Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration

Objectives and methods: Compared to age-matched healthy controls (n?=?55), patients with amyotrophic lateral sclerosis (ALS) (n?=?26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined.

Results and discussion: Among 26 ALS patients, 17 received edaravone (30?mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n?=?19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R?≥?0) as compared to the ingravescent group (ΔALSFRS-R?<??5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.     

Immunoreactivity of the phosphorylated axonal neurofilament H subunit (pNF-H) in blood of ALS model rodents and ALS patients: evaluation of blood pNF-H as a potential ALS biomarker

Levels of neurofilament subunits, potential biomarkers of motor axon breakdown, are increased in amyotrophic lateral sclerosis (ALS) patient's CSF but data on blood are not available. We measured blood levels of the phosphorylated axonal form of neurofilament H (pNF-H) by ELISA in transgenic rodent models of superoxide dismutase 1 (SOD1) ALS, and in 20 ALS patients and 20 similar aged controls monthly for 4 months. All symptomatic rodent ALS models showed robust levels of blood pNF-H, while control rodents or mice transgenic for unmutated SOD1 showed no detectable blood pNF-H. Average pNF-H levels in the G93A SOD1 mouse progressively increased from day 74 through death (day ∼130). Median blood pNF-H level in ALS patients was 2.8-fold higher than controls ( p  < 0.001). Median ALSFRS-R declined a median of 0.8 pt/month ( p  < 0.001); higher baseline pNF-H level appeared to be associated with faster ALSFRS-R decline over 4 months ( p  = 0.087). The median rate of decline in ALSFRS-R was 1.9 pt/month in patients with baseline pNF-H levels above the median pNF-H value of 0.53 ng/mL; ALSFRS-R declined at a median of 0.6 pt/month in patients below this level. The pNF-H levels were relatively stable month to month in individual patients, raising questions regarding the molecular pathogenesis of ALS. Baseline control human pNF-H levels were higher in men than women and increased minimally over time. These data suggest that blood pNF-H can be used to monitor axonal degeneration in ALS model rodents and support further study of this protein as a potential biomarker of disease prognosis in ALS patients.     

No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment.

Aim

To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV.

Methods

We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant.

Results

Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001).

Conclusion

This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS.     

Multi-Parametric Spinal Cord MRI as Potential Progression Marker in Amyotrophic Lateral Sclerosis

Objective

To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients.

Materials and Methods

After a first MRI (MRI₁), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI₂) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ_⊥, λ_//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score.

Results

At MRI₁, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI₁, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI₁ to MRI₂, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change.

Conclusion

Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.     

Effect of mesenchymal stromal cell transplantation on long-term survival in amyotrophic lateral sclerosis

Background aimsThanks to their immunomodulatory, tissue-protective and regenerative properties, mesenchymal stromal cells (MSCs) are a promising approach for amyotrophic lateral sclerosis (ALS); however, trials are limited and few follow-up studies have been published. This post-hoc analysis aims to describe the potential long-term effects of MSCs in ALS, analyzing data from two phase 1 clinical trials in ALS patients conducted by our group in 2002 and 2006.MethodsWe conducted two consecutive phase 1 prospective, open, pilot clinical trials, enrolling a total of 19 ALS patients. We followed patients for the duration of the disease. For each patient, we used the European Network to Cure ALS (ENCALS) survival prediction model to retrospectively calculate the expected survival at diagnosis. We then compared the predicted disease duration with the observed survival, analyzing patients at a single-patient level.ResultsUsing the ENCALS model, we predicted short survival in one patient, intermediate survival in three patients, long survival in three patients and very long survival in 12 patients. The difference between predicted and observed survival for the whole group was significant and demonstrated a mean predicted survival of 70.79 months (standard deviation [SD], 27.53) and a mean observed survival of 118.8 months (SD, 89.26) (P = 0.016). Based on the monthly ALS Functional Rating Scale–Revised progression rate (median, 0.64/month), we considered 10 of 19 patients slow progressors and nine of 19 patients fast progressors. Of the slow progressors, eight of 10 (80%) had significantly increased disease duration compared with predicted, and only two (20%) had decreased estimated disease duration. By contrast, five of nine (55%) fast progressors had increased disease duration, whereas four (45%) had decreased disease duration. To date, four patients are still alive.ConclusionsThe current study represents the first very long-term analysis of survival as an effect of MSC focal transplantation in the central nervous system of ALS patients, demonstrating that MSC transplantation could potentially slow down ALS progression and improve survival. Due to the interindividual variability in clinical course, at the current state of our knowledge, we cannot generalize the results, but these data provide new insights for planning the next generation of efficacy MSC clinical trials in ALS.     

