Citations

OBJECTIVE This study aimed to determine minimum clinically important difference (MCID) values for dysphagia using the Eating Assessment Tool-10 (EAT-10) in patients undergoing anterior cervical surgery, focusing on early dissatisfaction and later satisfaction thresholds to guide clinical decisions. METHODS Data were prospectively collected from patients undergoing anterior cervical surgery across three institutions from 2016 to 2024. Dysphagia severity was assessed preoperatively and at various postoperative stages up to 1 year using EAT-10. The inverse probability of treatment weighting was used to control for confounding variables. The retrospective study of patient data employed two analytical phases: the first phase examined the relationship between dissatisfaction at 3 months (indicated by a North American Spine Society satisfaction score > 2) and changes in EAT-10 scores from baseline to peak (i.e., worst) postoperative scores; the second phase focused on recovery, comparing changes in EAT-10 scores from peak postoperative scores to 12 months against satisfaction (score < 2) at 12 months. RESULTS The mean ± SD baseline EAT-10 score for the 1463 patients included in the study was 1.5 ± 4.7 and the mean peak score was 5.2 ± 7.4. The patients underwent anterior cervical discectomy and fusion (90%), arthroplasty (6%), or corpectomy (4%); a hybrid procedure was used in 1%. The phase 1 analysis indicated that a 4-point increase in EAT-10 score was a threshold for significant postoperative dissatisfaction in those without baseline dysphagia, with much higher thresholds observed in patients with any baseline dysphagia. In phase 2, among patients with baseline EAT-10 scores < 3 who experienced an increase to EAT-10 score ≥ 8 postoperatively, a subsequent decrease of 9 points by 12 months was necessary to report satisfaction. For patients with baseline scores 3–8 whose postoperative scores rose to ≥ 8, a subsequent decrease of 15 points was necessary for satisfaction. Patients with initial scores of ≥ 8 who did not improve to < 3 immediately after surgery required further reductions of 2–11 points to reach satisfaction. CONCLUSIONS The MCID thresholds from this study provide crucial benchmarks for assessing dysphagia changes after anterior cervical surgery, allowing tailored interventions. Patients with baseline dysphagia are less likely to experience early dissatisfaction, and high peak scores negatively impact long-term satisfaction. These findings emphasize the importance of proactive dysphagia management to enhance patient outcomes.

BACKGROUND Ulnar neuropathy at Guyon’s canal is rare, but when it occurs, it is frequently due to underlying masses, including extraneural and intraneural ganglion cysts, as well as adventitial cysts. The pathogenesis of these cysts, especially at a rare site, remains controversial. The articular theory, which is gaining popularity, posits that a joint connection via a nerve (or vascular) branch to a neighboring joint represents the pathway for their formation and propagation. OBSERVATIONS A recently published case of a patient with an ulnar intraneural ganglion at the wrist with a series of postoperative cystic recurrences was reevaluated, as it challenged the articular theory. No discrete articular branch had been identified on imaging or at surgery. Serial MR images were reinterpreted, which revealed that the original intraneural cyst was treated; new sequential cysts—an adventitial cyst and then a soft tissue ganglion—developed, all arising from the same wrist joint. LESSONS This case strengthens the principles of the articular theory for intraneural ganglion, adventitial, and soft tissue ganglion cysts. A small wrist connection from the ulnar intraneural ganglion was unrecognized and untreated. Scarring disrupted the original nerve pathway and pressure dynamics. New cysts developed through neighboring joint capsular rents along different pathways into other “compartments” (vessel or soft tissues). https://thejns.org/doi/10.3171/CASE25618

BACKGROUND Recently, the distribution of subparaneurial ganglion cysts involving the common peroneal and tibial nerves was described based on MRI analysis. Crossover in extreme cases was observed at the sciatic bifurcation through a mechanism comparable to a geyser, enabled by fenestrations in the epi- and paraneurium at the level of the bifurcation. The goal of this study was to investigate whether the geyser theory for crossover holds for other locations. OBSERVATIONS The authors’ prospectively maintained database of > 1100 cases of intraneural ganglion cysts in the world’s literature was queried for the existence of subparaneurial ganglion cysts at locations other than the knee. A previously unrecognized case involving the ulnar nerve originating from the elbow joint was found. Reinterpretation of the patient’s MRI studies showed circumferential subparaneurial distribution of a cyst over a long distance. Based on their previously reported geyser theory, the authors wondered if crossover had occurred at the level of the medial cord. A fenestration in the epi- and paraneurium at this level was confirmed on histological analysis of a normal cadaveric specimen. LESSONS This illustrative case shows that the geyser theory also holds in other locations. Surgical treatment of these subparaneurial cysts still follows the principles of the unified articular theory. https://thejns.org/doi/10.3171/CASE25671

