scholarly journals Lymphaticovenous Anastomosis for Age-Related Lymphedema

2021 ◽  
Vol 10 (21) ◽  
pp. 5129
Author(s):  
Shuhei Yoshida ◽  
Isao Koshima ◽  
Hirofumi Imai ◽  
Solji Roh ◽  
Toshiro Mese ◽  
...  

Introduction: Primary lymphedema is usually caused by intrinsic disruption or genetic damage to the lymphatics but may also be the result of age-related deterioration of the lymphatics. The aims of this study were to determine the characteristics of age-related lymphedema and to assess the effectiveness of lymphaticovenous anastomosis (LVA) in its treatment. Methods: Eighty-six patients with primary lymphedema affecting 150 lower limbs were divided into three groups according to whether the age of onset was younger than 35 years, 35–64 years, or 65 years or older. Indocyanine green (ICG) lymphography was performed, followed by LVA surgery. ICG lymphography images were visually classified according to whether the pattern was linear, low enhancement (LE), distal dermal backflow (dDB), or extended dermal backflow (eDB). The lower extremity lymphedema (LEL) index score was calculated before and after LVA. Lymphatic vessel diameter and detection rates were also recorded. Results: In the ≥65 group, the lymphedema was bilateral in 54 patients and unilateral in 1 patient. There was statistically significant deterioration in the LEL index score with progression from the linear, LE, dDB through to the eDB pattern in the ≥65 group. The lymphatic vessel diameter was significantly greater in the ≥65 group. The rate of improvement was highest in the ≥65 group. Conclusion: Age-related lymphedema was bilateral and deterioration started distally. The lymphatic vessels in patients with age-related lymphedema tended to be ectatic, which is advantageous for LVA and may increase the improvement rate.

Author(s):  
Paul W Turke

Abstract The severity of COVID-19 is age-related, with the advantage going to younger age groups. Five reasons are presented. The first two are well-known, are being actively researched by the broader medical community, and therefore are discussed only briefly here. The third, fourth, and fifth reasons derive from evolutionary life history theory, and potentially fill gaps in current understanding of why and how young and old age groups respond differently to infection with SARS-CoV-2. Age of onset of generalized somatic aging, and the timing of its progression, are identified as important causes of these disparities, as are specific antagonistic pleiotropic tradeoffs in immune system function.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Maurizio Ricci ◽  
Rita Compagna ◽  
Bruno Amato ◽  
Sercan Kenanoglu ◽  
Dominika Veselenyiova ◽  
...  

Background. ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the ARAP3 gene are associated with impaired lymphatic vessel formation. Objective. The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the ARAP3 gene in order to explore its role in the development of lymphedema. Methods and Results. We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including ARAP3. Three out of 235 probands proved to carry rare missense heterozygous variants in ARAP3. In the case of two families, other family members were also tested and proved negative for the ARAP3 variant, besides being unaffected by lymphedema. According to in silico analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins. Conclusions. Based on our results, we propose that variants in ARAP3 could be included in genetic testing for lymphedema.


2019 ◽  
Vol 12 (7) ◽  
pp. e229609
Author(s):  
Louise Dunphy ◽  
Amir Rani ◽  
Yaw Duodu ◽  
Yousef Behnam

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene which maps to the short arm of chromosome 19 and encodes the NOTCH3 receptor protein, predominantly expressed in adults by vascular smooth muscle cells and pericytes. The receptor has a large extracellular domain with 34 epidermal growth factor-like repeats encoded by exons 2–24, the site at which CADASIL mutations are most commonly found. Migraine with aura is often the earliest feature of the disease, with an increased susceptibility to cortical spreading depression suggested as a possible aetiological mechanism. Stroke, acute encephalopathy and cognitive impairment can also occur. Hypertension and smoking are associated with early age of onset of stroke. It diffusely affects white matter, with distinct findings on T2- weighted MRI, involving the external capsule, anterior poles of the temporal lobe and superior frontal gyri, displaying a characteristic pattern of leucoencephalopathy. Affected individuals have a reduced life expectancy. An effective treatment for CADASIL is not available. The authors describe a 35-year-old manwith an unremarkable medical history, presenting to the emergency department with slurred speech and increased confusion 3 days following a fall. He was a smoker and consumed 16 units of alcohol weekly. He was hypertensive and tachycardic. Physical examination confirmed increased tone in his lower limbs and dysarthria. His CT head showed severe cerebral atrophy, multiple small old infarcts and moderate background microvascular disease. Further investigation with an MRI head confirmed multiple white matter abnormalities with microhaemorrhages. The possibility of a hereditary vasculopathy was rendered as the appearances were thought consistent with a diagnosis of CADASIL. Genetic testing identified the NOTCH3 gene thus confirming the diagnosis. This paper provides an overview of the aetiology, clinical presentation, pathogenesis, investigations and management of CADASIL.


2020 ◽  
Vol 13 ◽  
pp. 175628482095922
Author(s):  
Judith J. de Jong ◽  
Marten A. Lantinga ◽  
Ina M. E. Thijs ◽  
Philip R. de Reuver ◽  
Joost P. H. Drenth

Background: Age is an important and objective risk factor for upper gastrointestinal (GI) malignancy. The accuracy of various age limits to detect upper GI malignancy is unclear. Determination of this accuracy may aid in the decision to refer symptomatic patients for upper GI endoscopy. The aim of this analysis was to synthesize data on upper GI malignancy detection rates for various age limits worldwide through meta-analysis. Methods: We searched MEDLINE, EMBASE, and Web of Science in November 2018. Selection criteria included studies addressing malignant findings at upper GI endoscopy in a symptomatic population reporting age at time of diagnosis. Meta-analyses were conducted to derive continent-specific cancer detection rates. Results: A total of 33 studies including 346,641 patients across 21 countries fulfilled the inclusion criteria. To detect >80% of malignant cases all symptomatic patients over 40 years of age should be investigated in Africa, over 50 years of age in South America and Asia, and over 55 years of age in North America and Europe. Conclusion: This systematic review and meta-analysis provides data on intercontinental variation in age at time of upper GI malignancy diagnosis in symptomatic patients referred for upper GI endoscopy. Guideline recommendations for age-based selection should be tailored to local age-related detection rates.


2022 ◽  
Author(s):  
Constantinos Constantinides ◽  
Laura KM Han ◽  
Clara Alloza ◽  
Linda Antonucci ◽  
Celso Arango ◽  
...  

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.64 years (95% CI: 3.01, 4.26; I2 = 55.28%) compared to controls, after adjusting for age and sex (Cohen's d = 0.50). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.


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