Freezing of gait (FOG) is among the most debilitating symptoms of Parkinson disease and related disorders, often resulting in falls and a loss of independence. FOG has an episodic and heterogeneous nature that makes it difficult to measure and treat. The field currently lacks a consensus on how to precisely define this phenomenon. For this reason, the International Consortium for Freezing of Gait convened a group of experts to establish an updated ‘clinical’ definition of FOG for use in the clinical setting and a ‘technical’ definition for assessors to use when scoring FOG episodes from video recordings as an outcome in fundamental research and clinical trials. Guidelines on how to classify people with Parkinson disease into subgroups of those with or without FOG (non-FOG) are also provided. This position paper presents these new definitions and guidelines, offering a foundation for harmonizing the study and management of FOG. Freezing of gait (FOG) is among the most debilitating symptoms of Parkinson disease. This Consensus Statement from the International Consortium for Freezing of Gait presents new guidelines for the definition and assessment of FOG, with the aim of harmonizing the study and management of the condition.
PURPOSE:Angiogenesis plays an essential role in neuroendocrine tumors (NETs). This study evaluates efficacy and safety of axitinib in extrapancreatic (ep)-NETs. PATIENTS AND METHODS:AXINET was an international, randomized, double-blind, placebo-controlled, phase II/III trial including patients age 18 years and older, with unresectable/metastatic G1-2 epNETs and up to two previous treatment lines. Patients were randomly assigned (1:1) to axitinib 5 mg or placebo, both orally twice a day, in combination with intramuscular octreotide long-acting release 30 mg once every 28 days until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months). The primary end point was investigator-assessed progression-free survival (PFS). Efficacy was also assessed by a blinded independent central review (BICR). RESULTS:From October 2011 to May 2019, 256 patients were assigned to axitinib (n = 126) or placebo (n = 130). Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) versus 13.1 months (95% CI, 10.9 to 18.6) in the axitinib and placebo groups, respectively (hazard ratio [HR], 0.86 [95% CI, 0.65 to 1.15]). The median BICR PFS was 16.6 months (95% CI, 13.5 to 24.2) versus 9.9 months (95% CI, 8.2 to 13.9) in the axitinib and placebo groups, respectively (HR, 0.71 [95% CI, 0.54 to 0.94], P = .017). Objective response rate (ORR) was significantly greater for axitinib per investigator assessment (17.5% v 4.6%; P = .001) and BICR (12.8% v 3.2%; P = .005). Most common grade ≥3 toxicities were hypertension (24.0% v 9.2%) and diarrhea (13.6% v 1.5%). CONCLUSION:Axitinib significantly increased PFS per BICR assessment and ORR both per investigator and BICR assessment compared with placebo, although the primary study end point was not met. Toxicity profile was manageable with no new safety concerns.
Tezepelumab, an anti–TSLP monoclonal antibody, has shown broad efficacy across severe asthma phenotypes. However, real-world evidence evaluating multidomain remission—integrating clinical, functional, and inflammatory domains—remains limited. The primary objective was to assess 12-month effectiveness and multidomain remission (clinical, biological, and complete remission) stratified by inflammatory phenotype, in a prospective multicentre real-world cohort of patients with severe asthma treated with tezepelumab. This prospective observational study included adults with severe asthma initiating tezepelumab across 14 specialised severe asthma units in Spain. Clinical outcomes (exacerbations, ACT, OCS use), lung function, and type 2 (T2) biomarkers (blood eosinophils, FeNO) were evaluated at baseline and 12 months. Clinical remission was defined using strict (no exacerbations, no maintenance OCS, ACT ≥ 20, FEV₁ ≥80
BACKGROUND:While quantitative MRI (qMRI) metrics effectively describe preoperative compression in degenerative cervical myelopathy (DCM), their use in identifying determinants of postoperative anatomical decompression remains limited, particularly in patients with suboptimal clinical trajectories. METHODS:In this retrospective cohort study, we analyzed 40 patients (78 segments) who underwent postoperative MRI due to suboptimal clinical recovery or late neurological worsening. Using Generalized Estimating Equations (GEE) to account for clustered data, we identified determinants for changes in maximum canal compromise (ΔMCC), transverse area of the cervical canal (ΔTACC), maximum spinal cord compression (ΔMSCC), transverse area of the spinal cord (ΔTASC), and compression ratio (ΔCR). Models controlled for surgical approach, demographics, and preoperative severity. RESULTS:Surgical intervention significantly improved all qMRI parameters (p < 0.001). The posterior approach achieved markedly greater canal expansion (ΔTACC B = -34.86, p < 0.001) and better restoration of cord morphology (ΔCR B = -6.33, p = 0.020). However, actual spinal cord re-expansion (ΔMSCC, ΔTASC) was not significantly determined by the surgical approach (p > 0.10) but was primarily constrained by preoperative severity (B = -0.73 and B = -0.81, respectively; both p < 0.001). Notably, isolated anterior compression significantly limited axial cord area re-expansion (B = -15.39, p = 0.018). Patients with ASA III showed significantly less sagittal cord expansion compared to those with ASA II (p = 0.029), while advanced age showed a strong trend toward reduced canal expansion (p = 0.079). Longer intervals to postoperative MRI were associated with greater measured decompression (p < 0.05), suggesting morphometric stabilization after the acute postoperative phase. CONCLUSIONS:In patients with suboptimal clinical recovery, a critical dissociation exists: spinal canal expansion is primarily determined by the surgical approach, whereas spinal cord re-expansion is constrained by preoperative severity and the specific compression pattern. These findings define the anatomical boundaries of surgical decompression and suggest that personalized planning must account for the "biological ceiling" of the cord. Quantitative MRI serves as an essential tool for establishing anatomical benchmarks in the postoperative assessment of DCM.
BACKGROUND AND AIMS:Post-operative recurrence (POR) of colonic Crohn's Disease (CD) after segmental (SC) or subtotal colectomy (STC) is scarcely described. Therefore, we aimed to report the rates and predictors of POR in this setting. METHODS:Multicentre, nationwide, retrospective study including colonic CD patients undergoing SC or STC. Clinical, endoscopic, radiologic and surgical POR were assessed and POR-free survival was compared between procedures. Cox regression determined predictors of post-colectomy POR. Inverse probability of treatment weighting (IPTW) was carried out for sensitivity analyses. RESULTS:A total of 224 patients were included (157 SC, 67 STC). Clinical POR occurred less frequently after SC than after STC (38% vs 63%, p = 0.001), as did endoscopic POR (50% vs 71%, p = 0.012); whereas radiologic and surgical POR rates were similar (p = 0.1 and p = 0.992, respectively). Clinical POR-free survival at 1 and 5 years was higher after SC than after STC (82% and 64.8% vs 67.6% and 39%, log-rank p = 0.001). Endoscopic POR-free survival followed a similar pattern (log-rank p < 0.001). In multivariable Cox regression, SC remained protective against clinical (HR 0.54 [0.36-0.81]) and early endoscopic POR (HR 0.54 [0.35-0.82]). After IPTW, SC was still associated with a significantly lower risk of clinical and endoscopic POR. CONCLUSION:Clinical and endoscopic POR rates are significantly lower following SC compared with STC in colonic CD, while radiologic and surgical recurrence rates were similar. SC shows a protective effect regarding clinical and early endoscopic POR. These data support segmental resection of colonic CD when feasible.
