Citations

ABSTRACT Aims Common genetic variants have been linked to an increased risk of non-ischaemic cardiomyopathy (NICM). The primary objective of this study was to evaluate the significance of these variants in a general population. Methods and results Thirteen NICM risk alleles, previously validated by meta-analyses of case-control genetic association studies, were used to determine genetic risk (GR) in a large, unselected cohort (n = 1897) of Olmsted County residents aged >45 years. Clinical and echocardiographic data, with biomarkers, were correlated with this NICM-GR over a median of 16 years of follow-up (interquartile range [IQR] 15–17). There were no significant differences between the study population quartiles, based on NICM-GR, in terms of age (median 61.6 [IQR 53.6–70.4]), sex (48% male), and cardiovascular risk factors. A significant correlation was detected by specific linear-regression models between NICM-GR and left ventricular (LV) ejection-fraction (beta [standard error]: −2.68 [0.68], p < 0.001), LV end-systolic-diameter (0.22 [0.06], p < 0.001), and LV end-diastolic-diameter (0.14 [0.06], p = 0.01). During follow-up, 46 subjects developed NICM. Using a 3:1 matched-cohort of non-NICM versus NICM patients, linear-regression analysis found a significant correlation between NICM-GR and NICM development (odds ratio 2.27, 95% confidence interval 1.06–4.85, p = 0.03). There was no significant association between these variants and heart failure biomarkers (aldosterone, natriuretic peptides, ST2, galectin-3). Conclusions The NICM-GR correlates with LV function and dimension, and subsequent development of NICM in the general population. The lack of correlation of these variants with cardiovascular risk factors and the renin–angiotensin–aldosterone axis or natriuretic peptides suggest different biological mechanisms involved. These findings support the need to explore newer pathophysiologic pathways in the development of NICM.

Abstract Objective To compare iron deposition in the substantia nigra (SN) as measured with quantitative susceptibility mapping (QSM) on antemortem magnetic resonance imaging (MRI) between individuals with and without Lewy‐related pathology at autopsy. Methods We performed a retrospective cohort study including 54 participants who underwent autopsy and antemortem MRI with QSM. Cases were classified as Lewy body disease (LBD)‐present (n = 13) if they had Lewy‐related pathology and LBD‐absent (n = 41) if they did not have Lewy‐related pathology. QSM was calculated for the whole SN and the two subregions: pars compacta (SNc) and pars reticulata (SNr). Nonparametric Wilcoxon rank‐sum tests were used to compare SN QSM values between LBD‐present and LBD‐absent cases. Area under the receiver operating characteristic (ROC) curve (AUC) analyses tested the accuracy of SN QSM values to distinguish the two groups. Associations of QSM values in the SN and its subregions with clinical features were tested with Spearman's correlations. Results The LBD‐present group had higher QSM values in the SNc ( P = 0.008) than the LBD‐absent group with no differences in SNr. QSM values of the SNc distinguished LBD‐present and LBD‐absent cases with good accuracy (AUC = 0.74) and correlated with the presence of parkinsonism and parkinsonism severity. Conclusions This study provides neuropathological confirmation of the utility of SNc QSM as an in vivo biomarker of Lewy‐related pathology. Imaging evidence of abnormal iron deposition in the SNc could potentially serve as a biomarker for inclusion in emerging research frameworks aimed at defining individuals with LBD based on their biological characteristics. Ultimately, this could facilitate more precise diagnoses and guide treatment strategies in LBD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background The optimal timing and type of venous thromboembolism chemoprophylaxis (VTEp) for adults with acute traumatic brain injury (TBI) remains unknown. This systematic review synthesized evidence on the timing and type of VTEp in adults with TBI and highlights evidence gaps. Methods We searched Ovid MEDLINE, Embase, and the Cochrane Library through November 4, 2024 for English language, randomized or non-randomized studies with a comparator that reported VTEp timing or agent in adults with acute TBI, and reported intracranial hemorrhage progression (ICHP), VTE, pulmonary embolism (PE), deep vein thrombosis (DVT), neurosurgical intervention (NSI), adverse events (AEs), length of stay (LOS), function, or mortality. Risk of bias (ROB) was assessed with ROBINS-I as low, moderate, serious, or critical risk in studies that used advanced analytic methods (AAMs) to control selection bias; all other studies were deemed critical risk. We qualitatively synthesized evidence and focused text reporting on studies with AAM. Results From 738 citations, 21 non-randomized studies met criteria (1 moderate, 20 critical ROB): 16 on VTEp timing, 7 on agents. Seven studies used AAM. For VTEp timing (five AAM studies), one study of adults with mostly mild TBI found no significant difference between Early and Late VTEp on ICHP (moderate ROB); no timing studies with AAM reported ICHP for adults with moderate or severe TBI. Findings were mixed for VTE timing on NSI and PE. Early VTEp was associated with fewer DVTs. There was no difference in mortality or serious AEs by VTEp timing. For VTEp agents, three studies with AAM found no significant difference between low molecular weight heparin (LMWH) and unfractionated heparin (UH) on ICHP, PE, DVT, and serious or overall AEs. Results were mixed for LMWH versus UH effects on NSI after VTEp, VTE, LOS and mortality. TBI severity labeling varied across studies and within measures, reducing comparability. Conclusions Clinical evidence on the timing and type of VTEp for adults with acute TBI is of insufficient quality for clinical decision-making. Prospective research designs, standardization of TBI severity labeling, and improved reporting of interventions and outcomes would advance the field. PROSPERO registration number CRD42023421534 Level of evidence Systematic Review, Level IV

