Citations

Abstract GNE myopathy (GNEM) is a neuromuscular disorder caused by biallelic mutations in the gene GNE , which encodes a bifunctional enzyme essential for the biosynthesis of sialic acid. Despite extensive characterization, no effective therapies or validated biomarkers exist, and the molecular mechanisms driving disease pathology remain poorly understood. This study identifies the proteoglycan serglycin as a preliminary candidate biomarker in GNEM and investigates the mechanisms underlying its dysregulation. Proteomic analysis of serum samples from GNEM patients revealed reduced circulating serglycin levels. In contrast, increased intracellular serglycin was observed in GNE knockout and GNEM patient iPSC-derived myoblasts, suggesting impaired secretion and/or degradation. To investigate the basis of this accumulation, intracellular trafficking and autophagic pathways were examined. Proteomic profiling from HEK GNE knockout cells revealed alterations in pathways involved in membrane trafficking, Golgi function, and glycoprotein processing, consistent with broader disruptions in the secretory system that may impair serglycin export and contribute to its intracellular retention. In GNEM iPSC-derived myoblasts, serglycin overlapped with LAMP1-positive lysosomal compartments and the ER-phagy receptor FAM134B, suggesting association with lysosomal and ER-phagy related pathways. Functional assays further indicated impaired autophagic flux in mutant cells. Together, these findings support a model in which combined defects in secretion and autophagic clearance contribute to intracellular serglycin accumulation and reduced circulating levels. This study identifies serglycin as a potential circulating biomarker for GNEM and highlights dysregulation of secretory and degradative pathways as converging features of disease pathology.

ABSTRACT Apheresis medicine is a continually evolving field with numerous studies published each year. To help apheresis practitioners stay up to date with the current literature, members of the American Society for Apheresis (ASFA) Attending Physician Subcommittee identified and summarized 10 seminal articles published in 2025, from the field of apheresis medicine. PubMed was used to identify articles published in four topics including donor apheresis, therapeutic apheresis, apheresis education, and apheresis collection for cellular therapy. These articles met at least one of the following criteria: novel findings, practice‐altering outcomes, international in scope, randomized‐controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA 9th Special Issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice‐Evidence‐Based Approach. Full length, peer‐reviewed manuscripts in English with data from human subjects were included while case reports, review articles, and meta‐analyses were excluded.

ABSTRACT Background Readmission is considered as a surgical quality indicator. More data regarding predictors of readmission and outcomes after surgery for colorectal liver metastasis are needed. Using a propensity score match to create a 1:2 match of cases:controls for 90‐day. Readmission, the matching variables used for balance included age, tumor size, estimated blood loss, and type of resection (minor or major). T‐tests were used for continuous measures, Fisher's exact test was used for categorical data, and the Kaplan–Meier method was used to estimate survival. p < 0.05 was considered significant. Methods Retrospectively examined 935 patients with CLM from 2000 to 2018. Using a propensity score match to create a 1:2 match of cases:controls for 90‐day. Readmission, the matching variables used for balance included age, tumor size, estimated blood loss, and type of resection (minor or major). T‐tests were used for continuous measures, Fisher's exact test was used for categorical data, and the Kaplan–Meier method was used to estimate survival. p < 0.05 was considered significant. Results 935 patients were included in the initial sample with 896 eligible for inclusion in the propensity matching. The average age of the population was 59% and 59% male. Overall readmission rate was 8.0%. Median time to readmission was 14 days. In the propensity score matched sample, readmitted patients had higher rates of organ space infection (28% vs 2% and p < 0.0001), bile leak (26% vs 1% and p < 0.0001), and liver failure (9% vs 2% and p = 0.042). There was no difference in LOS (7 days versus six days and p = 0.40), overall survival (median 39.7 vs 41.0 months and p = 0.79), or rate of adjuvant therapy (68% for both and p > 0.99). Conclusion Patients readmitted for intermediate and late complications after surgery for CLM can recover and receive adjuvant therapy with no adverse effect on overall survival. Organ space infection, bile leak, and liver failure are highly associated with readmission.

Purpose of review Circadian clocks are increasingly recognized as fundamental regulators of innate immune function, yet their relevance to allergy and clinical immunology has only recently been clarified. This review summarizes emerging evidence linking circadian regulation of innate immune cells to allergic inflammation and highlights the translational potential of circadian-informed therapeutic strategies. Recent findings Core clock components are rhythmically expressed in macrophages, mast cells, neutrophils and innate lymphoid cells, where they regulate inflammatory signalling, immunometabolism and activation thresholds. Disruption of these rhythms exaggerates cytokine production, inflammasome activation and mast cell mediator release, contributing to diurnal patterns of allergic disease such as nocturnal asthma. Human and experimental studies demonstrate that circadian misalignment driven by shift work, irregular sleep and mistimed feeding amplifies innate inflammation and worsens allergic outcomes. Summary Circadian regulation represents an underappreciated dimension of innate immunity in allergic disease. Aligning immunomodulatory therapies, vaccination, and lifestyle interventions with endogenous immune rhythms offers a rational approach to improving efficacy and reducing inflammatory burden. Future studies should prioritize time-stratified clinical trials and direct circadian phenotyping in allergic populations.