Background: Venous air embolism (VAE) is a potentially catastrophic complication during neurosurgical procedures, particularly in the sitting position. As practices vary widely, we conducted a survey to describe the global practice patterns for intraoperative detection and management of VAE. Methods: Following institutional review board (IRB) approval, we conducted a cross-sectional study using a 48-question online survey that was distributed via a snowball sampling approach, initially to the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) community and subsequently to international collaborators. Descriptive statistics summarized responses, and proportional comparisons between high-income and low- and middle-income country respondents were assessed using a χ 2 or the Fisher exact tests, as appropriate. Results: Of 307 responses, 297 were analyzed, representing 40 countries. Survey response rate was 25% among SNACC members. End-tidal carbon dioxide (EtCO 2 ) monitoring was the most frequently reported VAE monitoring modality, particularly for sitting craniotomies. Common barriers to implementing advanced monitoring included limited equipment availability and a lack of a transesophageal echocardiography (TEE) specialist. Decision-making for cases at VAE risk relied on team consensus (62%), review articles and primary literature (48%), and institutional protocols (42%). Among respondents, 89% expressed interest in consensus guidelines for VAE management. Conclusions: There is substantial global variability in both the preparation for and management of VAE during neurosurgical procedures. EtCO 2 is the preferred monitoring approach in routine practice, as resource limitations prevent the broader adoption of more sensitive techniques, such as TEE. The high interest in consensus guidelines underscores an opportunity for professional societies to standardize approaches and improve patient safety.

ABSTRACT Background In the United States, metoclopramide is the only medication approved for gastroparesis. There is a need to reappraise the main considerations involved in the approval of pharmacological treatments of gastroparesis. Objectives and Methods We conducted a literature review to address issues that might impact the approval of medications for gastroparesis. We appraised the epidemiology, clinical presentations, variations in diagnostic tests, and their thresholds for identification of gastroparesis. Based on the review, we proposed trial designs for proof of efficacy and safety of novel medications for gastroparesis. Results Based on epidemiological studies, the age‐adjusted prevalence in US population is 152,005 for all categories (definite, probable and possible) of gastroparesis. The major symptoms of gastroparesis are nausea, vomiting, early satiety and postprandial fullness and may lead to hospitalisation or emergency department visits. It is essential to appraise gastric emptying with a solid meal over at least 3 h using scintigraphy or a stable isotope breath test. Diagnostic thresholds have been established for these diagnostic tests and at present, reproducibility, normative data, and coefficient of variation are well established for the 320‐kcal real egg solid meal. Based on published guidelines on clinical efficacy of medications used in gastroparesis, we propose targeting the gastroparesis symptom subscales, such as nausea and vomiting, with pharmacological agents specifically directed at their causative mechanisms rather than targeting the underlying dysmotility. Conclusion The evidence documented here justifies consideration of gastroparesis as an orphan disease, as well as an innovative approach to supplement the regulatory bodies' recommendations and guidance to industry. We propose treatment trials of 4‐weeks duration and considering the use of specific symptoms of gastroparesis as clinical endpoints based on a pharmaceutical agent's mechanism of action, rather than using a total gastroparesis symptom score. Such an approach would include evidence of safety and efficacy of new medications targeting gastroparesis subscales, and approval for marketing would be based on the symptoms specifically ameliorated in robust trials.

Background Antifibrotic (AF) therapy has been shown to potentially reduce the risk of lung cancer (LC) in patients with idiopathic pulmonary fibrosis (IPF). Our study further assesses the impact of AF use and LC incidence in a real-world cohort with patient-level data. Methods A retrospective multisite cohort study involving patients with IPF followed at Mayo Clinic between 2005 and 2022 was conducted. We identified individuals with new diagnoses of LC in the pre-AF and post-AF eras and defined AF use as continuous treatment for 6 months or more before LC diagnosis. Given the inclusion of LC cases prior to the wide availability of AF therapy and potential differences in patients exposed and unexposed to treatment, propensity score analysis with inverse probability of treatment weighting (IPTW) was used to balance comparator groups. Fine and Gray modelling was used to explore risk factors for developing LC, reported as parameter subdistribution HRs (SHR). Results A total of 3313 patients with IPF were included (1161 treated and 2152 non-treated). LC incidence rates were lower for treated patients in the post-AF era (0.34 vs 1.25 per 100 person-years, p<0.001). After IPTW, 2148 treated were compared with 2167 non-treated individuals. AF treatment was independently associated with reduced LC risk (SHR 0.36 (0.16–0.82), p=0.02), while smoking history and higher forced vital capacity were associated with increased risk. Conclusion AF use appears to be associated with a reduced incidence rate and risk of LC in patients with IPF.