OBJECTIVE Spinal stereotactic radiosurgery (SSRS) is an established treatment modality for spinal metastatic disease. A common complication of SSRS is postradiation pathologic fracture. The authors evaluated the risk of pathologic fracture in sacral SSRS. METHODS All patients receiving SSRS in 1 to 5 fractions to 1 or more sacral levels between 2011 and 2020 at participating institutions were included. Demographic, histological, anatomical, and outcome data were obtained from electronic medical records. Data were analyzed using SPSS version 28. RESULTS Of 67 total patients, 50 (74.6%) were men and 17 (25.4%) were women. The most common tumor histologies were prostate adenocarcinoma (n = 16 [23.9%]) and renal cell carcinoma (n = 12 [17.9%]). Median (range) age at treatment was 63 (8–87) years. The mean ± SD (range) number of levels treated was 1.5 ± 0.7 (1–4) levels. Mean ± SD (range) bone density at S1 was 208.0 ± 74.4 (−3.0 to 443.3) Hounsfield units (HUs). Median (range) follow-up was 16.6 (1.5–132) months, median ± SD (range) overall survival was 24 ± 21.0 (1.7–83.3) months, and the 1-year local control rate was 83.6%. Fourteen patients (20.9%) experienced fracture within the radiation field. There was no association between fracture and patient sex (p = 0.32), age (p = 0.40), S1 HU (p = 0.28), tumor location according to Denis classification (p = 0.87), presence of pain (p = 0.66), single versus multifraction radiation (p = 0.44), or number of levels treated (p = 0.52). Patients experiencing in-field progression were more likely to experience fracture (61.5% vs 10.2%, p < 0.001), and patients experiencing fracture had a higher average Spine Instability Neoplastic Score than patients without fracture (5.7 vs 4.3, p = 0.049). Only local control remained as a factor associated with sacral fracture in the multivariate analysis. Of the patients experiencing fracture, 10 (71.4%) were symptomatic and 3 of those (30.0%) underwent post-SSRS surgical intervention. CONCLUSIONS Pathologic fracture may occur after sacral SSRS in a significant number of patients and is significantly associated with failure of local control.

Study Design: Single-center retrospective cohort study. Objective: To determine if the 4-rod construct (4RC) is protective against the occurrence of rod fractures when compared with the 3-rod construct (3RC) in adult spinal deformity (ASD) patients with long fusions to the sacrum. Summary of Background Data: Past studies have explored the different outcomes in subjects with dual-rod versus multirod constructs. There is a lack of literature distinguishing the ramifications of 3RC versus 4RC, particularly in the prevalence of rod fractures and rod fractures requiring subsequent revision surgery as a result of pseudarthrosis. Methods: ASD patients undergoing long instrumented fusions to the sacrum were dichotomized between the 3RC and 4RC cohorts. Outcomes of interest include the occurrence of rod fractures (RFs) and RFs requiring revision (RFR). Two-tailed independent-sample t test with Welch's correction and χ 2 /Fisher exact test were used for continuous and categorical variables, respectively. Multivariable logistic regression analysis was performed to assess whether the 4RC is protective against rod fractures when compared with the 3RC. Results: One hundred forty-five patients with a minimum 2-year follow-up were included (3RC=57, 4RC=88). Four RC had a greater body mass index (BMI) ( P =0.002), longer operating room (OR) time ( P =0.002), greater estimated blood loss (EBL) ( P =0.002), total instrumented levels (TIL) ( P =0.028), and more 3-column osteotomies (3COs) performed ( P =0.028). Four RC had greater baseline coronal vertical axis (CVA) (28.2±24.9 vs. 18.5±16.9 mm, P =0.006) and sagittal vertical axis (SVA) (55.1±64.8 vs. 30.4±41.8 mm, P =0.006). Three RC had a greater rate of RF (28.1% vs. 14.8%, P =0.0506) and RFR (14.9% vs. 10.2%, P =0.486) when compared with 4RC, but these findings were not statistically significant. After controlling for BMI, the use of 3-column osteotomies, total instrumented levels, change in coronal alignment (∆CVA), change in sagittal alignment (∆SVA), use of bone morphogenetic protein, and number of interbody fusions, 3RC was associated with 4.93× greater odds of experiencing RFs ( P =0.0078). However, significance fell short when adjusting for the occurrence of RFR [OR=2.58 (0.60–11.19), P =0.2067]. Conclusion: ASD patients having long fusions to the sacrum with 4RC across the lumbosacral junction are shown to be at lesser risk of developing rod fractures but not revision surgery as compared with 3RC at 2-year follow-up.

