Citations

BACKGROUND Bertolotti syndrome is an underrecognized cause of chronic low back pain. Back pain generated from Bertolotti syndrome is believed to result from altered weight dissipation mechanics and/or instability of the pseudoarticulation, while local nerve root compression may result in radiculopathy. Here, the authors describe the findings of a patient with treatment-refractory low back pain found to have a cystic lesion arising from a Bertolotti joint causing L5 nerve root compression. To their knowledge, this has not been previously described in the literature. OBSERVATIONS Despite early recognition of Bertolotti syndrome, the patient’s back pain remained resistant to many years of both conservative and surgical management. The novel finding of a cyst arising from the pseudoarticulation complicated the management. The patient is scheduled to undergo further surgery this year. LESSONS This case highlights a pseudocyst associated with a Bertolotti joint. The cyst introduced additional clinical uncertainty to what is already an uncommon and difficult to treat condition. Resection of the Bertolotti joint failed to improve the patient’s symptoms. Postoperatively, a complex hemorrhagic pseudocyst was seen on imaging, possibly due to the pseudoarticulation with persistent motion. Ongoing efforts to characterize Bertolotti syndrome and its associated imaging findings are necessary to better optimize management strategies in these patients. https://thejns.org/doi/10.3171/CASE25948

BACKGROUND Intraneural ganglion cysts (IGCs) are mucinous lesions that originate from adjacent synovial joints. According to the articular theory, synovial fluid tracks from a joint into the parent nerve through an articular branch. In uncommon sites such as the sural nerve, this connection can be difficult to identify. This report illustrates the use of a preoperative intra-articular fluorescein injection as a tool to identify the articular branch during surgery. OBSERVATIONS A 60-year-old woman presented with lateral foot pain, numbness, and a palpable mass along the left sural distribution. MRI showed a large cyst extending along the course of the sural nerve with connection to the subtalar joint. Fluorescein was injected preoperatively into this joint to detect the articular branch intraoperatively with ultraviolet illumination. The connection was transected at the joint origin, and the cyst was decompressed, preserving the parent nerve. Postoperatively, the patient had complete pain relief and sensory recovery, and MRI at 3 and 8 months confirmed resolution of the cyst. LESSONS Sural IGCs conform to the articular theory and can be managed effectively by transection of the articular branch. Preoperative intra-articular fluorescein injection is a useful tool to detect the articular branch that can be difficult to find in sural IGCs. https://thejns.org/doi/10.3171/CASE251018

Background/Objectives: Heterotopic ossification (HO), the aberrant formation of bone within soft tissues, arises either from rare genetic mutations or more commonly from traumatic insults. It is a major cause of morbidity not only in individuals harboring causative mutations, but also in those undergoing musculoskeletal surgery or trauma and in soldiers sustaining blast or burn injuries. Bone morphogenetic protein (BMP) signaling is a central driver of both hereditary and acquired forms of HO. Primary cilia are nonmotile, antenna-like organelles that extend from the cell surface and serve as crucial sensory and signaling hubs by concentrating key pathway components within a confined volume at the ciliary tip. However, their functional role in the pathogenesis of traumatic HO remains poorly understood. Methods: We investigate the role of primary cilia in traumatic HO using a genetically modified mouse model and cellular model. Results: We demonstrate that BMP signaling is attenuated when primary cilia function is disrupted. Both ciliation frequency and ciliary length were reduced in Scleraxis-CreERT2; Intraflagellar transport 88 floxed/floxed (Scx-CreERT2;Ift88fl/fl) tenocytes. Deletion of Ift88 effectively suppressed pathological BMP signaling and inhibited HO formation. Conclusions: These findings establish that functional primary cilia are required for traumatic HO development and highlight ciliary regulation as a potential therapeutic avenue for preventing or mitigating post-traumatic HO.

