Citations

Purpose of review Photon-counting detector computed tomography (PCD-CT) represents a major technological advancement in computed tomography, offering improved spatial resolution, reduced image noise, and increased dose efficiency compared with conventional energy-integrating detector CT (EID-CT). Because many clinically relevant structures within the temporal bone are submillimeter in size, the temporal bone represents an ideal region for determining whether these technical improvements translate into meaningful clinical benefits. This review evaluates the emerging literature on PCD-CT in temporal bone imaging and examines whether higher spatial resolution meaningfully impacts clinical decision-making. Recent findings Recent studies demonstrate improved visualization of middle ear anatomy, ossicular prostheses, cochlear implant electrode arrays, and superior semicircular canal dehiscence with PCD-CT compared with conventional CT. Improved spatial resolution and reduced metal artifact have been shown to enhance assessment of prosthesis positioning, cochlear duct measurements, and differentiation of true versus near semicircular canal dehiscence. However, given the recent availability of PCD-CT, most studies to date have focused on cadaveric studies, phantom studies, or patient studies evaluating image quality rather than diagnostic accuracy or clinical outcomes. Summary PCD-CT provides substantially improved visualization of submillimeter temporal bone structures and may improve diagnostic confidence in select clinical scenarios. Nevertheless, evidence demonstrating improved clinical outcomes remains limited, and further clinical studies are needed to define the role of PCD-CT in routine temporal bone imaging.

Importance Tofersen is a disease-modifying antisense oligonucleotide therapeutic for people living with SOD1 –amyotrophic lateral sclerosis ( SOD1 -ALS). Autopsy tissue donors have provided the first opportunity to study the distribution of intrathecally administered tofersen in human central nervous system tissues. Objectives To determine the tissue distribution of tofersen and to provide the first estimates of SOD1 reduction in human somatic motor systems tissues. Design, Setting, and Participants This was a cross-sectional autopsy tissue case series conducted between 2018 and 2026. Autopsies were performed at 3 US academic medical institutions. Tissue samples from 8 deceased patients who lived with SOD1 -ALS, participated in tofersen clinical trials (ClinicalTrials.gov Identifiers NCT02623699 [An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)] and NCT03070119 [Long-Term Evaluation of BIIB067 (Tofersen)]) or the Expanded Access Program, and whose families authorized autopsies were eligible for this study. All autopsy tissue donors known at the time of this study were included (none were excluded). Analyses were conducted between August 2020 and January 2026. Exposures Participants received multiple intrathecal 20- to 100-mg tofersen doses. Main Outcomes and Measures Tofersen tissue concentrations were measured using hybridization enzyme-linked immunosorbent assay (ELISA). SOD1 messenger RNA (mRNA) and protein reduction estimates, defined as percentage SOD1 levels in this study’s recently treated autopsy tissue donors compared to a cohort of samples from tofersen-naive SOD1 -ALS autopsy tissue donors, were measured using quantitative reverse transcription polymerase chain reaction (PCR) and ELISA. Histological localization of tofersen and SOD1 transcripts were studied using immunohistochemistry and in situ hybridization assays. Results In 8 tofersen-treated autopsy tissue donors (5 male and 3 female donors; age range, 42-66 years), spinal cord and motor cortical tissue tofersen concentrations strongly correlated with predictions based on individual dosing histories and a preclinical pharmacokinetic model. For 3 recently treated autopsy tissue donors, reductions in lumbar spinal cord tissue SOD1 mRNA and protein levels ranged from 45% to 84% despite not having been administered 1 to 2 scheduled doses before autopsy. Residual somatic motor neurons demonstrated tofersen transduction and low SOD1 mRNA probe hybridization. Misfolded SOD1 protein inclusions were detected in residual motor neurons of tofersen-naive SOD1- ALS tissue donor controls and tofersen-treated tissue donors. Meningeal and perivascular lymphocytic immune responses were observed in 5 recently treated tissue donors but were not apparent in tissue donors with remote final tofersen doses. Conclusions and Relevance This case series presents the first emerging autopsy tissue data confirming the predicted distribution of tofersen and robust SOD1 protein reduction in human somatic motor systems tissues.