ABSTRACT The novel HLA‐A*26:268 allele is characterised by a single nucleotide substitution in exon 7.

Abstract Anterior and posterior cruciate ligament (ACL and PCL) reconstruction poses the risk of residual anterior or posterior tibial translation, respectively. As a result, patients may have residual knee instability and laxity, which can contribute to poor outcomes and graft failure. Ultimately, minimizing anterior and posterior tibial translation through proper ACL and PCL graft tensioning has the potential to improve clinical and functional outcomes in the setting of ACL and PCL reconstruction surgery. This technique aims to show a reproducible method for “setting” anterior and posterior tibial translation in the setting of ACL and PCL reconstructions.

Abstract Objective . Penile vibro-elastography (PVE) is complicated by reverberant shear wavefields from the cylindrical geometry of the corpus cavernosum (CC), which bias shear wave speed (SWS) estimates. This study evaluated local phase velocity imaging with wavefield-based filtering (LPVI-WBF) for CC stiffness assessment in post-prostatectomy erectile dysfunction (ED), compared against phase gradient (PG) and time-of-flight (TOF) methods. Approach . Six patients with post-prostatectomy ED underwent PVE at four longitudinal visits (902 acquisitions). SWS was estimated in flaccid and erect states at 100, 150, and 200 Hz using LPVI-WBF, PG, and TOF. Wavefield composition was quantified via the standing wave index. Simulations evaluated accuracy and frequency stability under clean and reverberant conditions. Main results . Reverberant components dominated penile acquisitions, with traveling wave energy absent in 59% of acquisitions and mean standing wave fraction of 57 ± 17%. LPVI-WBF was the only method producing physiologically consistent estimates, with erect SWS exceeding flaccid (3.59 ± 0.48 vs 3.25 ± 0.58 m s −1 , p < 0.0001). PG and TOF yielded reversed results ( E < F, p < 0.0001). The dispersion exponent was near-zero for LPVI-WBF ( α = 0.048, p = 0.21), consistent with weakly viscoelastic tissue, while PG ( α = 0.184) and TOF ( α = 0.321) showed significant frequency dependence from reverberant contamination. Simulations confirm PG accuracy in clean wavefields but collapse under reverberant ones. Significance . LPVI-WBF produced SWS estimates consistent with expected CC biomechanics across all patients and frequencies, a criterion PG and TOF failed to satisfy. Phantom validation and multi-directional wavefield simulation are needed to establish accuracy.

VEXAS syndrome is a clonal hemato-inflammatory disorder impacting older, predominantly male patients, characterized by systemic inflammation and progressive bone marrow failure. It is caused by somatic mutations in UBA1, an X-linked gene, essential for initiating cellular ubiquitination. Loss-of-function mutations, most commonly M41 missense variants, lead to decreased expression of the cytoplasmic isoform, UBA1b, resulting in accumulation of misfolded proteins and activation of the endoplasmic reticulum stress pathway. Patients classically present with systemic and often refractory inflammation, requiring chronic glucocorticoid treatment and targeted immunosuppressive therapies. A central hallmark of this syndrome is progressive bone marrow failure and associated cytopenia, with a diagnosis of myelodysplastic syndromes (MDS) being reported in approximately 30-50% of patients while only 1% of unselected MDS patients have UBA1 mutations. This review examines current literature on distinct MDS features reported in VEXAS syndrome. We first summarize the defects and alterations in the hematopoietic system from UBA1 mutations, including associated peripheral blood and bone marrow findings. Next, we describe the histological and molecular characteristics of patients with VEXAS syndrome, with and without MDS, and review potential treatment strategies, including responses to hypomethylating agents. Finally, we highlight that VEXAS-associated MDS is a challenging diagnosis but one with unique clinical, laboratory, and morphological features, including prognostic implications.

Abstract Studies have reported conflicting findings regarding the contribution of germline variants or somatic genomic drivers to racial disparities in multiple myeloma. To comprehensively investigate somatic drivers in relation to inherited genetics in multiple myeloma, we combined newly sequenced whole-genome sequencing data with publicly available datasets (total n = 1,286). Overall, we did not identify germline or somatic genomic differences that explain the different risk of developing multiple myeloma between patients with genetic similarity to African (AFR) or European (EUR) reference populations. A difference in the detectability and timing of APOBEC-associated and germinal center mutational activity was observed. Integrating epidemiologic data and mutational signature-based temporal estimates, we challenge the assumption that individuals in the AFR group develop multiple myeloma at a younger age. Finally, we demonstrate that, with equal access to efficacious therapies, patients in the AFR and EUR groups have equivalent clinical outcomes. Significance: Multiple myeloma is reported to occur at higher rates in individuals who self-identify as non-Hispanic Black. In this large dataset, genomic drivers occur at the same rate among ancestry groups, except for APOBEC mutagenesis. With equivalent therapy, clinical outcomes did not differ for patients grouped by genetic ancestry similarity.