Abstract Background Surrogate endpoints are increasingly used as the basis of cancer drug approvals. A strong association between treatment effects on the surrogate and true endpoint is essential for their validation as reliable endpoints. We assess the current evidence of trial-level surrogacy for colorectal cancer (CRC) endpoints through a novel framework. Methods We developed a framework to grade the quality of oncology surrogate endpoints in 7 domains of the surrogate relationship: data source quality (A-B); disease setting homogeneity (0-3); uniformness of surrogate and true endpoint definitions (0-3); number of trials evaluated (0-4); and individual- (0-2) and trial-level associations (0-8). We screened PubMed using keywords and medical subject headings terms for meta-analyses published before July 6, 2024, validating surrogate endpoint associations across CRC trials. Two reviewers blindly assessed each article before reaching a consensus score. The main outcomes were framework-derived evidence scores and reported trial-level associations (R2) with overall survival. Results A total of 18 articles were identified, containing 39 evaluations of 12 unique surrogate endpoints for overall survival. Evidence scores ranged from B6 to A23. Only disease-free survival consistently demonstrated high-quality evidence of trial-level surrogacy (≥A18, median R2 = 0.92). Progression-free survival and objective response rate were low-quality surrogates in metastatic CRC (progression-free survival: B6-A15, median R2 = 0.55; objective response rate: B6-A13, median R2 = 0.33). Other evaluated endpoints were demonstrated to be unreliable surrogates. Conclusion Disease-free survival shows high-quality surrogacy in stage II-III colon cancer. Endpoints identified in the metastatic setting demonstrate inconsistent surrogacy evidence. Reassessment and identification of new endpoints are warranted, particularly with immunotherapy.

Abstract Asthma in the elderly (AIE) represents a unique challenge, necessitating better understanding of the mechanisms that drive airway hyperreactivity and remodeling (thickened, fibrotic airways). Normal aging is associated with increased lung stiffness, and thus the influence of mechanical forces on bronchial airways (breathing, sighs, CPAP) likely changes, potentially increasing with AIE and resultant remodeling, overall highlighting the need to understand the importance of mechanobiology in aging and AIE. Here, mechanosensitive Piezo (Pz) channels are highly expressed in the lung, including within airway epithelium and smooth muscle (ASM) but their specific roles particularly with aging remain largely unexplored. In this study, we used human ASM cells from young vs. old (≥65 y) non-asthmatics vs asthmatics to test the hypothesis that normal aging blunts Pz expression and functionality at baseline as well as in response to mechanical stretch, whereas asthma, particularly, AIE ASM leads to enhanced Pz expression promoting fibrosis and remodeling. Both Pz1 and Pz2 were expressed in ASM and increased in AIE. Oscillatory mechanical stretch mimicking breathing with superimposed static stretch increased Pz, especially in AIE: effects exacerbated by Pz activator Yoda1 and blunted by Pz inhibitor GsMTx4. Stretch or Yoda1 increased Wnt3a, β-catenin and GSK3β activation particularly in AIE, while ASM proliferation and extracellular matrix production remained preserved or even heightened in elderly ASM. Conversely, Pz1 inhibition by GsMTx4 potently reduced ECM deposition, particularly in AIE cells, highlighting Pz1's pivotal role in modulating ECM deposition. Overall, our findings indicate Pz1 as a mechanosensitive regulator of airway remodeling in AIE.

Purpose: The anatomic position of the appendix may influence both the clinical presentation and diagnostic imaging accuracy in pediatric appendicitis, but its impact remains uncertain. This study aimed to determine the prevalence of retrocecal appendicitis in children and to evaluate whether appendix positioning affects ultrasound diagnostic performance or clinical outcomes. Methods: This was a retrospective cohort study including all children 0 to 18 years of age who presented to the Mayo Clinic Rochester Emergency Department between 2018 and 2023 and were diagnosed with appendicitis during their evaluation or subsequent hospitalization. Appendix location was determined by imaging or surgical documentation. Demographics, symptoms, signs, and complication rates were collected for patients with retrocecal appendicitis (RCA) and non-retrocecal appendicitis (NRCA). Results: Four hundred seven patients were included with 12.5% having RCA. Ultrasound was obtained in 92% of patients with RCA versus 82% of NRCA (rate difference: 10%, 95% CI: 2%-19%, P =0.018). In patients who received ultrasound imaging, findings were equivocal or falsely negative in 53% of RCA patients versus 30% of NRCA patients (RD = 24%, 9%-39%; P =0.003). Computed tomography (CT) was obtained in 51% of RCA patients versus 29% of NRCA (RD = 22%, 8%-37%; P =0.003) and was equivocal or falsely negative at similar rates in RCA (12%) and NRCA (13%; P =0.88). Clinically, there were no differences in diarrhea, emesis, location of abdominal pain, or white blood cell counts between RCA and NRCA. Rates of perforation, abscess formation, hospitalization longer than 7 days, and repeat hospitalizations were also similar. Conclusions: Retrocecal appendicitis is a common anatomic variant in children that presents with similar clinical features and outcomes compared with non-retrocecal appendicitis. However, its retrocecal position reduces the diagnostic sensitivity of limited abdominal ultrasound, often necessitating additional imaging with computed tomography. Despite these diagnostic challenges, retrocecal positioning is not associated with a worsened clinical course.