Abstract Alport syndrome is caused by mutations in the type IV collagen genes COL4A3, COL4A4, and COL4A5 which are expressed in podocytes in the glomerulus of the kidney. Mutation of these genes disrupts blood filtration by the kidney leading to proteinuria and kidney failure. There is no cure for Alport Syndrome. Current therapies do not treat the genetic cause of the disease, but instead aim to delay the disease by reducing blood pressure in the kidney. Here we tested the ability of mRNA therapy to treat the disease. Mice with X-linked Alport syndrome (XLAS) due to mutation of Col4A5 were treated intravenously with lipid nanoparticles (LNPs) carrying three mRNAs encoding COL4A3, COL4A4, and COL4A5 to produce trimeric collagen IV repair proteins. This intravenous mRNA therapy significantly reduced proteinuria and blood urea nitrogen. Protection against the syndrome was maintained provided that LNP-mRNA injections were continued. However, efficacy was lost when therapy was terminated. These data provide proof of principle to apply a genetic mRNA therapy to halt progression of Alport syndrome in a mouse model of XLAS. These data also demonstrate that damage to the kidney filtration barrier can be leveraged to deliver large molecular therapies to podocytes and other cells within the kidney to treat Alport syndrome and other kidney genetic diseases.

Early allograft failure (EAF) after living donor liver transplantation (LDLT) remains a clinical challenge. Existing prediction models developed for deceased donor transplantation poorly apply to LDLT due to distinct surgical and physiological factors. This study identifies clinical determinants of EAF and develops an LDLT-specific prediction model. We conducted a multicenter retrospective cohort study from 17 high-volume LDLT centers (January 2016–December 2020) with external validation at a tertiary center in Saudi Arabia (January 2015–December 2022). The primary outcome was EAF (graft loss or patient death ≤90 d). Multivariable mixed-effects logistic regression identified preoperative/intraoperative risk factors. The EAGLE-LDLT model was constructed using postoperative laboratory values. Performance was compared against established models (EAD, MEAF, A2ALL) using ROC analysis and decision curve analysis. The development cohort included 2944 adult LDLT recipients (67.7% male; median age 55 y; median MELD 14) with a 5.5% EAF rate. External validation included 1020 recipients (median MELD 21, 6.7% EAF). Independent risk factors for EAF were MELD (OR 1.06, 95% CI 1.04–1.08), donor BMI (OR 1.05, 95% CI 1.00–1.10), portal vein thrombosis (OR 1.73, 95% CI 1.13–2.63), and hepaticojejunostomy (OR 1.58, 95% CI 1.06–2.36). The EAGLE-LDLT model incorporating peak ALT (>468 U/L), peak INR (>1.9), and bilirubin (>3.5 mg/dL) and INR (>1.3) at POD7, demonstrated superior discrimination (AUC=0.81) compared with MEAF (AUC=0.77, p =0.004), EAD (AUC=0.67, p <0.001), and A2ALL (AUC=0.65, p <0.001). EAGLE-LDLT achieved balanced sensitivity (75.0%) and specificity (73.7%), effectively stratifying patients into high-risk (15% of patients; 40.4% EAF incidence) and low-risk groups. Preoperative and intraoperative clinical factors predict EAF in LDLT. The EAGLE-LDLT model accurately identifies LDLT recipients at the highest risk for EAF postoperatively.

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide, and despite advances in treatment, immune suppression remains an obstacle to effective therapy. Effector CD4+ T cells (CD4+ Teff) are critical for antitumor immunity, but their function is often inhibited by regulatory T cells (Treg), which accumulate in lung tumors and mediate suppressive functions through multiple mechanisms. This suppression leads to tumor progression and poor patient outcomes. However, the mechanisms underlying Treg-mediated suppression are not fully understood. Herein, we identify the extracellular adenosine 5-triphosphate receptor P2RX7 as a key regulator of Treg function in lung tumors. In a murine lung cancer model induced by Lewis lung carcinoma cells, we found that P2RX7 enhanced the suppressive capacity of tumor-infiltrating Tregs, promoting tumor growth. In T cell–specific P2RX7-knockout (P2RX7-KO) mice, reduced Treg infiltration was accompanied by increased CD4+ Teff accumulation and improved tumor control. Treg-specific P2RX7-KO mice exhibited reduced tumor growth, confirming a Treg-intrinsic role of P2RX7. Suppression assays revealed that tumor-infiltrating wild-type Tregs had greater suppressive activity compared with P2RX7-KO Tregs, which failed to inhibit type 1 and follicular helper T–like responses. This was associated with increased tumor-specific IgG production by lung B cells in P2RX7-KO mice. We also observed that wild-type Tregs expressed higher levels of the immunosuppressive molecule CTLA-4 when compared with P2RX7-KO Tregs. Thus, we conclude that P2RX7 expression on Tregs is essential for their suppressive function in lung cancer and targeting P2RX7 may constitute a strategy to improve lung cancer treatment by alleviating Treg-mediated immune suppression.