scholarly journals SOD1 Mutation Spectrum and Natural History of ALS Patients in a 15-Year Cohort in Southeastern China

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu-Xi Chen ◽  
Hai-Feng Xu ◽  
Pei-Shan Wang ◽  
Xin-Xia Yang ◽  
Zhi-Ying Wu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Diagnostic Delay ◽  
Mutation Spectrum ◽  
Survival Duration ◽  
Southeastern China ◽  
History Of ◽  
Male Patients ◽  
The Mean ◽  
Als Patients

Background: Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials.Methods: We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed.Results: We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, 32 probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) vs. 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 vs. 16 months, p = 0.05).Conclusion: Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.

scholarly journals SOD1 mutation spectrum and natural history of ALS patients in a 15-year Cohort in Southeastern China

2021 ◽  
Author(s):  
Lu-xi Chen ◽  
Hai-feng Xu ◽  
Pei-Shan Wang ◽  
Xin-Xia Yang ◽  
Zhi-Ying Wu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Diagnostic Delay ◽  
Mutation Spectrum ◽  
Survival Duration ◽  
Southeastern China ◽  
History Of ◽  
Male Patients ◽  
The Mean ◽  
Als Patients

Abstract Background Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials. Methods We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed. Results We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, thirty-two probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) years vs 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 months vs 16 months, p = 0.05). Conclusion Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in Southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.

Revisiting the Natural History of Chronic Scaphoid Nonunions: A Retrospective Study of 20 Cases

2021 ◽  
Author(s):  
J. Terrence Jose Jerome
Keyword(s):  
Retrospective Study ◽  
Natural History ◽  
Functional Outcome ◽  
Grip Strength ◽  
Scaphoid Nonunion ◽  
Proximal Pole ◽  
Degenerative Arthritis ◽  
Level Of Evidence ◽  
History Of ◽  
The Mean

Abstract Background The natural history of scaphoid nonunion is the development of degenerative arthritis. A lot of information is still unclear about this progression. The purpose of this study is to analyze patients with scaphoid nonunions who had not received any kind of treatment and to assess the functional outcome. Materials and Methods This is a retrospective study that analyzed the patients with chronic scaphoid nonunions between 2009 and 2019. None of the patients received any treatment. The age at the time of injury, examination, pattern of fracture, types of scaphoid nonunion, symptoms, and duration of nonunion were noted. Diagnosis was confirmed by radiographs, computed tomography (CT) scan, and magnetic resonance imaging (MRI). Scapholunate and radiolunate angles were recorded. Pain score, modified mayo wrist score, grip strength, range of movement, and the functional outcome of these scaphoid nonunions were analyzed. A statistical correlation between the scaphoid nonunion presentations and the functional outcome was assessed. Results The mean age of the patients was 62 years (range: 35–82 years.). There were 17 male and 3 female patients. There were 9 waist and 11 proximal pole scaphoid nonunions. The mean duration of scaphoid nonunion was 34 years (range: 10–62 years). None of the patients had avascular necrosis (AVN) of the proximal scaphoid. The age at examination, gender, side of injury, fracture pattern (waist/proximal pole), fracture displacement ≤ 1 mm or > 1 mm, nonunion duration, and radiographic arthritic parameters had no significant impact on the functional outcome. Conclusions Untreated chronic scaphoid nonunion leads to the development of degenerative arthritis over a period of years, which is still unpredictable. Most of the patients become aware of the nonunion following a precedent injury or other reasons. Most of the patients have fair/good functional outcome despite reduced range of movements and grip strength. Many do not favor surgical intervention in the course of nonunion. Chronic nonunions open a lot of unanswered questions. Clinical relevance There have been numerous studies on the treatment aspects of scaphoid nonunion, with little knowledge about certain people with nonunion who did not have any kind of treatment. The demographics, clinical findings, and radiological parameters do confirm the progression of these nonunion to arthritis, but most of them had fair-to-good outcome throughout their life. It opens our thinking about the real need of treatment in such nonunions and raises numerous questions about the disease. Level of evidence This is a Level IV study.

