Citations

ABSTRACT Background Monoclonal gammopathy of thrombotic significance (MGTS) is a recently described chronic prothrombotic condition characterized by monoclonal anti-PF4 antibodies that are detected above the polyclonal antibody background in patient sera (i.e. present as monoclonal gammopathy of undetermined significance, MGUS). Due to conflicting data in the published literature on antibody clonality in heparin-induced thrombocytopenia (HIT), we evaluated clonality and abundance of anti-PF4 antibodies in HIT, including investigating whether an MGUS, if present in HIT, represents the causative anti-PF4 antibody. Methods Blood samples from 15 patients with HIT were subject to Platelet Factor 4-dependent antigen-based and functional tests. The unmanipulated serum antibody repertoire and isolated anti-PF4 antibodies were subjected to mass spectrometric evaluation. Results Two of the 15 HIT patients had an IgG MGUS. Notably, anti-PF4 antibodies were not synonymous with the MGUS antibody in either of the two patients. Eight of the 15 patients demonstrated monoclonal anti-PF4 antibodies, however, none of the anti-PF4 antibodies were detectable as an MGUS upon evaluation of the entire serum antibody repertoire, reflecting their low abundance. In the seven patients with multiple anti-PF4 antibodies, non-monoclonality was confirmed by analysis of deglycosylated antibody heavy chains. Conclusions Anti-PF4 HIT antibodies are monoclonal in approximately 50% of HIT patients, however, antibody abundance is low such that they are not detectable over the polyclonal IgG background (i.e. are MGUS-negative), differentiating HIT from MGTS. This observation helps explain the transient nature of HIT relative to the persistent prothrombotic state seen in MGTS.

Introduction The introduction of the purpose‐built single‐port (SP) robotic platform has allowed for the advent of regionalized minimally invasive surgical approaches for robotic radical prostatectomy (RARP), including the extraperitoneal and transvesical techniques. This study sought to develop a best practice consensus on the key principles, patient selection, surgical techniques, expected clinical outcomes, and learning curves pertaining to SP‐RARP. Methods A modified Delphi consensus was developed by a panel of experts, consisting of a 33‐item questionnaire, with each statement rated using a binary Likert scale (‘agree’ or ‘disagree’). The survey was distributed via email to all practicing SP‐RARP surgeons across the USA and Europe. Consensus was defined as ≥75% agreement on a given statement. Results A total of 53 surgeons participated in the Delphi Consensus across the two rounds. Of 33 statements, 28 (84.8%) reached agreement in the first round. The remaining consensus was achieved in the second round, involving 35 surgeons, and with one additional statement. The panel agreed that, although are no absolute contraindications to SP‐RARP, the preference towards specific SP‐RARP techniques should remain guided by the individual patients and surgical expertise. Although the SP extraperitoneal technique is recommended to pursue pelvic lymph node dissections, the panel agreed that transvesical SP‐RARP showed promise in promoting shorter hospital stay, faster recovery of urinary continence, and utility in patients with extensive prior abdominal surgery. Consensus was also reached on the need for a structured training pathway, with most recommending beginning with extraperitoneal SP‐RARP before advancing to the transvesical approach. Conclusion This Delphi consensus demonstrates broad agreement among experienced SP surgeons in the USA and Europe, forming the foundation for future research on the clinical utility and necessary training pathways for SP‐RARP. Nevertheless, empirical validation based on clinical data from large cohort studies remains important.

ABSTRACT Background The adoption of angle‐based minimally invasive glaucoma surgery (MIGS) procedures has accelerated in recent years; however, inherent limitations remain. Imaging‐based techniques across the pre‐, intra‐ and post‐operative stages of surgery may facilitate patient selection and improve surgical outcomes. This systematic review explores the application of imaging‐based techniques to visualise aqueous humour outflow (AHO) in angle‐based MIGS. Methods A literature search was performed on PubMed, EMBASE and Cochrane Library from inception to 16 February 2025. Cohort, cross‐sectional and observational studies reporting the use of imaging‐based techniques to visualise AHO in angle‐based MIGS were included in this review. Results An initial 393 studies were identified, with 21 studies included in final analysis. Imaging techniques reported in literature included various methods to directly observe episcleral veins, haemoglobin venous imaging (HVI), fluorescein and indocyanine green (ICG) aqueous angiography, channelogram and anterior segment optical coherence tomography angiography (AS‐OCTA). Visualisation of AHO pre‐ and intra‐operatively may predict surgical outcomes, aiding in patient selection and surgical prognostication. Intra‐operative imaging may facilitate targeted placement of MIGS in areas of initially angiographically low or high areas of AHO. AHO assessment pre‐, intra‐ and post‐operatively may allow comparative analysis of surgical success and efficacy across various angle‐based MIGS. Conclusions Imaging‐based techniques visualising AHO have significant potential to improve surgical outcomes of angle‐based MIGS.

