Risk factors for survival in patients with von Hippel-Lindau disease

2018 ◽  
Vol 55 (5) ◽  
pp. 322-328 ◽  
Author(s):  
Jiang-Yi Wang ◽  
Shuang-He Peng ◽  
Teng Li ◽  
Xiang-Hui Ning ◽  
Sheng-Jie Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Median Survival ◽  
Chinese Patients ◽  
Onset Age ◽  
Von Hippel Lindau ◽  
Risk Of Death ◽  
Truncating Mutation ◽  
Vhl Disease ◽  
Mutation Type

BackgroundHistorically, von Hippel-Lindau (VHL) disease is characterised by a poor survival. Although genotype–phenotype correlation has been described in many studies, the risk factors for VHL survival remain unclear. This study aims to evaluate the median survival of Chinese patients with VHL disease and explore whether VHL survival is influenced by genetic and clinical factors.MethodsIn this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan-Meier plot and Cox regression model were used to evaluate the median survival and assess how survival was influenced by birth year, birth order, sex, family history, mutation type, onset age and first presenting symptom.ResultsThe estimated median life expectancy for Chinese patients with VHL disease was 62 years. Patients with early-onset age, positive family history and truncating mutation types had poorer overall and VHL-related survival. Patients with haemangioblastoma as their first presenting symptom were related to a higher risk of death from central nervous system haemangioblastoma than those with abdominal lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004).ConclusionsThis largest VHL survival analysis indicates that onset age, family history, mutation type and first presenting symptom have an effect on the survival of patients with VHL disease, which is helpful to genetic counselling and clinical decision-making.

scholarly journals Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients

2021 ◽  
pp. jmedgenet-2021-108216
Author(s):  
Kenan Zhang ◽  
Jianhui Qiu ◽  
Wuping Yang ◽  
Kaifang Ma ◽  
Lei Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Risk Factor ◽  
Survival Analysis ◽  
Life Expectancy ◽  
Independent Risk Factor ◽  
Onset Age ◽  
Affected Offspring ◽  
Von Hippel Lindau ◽  
Vhl Disease

BackgroundVon Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors.MethodsIn this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis.ResultsThe estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group.ConclusionThis study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.

Unique clinical features of cryptococcal meningitis among Chinese patients without predisposing diseases against patients with predisposing diseases

2019 ◽  
Vol 57 (8) ◽  
pp. 944-953 ◽  
Author(s):  
Lijun Xu ◽  
Xinyue Zhang ◽  
Yongzheng Guo ◽  
Ran Tao ◽  
Xiahong Dai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Serum Albumin ◽  
Amphotericin B ◽  
Clinical Features ◽  
Cryptococcal Meningitis ◽  
White Blood Cells ◽  
Chinese Patients ◽  
Fungal Burden ◽  
Risk Of Death ◽  
Culture Positivity

Abstract The clinical features of cryptococcal meningitis (CM) in patients without predisposing diseases (PD) remain unclear. In sum, 162 of the 167 patients without PD and 162 of the 309 patients with PD were enrolled after propensity score matching. Demographic characteristics, symptoms, blood, and cerebrospinal fluid (CSF) characteristics were compared between the two groups. Kaplan-Meier curves and a Cox proportional hazards model were used to assess the factors associated with 10-week mortality. In total, approximately 35.1% of CM patients were without PD. CM patients without PD had blood profiles of higher white blood cells (WBC) [8.9(6.7–11.0) × 109/l], hemoglobin (128.4 ± 20.9 g/l), platelets [(226.2 ± 64.1) × 109/l], and serum albumin (41.2 ± 5.8 g/l) (all P ≤ .001) and CSF profiles of lower glucose (2.0 ± 1.2 mmol/l), pleocytosis [65.0 (18.0–160.0) × 106/l] and higher total protein [0.9 (0.7–1.4)g/l] (all P < .05). CM patients without PD had lower Cryptococcus culture positivity in CSF (62.5% vs. 74.1%, P = .039) but higher 2-week of CSF culture sterilization rates (69.4% vs. 51.3%, P = .031). The overall 10-week survival rate was 84.7% in patients without PD and 81.1% in patients with PD (Log-rank P = .439). CSF glucose <1.5 mmol/l, CSF fungal burden >20 cells/high power field and treatment lacking amphotericin B had a 3–4 times higher risk of death in patients without PD, whereas serum albumin <35 g/l, CSF glucose < 1.5 mmol/l, and CSF WBC <55 × 106 cell/l were risk factors for patients with PD. CM patients without PD had unique blood and CSF profiles, especially, had lower Cryptococcus culture positivity in CSF, and higher 2-week CSF culture sterilization. Low CSF glucose levels, higher fungal burden, and treatment without amphotericin B were risk factors for 10-week mortality.

