Publications

UNLABELLED: We aimed to assess trabecular bone score (TBS) alongside lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in patients with transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) compared with healthy controls. A cross-sectional study was conducted involving adult thalassemia patients and healthy controls matched at a 2:1 ratio by age and sex. LS and FN BMD and TBS were measured using dual-energy X-ray absorptiometry. Univariate and multivariate analyses were performed to identify factors influencing TBS. The study protocol was approved by the institutional ethics committee. Eighty-six thalassemia patients (mean ± SD age 32.2 ± 11.9 years; 60.5% women) and 172 healthy controls (mean ± SD age 33.7 ± 10.9 years; 60.5% women) were included. Thalassemia patients had significantly lower BMI, LS Z-score, FN Z-score and TBS than controls (all p < 0.001). Only 24.4% of thalassemia patients had normal TBS (≥ 1.350) compared to 77.9% of controls, with a tenfold higher prevalence of degraded microarchitecture (TBS < 1.200). Although TDT patients exhibited more severe disease features than NTDT patients, TBS was similarly reduced in both groups. In multivariate analysis adjusted for age, sex, BMI, and LS BMD, TDT status remained independently associated with lower TBS (β = − 0.047; 95% CI: − 0.083 to − 0.012). No significant correlations were found between TBS and hemoglobin, serum ferritin, lactate dehydrogenase or glucose levels. This study provides new evidence that TBS was significantly impaired in Southeast Asian patients with thalassemia, independent of BMD, with a disproportionate reduction observed particularly in TDT patients.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00223-026-01483-0.

BACKGROUND: Post-traumatic breast implant and tissue expander (TE) complications are increasingly relevant as more patients undergo reconstructive or cosmetic breast surgery. Prior studies are limited to case reports, with little known about the mechanisms of injury or timing of clinical recognition.

METHODS: Using the Nationwide Readmission Database (2017-2020), we identified adults with trauma admissions followed by breast implant-related diagnoses or procedures. Mechanisms of injury (MOI) and clinical presentations were characterized using ICD-10 codes. Patients were classified as having received "immediate" management (diagnosis or procedure during index admission) or "delayed" (on readmission). Cox regression identified predictors of earlier diagnosis or intervention.

RESULTS: A total of 573 patients with post-traumatic implant complications were included (488 breast implants, 85 TEs). Falls were the most common MOI (53.2%), followed by transport accidents (25.0%). TEs were disproportionately associated with burn injuries (20.5% vs. 4.9% in non-TEs). At presentation, 78.2% of patients were diagnosed with implant rupture or underwent surgical correction. Rib or clavicle fractures (21.1%) and breast symptoms (12.6%) were associated with earlier diagnosis, but not with likelihood of surgery. Plastic surgery consultation significantly decreased time to surgery. Age, sex, and ZIP code did not have notable effects on diagnostic and surgical timing.

CONCLUSIONS: Post-traumatic breast implant complications often present without breast-specific symptoms, resulting in diagnostic delays. Trauma protocols should include routine breast imaging in patients with implants, especially after transport, burn, or blunt-force injuries. TE patients may be uniquely susceptible to thermal injury and warrant focused preventive counseling.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

IMPORTANCE: Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are attributable to a pathogenic variant in the superoxide dismutase 1 (SOD1) gene. Tofersen, an intrathecal antisense oligonucleotide designed to reduce SOD1 protein synthesis, is the first and only approved therapy for the treatment of ALS in adults who have a variant in the SOD1 gene.

OBJECTIVE: To evaluate the long-term effects of tofersen in adults with SOD1-ALS.

DESIGN, SETTING, AND PARTICIPANTS: The phase 3, randomized, double-blind, placebo-controlled VALOR trial (A Study to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tofersen in SOD1-ALS; conducted from March 2019 to July 2021) evaluated tofersen use over 28 weeks in adults (18 years and older) with weaknesses attributable to ALS and a confirmed SOD1 pathogenic variant at 32 sites in 10 countries; participants could then enroll in an open-label extension (OLE; completed August 2024).

INTERVENTION AND EXPOSURE: Adults with SOD1-ALS were randomly assigned 2:1 to receive tofersen (100 mg) or placebo over a 24-week period in the VALOR study. All participants in the OLE were treated with tofersen.

MAIN OUTCOMES AND MEASURES: Integrated analysis of VALOR and the OLE study aimed to compare early start vs placebo/delayed start (approximately 6 months later) treatment with tofersen. Key efficacy end points included measures of axonal injury and neurodegeneration (neurofilament), function and strength, quality of life, and survival.