Caregiver burden in amyotrophic lateral sclerosis is more dependent on patients’ behavioral changes than physical disability: a comparative study

Background

Behavioral changes in patients with amyotrophic lateral sclerosis (ALS) mirror those found in frontotemporal dementia (FTD). Considering the high rate of neuropsychiatric symptoms found in ALS patients, this paper examines whether caregiver burden is associated with behavioral changes over and above the physical disability of patients with ALS, and if the presence of caregivers’ depression, anxiety and stress also impacts on caregiver burden.

Methods

140 caregivers of patients with ALS participated in a postal survey investigating patients’ neuropsychiatric symptoms (Cambridge Behaviour Inventory Revised CBI-R), motor function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised - ALSFRS-R), caregiver burden (Zarit Burden Interview), and caregiver mood (Depression, Anxiety and Stress Scale- DASS21). Seventy four percent of them were caregivers of patients with limb onset and 25.7% were caregivers of patients with bulbar onset.

Results

Moderate to severe behavioral changes were reported in 10-40% of patients with ALS. The levels of depression, anxiety and stress in the caregivers reached 20%. Burden was high in 48% of the caregivers. The strongest predictor of high caregiver burden was ALS patients’ abnormal behavior rather than physical disability, with an odds ratio of 1.4, followed by caregivers’ stress.

Conclusions

Our study has identified that behavioral changes (e.g. disinhibition, impulsivity) and caregiver stress have greater impact on caregiver burden than level and pattern of physical disability.

     

CX3CR1 Is a Modifying Gene of Survival and Progression in Amyotrophic Lateral Sclerosis

The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142 sporadic [sALS] and 45 familial) and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379) and T280M (rs3732378) genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline) and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249^I/I or 249^V/I genotypes presented a shorter survival time (42.27±4.90) than patients with 249^V/V genotype (67.65±7.42; diff −25.49 months 95%CI [−42.79,−8.18]; p = 0.004; adj-p = 0.018). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249^I alleles (diff = −29.78 months; 95%CI [−49.42,−10.14]; p = 0.003). The same effects were also observed in the spinal sALS patients with 249^I–280^M haplotype (diff = −27.02 months; 95%CI [−49.57, −4.48]; p = 0.019). In the sALS group, the CX3CR1 249^I variant was associated with a faster progression of the disease symptoms (OR = 2.58; 95IC% [1.32, 5.07]; p = 0.006; adj-p = 0.027). There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease''s symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.     

Using automated electronic medical record data extraction to model ALS survival and progression

Background

To assess the feasibility of using automated capture of Electronic Medical Record (EMR) data to build predictive models for amyotrophic lateral sclerosis (ALS) outcomes.

Methods

We used an Informatics for Integrating Biology and the Bedside search discovery tool to identify and extract data from 354 ALS patients from the University of Kansas Medical Center EMR. The completeness and integrity of the data extraction were verified by manual chart review. A linear mixed model was used to model disease progression. Cox proportional hazards models were used to investigate the effects of BMI, gender, and age on survival.

Results

Data extracted from the EMR was sufficient to create simple models of disease progression and survival. Several key variables of interest were unavailable without including a manual chart review. The average ALS Functional Rating Scale – Revised (ALSFRS-R) baseline score at first clinical visit was 34.08, and average decline was ??0.64 per month. Median survival was 27?months after first visit. Higher baseline ALSFRS-R score and BMI were associated with improved survival, higher baseline age was associated with decreased survival.

Conclusions

This study serves to show that EMR-captured data can be extracted and used to track outcomes in an ALS clinic setting, potentially important for post-marketing research of new drugs, or as historical controls for future studies. However, as automated EMR-based data extraction becomes more widely used there will be a need to standardize ALS data elements and clinical forms for data capture so data can be pooled across academic centers.

