 and December 2024 were retrospectively reviewed. Surgical success was defined as the absence of secondary intervention (endoscopic or surgical), resolution or improvement of symptoms, and stable or improved postoperative imaging findings. RESULTS:A total of 21 cases met the inclusion criteria. Median operative time was 109 min. Median follow-up was 73 weeks. Overall surgical success was achieved in 95% of patients. There were no intraoperative complications, and the median estimated blood loss was 15 mL. Most patients were discharged the same day (18/21, 86%), with no Clavien-Dindo grade ≥ III complications. Postoperative renal scintigraphy was obtained in 8 patients, all of whom demonstrated improved drainage (T½ <20 min). The remaining patients were followed with clinical assessment and postoperative imaging. One patient developed recurrent obstruction after stent removal and was successfully managed with secondary endopyelotomy. CONCLUSIONS:SP robotic non-transecting Y-V flap pyeloplasty with stricturoplasty appears feasible and safe in selected patients with primary UPJO, with favorable short-term outcomes in this single-surgeon retrospective series. Further study with standardized functional follow-up is needed to define durability and appropriate patient selection.

PURPOSE OF REVIEW/OBJECTIVE:Balance depends on accurate perception of self-motion and verticality and on multisensory integration for stance, and gait. In Parkinson's disease, balance is commonly impaired and variably affected by treatment. Although vestibular and multisensory contributions are increasingly recognized, progress is limited by fragmented evidence, inconsistent methods, and artifact-prone measures. We provide a consensus roadmap across four domains - video-oculography/vHIT, VEMPs, posturography, and perceptual paradigms - to improve clinical translation of balance research in Parkinson's disease. RECENT FINDINGS/RESULTS:An interdisciplinary taskforce conducted a comprehensive literature review and a modified Delphi process (≥80% agreement), using virtual meetings, surveys, and an in-person consensus session. Oculography/vHIT shows largely preserved aVOR in Parkinson's disease but is vulnerable to Parkinson's disease specific artifacts, requiring standardization. VEMPs relate to brainstem and non-motor features but are limited by EMG-dependent confounds. Posturography reveals impaired multisensory integration with visual dependence and cholinergic contributions; reactive-capacity measures outperform sway alone. Perceptual paradigms show task-specific distortions and increased variability linked to axial/postural syndromes. SUMMARY/CONCLUSIONS:This consensus offers a practical roadmap, de-emphasize aVOR/vHIT as primary unsteadiness outcomes; use VEMPs as ancillary measures; prioritize posturography probing adaptability and reactive stepping; integrate wearables and neurochemical imaging; and adopt consortium-level minimum datasets to enable reproducible, phenotype-aware advances in Parkinson's disease balance research.

PURPOSE/OBJECTIVE:Corneal cross-linking (CXL) induces both mechanical and geometrical changes in the cornea, which are typically overlooked in pre-operative planning. We developed and calibrated a patient-specific finite element model (FEM) to predict the topographic alterations resulting from CXL and applied it to three patients with keratoconus (KC) as a proof of concept. METHODS:To calibrate the model, we performed nanoindentation and ex vivo optical coherence elastography (OCE) inflation tests before and after CXL on five human donor corneas. Nanoindentation results tuned the visco-hyperelastic parameters, while ex vivo OCE axial strains were used for validation. Personalized corneal models were generated from the topographies of the three KC patients, with regional stiffness in the affected areas adjusted based on axial strain measured by in vivo pressure-modulated OCE. Simulated CXL outcomes were then compared to 6-month clinical results. RESULTS:CXL induces a 16-fold increase in the fiber-related mechanical parameters and reduces the viscoelasticity time constant by three. In vivo OCE measurements showed an average mechanical weakening of 57% in the KC regions. When compared to the clinical topography at the 6-month follow-up, the CXL-induced curvature changes predicted by the model were -1.5 D vs. -1.76 D, -1.65 D vs. -1.91 D, and -1.76 D vs. -1.57 D, for the three patients, respectively. CONCLUSION/CONCLUSIONS:By combining FEM with in vivo corneal mechanical characterization, patient-specific topographic changes can be predicted, which has the potential to improve the planning of CXL treatments.