scholarly journals rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics

2021 ◽  
Vol 27 ◽  
Author(s):  
Gyula Remenyi ◽  
Zsuzsanna Bereczky ◽  
Réka Gindele ◽  
Aniko Ujfalusi ◽  
Arpad Illes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
Gene Mutations ◽  
Tissue Oxygen ◽  
Blood Cell Count ◽  
Von Hippel Lindau ◽  
The Family ◽  
Red Blood Cell Count ◽  
Vhl Disease ◽  
Secondary Causes

Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline VHL mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. VHL polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for VHL mutations. There were no classical somatic VHL mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 VHL c.-195G&gt;A polymorphism accompanied by erythrocytosis. These patients are Jak-2 negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.

scholarly journals Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease

2019 ◽  
Author(s):  
Jiangyi Wang ◽  
Xiang Peng ◽  
Cen Chen ◽  
Xianghui Ning ◽  
Shuanghe Peng ◽  
...  
Keyword(s):  
Birth Order ◽  
Statistical Methods ◽  
Order Effect ◽  
Phenotypic Heterogeneity ◽  
The Other ◽  
Onset Age ◽  
Genetic Anticipation ◽  
Von Hippel Lindau ◽  
Birth Order Effect ◽  
Vhl Disease

AbstractVon Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The current recommendations have proposed uniform surveillance strategies for all patients, neglecting the obvious phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in VHL disease and the underlying mechanism. A total of 151 parent-child pairs were enrolled for genetic anticipation analysis, and 77 sibling pairs for birth order effect analysis. Four statistical methods were used to compare the onset age of patients among different generations and different birth orders. The results showed that the average onset age was 18.9 years earlier in children than in their parents, which was statistically significant in all of the four statistical methods. Furthermore, the first-born siblings were affected 8.3 years later than the other ones among the maternal patients. Telomere shortening was confirmed to be associated with genetic anticipation in VHL families, while it failed to explain the birth order effect. Moreover, no significant difference was observed for overall survival between parents and children (p=0.834) and between first-born patients and the other siblings (p=0.390). This study provides definitive evidence and possible mechanisms of intra-familial phenotypic heterogeneity in VHL families, which is helpful to the update of surveillance guidelines.

Clinical characteristics and risk factors for headache associated with non-functioning pituitary adenomas

Cephalalgia ◽  
2016 ◽  
Vol 37 (4) ◽  
pp. 348-355 ◽  
Author(s):  
Bin Yu ◽  
Nan Ji ◽  
Yun Ma ◽  
Bao Yang ◽  
Peng Kang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pituitary Adenoma ◽  
Family History ◽  
Cavernous Sinus ◽  
Clinical Characteristics ◽  
Chinese Patients ◽  
Primary Headaches ◽  
Endocrine Activity ◽  
Cavernous Sinus Invasion ◽  
History Of

Background Headaches associated with pituitary adenoma have been reported to be related to the structural characteristics and endocrine factors of the tumour itself. Objectives The objective of this study was to investigate the prevalence and clinical characteristics of, and the risk factors for, non-functioning pituitary adenoma (NFPA)-associated headaches in Chinese patients with normal endocrine activity. Methods Ninety-seven patients with a NFPA with normal endocrine laboratory results were prospectively enrolled in this study. The relevant clinical demographic data were collected and examined with the appropriate statistical methods. Results The pre-operative prevalence of tumour-associated headaches was 48.5%; 87.2% of these patients had migraine-like headaches. A family history of primary headache (odds ratio (OR) 3.67; p = 0.032) and a higher tumour Knosp grade (OR 1.83; p = 0.001) were identified as risk factors for the occurrence of NFPA-associated headaches. The patient’s age, sex, visual disturbances, optic chiasm compression, tumour size and tumour volume were not significantly associated with NFPA-associated headaches ( p > 0.05). In addition, headache severity was significantly correlated with the Knosp grade ( r = 0.339; p = 0.001). The sides of the headaches and of cavernous sinus invasion were significantly concordant (48.9% agreement; κ = 0.257; p = 0.007). Conclusions Migraine-like headaches are a common clinical manifestation in patients with NFPAs. A family history of primary headaches and cavernous sinus invasion are risk factors for NFPA-associated headaches.