     

胸腔镜局麻下治疗结核性胸膜粘连及包裹

目的:研究胸腔镜局麻下治疗结核性胸膜粘连及包裹的方法及临床效果。方法:以我院自2014年3月23日-2016年3月23日收治的68例结核性胸膜炎粘连包裹患者为研究对象,采用随机数表法分成两组。观察组接受胸腔镜局麻下粘连分离术治疗,对照组采取常规穿胸水引流术治疗,比较两组临床效果。结果:观察组总有效率(94.12%)高于对照组总有效率(85.29%),组间差异显著(P0.05)。观察组患者治疗后6个月BORG评分低于治疗后1个月,差异有统计学意义(P0.05)。观察组患者治疗后1、3、6个月BORG评分均显著低于对照组(P0.05)。接受治疗后3、6个月,对照组患者BORG评分均低于治疗后1个月,差异均有统计学意义(P0.05)。观察组患者治疗后6个月FVC水平高于治疗后3个月(P0.05)。相较于对照组,观察组患者治疗后1、3、6个月FVC水平明显更高(P0.05)。结论:胸腔镜局麻下治疗结核性胸膜粘连及包裹效果十分显著,可明显改善患者肺功能和临床症状,对患者有利。     

糖皮质激素联合免疫球蛋白治疗机械通气的吉兰巴雷综合征的临床疗效分析

目的:分析糖皮质激素联合免疫球蛋白治疗需要机械通气的吉兰巴雷综合征的临床疗效。方法:回顾性分析2008年1月至2016年7月西安市六家医院收治的采用机械通气的吉兰巴雷综合征患者的临床资料,并对其进行随访,比较单用免疫球蛋白与糖皮质激素联合免疫球蛋白的疗效差异。结果:两组在出院时及出院后6个月的总有效率(MRC及HFGS的改善率)、死亡率、机械通气时间、住院时间、在ICU住院时间、出院时及出院后6个月的MRC总得分和HFGS得分以及并发症发生率比较差异均无统计学意义(P0.05)。结论:对于机械通气的吉兰巴雷综合征患者,在使用免疫球蛋白的基础上增加糖皮质激素的使用,对其短期(出院时)及较长期(出院后6个月)的临床疗效和安全性均无显著影响。     

Is cerebrospinal fluid obtained for diagnostic purpose a good material for biomarker studies in amyotrophic lateral sclerosis?

Abstract

The cerebrospinal fluid (CSF) used for identification of molecular biomarkers in amyotrophic lateral sclerosis (ALS) is mainly obtained from lumbar puncture (LP) performed to exclude other causes of motor neuron damage.

Aim: The aim of the study was to analyze whether CSF of ALS patients obtained for diagnostic purposes is suitable for biomarker studies in the entire ALS population.

Material and methods: We analyzed the medical data, LP frequency and CSF parameters in 568 ALS patients.

Results: LP was performed in 34% of cases. Patients who underwent LP were significantly younger and more frequently presented limb onset ALS, there were no differences in the clinical phenotypes.

Conclusion: CSF obtained for diagnostic purposes can be used for biomarkers studies in ALS.     

噻托溴铵联合奥达特罗治疗慢性阻塞性肺疾病患者的疗效及对免疫功能的影响

目的:探讨噻托溴铵联合奥达特罗治疗慢性阻塞性肺疾病(COPD)患者的疗效及对免疫功能的影响。方法:选取我院于2018年10月到2019年10月期间接收的108例COPD患者,按照随机数字表法将患者分为噻托溴铵组(n=36,噻托溴铵治疗)、奥达特罗组(n=36,奥达特罗治疗)、联合组(n=36,噻托溴铵联合奥达特罗治疗),比较三组患者疗效、肺功能、免疫功能及不良反应。结果:联合组治疗3个月后的临床总有效率、肺活量(FVC)、第1秒用力呼气容积(FEV1)、FEV1/FVC、CD3+、CD4+、免疫球蛋白G(Ig G)、免疫球蛋白M(Ig M)均高于奥达特罗组、噻托溴铵组(P0.05)。奥达特罗组、噻托溴铵组治疗3个月后的的临床总有效率、FVC、FEV1、FEV1/FVC、CD3+、CD4+、Ig G、Ig M比较差异无统计学意义(P0.05)。三组治疗期间不良反应发生率整体比较差异无统计学意义(P0.05)。结论:噻托溴铵联合奥达特罗治疗COPD患者,疗效显著,可有效改善免疫功能及肺功能,且不增加不良反应发生率。     

Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial

Background aimsDendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2⁺ patients) or with autologous/allogeneic tumor lysate (HLA-A2^? patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-α2b.ResultsOf 46 patients who initiated treatment, 10 stopped treatment within 1–4 weeks because of rapid disease progression and deterioration. After 8 weeks, 36 patients were evaluable: no patient had an objective response, 11 patients had stable disease (SD); six had continued SD after 4 months, and three patients had prolonged SD for more than 6 months. The mean overall survival time was 9 months, with a significantly longer survival (18.4 months) of patients who attained SD compared with patients with progressive disease (PD) (5 months). Induction of antigen-specific T-cell responses was analyzed by multidimensional encoding of T cells using HLA-A2 major histocompatibility complex (MHC) multimers. Immune responses against five high-affinity vaccine peptides were detectable in the peripheral blood of six out of 10 analyzed HLA-A2⁺ patients. There was no observed correlation between the induction of immune responses and disease stabilization. A significant lower blood level of regulatory T cells (CD25^high CD4 T cells) was demonstrable after six vaccinations in patients with SD compared with PD.ConclusionsVaccination was feasible and safe. Treatment-associated SD was observed in 24% of the patients. SD correlated with prolonged survival suggesting a clinical benefit. Differences in the level of regulatory T cells among SD and PD patients could indicate a significant role of these immune suppressive cells.     

丹参川芎嗪注射液联合NIPPV治疗COPD合并呼吸衰竭的临床疗效

目的:探讨丹参川芎嗪注射液联合无创正压通气(NIPPV)治疗慢性阻塞性肺病COPD合并呼吸衰竭的临床疗效。方法:选择2015年1月至2016年12月在我院进行治疗的COPD合并呼吸衰竭患者70例,随机分为两组,每组35例。对照组患者采用NIPPV治疗,观察组在此基础上给予丹参川芎嗪注射液静脉滴注。比较两组患者治疗期间的动脉血气分数、肺功能指标,评价两组患者治疗前后的病情状况以及阻塞性肺病及支气管哮喘生理状况。结果:治疗后3 d以及10 d,观察组动脉血氧分压(PaO_2)、一秒用力呼气容积(FEV1)、用力肺活量(FVC)以及FEV1/FVC均显著高于对照组(P0.05),观察组动脉二氧化碳分压(PaCO_2)显著低于对照组(P0.05),而两组间动脉血氧饱和度(SaO_2)、pH比较差异无统计学意义(P0.05)。治疗后,观察组的急性生理性与慢性健康状况(APACHEⅡ)以及慢性阻塞性肺疾病和支气管哮喘生理(CAPS)评分均显著低于对照组(P0.05)。结论:丹参川芎嗪注射液辅助NIPPV有利于COPD合并呼吸衰竭患者肺功能的恢复,改善患者血气指标和预后。     

无创正压通气联合纤维支气管镜肺泡灌洗对老年AECOPD合并Ⅱ型呼吸衰竭患者肺功能及血气指标的影响

目的:观察无创正压通气(NIPPV)联合纤维支气管镜(FB)肺泡灌洗对老年急性加重期慢性阻塞性肺疾病(AECOPD)合并Ⅱ型呼吸衰竭患者肺功能及血气指标的影响,为临床治疗方案的选择提供依据。方法:选取82例于2017年1月～2019年1月间在我院住院治疗的老年AECOPD合并II型呼吸衰竭患者。根据治疗方法将患者分为观察组(NIPPV联合FB肺泡灌洗治疗,n=42)与对照组(单独NIPPV治疗,n=40)。观察两组患者的住院时间及抗菌药静脉滴注时间,并比较治疗前及治疗后两组患者的血气指标[pH值(pH)、氧分压(PaO_2)、二氧化碳分压(PaCO_2)、血氧饱和度(SaO_2)]、肺功能指标[一秒钟用力呼气容积(FEV1)、肺活量(FVC)、呼气峰值流速(PEF)]的变化情况。记录两组患者治疗过程中的并发症发生情况。结果:观察组住院时间及抗菌药物静脉滴注时间均明显短于对照组(P0.05)。治疗后,两组pH、PaO_2、SaO_2明显上升,而PaCO_2明显下降(P0.05),且与对照组比较,观察组的pH、PaO_2、SaO_2明显较高,而PaCO_2明显较低(P0.05)。治疗后,对照组FEV1、FVC、PEF无明显变化(P0.05),观察组FEV1、FVC、PEF均明显升高且高于对照组(P0.05)。两组患者不良反应发生率比较差异无统计学意义(P0.05)。结论:NIPPV联合FB肺泡灌洗治疗对老年AECOPD合并II型呼吸衰竭患者血气指标及肺功能均有较好的改善效果,能明显缩短患者的住院时间及抗菌药静脉滴注时间,且安全性良好。     

