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Background/Objectives: To identify predictors of successful fusion and adjacent segment disease (ASD) following ALIF. Methods: Records of patients undergoing one- or two-level ALIF were queried for baseline and postoperative radiographic data, demographics, operative notes, and implant characteristics. All had ≥1 year of follow-up with CT, and multivariable Cox regression was used to identify predictors of radiographic fusion through the interbody, ASD, and ASD requiring reoperation. Results: In total, 177 patients (median 59 yr; 52.5% male) were treated at 245 unique levels, of which 193 fused (81.3% with posterior fixation and 59.6% with standalone), 43 had ASD (17.6%), and 14 had ASD requiring reoperation (5.7%). Fusion was predicted by anterior cage placement (HR 0.94/mm; 95% CI [0.90, 0.98]; p = 0.003) and BMP use (HR 1.92; [1.15, 3.18]; p = 0.012). Radiographic ASD was predicted by older age (HR 1.08 per year; [1.03, 1.14]; p < 0.001), undergoing a revision [vs. index] fusion operation (HR 3.51; [1.44; 8.59]; p = 0.006), lower preoperative disc height (HR 0.83/mm; [0.74, 0.94]; p = 0.003), and preoperative facet vacuum phenomenon (HR 2.46; [1.18, 5.15]; p = 0.017). None of the extracted variables predicted reoperation for ASD. Conclusions: BMP use along with anterior cage placement and posterior fixation may improve the odds of fusion through the interbody following one- or two-level ALIF. Adjacent segment pathology is more common in patients with greater preoperative degenerative pathology (vacuum sign; more collapsed disc) and advanced age. Pelvic fixation did not improve fusion odds, but the data highlight the benefits of supplementary posterior fixation vs. standalone ALIF.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Summary Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine. 1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions. 1–3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres. 4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

Abstract Solitary plasmacytoma of bone (SPB) is a localized plasma cell neoplasm associated with a substantial risk of progression to multiple myeloma (MM), yet the role of adjuvant systemic therapy following definitive radiation therapy (RT) remains undefined. We conducted a randomized phase III trial (Alliance A061402) to evaluate whether the addition of systemic therapy with ixazomib, lenalidomide, and dexamethasone (IXA-LEN-DEX) to zoledronic acid (ZA) improves outcomes compared with ZA alone in patients with SPB and minimal (< 10%) bone marrow plasma cell involvement following RT. Patients were randomized to receive six 28-day cycles of IXA-LEN-DEX-ZA or ZA alone. The primary endpoint was time to progression (TTP) to MM. The study was closed early due to poor accrual after enrolling 11 patients (IXA-LEN-DEX-ZA, n = 5; ZA, n = 6). All patients completed RT and planned treatment without dose reductions. The combination regimen was well tolerated, with limited grade ≥ 3 toxicities, including hypophosphatemia and lymphopenia. At follow-up extending beyond 4 years, the 1- and 4-year progression rates to MM in the IXA-LEN-DEX-ZA arm were 0% and 33%, respectively, compared with 37.5% and 58.3% at 1 and 2 years in the ZA-alone arm. Although underpowered, these findings demonstrate the feasibility and tolerability of an all-oral adjuvant systemic regimen in SPB and provide prospective data supporting further investigation of systemic strategies to delay progression to MM.

Background COVID‐19 and other respiratory viral infections can cause cardiovascular complications. SARS‐CoV‐2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID‐19 and enrolled in the ACTIV‐4a (Accelerating COVID‐19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy. Methods We quantified SARS‐CoV‐2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine–Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death. Results In 93 patients, SARS‐CoV‐2 RNA and N‐antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90‐day death (hazard ratio [HR], 1.31 [95% CI, 1.17–1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24–1.47]). Viral RNA more effectively predicted survivorship than N‐antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%–32.3%; P =0.048) after adjustment for age and sex of the relationship between viral RNA and the 90‐day mortality rate. Conclusions Elevated plasma SARS‐CoV‐2 RNA levels are associated with death in ACTIV‐4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung–blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04505774.

Abstract The intestinal epithelium harbors a large population of microbiota-dependent CD8αβ + T cells whose antigen specificity and regulation are ill-defined. By identifying MHCIa-restricted TCRs and generating tetramers against the gut commensal Segmented Filamentous Bacteria, we demonstrate that a single commensal species drives a clonally expanded, antigen-specific CD8αβ + T cell within the intraepithelial lymphocyte compartment. Mechanistically, the intestinal epithelium coordinates coincident signals governing this population: peptide:MHC-dependent TCR engagement drives pIEL accumulation, while αvβ6-mediated TGFβ activation restraints effector cell differentiation. Perturbation of epithelial cell-mediated TGFβ activation diverts commensal-specific CD8 + T cells toward inflammatory differentiation states transcriptionally convergent with those observed in ulcerative colitis. The intestinal epithelium thus functions as a dual-signal organizer of commensal-specific CD8 + T cell responses, coupling differentiation to restraint through spatially coincident molecular cues.