Drug-induced QT prolongation (diQTP) can lead to rare, but potentially fatal adverse effects of many medications, yet individual susceptibility varies due to both clinical and genetic factors. SDHAF3 p.F53L (rs62624461) is a genetic variant that plays a role in mitochondrial function and was previously associated with diQTP in one small prior study. Therefore, the objective of this retrospective pharmacogenetic study was to evaluate whether SDHAF3 p.F53L is associated with clinically significant diQTP. Data were obtained from the Michigan Genomics Initiative, which links genotype information with electronic health records at Michigan Medicine. Adult patients with available genotype and electrocardiogram data who received at least one high-risk QT-prolonging drug between 2001 and 2022 were included. The analysis was limited to 5848 patients of European ancestry, of whom 320 (5.5%) were carriers of the SDHAF3 p.F53L variant. QT prolongation was defined as a QTc greater than or equal to 500 ms or an increase greater than 60 ms from baseline during high-risk QT-prolonging drug prescription. Logistic regression under a dominant genetic model assessed associations between variant carrier status and diQTP, with and without propensity score adjustment. Baseline demographics and comorbidities were similar between carriers and noncarriers. No significant association was observed between SDHAF3 p.F53L and diQTP [unadjusted odds ratio (OR) = 1.06, 95% confidence interval (CI) = 0.76–1.48, P = 0.742; adjusted OR = 1.05, 95% CI = 0.74–1.51, P = 0.773]. These results suggest that SDHAF3 p.F53L does not meaningfully influence diQTP risk in a large, real-world clinical cohort. Future studies should examine this variant across diverse populations.

Abstract Background Glioblastoma (GBM) remains a devastating cancer with limited treatment options, largely due to its heterogeneity. While supramaximal resection has recently provided survival benefits, therapeutic profiling of different tumor compartments, particularly its infiltrative edge remains largely unexplored. Methods Here, we leveraged magnetic resonance imaging (MRI)-guided multi-sampling, collecting 2 cores and 2 margins per case, to query GBM heterogeneity. Whole-exome and RNA-seq with drug testing in two patient-derived 3D models were used to reveal similarities and differences in genomic and transcriptomic makeups, cellular compositions, and drug responses across cores and margins. Bioinformatics interrogations further identified response biomarkers. Results Mutation analysis showed that oncogenes exhibited a higher degree of spatial heterogeneity than tumor suppressor genes, regardless of MRI status. While the mesenchymal transcriptional subtype with extracellular matrix remodeling, stress response, and immune programs were preferentially enriched in enhancing cores, proneural tumors with neurological processes favored non-enhancing margins. Using a 15-drug GBM-targeted panel, ERK (ulixertinib) and PI3K pathway (paxalisib, CC-115) inhibitors showed preferential efficacy in enhancing cores and non-enhancing margins, respectively. The anti-apoptosis, pan-Bcl2 agent navitoclax and the epigenetic drug trotabresib represented the most effective, tumor-wide monotherapies. Importantly, drug combinations generally outperformed single agents across all regions. Conclusions This work demonstrates the regional heterogeneity of therapeutic vulnerabilities in GBM ex vivo, showing various drugs with tumor-wide or MRI-enhancement informed activity. These findings offer preclinical bases of numerous monotherapies and drug combinations for future clinical trial design.