Natural History of Patients Taking Rifaximin-α for Recurrent Hepatic Encephalopathy and Risk of Future Overt Episodes and Mortality: A Post-hoc Analysis of Clinical Trials Data

2016 ◽  
Vol 38 (5) ◽  
pp. 1081-1089.e4 ◽  
Author(s):  
Christian A. Bannister ◽  
James G. Orr ◽  
Alan V. Reynolds ◽  
Mark Hudson ◽  
Peter Conway ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hepatic Encephalopathy ◽  
Natural History ◽  
Post Hoc Analysis ◽  
History Of ◽  
Post Hoc

Natural history of coronary atherosclerosis using quantitative angiography in men, and implications for clinical trials of coronary regression

1993 ◽  
Vol 71 (10) ◽  
pp. 766-772 ◽  
Author(s):  
Peter H. Stone ◽  
C. Michael Gibson ◽  
Richard C. Pasternak ◽  
Kathy McManus ◽  
Lazaro Diaz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Coronary Atherosclerosis ◽  
History Of ◽  
Quantitative Angiography

The natural history of pineal cysts in children and young adults

2010 ◽  
Vol 5 (2) ◽  
pp. 162-166 ◽  
Author(s):  
Wajd N. Al-Holou ◽  
Cormac O. Maher ◽  
Karin M. Muraszko ◽  
Hugh J. L. Garton
Keyword(s):  
Natural History ◽  
Mr Imaging ◽  
Initial Study ◽  
Older Children ◽  
Imaging Evaluation ◽  
Imaging Appearance ◽  
Imaging Characteristics ◽  
History Of ◽  
The Mean

Object The authors reviewed their experience with pediatric pineal cysts to define the natural history and clinical relevance of this common intracranial finding. Methods The authors identified all patients with pineal cysts who had been clinically evaluated at their institution over an 11.5-year interval and were < 25 years of age at the time of diagnosis. All inclusion criteria were met in 106 patients, and included repeated MR imaging as well as repeated clinical evaluation over at least a 6-month interval. Results The mean age at diagnosis was 11.7 ± 7.2 years. Forty-two patients were male and 64 were female. On follow-up MR imaging evaluation at a mean interval of 3.0 years from the initial study, 98 pineal cysts had no increase in size and no change in imaging appearance. Six pineal cysts increased in size and 2 others had a change in imaging characteristics without associated growth. Younger age was associated with cyst change or growth on follow-up imaging (p = 0.02). The mean age of patients with cysts that changed or grew was 5.5 years, and the mean age of patients with stable pineal cysts was 12.2 years. Initial cyst size and appearance on MR imaging were not significant predictors of growth or change in imaging appearance at follow-up. Similarly, the patient's sex was not a significant predictor of growth or change in imaging characteristics. Conclusions Follow-up imaging and neurosurgical evaluation may be considered optional in older children with pineal cysts.

Watchful Waiting for Ventral Hernias: A Longitudinal Study

2014 ◽  
Vol 80 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Charles F. Bellows ◽  
Celia Robinson ◽  
Robert J. Fitzgibbons ◽  
Larry S. Webber ◽  
David H. Berger
Keyword(s):  
Natural History ◽  
Repeated Measures ◽  
Watchful Waiting ◽  
Recurrence Rates ◽  
Safe Option ◽  
Sf 36 ◽  
History Of ◽  
The Mean ◽  
Ventral Hernias

Ventral hernias are a common clinical problem. Immediate repair is recommended for most ventral hernias despite significant recurrence rates. This practice may be related to a lack of understanding of the natural history of ventral hernias. The purpose of this study was to determine the natural history of ventral hernias and to determine if watchful waiting is an acceptable and safe option. Forty-one patients with ventral hernias were enrolled in a longitudinal cohort study of watchful waiting. Primary outcomes were functional impairment resulting from hernia disease as measured by the Activities Assessment Scale (AAS) and changes from baseline to two years in the physical and mental component score of the SF-36 Health Survey. Secondary outcomes included complications such as incarceration. Mixed-effects model for repeated measures and Student's t tests were used to evaluate scale performance. The mean age of enrollees was 64 years, and the mean hernia size was 239 cm2. Eleven patients were lost to follow-up, and seven patients died of other causes. All remaining patients were followed for two years. There was one incarceration during the follow-up period. There was no deterioration in the AAS score (baseline vs 24 months = 28 vs 25, P = 0.60). There was deterioration of the physical functioning dimension of the SF-36 (baseline vs 24 months = 40 vs 32, P < 0.01), but the mental functioning dimension was improved (45 vs 51; P = 0.01). Watchful waiting was a safe option for patients in this study with ventral hernias.