ABSTRACT Background Antiplatelet management in patients hospitalised for gastrointestinal bleeding (GIB) after percutaneous coronary intervention (PCI) requires balancing risks of rebleeding and clinical vascular events. Aims Evaluate the impact of antiplatelet resumption timing post‐endoscopy on rebleeding and clinical vascular events. Methods We performed a retrospective nationwide cohort study of patients hospitalised with post‐PCI GIB on dual antiplatelet therapy (DAPT) using the Vizient Clinical Database. Co‐primary outcomes were 30‐day rebleeding and 90‐day clinical vascular events after endoscopy. Multivariable Cox proportional hazards regression analysis was performed. Results Among 2979 patients with both antiplatelet agents held before endoscopy for GIB (46.0% upper; 34.8% lower), antiplatelet resumption > 7 days post‐endoscopy was associated with decreased 30‐day rebleeding (hazard ratio [HR] 0.66; 95% confidence interval [CI] [0.49–0.87]) and increased 90‐day clinical vascular events (HR 1.18 [1.02–1.36]) compared to restarting ≤ 1 day post‐endoscopy. Among 869 patients with one antiplatelet agent held before endoscopy for GIB (47.3% upper; 36.3% lower), resumption at > 7 days vs. ≤ 1 day had HR 0.69 (0.41–1.14) for rebleeding and HR 1.41 (0.97–2.04) for clinical vascular events. HRs for antiplatelet resumption > 3 days vs. ≤ 1 day post‐endoscopy were similar. Conclusions Antiplatelet resumption > 7 days after endoscopy in patients hospitalised with post‐PCI GIB is associated with decreased 30‐day rebleeding but increased 90‐day clinical vascular events compared with resumption ≤ 1 day post‐endoscopy. Similar tradeoffs were noted with antiplatelet resumption > 3 days post‐endoscopy. To optimise competing risks of rebleeding versus clinical vascular events, antiplatelet therapy should be resumed no later than 7 days post‐endoscopy, and preferably within 3–4 days.

Abstract Lentigo maligna (LM) is a subtype of cutaneous melanoma in situ that develops on chronically sun‐damaged skin in elderly individuals. Its diagnosis and management remain challenging due to its slow progression, frequent occurrence on cosmetically sensitive areas in frail individuals, and tendency for subclinical peripheral extension. Despite its potential for invasive transformation, the natural history of LM remains incompletely understood and evidence‐based management strategies for this specific entity remain limited. This work aims to bridge the gap between scarce high‐quality evidence and the clinicians' need for practical guidance on LM management by formulating evidence‐based and expert consensus‐driven recommendations for diagnosis, treatment and follow‐up. Under the coordination of the International Dermoscopy Society, a global, multidisciplinary consortium of 53 experts—including dermatologists, dermato‐oncologists, dermatologic surgeons, radiologists, radiotherapists, pathologists and epidemiologists—formulated recommendations through structured consensus, informed by a comprehensive review of current scientific evidence and clinical practice standards. Optimal management of LM requires accurate diagnosis and individualized treatment planning. Non‐invasive skin imaging techniques, especially dermoscopy and reflectance confocal microscopy, aid in diagnosis, biopsy orientation, lesion delineation and post‐treatment monitoring. Multiple partial biopsies help confirm diagnosis and rule out invasion. Complete surgical excision remains the first treatment option. No definitive safety margins can be recommended for standard surgery; margin‐controlled techniques are preferable for large or ill‐defined lesions. Topical imiquimod and radiotherapy are effective alternatives where surgery is unsuitable. Topical imiquimod is useful as primary, adjuvant or neoadjuvant therapy. Blind destructive methods should be avoided. Close clinical and imaging follow‐up is needed. Patient‐centred care, shared decision‐making, and a multidisciplinary approach are critical for optimal outcomes. These international consensus recommendations summarize current best practices for LM management, offering practical, evidence‐informed guidance to clinicians while acknowledging the potential of future research in refining these conclusions.