scholarly journals Early Axonal Dysfunction of the Peripheral Nervous System Influences Disease Progression of ALS: Evidence From Clinical Neuroelectrophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Huiyan Yu ◽  
Lu Chen ◽  
Shuo Zhang ◽  
Jing He ◽  
Dongsheng Fan

Objective: To assess the prognostic value of the decrement in compound muscle action potential amplitude within 12 months of symptom onset (CMAP-12 amplitude) for the survival of patients with amyotrophic lateral sclerosis (ALS).Methods: Patients were stratified into 4 groups according to the decrement of the CMAP-12 amplitudes: normal (≥the lower limit of normal, LLN), mild (<LLN but ≥50% of LLN), moderate (<50% but ≥30% of LLN) and severe (<30% of LLN). All patients were followed up every 3 months. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression.Results: A total of 149 patients were included in the analysis [90 males (60.4%); mean age at onset, 50.7 years]. The decrement of CMAP-12 amplitudes was normal in 24.2% of patients, mild in 22.1%, moderate in 15.4% and severe in 38.3%. Kaplan–Meier analysis showed there was a significant difference in the overall survival across the 4 groups (p < 0.05). Further pairwise comparisons identified significant differences in survival between the normal vs. the moderate group (p < 0.05) and the normal vs. the severe group (p < 0.01). There was a significant inverse correlation between the CMAP-12 amplitude and overall survival. Compared to that in the normal group, survival in the moderately and severely decreased groups was significantly shorter (HR 3.394, 95% CI 1.292–8.917, p = 0.013; and HR 4.732, 95% CI 2.032–11.017; p = 0.000, respectively).Conclusions: Our results suggest that CMAP-12 amplitude could be a prognostic indicator of disease progression in ALS. More importantly, our findings provide clinical evidence for the viewpoint that early axonal dysfunction of the peripheral nervous system accelerates disease progression of ALS.

2020 ◽  
Author(s):  
Huiyan Yu ◽  
Lu Chen ◽  
Shuo Zhang ◽  
Jing He ◽  
Dongsheng Fan

Abstract Background:Studies have indicated that more axonal dysfunction in early ALS predictive of more aggressive phenotypes. However, as an important electrophysiological index to detect motor axonal damage, the prognostic value of compound muscle action potential (CMAP) in ALS remains unclear. We aimed to determine if CMAP could be a prognostic indicator of disease progression in early ALS.Methods: Patients were stratified into 4 groups according to the decrement of the CMAP amplitude within 12 months of symptom onset (CMAP-12 amplitudes): normal (≥the lower limit of normal, LLN), mild (<LLN but ≥50% of LLN), moderate (<50% but ≥30% of LLN) and severe (<30% of LLN). All patients were followed up every 3 months. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression.Results: A total of 149 patients included in the analysis [90 male (60.4%); mean age at onset, 50.7 years]. The decrement of CMAP-12 amplitudes was normal in 24.2%, mildly in 22.1%, moderately in 15.4% and severely in 38.3%. Kaplan-Meier analysis showed there was a significant difference in the overall survival across the 4 groups (p<0.05). Further pairwise comparison found there were significant differences in survival between the normal vs. the moderately groups (p<0.05), and the normal vs. the severely groups (p<0.01). There was a significant inverse correlation between the CMAP-12 amplitude and overall survival. Compared to the normal group, survival in the moderately and severely decreased groups were significantly shorter (HR 3.394, 95%CI 1.292-8.917, p=0.013; and HR 4.732, 95%CI 2.032-11.017; p=0.000, respectively).Conclusions: Our results suggested that CMAP-12 amplitude could be a prognostic indicator of disease progression in ALS. More importantly, it provided clinical evidences to the viewpoint that early axonal dysfunction of peripheral nervous system accelerates disease progression of ALS.


Author(s):  
Claudius E. Degro ◽  
Richard Strozynski ◽  
Florian N. Loch ◽  
Christian Schineis ◽  
Fiona Speichinger ◽  
...  

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.


2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.


2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Allison Taylor ◽  
Kimberley Doucette ◽  
Bryan Chan ◽  
Xiaoyang Ma ◽  
Jaeil Ahn ◽  
...  

