Cyanide (CN) is a potent, fast-acting toxicant that impacts endogenous biomolecules in the nervous system, including acid-sensing ion channels (ASICs), which play a vital role in various neurological and psychological conditions. Here, we demonstrate that CN rapidly potentiates ASIC currents in cultured mouse cortical neurons in a dose-dependent manner while causing a leftward shift in the pH dose–response curve. Notably, this potentiation was unaffected by a 30-min CN treatment or the presence of ATP in the recording pipette. Further investigations into the role of zinc revealed that TPEN, a high-affinity zinc chelator, did not enhance ASIC currents following CN pretreatment, nor did CN influence the potentiation of ASIC currents induced by TPEN. Low-affinity zinc blocked the potentiation of ASIC currents by CN. CN potentiated ASIC currents in cortical neurons from ASIC2 but not from ASIC1a knockout mice. In experiments with CHO cells expressing homomeric ASIC1a and heteromeric ASIC1a/2, CN potentiated ASIC1a currents but had no effect on homomeric ASIC1b, ASIC2a, or ASIC3 channels. Mutating lysine 133 (K133) to arginine (R) in the extracellular domain of ASIC1a abolished CN’s effect, suggesting that CN potentiates ASIC1a currents primarily via high-affinity zinc binding, with K133 being critical for this modulation.

Study Design: Retrospective single-center cohort study; exploratory feasibility analysis. Objective: To describe the feasibility and 12-month clinical and radiographic outcomes of posterior spinal fusion (PSF) for adult spinal deformity (ASD) with versus without lower limb arthroplasty performed during the same hospital admission, as a hypothesis-generating basis for a subsequent prospective study. Background: Hip-spine and knee-spine syndromes describe the biomechanical interdependence of the lower extremities and the spine. Sequential surgical management is well described, but outcomes when arthroplasty and spinal fusion are performed during a single hospitalization remain poorly characterized. Materials and Methods: We retrospectively reviewed 45 consecutive adult patients who underwent T12–pelvis PSF for ASD at a single academic center between January 2019 and December 2023. All patients received a standardized T12–pelvis construct with selective laminectomies at symptomatic levels. Patients who underwent concurrent lower limb arthroplasty under the same anesthetic event (concurrent group, n = 18; 16 TKA, 2 THA) were compared descriptively with those who underwent PSF alone (spine-only group, n = 27). Clinical outcomes (Oswestry Disability Index, VAS Back and Leg pain) and radiographic sagittal parameters (PI, LL, PT, SS, TK, TPA, SVA) were assessed at baseline and 12 months. Paired within-patient change was analyzed by the Wilcoxon signed-rank; between-group comparisons used Mann–Whitney U for continuous and Fisher exact for categorical variables. A sensitivity ordinary least-squares regression adjusting for age was prespecified. Exact denominators are reported at every time point. Results: The concurrent group was significantly older (74.1 ± 6.1 vs . 65.6 ± 10.2 yr, P = 0.003) with similar BMI and comorbidity profile. Anesthesia time (291.5 ± 84.8 vs . 306.6 ± 99.4 min, P = 0.57) and length of stay (5.8 ± 2.1 vs . 6.2 ± 3.7 d, P = 0.90) did not differ. Among patients with available 12-month radiographs (24/45, 53%), all were assessed as fused. Within-patient paired change in ODI was −18.0 (n = 5) in concurrent vs . −7.7 (n = 14) in spine-only (between-group P = 0.150). ΔVAS Leg reached nominal significance in unadjusted paired analysis (−4.4 vs . −1.5, P = 0.037) but was not significant after adjustment for age (β = −2.5, 95% CI: −6.0 to +1.1, P = 0.17). Structured complications were comparable between groups: proximal junctional failure occurred in 1/18 (6%) concurrent and 2/26 (8%) spine-only patients ( P = 1.00); screw loosening in 3/18 (17%) and 4/21 (19%) respectively ( P = 1.00). No radiographic parameter differed significantly between groups after adjustment. Conclusions: Concurrent lower limb arthroplasty with PSF under a single anesthetic event was feasible in this small ASD cohort, with comparable anesthesia time, length of stay, fusion rates among assessed patients, and structured complication rates. No statistically significant advantage was detected for clinical or radiographic outcomes after adjustment for age. These exploratory findings are hypothesis-generating and require confirmation in prospective multi-institutional studies before any comparative effectiveness inference can be drawn. Level of Evidence: Level III, therapeutic.