The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron dysfunction and loss, rapidly progressive muscle weakness, wasting and death. Many factors, including mitochondrial dysfunction, may contribute to ALS pathogenesis. Riluzole, which has shown only modest benefits in a measure of survival time without demonstrated effects on muscle strength or function, is the only approved treatment for ALS. We tested the putative mitochondrial modulator dexpramipexole (KNS-760704; (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine) in subjects with ALS in a two-part, double-blind safety and tolerability study, with a preliminary assessment of its effects on functional decline and mortality. In part 1, the effects of dexpramipexole (50, 150 or 300 mg d(-1)) versus placebo were assessed over 12 weeks. In part 2, after a 4-week, single-blind placebo washout, continuing subjects were re-randomized to dexpramipexole at 50 mg d(-1) or 300 mg d(-1) as double-blind active treatment for 24 weeks. Dexpramipexole was safe and well tolerated. Trends showing a dose-dependent attenuation of the slope of decline of the ALS Functional Rating Scale-Revised (ALSFRS-R) in part 1 and a statistically significant (P = 0.046) difference between groups in a joint rank test of change from baseline in ALSFRS-R and mortality in part 2 strongly support further testing of dexpramipexole in ALS.     

Bi PAP呼吸机无创通气联合氧气驱动雾化吸入对慢阻肺合并呼吸衰竭的疗效

摘要 目的：研究Bi PAP呼吸机无创通气以及氧气驱动雾化吸入联用对慢性阻塞性肺疾病（慢阻肺）合并呼吸衰竭的疗效。方法：选择2016年12月～2018年12月我院的121例慢阻肺合并呼吸衰竭患者,随机分为两组。对照组采用Bi PAP呼吸机无创通气疗法,观察组联合氧气驱动雾化吸入布氨溴索和地奈德混悬液。比较两组的呼吸频率、血气指标和心率;血清肺表面活性相关蛋白D(Pulmonary surfactant related protein,SP-D)以及部活化调节趋化因子(PARC/CCL18)水平、肺功能。结果：观察组的有效率明显高于对照组(P<0.05);治疗后,两组的呼吸频率、血气指标和心率明显改善(P<0.05),且观察组的呼吸频率、血气指标和心率明显优于对照组(P<0.05);治疗后,两组的血清PARC/CCL18 以及SP-D水平均明显降低(P<0.05),且观察组的血清PARC/CCL18 以及SP-D水平明显低于对照组(P<0.05);治疗后,两组的FEV₁%、呼吸困难指数以及FEV₁/FVC明显改善(P<0.05),且观察组的FEV₁%、呼吸困难指数以及FEV₁/FVC明显优于对照组(P<0.05)。结论：Bi PAP呼吸机无创通气以及氧气驱动雾化吸入联用能改善慢阻肺合并呼吸衰竭的血气指标、生命体征和肺功能,降低血清 PARC/CCL18 以及SP-D水平。     