Natural history of renal tumours in von Hippel-Lindau disease: a large retrospective study of Chinese patients

2019 ◽  
Vol 56 (6) ◽  
pp. 380-387 ◽  
Author(s):  
Xiang Peng ◽  
Jinchao Chen ◽  
Jiangyi Wang ◽  
Shuanghe Peng ◽  
Shengjie Liu ◽  
...  
Keyword(s):  
Natural History ◽  
Tumour Growth ◽  
Age Of Onset ◽  
Tumour Size ◽  
Von Hippel Lindau ◽  
Renal Tumours ◽  
History Of ◽  
The Mean ◽  
Vhl Disease ◽  
Mutation Type

BackgroundHistorically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease.MethodsIn this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease.ResultsThe mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC.ConclusionThis large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.

Mortality in dementia is predicted by older age of onset and cognitive presentation

2021 ◽  
pp. 000486742110410
Author(s):  
Samantha M Loi ◽  
Paraskevi Tsoukra ◽  
Zhiben Chen ◽  
Pierre Wibawa ◽  
Tamara Mijuskovic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Median Survival ◽  
Symptom Onset ◽  
Age Of Onset ◽  
Hazard Ratio ◽  
Survival Duration ◽  
Future Planning ◽  
Presenting Symptoms ◽  
Risk Of Death ◽  
Increased Risk

Objectives: Survival information in dementia is important for future planning and service provision. There have been limited Australian data investigating survival duration and risk factors associated with mortality in younger-onset dementia. Methods: This was a cross-sectional retrospective study investigating survival in inpatients with a diagnosis of dementia admitted to a tertiary neuropsychiatry service from 1991 to 2014. The Australian Institute of Health and Welfare National Death Index was used to obtain mortality information. Results: A total of 468 inpatients were identified, of which 75% had symptom onset at ⩽65 years of age (defined as younger-onset dementia). Dementia was categorised into four subtypes, Alzheimer’s dementia, frontotemporal dementia, vascular dementia and other dementias; 72% of the patients had died. Overall median survival duration was 10.6 years with no significant differences in duration within the dementia subtypes ( p = 0.174). Survival in older-onset dementia (symptom onset at >65 years of age) was about half of that in younger-onset dementia (median survival 6.3 years compared to 12.7 years, respectively). Independent predictors of mortality were having older-onset dementia (hazard ratio: 3.2) and having initial presenting symptoms being cognitive in nature (hazard ratio: 1.5). Females with an older-onset dementia had longer survival compared to males with an older-onset dementia, and this was reversed for younger-onset dementia. Older-onset dementia and younger-onset dementia conferred 3 and 6 times, respectively, increased risk of death compared to the general population. Conclusion: This is the largest Australian study to date investigating survival and risk factors to mortality in dementia. We report important clinical information to patients with dementia and their families about prognosis which will assist with future planning. Our findings suggest that for both older-onset dementia and younger-onset dementia, ‘new onset’ psychiatric symptoms precede the cognitive symptoms of a neurodegenerative process. This, and sex differences in survival depending on the age of onset of the dementia warrant further investigation.

Characteristics and Clinical Outcome of 295 Patients with Relapsing Polychondritis

2021 ◽  
pp. jrheum.210062
Author(s):  
Nan Chen ◽  
Yi Zheng
Keyword(s):  
Respiratory Symptoms ◽  
Age Of Onset ◽  
Disease Onset ◽  
Relapsing Polychondritis ◽  
Chinese Patients ◽  
Onset Age ◽  
Risk Of Death ◽  
Progressive Dyspnea ◽  
High Prevalence ◽  
Laryngeal Involvement

Objective This study analyzes the clinical features of Chinese patients with relapsing polychondritis (RP). Methods The clinical data of 295 patients with RP of Beijing Tongren Hospital were retrospectively analyzed. Results The mean age of onset was 41.0 ± 15.0 years. The sex ratio was 1:1. Up to 70.5% of the patients had airway involvement during the disease course; among them, the larynx was most commonly affected (82.2%). Exactly 25.7% of the patients with laryngeal involvement underwent tracheotomy due to progressive dyspnea or acute laryngeal obstruction. Younger onset age and initially presenting with respiratory symptoms were independent risk factors for tracheotomy in patients with RP with laryngeal involvement. The risk of tracheotomy in patients who presented with respiratory symptoms was 2.354 times higher than that in patients who presented with other symptoms (hazard ratio [HR], 2.354; 95% confidence interval [CI], 1.230–4.503; p =0.010). The risk of tracheotomy increased by 4.8% for every 1 year decrease in the onset age (HR, 0.952; 95% CI, 0.931–0.973; p < 0.001). The incidence of lower respiratory tract infection was much higher in patients with airway involvement than that in those without airway involvement. The main cause of death was respiratory failure due to airway obstruction. Conclusion There is a high prevalence of airway involvement in Chinese patients with RP. Laryngeal involvement is associated with a high risk of death. More attention should be paid to RP patients with laryngeal involvement who are young at disease onset and present with respiratory symptoms.

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