Background: Posterior medial meniscus root tears (PMMRTs) are frequently observed injuries that alter tibiofemoral biomechanics, yet the long-term outcomes are poorly described. Purpose: To perform a systematic review and meta-analysis of the current literature on long-term clinical and radiographic outcomes of operatively managed PMMRTs. Study Design: Meta-analysis and systematic review; Level of evidence, 4. Methods: A systematic review was performed with the inclusion criteria of English-language studies, diagnosis of PMMRT on magnetic resonance imaging, and minimum 5-year radiographic or patient-reported outcome (PRO) metrics. Data analysis included management strategy, surgical technique, meniscal extrusion, medial joint space, PROs, and radiographic measurements. Failure was defined as conversion to arthroplasty, subsequent partial medial meniscectomy (PMM) and/or proximal tibial osteotomy, or clinical failure on PROs. Continuous outcome variables were analyzed with a random effects meta-analysis of mean differences. Chi-square meta-analysis was also used to analyze categorical variables. Results: Twelve studies were identified with >5-year follow-up after PMMRT (mean ± SD, 84.1 ± 11.0 months). Five studies performed PMM, 6 performed medial meniscus root repair (MMR), and 1 utilized either meniscectomy or repair. There were 797 total patients (female, n = 667; 83.7%), with mean ages ranging from 47.2 to 65. Both interventions showed significant PRO improvements after surgery: PMM (pre- vs postoperative Lysholm, 56.1 vs 68.2; P < .01) and MMR (Lysholm, 52.1 vs 83.1; International Knee Documentation Committee [IKDC], 40.0 vs 72.8; P < .01). MMR had significantly lower Kellgren-Lawrence grades (PMM vs MMR, 2.4 vs 1.8; P < .01) and superior IKDC scores (46.5 vs 72.8; P < .01) as compared with PMM. Additionally, PMM had a significantly higher failure rate (23% vs 5.3%) and conversion to knee arthroplasty (20.5% vs 3.5%) as compared with MMR, with odds ratios of 9.8 and 10.2, respectively. Conclusion: This systematic review and meta-analysis of studies with >5-year minimum follow-up found that PMM was associated with a 10-fold increase in clinical failure and conversion to knee arthroplasty relative to MMR in observational studies. In addition, MMR demonstrated superior Kellgren-Lawrence grades and IKDC scores as compared with PMM. The findings of the current analysis suggest that MMR is associated with superior outcomes as compared with PMM at mid- to long-term follow-up.

Purpose To evaluate retear rates, clinical outcomes, and complications of a consecutive series of full‐thickness rotator cuff repair cases augmented with an autograft biceps patch. Methods A retrospective review was performed of patients undergoing rotator cuff repair with autograft biceps patch augmentation. Patients underwent either magnetic resonance imaging or ultrasound to evaluate rotator cuff repair integrity at a minimum of 6 months postoperatively. Patient‐reported outcomes including the American Shoulder and Elbow Surgeons Score and Single Assessment Numeric Evaluation score were also collected and evaluated for clinical significance at a minimum of 12 months postoperatively. Analysis of retear rates was performed by comparing observed retear rates to expected retear rates using the modified Rotator Cuff Healing Index score. Results The final cohort included 25 rotator cuff repair cases. Postoperative imaging was obtained by magnetic resonance imaging in 22 patients at a mean of 9 months postoperatively (range, 6.0‐15.3 months) and ultrasound in 3 patients at a mean of 30.4 months (range, 28.8‐32.2 months). The expected retear rate using the modified Rotator Cuff Healing Index score was 21.5% for the entire cohort. There was 1 retear, resulting in an actual retear rate of 4% at an average of 23.5‐month follow‐up ( P = .0196). The average Single Assessment Numeric Evaluation score was 93 (standard deviation 9), and the average American Shoulder and Elbow Surgeons Score was 96 (standard deviation 6.3) at an average of 23.5‐month follow‐up (range 14‐32). Patient acceptable symptomatic state was achieved by 96% of the cohort for the American Shoulder and Elbow Surgeons Score and 88% of the cohort for the Single Assessment Numeric Evaluation score. There were no cases of reoperation or complications. Conclusions In this consecutive series, the biceps autograft “smash” patch for rotator cuff augmentation resulted in a low rate of retears, favorable patient‐reported outcomes, and no complications. This augmentation option has the potential to be safe and effective for improving rotator cuff repair healing rates. Level of Evidence Level IV, retrospective case series.

This case series describes multicenter experience with interleukin 6 (IL-6) receptor blockers used during attacks in aquaporin 4–immunoglobulin G–positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).