RESULTS: VALOR enrolled 108 participants with 42 unique SOD1 pathogenic variants (mean [SD] age: placebo/delayed-start group 51.2 [11.6] [n = 36]; early-start group: 48.1 [12.6] [n = 72]) with 19 (53%) and 43 (60%) of participants being male in the placebo/delayed- and early-start groups, respectively. Overall, 95/108 participants (88%) enrolled in the OLE, and 46 participants completed the OLE (early-start group, 34 [47%]; placebo/delayed-start group, 12 [33%]). At OLE completion, participants could have accumulated 3.5 years or more (range, 192-276 weeks) of follow-up from the start of VALOR. Over 148 weeks, earlier initiation of tofersen (compared to later initiation) was associated with numerically less decline in measures of clinical function (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, -9.9 vs -13.5 points), respiratory function (slow vital capacity, -13.8% vs -18.1%), muscle strength (handheld dynamometry megascore, -0.38 vs -0.43 points), and quality of life (Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 score, 17.0 vs 22.5 points; EuroQol 5 Dimension, 5 Level Questionnaire score, -0.1 vs -0.2 points). Tofersen prolonged survival relative to the expected natural history of SOD1-ALS. Most adverse events were consistent with ALS progression or known procedural adverse effects. All serious neurological adverse events were reversible; few led to tofersen discontinuation.

CONCLUSIONS AND RELEVANCE: Final data from VALOR and the OLE demonstrated the benefit of tofersen in SOD1-ALS and provide clear rationale for its use in this population.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: VALOR NCT02623699; OLE NCT03070119.

PURPOSE: Uncorrected refractive error (URE) is the leading cause of vision impairment, especially in rural, underserved areas. We previously evaluated the accuracy of a smartphone app for measuring spherical equivalent refraction. In this study, we evaluated the benefits of vision correction based on the prescription given by the app.

METHODS: The app estimates myopic refractive error by measuring the far point distances for reading 20/20 Tumbling E letters. Trial lenses rounded to 0.25 diopter (D) were fitted to 100 patients (myopic refractive error, astigmatism < 1.5 D) visiting MCM Eye Unit in Addis Ababa, Ethiopia. The age range of the participants was 10 to 68 years (mean = 31.3 ± 13.0 years). The refraction measurement and visual acuity (VA) tests were all performed without cycloplegia.

RESULTS: The range of spherical equivalent refractive error was -0.5 D to -6 D (interquartile range [IQR] = -2.25 D to -0.95 D), and the range of astigmatism was 0 to -1.25 D (IQR = -0.5 D to 0 D), according to subjective refraction performed by a study optometrist. On average, the uncorrected VA of the 200 eyes was 0.57 ± 0.32 logMAR. With the spherical equivalent correction based on the refraction app, their VA was improved significantly to 0.03 ± 0.09 logMAR-more than 5 lines of improvement, on average.

CONCLUSIONS: This study indicates that using the app to determine the spherical equivalent prescription for vision correction addresses the URE problem, whereas its effect for prominent astigmatism is yet to be evaluated.

TRANSLATIONAL RELEVANCE: This approach, which requires minimal training, has potential in fighting avoidable blindness in underserved areas lacking optometry services, such as remote Sub-Saharan Africa.

BACKGROUND: Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals and is increasingly diagnosed in childhood. Growing evidence suggests an association between CD and metabolic syndrome (MetS), potentially mediated by chronic inflammation, intestinal dysbiosis, oxidative stress, and micronutrient deficiencies. In addition, although a gluten-free diet (GFD) is essential for intestinal recovery, its frequent reliance on ultra-processed, energy-dense products may adversely affect metabolic health, particularly in pediatric patients.

OBJECTIVE: This narrative review aims to examine the relationship between CD and MetS, with a specific focus on pediatric populations, by analyzing shared pathophysiological mechanisms, the metabolic impact of a GFD, and preventive nutritional strategies to reduce long-term cardiometabolic risk.

METHODS: A narrative review was performed using PubMed and Scopus databases, focusing on studies published in the past 15 years. Search terms included "Celiac Disease," "Metabolic Syndrome," "Child," "Adolescent," "Risk Factors," and "Prevention." Among 229 identified papers, 43 were selected after critical appraisal. Evidence was synthesized on epidemiology, mechanisms, dietary effects, and preventive strategies.

RESULTS: Studies indicate that MetS prevalence in CD ranges from 3 to 11% at diagnosis and may rise to 14-29% after 1 year on a GFD, particularly in adults. In children, complete MetS is rare, though isolated components, central adiposity, dyslipidemia, and hypertension, are increasingly observed. Mechanistically, gluten-induced barrier disruption, inflammation, dysbiosis, and nutritional imbalances contribute to systemic metabolic alterations. Adherence to a Mediterranean-style GFD emphasizing whole, naturally gluten-free foods reduces cardiometabolic risk.

CONCLUSION: CD and MetS share interconnected inflammatory and metabolic pathways. While GFD remains essential for CD management, it necessitates tailored nutritional guidance and metabolic monitoring. Early lifestyle-based interventions-promoting balanced diet quality, micronutrient adequacy, and physical activity, offer key opportunities to prevent metabolic complications in children with CD.

OBJECTIVE: To propose a mechanistic framework for the use of transcranial photobiomodulation (tPBM) as an adjunctive treatment in Rett syndrome (RTT).