Abstract Endocytosis regulates receptor trafficking and signaling, yet its role in colorectal cancer (CRC) remains unclear. We analyzed transcriptomic data from 15,025 CRC tumors to evaluate gene expression in clathrin-mediated endocytosis (CME) and the endosomal sorting complexes required for transport (ESCRT) pathway. Pathway-level signatures were compared across consensus molecular subtypes (CMS) and examined in relation to oncogenic signaling programs, while individual endocytosis-related genes were evaluated for associations with clinical outcomes in an independent randomized trial cohort. Expression of CME and ESCRT pathways varied by CMS, with the highest expression in CMS4 and the lowest in CMS3. Endocytosis signatures correlated with multiple oncogenic signaling pathways, including MAPK, TGF-β, WNT, PI3K, NOTCH, and angiogenesis, suggesting broad links between endocytic activity and tumor biology. In the randomized phase III CALGB/SWOG 80405 trial, low expression of AP2M1 —a core adaptor in the CME complex—was significantly associated with longer overall survival and progression-free survival in patients treated with anti-EGFR agents, but not in those receiving anti-VEGF agents. These findings suggest that endocytic trafficking may be associated with oncogenic signaling and differential therapeutic benefit in patients with metastatic CRC. The endocytosis pathway reflects biologically relevant heterogeneity in CRC and may help guide therapeutic stratification.

Abstract Background The multicentre ALaCaRT and ACOSOG Z6051 randomized trials were unable to demonstrate non-inferiority of laparoscopic versus open surgery for rectal cancer with respect to a composite pathology metric indicating successful resection. Neither trial was individually powered to detect differences in long-term recurrence or survival. This planned meta-analysis determined long-term oncological outcomes of laparoscopic versus open proctectomy for rectal adenocarcinoma. Methods This prospective meta-analysis included individual patient data from patients with cT1–3 N0–2 M0 rectal adenocarcinoma enrolled in the ALaCaRT and ACOSOG Z6051 trials. Pathologically successful resection was defined as complete or near-complete total mesorectal excision, a clear circumferential resection margin (CRM; > 1 mm), and a clear distal resection margin (> 1 mm). The non-inferiority margin for disease-free survival (DFS) was an absolute difference of 5% at least 3 years after surgery. Results The combined data set included 935 patients (65.6% men, mean age 60.7 years, mean body mass index 26.7 kg/m2) randomized to open (457 patients) or laparoscopic (478 patients) proctectomy. Pathologically successful resection was lower in the laparoscopic than open group (85.1% versus 89.9%, respectively; pooled estimate 4.6% difference; 95% confidence interval (c.i.) −8.6% to −0.5%). The median follow-up was 60.2 (interquartile range 49.9–61.1) months. Three-year DFS was 75.2% (95% c.i. 71.1% to 79.2%) and 76.5% (95% c.i. 72.5% to 80.6%) for the laparoscopic and open groups, respectively (pooled estimate difference −1.5%; 95% c.i. −7.2% to 4.2%). Non-inferiority of laparoscopic surgery was not demonstrated because the lower one-sided 95% c.i. (−6.3% to 100%) crossed −5%. Three-year locoregional recurrence was higher in laparoscopic than open group (5.4% (95% c.i. 3.3% to 7.5%) versus 2.0% (95% c.i. 0.7% to 3.4%), respectively; pooled estimate 3.1% difference (95% c.i. 0.6% to 5.6%)). A clear CRM was the most significant and only pathological predictor of both DFS (P < 0.0001) and overall survival (P < 0.0001). Conclusion Laparoscopic proctectomy led to a lower rate of pathologically successful resection and a higher rate of locoregional recurrence at 3 years. The possibility of subsequent poorer DFS or overall survival rate requires further evaluation, because this analysis was not specifically powered for these endpoints.

ABSTRACT The hip capsule is a dense, fibrous structure that plays a crucial role in providing hip stability. Its biomechanical function is tied to its complex anatomy, which includes the iliofemoral, pubofemoral, and ischiofemoral ligaments, along with the circumferential fibers of the zona orbicularis. Anatomic and biomechanical studies with advanced imaging and arthroscopic techniques have provided better understanding of the capsular morphology and its contribution to hip stability. Additionally, these studies provide insight into how capsulotomy and subsequent capsular management at the time of hip arthroscopy can potentially influence postoperative outcomes. Growing clinical evidence supports capsular preservation and repair at the time of primary hip arthroscopy and demonstrates the potential negative outcomes of capsular deficiency, such as pain, dysfunction, and instability. This review provides a comprehensive overview of the gross, arthroscopic, radiologic, and biomechanical anatomy of the hip capsule.