Introduction The literature suggests a widespread reduction in the availability and accessibility of newer treatment options among marginalized groups in AML. Studies from large national databases point to lower socio-economic status, Hispanic and African American race, Medicare or no insurance, being unmarried, treatment at non-academic centers, and rural residence as negatively impacting overall survival (OS) and rates of chemotherapy utilization in AML patients (Patel et al. 2015, Jaco et al. 2017, Bhatt et al. 2018, Master et al. 2016). We hypothesized that facility affiliation and pt volume would also have important effects on time to treatment (TTT) and OS in AML, even when these socioeconomic disparities were accounted for. Methods For this retrospective analysis, we used NCDB data that included 124,988 pts over the age of 18 with AML between the years 2004-2016. Variables analyzed included facility types described as community cancer programs (CP), comprehensive community cancer programs (CCP), academic/research center cancer programs (AC) and integrated network cancer programs (IN), and volume of facilities defined as high volume (HV) and low volume (LV). HV facilities had case volumes of ≥ 99th percentile and all other facilities were classified as LV. Multivariate analyses (MVA) included demographic and socioeconomic covariables. We used Cox proportional hazard analysis for both TTT and OS MVA. The Kaplan-Meier method was used to estimate median TTT and OS, and the log rank test used to compare TTT and OS across predictor variables. Results The median age of AML patients was 63 yrs (range 18-90) with 54% males, and 86% Caucasian. Five percent of patients were treated at CP, 30% at CCP, 44% at AC, and 10% at IN. 21% at HV facilities and 79% at LV facilities. Median TTT in days at CP facilities was 7, compared to 5 days in CCP and AC facilities versus 4 days at IN (p&lt;0.0001). TTT was 5 days at HV facilities versus 4 days at LV facilities (p&lt;0.0001). Kaplan-Meier curves showed that TTT was similar between HV and LV facilities(figure 1). The median OS was 3.25 months in CP compared to 4.34 months at CCP, 5.06 months at IN and 9.53 months at AC (p&lt;0.0001). For facility volume, the median OS was 13.11 months in HV facilities compared to 6.93 months in LV facilities (p&lt;0.0001). When sex, race, age, Hispanic Origin, education, urban/rural residence, Charlson-Deyo Comorbidity score and Great Circle Distance were adjusted for in MVA (table 1), the OS was higher in AC versus CP facilities (hazard ratio [HR] of 0.90 (0.87-0.93, p&lt;0.0001), and there was no statistically significant difference with comparison of other facility types to CP. Similarly, there was a lower OS at LV versus HV facilities with a HR of 1.14 (1.12-1.16, p&lt;0.0001). CCP facilities had a shorter TTT compared to CP with a HR of 1.21 (1.17-1.26, p&lt;0.0001). AC had a shorter TTT than CP with a HR of 1.17 (1.13-1.22, p&lt;0.0001), and IN had a shorter TTT compared to CP with a HR of 1.29 (1.24-1.34, p&lt;0.0001). Additionally, TTT in the MVA for facility volume was shorter in LV facilities compared to HV facilities with HR of 1.05 (1.04-1.07, p&lt;0.0001) [table 1]. Conclusion When adjusting for various socioeconomic factors, we found that TTT was longest in CP compared to CCP, AC, and IN. Treatment at a LV facility resulted in a decreased overall survival. LV facilities may be less familiar with treatment regimens for AML, less likely to use novel treatment options, and be less familiar with the disease. We showed that treatment at an AC compared to CP, CCP and IN facilities improved survival. Given poor outcomes for AML, these results show the importance of going to AC and HV facilities with more experience in treating AML for improved outcomes. Disclosures Lai: Astellas: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy; Agios: Consultancy; Macrogenics: Consultancy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Judy Tung ◽  
Musarrat Nahid ◽  
Mangala Rajan ◽  
Lia Logio

Abstract Background Academic medical centers invest considerably in faculty development efforts to support the career success and promotion of their faculty, and to minimize faculty attrition. This study evaluated the impact of a faculty development program called the Leadership in Academic Medicine Program (LAMP) on participants’ (1) self-ratings of efficacy, (2) promotion in academic rank, and (3) institutional retention. Method Participants from the 2013–2020 LAMP cohorts were surveyed pre and post program to assess their level of agreement with statements that spanned domains of self-awareness, self-efficacy, satisfaction with work and work environment. Pre and post responses were compared using McNemar’s tests. Changes in scores across gender were compared using Wilcoxon Rank Sum/Mann-Whitney tests. LAMP participants were matched to nonparticipant controls by gender, rank, department, and time of hire to compare promotions in academic rank and departures from the organization. Kaplan Meier curves and Cox proportional hazards models were used to examine differences. Results There were significant improvements in almost all self-ratings on program surveys (p < 0.05). Greatest improvements were seen in “understand the promotions process” (36% vs. 94%), “comfortable negotiating” (35% vs. 74%), and “time management” (55% vs. 92%). There were no statistically significant differences in improvements by gender, however women faculty rated themselves lower on all pre-program items compared to men. There was significant difference found in time-to-next promotion (p = 0.003) between LAMP participants and controls. Kaplan-Meier analysis demonstrated that LAMP faculty achieved next promotion more often and faster than controls. Cox-proportional-hazards analyses found that LAMP faculty were 61% more likely to be promoted than controls (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.16–2.23, p-value = 0.004). There was significant difference found in time-to-departure (p < 0.0001) with LAMP faculty retained more often and for longer periods. LAMP faculty were 77% less likely to leave compared to controls (HR 0.23, 95% CI 0.16–0.34, p < 0.0001). Conclusions LAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Damian A. Laber ◽  
Xuebo Yan ◽  
Xiaochun Xu