Introduction BACH2-related immunodeficiency and autoimmunity (BRIDA) increases the risk of developing B cell lymphoma. We present a case of a patient with a known history of common variable immunodeficiency (CVID) and BACH2 variant of uncertain significance, presenting with hypercalcemia and acute kidney injury (AKI), found to have T cell histiocyte-rich large B cell lymphoma of the spleen. Case Description 46-year-old male with CVID-like clinical picture with variant of uncertain significance in BACH2 (Combined Annotation Dependent Depletion [CADD] 25.2, allele frequency 2) and granulomatous-lymphocytic interstitial lung disease (GL-ILD), admitted for acute kidney injury with hypercalcemia. He is pancytopenic, hypercalcemic, with marked splenomegaly on CT. PET-CT showed retroperitoneal and iliac chain lymphadenopathy along with mixed changes of osseous/marrow lesions with new lesions in the thoracic spine and left mid femur. There is a notable improvement in GL-ILD on CT chest while the patient is on prednisone. Renal biopsy showed acute tubular injury with increased deposition of calcium phosphate, along with moderate interstitial fibrosis and tubular atrophy with mild fibrointimal thickening of arteries. No monoclonal protein detected in the serum, negative JC virus, BK virus, EBV, CMV, and HIV. Splenic biopsy showed B cell lymphoma with features of micronodular T cell/histiocyte-rich large B cell lymphoma of the spleen. Patient initiated on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment protocol. Discussion BACH2 is a regulator of T and B cell differentiation and maturation. The effect of BACH2 on T cells involves limiting the differentiation of regulatory T (Treg) cells, which aid in preventing autoimmunity. BACH2 mutations have been described in the literature in patients with CVID and autoimmunity, such as ulcerative colitis. Lymphoma can cause hypercalcemia, which can lead to acute kidney injury. This patient has a variant of uncertain significance in BACH2 with CADD 25.2, allele frequency 2. His clinical picture of CVID, acute kidney injury in the setting of hypercalcemia, and newfound B cell lymphoma of the spleen may be due to this variant of uncertain significance. Further studies need to be conducted to better understand this gene and its role in CVID and B cell lymphoma. Tabular data are included as downloadable supplement files.

Multi-listing (ML) increases the odds of transplantation compared with single-center listing. However, not all patients have equivalent access to ML. The recent allocation policy change prioritized distance from the donor hospital in an attempt to decrease geographic disparities. This study assessed access to liver transplant (LT) given ML practices before and after the acuity circles policy change. United Network for Organ Sharing data were queried for LTs between January 1, 2016, and November 1, 2024. Patients were grouped by listing at one versus multiple centers and by acuity circle era (ACE). Cohort characteristics and comparisons were described using chi-square and Wilcoxon rank tests. Multivariable logistic regressions and propensity score match (PSM) were performed to assess associations between ML and LT. The final cohort consisted of 105,030 patients; 4084 (3.9%) were multi-listed. Racial/ethnic minority groups, less educated, and publicly insured candidates were less often multi-listed. ML was positively associated with LT in all analyses (overall: OR=1.180, p <0.001; PSM: OR=1.164, p =0.001; pre-ACE: OR=1.127, p =0.015; post-ACE: OR=1.218, p <0.001). Education, race/ethnicity, and insurance type were also associated with LT across all analyses. ML patients were more often transplanted at their primary center with a significant increase in primary center LT post-ACE (53.4% vs. 63.4%, p <0.001). ML and LT had a positive correlation. There was a negative association between minority groups and ML as well as LT. Although acuity circles decreased geographic disparities, they did not change ML accessibility across candidates.

Abstract The International League Against Epilepsy (ILAE) is a global organization dedicated to improving the lives of people with epilepsy through education, research, and advocacy. Recognizing the need for broader engagement and multidisciplinary collaboration, the ILAE has established five sections: Young Epilepsy Section (YES), Nursing, Social Work and Social Services (SWSSS), Neurotechnology, and Pharmacy. These sections aim to strengthen professional networks, enhance education, and promote innovation in epilepsy care. YES fosters leadership and participation among early‐career professionals, whereas the Nursing Section addresses gaps in epilepsy‐specific training and competency development. SWSSS emphasizes psychosocial care, advocacy, and health equity, supporting Intersectoral Global Action Plan (IGAP) objectives through culturally sensitive interventions. The Neurotechnology section advances the integration and development of innovative tools for diagnosis and treatment, and the Pharmacy section focuses on optimizing medication management and access to antiseizure medications globally. Collectively, these sections contribute to the WHO IGAP by improving policy, care delivery, research, and public health responses. Looking ahead, ILAE seeks to expand multidisciplinary participation, encourage cross‐sectional collaboration, and maintain its role as a leading force in global epilepsy care. Through these initiatives, ILAE continues to build capacity, foster inclusivity, and drive progress toward equitable, comprehensive epilepsy services worldwide. Plain Language Summary The International League Against Epilepsy (ILAE) is the global organization responsible for all healthcare professionals involved in the care of those with epilepsy. Recognizing the increasing number of different disciplines now contributing to epilepsy care, and the need to develop professionals of the future, the ILAE has recognized “sections” of like‐minded individuals to encourage networking and communication. Together, these sections contribute to the WHO Intersectoral Global Action Plan (IGAP) by improving policy, care delivery, research, and public health responses. Moving forward, the ILAE seeks to expand multidisciplinary participation, encourage collaboration, and maintain its role as a leading force in global epilepsy care.