BACKGROUND DATA: RTT is a severe X-linked neurodevelopmental disorder caused mainly by MECP2 variants, with limited disease-modifying therapies. tPBM delivers red-to-near-infrared light to the brain and shows promising effects in several neurocognitive and neuropsychiatric conditions.

METHODS: We reviewed key cellular mechanisms of RTT, namely mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired synaptic plasticity, and summarized established bioenergetic, redox, anti-inflammatory, and neurotrophic actions of tPBM.

RESULTS: The convergence between these pathways suggests that tPBM could partially compensate for bioenergetic and signaling abnormalities in RTT, acting as a multi-target, pathophysiology-informed neuromodulation strategy.

CONCLUSIONS: Although speculative, this mechanistic convergence supports prioritizing preclinical studies in Mecp2-deficient models and early-phase feasibility trials of tPBM in individuals with RTT.

IMPORTANCE: Predischarge car seat tolerance screening (CSTS) has been recommended by the American Academy of Pediatrics since 1991 for preterm and at-risk full-term-born infants. However, it remains unclear whether routine CSTS prevents adverse outcomes after discharge.

OBJECTIVE: To estimate the frequency of failed CSTS and its association with adverse postdischarge outcomes.

DATA SOURCES: PubMed, Embase, and Web of Science were searched for English-language studies published before June 2025.

STUDY SELECTION: Randomized trials, nonrandomized intervention studies (utilizing a comparison group discharged without CSTS), and single-group observational studies were eligible.

DATA EXTRACTION AND SYNTHESIS: Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline by 2 reviewers. Study quality was assessed using the Risk of Bias in Nonrandomized Studies tool.

MAIN OUTCOMES AND MEASURES: Outcomes were 30-day readmission, mortality, and predischarge length of stay for intervention studies, and first and subsequent CSTS failure rates for single-group studies. Random-effects models were used to pool data, and generalized linear mixed models were used to estimate pooled treatment effects from 2-group studies and CSTS failure event rates from all included studies.

RESULTS: A total of 21 studies were included. No randomized trials were identified. Three nonrandomized intervention studies (54 358 participants; 27 786 participants without CSTS) reported postdischarge outcomes. There was no difference in 30-day mortality (2 studies; not pooled due to 0 events), 30-day readmissions (odds ratio, 1.05; 95% CI, 0.86-1.28; 3 studies; 54 559 participants), or combined 30-day mortality or readmission (odds ratio, 1.17; 95% CI, 0.95-1.43; 2 studies; 49 420 participants) among infants receiving predischarge CSTS compared with those that did not. Pooled analysis estimated 8.62 (95% CI, 6.42-11.47) first-test failures per 100 patients (21 studies; 39 052 participants) and 24.40 (95% CI, 6.44-34.64) repeat-test failures per 100 patients (11 studies; 912 participants).

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of predischarge CSTS for preterm and at-risk full-term-born infants, CSTS was not associated with a reduction in postdischarge readmission or mortality. These findings call into question whether routine CSTS before discharge improves outcomes in preterm or at-risk full-term infants.

OBJECTIVE: To investigate the effects of a collegiate ice hockey season and the repetitive head impacts (RHI) experienced on the neurologic health using a multifaceted assessment battery.

DESIGN: Cross-sectional.

SETTING: Research laboratory.

PARTICIPANTS: Thirty-six male collegiate club ice hockey players.

INDEPENDENT VARIABLES: Time (preseason, midseason, postseason) and head impact measures (number of impacts, mean linear acceleration).

MAIN OUTCOME MEASURES: Athletes wore Smart Impact Monitor (SIM-G) accelerometers throughout 1 season and completed testing at preseason, midseason, and postseason. The battery included a 22-item graded symptom checklist, Standardized Assessment of Concussion, Balance Error Scoring System, Trails A & B, King-Devick, Near Point Convergence, Clinical Reaction Time, Tandem Gait (single- and dual-task), and computerized neurocognitive testing (ImPACT).

RESULTS: There was a significant main effect of time, with improved performance, on the Standardized Assessment of Concussion (F(2, 70) = 4.43, P = 0.015), Trails A (F(2, 67) = 7.16, P = 0.002), Trails B (F(2,71) = 5.19, P = 0.008), King-Devick (F(2, 72) = 4.31, P = 0.017), Clinical Reaction Time (F(2, 69) = 4.54, P = 0.014), ImPACT Verbal Memory (F(2, 76) = 3.82, P = 0.026), and Tandem Gait (ST: F(2, 76) = 6.11, P = 0.003; DT: F(2, 78) = 4.65, P = 0.012). Multiple regression analyses identified an association between the overall head impact model and Visual Motor score (R2 = 0.354, F(2, 29) = 3.698, P = 0.016), whereby increased head kinematics corresponded to higher (better) Visual Motor performance.

CONCLUSIONS: A season of collegiate ice hockey RHI did not negatively affect multifaceted clinical assessments. Additional investigation is warranted to determine the effect of RHI sustained during collegiate hockey participation later in life.