3068 Background: Raf1 kinase inhibitor protein (RKIP) is able to bind Raf1 to inhibit Ras-Raf-MEK-ERK signaling, a major oncogenic pathway. It has been reported that reduced RKIP expression associates with poor prognosis in many cancers, including gastric adenocarcinoma, gliomas and bladder cancer. However, there are only several studies on its role in non-small cell lung cancer (NSCLC) and the conclusion is still controversial. Hence, we performed this study to assess the prognostic significance of RKIP in our NSCLC population. Methods: Between June 2017 and June 2020, 156 NSCLC patients treated at our hospital were included for the present study. None of the patients had received chemotherapy, radiotherapy or surgery before. Their tumor tissues and surrounding normal lung tissues were collected for immunostain and western blot analysis of RKIP expression and ERK signaling. We collected information about gender, age, histological differentiation, tumor size, TNM stage, and lymph node status. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of various variables in a univariate and multivariate setting. Results: Immunostain and western blot results showed a lower RKIP expression and a higher p-ERK level in cancer tissues compared with the surrounding normal tissues. A reduced RKIP expression with high level of p-ERK was also observed in TNM stages III and IV as compared with I and II. Pearson's chi-squared test confirmed low RKIP expression associated with poorer TNM stage ( p< 0.001) and N-stage ( p< 0.05). No significant correlation was observed between RKIP expression level and gender, age, histological type or tumor size. Kaplan-Meier survival analysis revealed that patients with low RKIP expression had significantly worse overall survival than patients with high RKIP expression ( p= 0.019, log-rank). This conclusion was consistent in the stage I&II patients ( p= 0.011, log-rank) but not in the stage III&IV patients ( p= 0.711, log-rank). Univariate Cox proportional hazards regression analysis indicated Tumor size, TNM stage and RKIP expression significantly affected overall survival of the NSCLC patients. Multivariate Cox proportional hazards regression analysis confirmed RKIP expression remained a significant predictor of survival after correcting for the effects of Tumor size and TNM stage (hazard ratio = 1.730, 95% confidence interval = 1.017 – 2.942, p = 0.043). Conclusions: In this study, low RKIP expression was a poor prognostic indicator in NSCLC as it significantly correlated with poorer TNM stage, N-status, and overall survival. Our findings suggest that by inhibiting Ras-Raf-MEK-ERK pathway RKIP may play an anti-tumor role in NSCLC.


2021 ◽  
Vol 21 ◽  
Author(s):  
Minyong Peng ◽  
Shan Li ◽  
Hui Xiang ◽  
Wen Huang ◽  
Weiling Mao ◽  
...  

<P>Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. <P> Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. <P> Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. <P> Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80). <P> Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.</P>


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
KOSUKE DOI ◽  
Yasuhiro Hamatani ◽  
Akiko Fujino ◽  
...  

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii80-iii80
Author(s):  
M Yahia-Cherif ◽  
O De Witte ◽  
C Mélot ◽  
F Lefranc

Abstract BACKGROUND The aim of this study was i) to analyse the effect of repeat surgeries on the survival of patients with focally recurrent glioblastoma who have benefited from temozolomide treatment and ii) to identify potential prognostic factors for survival. MATERIAL AND METHODS Cases from 2005 to 2014 in the glioblastoma database of our department were retrospectively reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) as a function of time after one, two and three surgical resections. All patients received the standard of care after the first surgery (temozolomide during and after radiotherapy) and adjuvant treatment after repeat surgeries. RESULTS One hundred-thirty-two glioblastoma patients (median age: 57 years) were included in the study. Among them, 68, 53 and 11 patients underwent one, two and three surgical resections, respectively. The median OS was 11, 16 and 18 months, respectively, for patients who underwent one, two and three surgical resections. Patients who underwent two (p<0.001) or three (p<0.01) surgeries survived significantly longer than patients who underwent only one. No significant difference was observed between patients who underwent two versus three surgeries (p=0.76). A second resection performed more than 6 months after the initial resection was the only factor associated with prolonged survival (p=0.008). CONCLUSION Glioblastoma patients who benefited from temozolomide treatment and underwent surgery for recurrent glioblastoma exhibited a significant increase in survival compared with patients who did not undergo a second surgery. By contrast, a third surgery for a second recurrence did not contribute to any significant survival benefit.


Sign in / Sign up

Export Citation Format

Share Document