慢性阻塞性肺疾病患者中血清亲环素A、趋化因子CX3CL1表达水平及临床意义

摘要 目的：探讨慢性阻塞性肺疾病（COPD）患者中血清亲环素A（CyPA）、趋化因子CX3CL1以及其他炎性指标的表达水平及其临床意义。方法：选取2019年1月-2021年6月本院收治的COPD患者120例作为研究对象,其中68例患者为急性加重期组,52例患者为稳定期组;另选取体检健康者45例作为对照组。收集所有受试者的临床资料,检测其血清中CyPA、CX3CL1、C反应蛋白（CRP）、白细胞介素-6（IL-6）以及基质金属蛋白酶-9（MMP-9）水平,比较3组患者各参数的差异,并与肺功能进行相关性分析,比较急性加重期患者治疗前后各指标的差异。结果：急性加重期组患者的血清 CyPA、CX3CL1、CRP、IL-6、MMP-9水平均明显高于稳定期组和对照组患者,稳定期组患者的血清 CyPA、CX3CL1、CRP、IL-6、MMP-9水平均明显高于对照组患者（均P＜0.05）;而急性加重期组患者的第1s用力呼气量（FEV₁）、用力肺活量（FVC）、第1s用力呼气量（FEV₁）与用力肺活量（FVC）的比值（FEV₁%）、最大呼气峰流速（PEF）以及最大呼气中期流速（MMEF）明显低于稳定期组和对照组患者,稳定期组患者的FEV₁、FVC、FEV₁/FVC、PEF、MMEF明显低于对照组患者（均P＜0.05）。COPD患者的血清CyPA、CX3CL1、CRP、IL-6、MMP-9水平与FEV₁、FVC、FEV₁/FVC、PEF、MMEF呈负相关（P<0.05）。与治疗前相比较,急性加重期组患者在治疗后血清CyPA、CX3CL1、CRP、IL-6、MMP-9水平明显下降,而FEV₁、FVC、FEV₁/FVC、PEF、MMEF明显上升（均P＜0.05）。结论：COPD患者的血清CyPA、CX3CL1、CRP、IL-6、MMP-9水平可在一定程度上预测患者的严重程度,同时也可以作为急性加重期治疗后效果的评价指标。     

Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study

Background aimsMesenchymal stem cells/marrow stromal cells (MSC) represent a promising tool for stem cell-based clinical trials in amyotrophic lateral sclerosis (ALS). We present the results of long-term monitoring of 19 ALS patients enrolled in two phase I clinical trials of autologous MSC transplantationMethodsNineteen patients (11 male and eightfemale) with ALS were enrolled in two consecutive phase I clinical trials. The patients were followed-up for 6–9 months and then treated with autologous MSC isolated from bone marrow and implanted into the dorsal spinal cord with a surgical procedure. The patients were monitored regularly before and after transplantation with clinical, psychological and neuroradiologic assessments every 3 months, at the tertiary referral ALS center in Novara (Italy), until deathResultsFollow-up brain magnetic resonance imaging (MRI) revealed no structural changes (including tumor formation) relative to the baseline throughout the follow-up. There was no deterioration in the psychosocial status and all patients coped well. No clear clinical benefits were detected in these patients but the recruitment and selection of appropriate patients into larger trials will be needed to test the efficacy of the treatmentConclusionsThis study is the first to show the safety of MSC transplantation in the central nervous system during a follow-up of nearly 9 years, and is in support of applying MSC-based cellular clinical trials to neurodegenerative disorders.     

腹式呼吸训练法对COPD伴Ⅱ型呼吸衰竭患者肺通气状态、血气指标及运动耐力的影响

摘要 目的：探讨腹式呼吸训练法对慢性阻塞性肺疾病（COPD）伴Ⅱ型呼吸衰竭患者肺通气状态、血气指标及运动耐力的影响。方法：选择我院2020年07月2022年12月期间收治的100例COPD伴Ⅱ型呼吸衰竭患者,根据随机数字表法将患者分为对照组[常规治疗基础上接受双水平气道正压（BIPAP）辅助通气,n=50]和研究组（对照组的基础上接受腹式呼吸训练法干预,n=50）。对比两组临床相关指标、肺通气状态、血气指标及运动耐力指标。结果：研究组的喘憋消失时间、体温恢复正常时间、住院时间、肺部啰音消失时间短于对照组（P<0.05）。两组干预1周后第1秒呼气的最大容积（FEV₁）、最大自主分钟通气量（MVV）、用力肺活量（FVC）均升高,且研究组高于对照组（P<0.05）。两组干预1周后氧分压（PaO2₂）、血氧饱和度（SpO₂）均升高,且研究组高于对照组;二氧化碳分压（PaCO₂）下降,且研究组低于对照组（P<0.05）。两组干预1周后6 min步行距离（6MWT）升高,且研究组高于对照组（P<0.05）。结论：腹式呼吸训练法有助于改善COPD伴Ⅱ型呼吸衰竭患者的临床症状,调节肺通气状态、血气指标,提高运动耐力。