scholarly journals Integrating Biomarker Outcomes into Clinical Trials for Alzheimer’s Disease in Down Syndrome

2020 ◽  
pp. 1-4 ◽  
Author(s):  
M.S. Rafii ◽  
S. Zaman ◽  
B.L. Handen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Down Syndrome ◽  
Natural History ◽  
New Information ◽  
History Of ◽  
Clinically Meaningful Outcomes

The NIH-funded Alzheimer’s Biomarker Consortium Down Syndrome (ABC-DS) and the European Horizon 21 Consortium are collecting critical new information on the natural history of Alzheimer’s Disease (AD) biomarkers in adults with Down syndrome (DS), a population genetically predisposed to developing AD. These studies are also providing key insights into which biomarkers best represent clinically meaningful outcomes that are most feasible in clinical trials. This paper considers how these data can be integrated in clinical trials for individuals with DS. The Alzheimer’s Clinical Trial Consortium - Down syndrome (ACTC-DS) is a platform that brings expert researchers from both networks together to conduct clinical trials for AD in DS across international sites while building on their expertise and experience.

The Natural History of Conservatively Managed Symptomatic Intramedullary Spinal Cord Cavernomas

Neurosurgery ◽  
2007 ◽  
Vol 60 (5) ◽  
pp. 865-872 ◽  
Author(s):  
Siddharth Kharkar ◽  
John Shuck ◽  
James Conway ◽  
Daniele Rigamonti
Keyword(s):  
Spinal Cord ◽  
Natural History ◽  
Duration Of Symptoms ◽  
Intramedullary Spinal Cord ◽  
Additional Information ◽  
History Of ◽  
The Mean ◽  
Spinal Cavernomas ◽  
Time Of Presentation

Abstract OBJECTIVE The presentation and natural history of untreated, symptomatic intramedullary spinal cavernomas at our institution were analyzed. The objective is to provide additional information regarding the natural history of conservatively managed, symptomatic, intramedullary spinal cord cavernous malformations. METHODS The medical records of patients treated in our institution between 1989 and 2002 were reviewed to identify those with intramedullary cavernomas. The medical, radiological, surgical, and pathological records from these patients were retrospectively reviewed and analyzed. RESULTS Fourteen patients were included in the study. The mean age at presentation was 42 years. Four lesions (29%) were located in the cervical region and 10 lesions (71%) were present in the thoracolumbar spinal cord. All patients were symptomatic at the time of presentation. In this cohort of 14 patients, 10 patients (71%) were conservatively managed. For these patients, the mean duration of symptoms before presentation was 10 months. The mean duration of follow-up from the time of presentation was 80 months. The median McCormick grade for conservatively treated patients at presentation was II. During this period, none of the conservatively managed patients had an acute intramedullary bleed. In nine patients, the McCormick grade at the last follow-up evaluation was the same as or better than their score at presentation. Four patients (29%) were treated surgically. The mean duration of symptoms before presentation was 33 months. The mean duration of follow-up from the time of presentation was 42 months. In two surgical patients, the McCormick grade at the last follow-up evaluation remained unchanged compared with their score at presentation, whereas the McCormick grade improved in one patient and deteriorated in another patient. CONCLUSION This cohort of conservatively managed patients with symptomatic, intramedullary spinal cord cavernomas was clinically stable throughout the follow-up period. In this series, patients harboring symptomatic spinal cord cavernous malformation did not have significant, permanent neurological decline during the follow-up period when treated with the conservative approach of observation. This data provides additional information for determining the appropriate treatment strategy for patients with intramedullary spinal cavernomas.

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