Study Design. Post hoc analysis of prospectively-collected data. Objective. To identify factors predicting the most (and least) satisfaction following surgery for cervical spondylotic myelopathy (CSM). Summary of Background Data. Patient satisfaction affects long-term outcomes after surgery but the preoperative factors that influence postoperative satisfaction have not been well studied in patients with CSM. Methods. We conducted a post hoc analysis of prospectively-collected data from the Quality Outcomes Database (QOD) CSM registry cohort. Baseline and surgical characteristics were compared for patients with CSM reporting the most [North American Spine Society Satisfaction Score (NASS) 1] and least (NASS 4) satisfaction 24 months postoperatively. A multivariable logistic regression model was constructed using backward stepwise elimination to determine significant predictors of most versus least satisfaction. Twenty-four-month patient-reported outcomes (PROs) were compared. Results. Overall, 1141 patients were prospectively enrolled with 948 (83.1%) reaching 24-month follow-up. Of these, 699 met prespecified inclusion criteria: 610 (87.3%) were most satisfied and 89 (12.7%) were least satisfied. Though there were mean improvements in all 24-month PROs for the most satisfied cohort ( P <0.001), there were no significant improvements in 24-month PROs for the least satisfied cohort ( P >0.05). Using multivariable logistic regression modeling, a preoperative symptom of upper extremity weakness (OR=2.5, P =0.003), subjective myelopathy (OR=2.0, P =0.04), absence of numbness complaints (OR=2.2, P =0.003), symptom duration under 12 months (OR=1.6, P =0.047), Caucasian race (OR=2.3, P =0.001), participation in activities outside of the home (OR=2.0, P =0.04), anterior approach (OR=2.3, P <0.001), and higher baseline quality of life (OR=4.0, P =0.01) were predictive of the most satisfaction. Conclusion. Compared with the least satisfied, those most satisfied following surgery for CSM more often had a preoperative symptom of arm weakness, subjective myelopathy, the absence of numbness complaints, symptom duration under 12 months, higher baseline quality of life, and participation in activities outside of the home. Compared with a posterior approach, an anterior approach was associated with the most satisfaction. Taken together, early surgical treatment--before myelopathic symptoms significantly impact one's quality of life--may be considered to optimize patient satisfaction following CSM surgery.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

Abstract INTRODUCTION Neurodegenerative diseases often involve overlapping alpha‐synuclein (asyn), amyloid beta, and tau proteinopathies, yet the mechanisms, impact, and directionality of their interactions remain unclear. METHODS We induced brain‐wide neuronal asyn/tau pathologies via viral expression of wild‐type asyn, mutant asyn E46K , mutant tau A152T , or both asyn E46K /tau A152T in adult amyloidosis knock‐in mice and controls, either post‐plaque deposition (6 months old) or pre‐plaque (3 months old). Open‐field behavior was assessed baseline and 3 and 6 months post‐transduction, followed by neuropathology and neuroinflammation analyses. RESULTS Post‐plaque induction in amyloid mice increased asyn/tau total and phosphorylated levels and exacerbated amyloid‐related hyperlocomotion/anxiety. Pre‐plaque induction produced robust phosphorylated pathologies irrespective of amyloid, while causing similar amyloid‐dependent behavioral synergy. Tau pathology drove LGALS3 + inflammatory glial responses in white‐matter fibers. DISCUSSION Amyloid context gates vulnerability, with certain synergies manifesting across stages. White‐matter gliosis is a novel mechanism of tau A152T risk. Together, our data argue for the development of stage‐aware, multitarget interventions and biomarkers.

ABSTRACT Objective To evaluate long‐term failure rates and complications after retropubic and transobturator midurethral sling procedures for primary stress urinary incontinence (SUI). Design Retrospective cohort study. Setting Academic medical centre. Population A previously described cohort of patients ( n = 1881) who underwent midurethral sling procedures (2002–2012) and a covariate‐matched cohort of patients with retropubic ( n = 570) or transobturator ( n = 317) slings. Methods Health record review with follow‐up extended by 9 years (through December 31, 2022). Main Outcome Measures Treatment failure (reoperation for recurrent SUI) and procedure‐associated complications. Results The duration of assessment was extended by 6.9 years for the retropubic group and by 6.4 years for the transobturator group. The median (IQR) follow‐up was 11.1 (5.1–14.5) years (retropubic, 11.4 [5.9–14.6]; transobturator, 9.6 [2.6–13.7]). Higher risk of reoperation was observed with transobturator (8.8%) than retropubic (4.4%) slings (unadjusted hazard ratio [HR], 2.29 [95% CI, 1.49–3.54]; p < 0.001; covariate‐matched analysis HR, 1.91 [95% CI, 1.15–3.17]; p = 0.01). The increased risk of reoperation with a transobturator sling was higher when the procedure was combined with prolapse repair (unadjusted HR, 6.34 [95% CI, 3.09–13.02]; p < 0.001; covariate‐matched analysis HR, 3.96 [95% CI, 1.35–11.58]; p = 0.01). Higher rates of reoperation for urinary retention were observed for the retropubic group than for the transobturator group (covariate‐matched analysis HR, 8.39 [95% CI, 1.11–63.22]; p = 0.04). Conclusion In this long‐term follow‐up study, midurethral slings had a low failure rate. Women with SUI undergoing transobturator sling placement plus prolapse repair had a greater risk of reoperation. However, women with retropubic slings had a greater risk of urinary retention requiring intervention.