Objectives: This practice parameter was revised collaboratively by the American College of Radiology (ACR), and American Radium Society (ARS). Image-guided radiation therapy (IGRT) uses various imaging modalities to maximize the accuracy and precision of radiation treatment delivery. Methods: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters–Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Results: This practice parameter for IGRT addresses qualifications and responsibilities of personnel, clinical IGRT implementation, documentation, quality control and improvement, safety, and patient education. Since the publication of the ACR–ASTRO Practice Parameter in 2019, there is now more clarity as to what criteria and parameters need to be documented in the medical record, a better appreciation of the large amount of imaging data, how to interpret such data, as well as the complex interactions of multiple systems in the implementation of IGRT. Conclusions: This practice parameter assists practitioners in the clinical use of IGRT. IGRT should complement and be used in combination with other quality assurance processes. IGRT is a rapidly evolving field, and practitioners should have a thorough understanding of its strengths and potential limitations.

Purpose To establish international expert consensus on surgical techniques, complications, and rehabilitation protocols for lateral extra‐articular procedures (LEAPs) performed adjunctively with anterior cruciate ligament reconstruction. Methods Fifty‐five knee surgeons from 17 countries on 5 continents completed a 3‐round modified Delphi process. In the final round, 16 statements on LEAP techniques and complications were scored on a 5‐point Likert scale; ≥75% “agree/strongly agree” constituted consensus. When appropriate, strength of recommendation was graded. Statements lacking support were revised until consensus or abandonment. Results Six statements achieved unanimous consensus (100%), 2 had strong consensus (90%‐99.9%), and 3 reached consensus (75%‐89.9%); 4 were removed. Key technical recommendations were as follows: (1) in iliotibial band procedures, the graft strip should pass beneath the lateral collateral ligament; (2) an anatomic technique is mandatory for anterolateral ligament reconstruction; and (3) no single LEAP is clinically superior to another. Unanimous agreement indicated that modern LEAPs do not increase lateral compartment osteoarthritis risk, carry a low complication rate, and do not necessitate changes to rehabilitation or return‐to‐play timelines. Conclusions Consensus defined core surgical principles and confirmed the safety of adding LEAPs to anterior cruciate ligament reconstruction. When an iliotibial band graft is used, it should be routed deep to the lateral collateral ligament and fixed between 0° and 60° of knee flexion under low tension. For anterolateral ligament reconstruction, femoral fixation should be in full extension at a posterior‐proximal point relative to the lateral epicondyle. Although no single LEAP proved superiority, adherence to these principles permits safe, effective surgery without altering standard rehabilitation or return‐to‐sport protocols and without increasing osteoarthritis risk. Level of Evidence Level V, expert opinion.

Purpose To define expert consensus on whether and how lateral extra‐articular procedures (LEAPs) should accompany anterior cruciate ligament (ACL) reconstruction to optimize outcomes in ACL‐deficient knees. Methods Fifty‐five knee surgeons from 17 countries on 5 continents completed a 3‐round modified Delphi process. Twenty‐one statements on patient selection for combined ACL reconstruction (ACLR) + LEAPs were graded on 5‐point Likert scales; ≥75% “agree/strongly agree” signified consensus. Strength of recommendation was ranked, and statements failing the threshold were revised or discarded after discussion. Results One statement achieved unanimous agreement (100%): it is strongly recommended to add a LEAP for active patients ≤25 years receiving hamstring‐autograft ACLR to reduce graft failure. Strong consensus (≥90%) supported LEAPs in primary ACLR when grade 3 pivot shift (97.9%), knee hyperextension (97.9%), skeletally immature status (79.5%), revision ACLR (91.5%), return to pivoting sports (93.2%), active patients ≤25 years using nonhamstring grafts (90.7%), grade 3 Lachman test (90%), and when multiple relative risk factors coexist (statement 36, 97.1%). Consensus (75%‐89.9%) favored LEAPs for chronic symptomatic ACL deficiency (86.1%), posterior tibial slope >12° (85.7%), and a history of contralateral ACL injury (88.9%). Eight statements did not reach consensus regarding small‐diameter autografts, female athletes, imaging signs of anterolateral injury (e.g., Segond fracture, lateral femoral‐notch sign), and concomitant meniscal procedures. One statement on LEAPs with primary ACL repair was withdrawn because the project focused on reconstruction. Conclusions International experts strongly recommend adding a LEAP in young active patients undergoing hamstring‐autograft ACLR and in cases of high‐grade rotational or anterior laxity, knee hyperextension, revision surgery, or returning to pivoting sports. Unresolved issues include small graft size, female athletes, imaging findings of rotational instability, and concurrent meniscal procedures, highlighting priorities for future research. Level of Evidence Level V, expert opinion.

Abstract Organoids, which are tiny, lab-grown 3D structures that mimic some organizational and functional properties of human organs, are slowly transforming the face of systems and developmental biology, biomedical research, pharmaceutical testing, environmental toxin testing, and healthcare. Significant investments are essential for the mass production, preservation, and distribution of organoids, with the aim to accelerate innovation and progress across multiple fields—much like the investments made in cell and biologics manufacturing over the past 2 decades.