The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Retrospective analysis of clinical characteristics and prognostic factors for pathologic fracture in 44 patients with extremity osteosarcoma

Objective: The aim of this study was to identify the clinical features and prognostic factors associated with extremity osteosarcoma with pathologic fracture. Methods: The clinical records of 271 patients with extremity osteosarcomas were retrospectively reviewed. The data obtained covered the period from October 2003 to May 2012, and included sex, age, tumor site etc. The mean follow-up time was 25.2 months(ranged from 1 to 117). Chi-square method and Kaplan-Meier method were used to compare clinical differences and overall survival between patients with or without pathologic fracture, respectively. The univariate analysis was used to determine the prognostic factors related with survival rate by log-rank test. The multivariate analysis of prognosis was performed by COX proportional hazards regression model. Results: The proportions of patients having a tumor's diameter of 10 cm or more(P = 0.038), locating upper limbs(P = 0.004) and receiving amputation surgery(P = 0.02) were significantly higher with pathological fracture group than without pathological fracture group. The local recurrence rate(P = 0.000) was also significantly higher in the pathological fracture group. The median survival time of patients with or without pathological fracture was 16(95% confidence interval: 14.6–17.4) months and 22(95% confidence interval: 19.8–24.1) months(P = 0.002). The Log-rank univariate analysis indicated that the tumor size, Enneking's surgical staging, Karnofsky performance status(KPS) score, cycles of adjuvant chemotherapy, local recurrence and metastasis were significantly related to overall survival. Multivariate Cox regression analysis revealed KPS score, cycles of adjuvant chemotherapy and metastasis were independent prognostic factors(P < 0.05). Conclusion: Compared with the patients without pathological fracture, a higher proportion of patients receiving amputation surgery or having larger tumor size, humeral osteosarcoma or local recurrence was observed in patients with pathological fracture, and the prognosis of these patients was poor. The independent prognostic factors of extremity osteosarcoma with pathologic fracture were the KPS score, cycles of adjuvant chemotherapy and metastasis.