scholarly journals Early-Life Factors and Risk of Multiple Sclerosis: An MR-EWAS

2020 ◽  
Vol 54 (6) ◽  
pp. 433-445
Author(s):  
Lazaros Belbasis ◽  
Vanesa Bellou ◽  
Ioanna Tzoulaki ◽  
Evangelos Evangelou
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Early Life ◽  
Significant Risk ◽  
Perinatal Period ◽  
Age At Menarche ◽  
Early Life Factors ◽  
Average Body

<b><i>Background:</i></b> Although several risk factors are associated with multiple sclerosis (MS) in adulthood, evidence for risk factors acting from birth to adolescence is scarce. <b><i>Methods:</i></b> We conceived a 2-step study design, where signals from an Environment-Wide Association Study are prioritized for follow-up in a Mendelian Randomization study (MR-EWAS), to examine the association of early-life factors with risk of MS. The EWAS was conducted in UK Biobank, where we agnostically selected all the available risk factors acting from the perinatal period until the adolescence, including perinatal factors, anthropometric characteristics during childhood, male and female sexual factors, and skin phenotypic characteristics. We prioritized statistically significant risk factors to perform a 2-sample MR study using publicly available summary-level genetic data. We also calculated the power of the 2-step MR-EWAS approach under several scenarios and compared it against a 1-step hypothesis-free MR approach to detect risk factors of MS. <b><i>Results:</i></b> In the EWAS, an increase per 1 year in age at menarche was associated with a lower risk of MS (OR = 0.93; 95% CI: 0.90–0.96) and a plumper than average body size at the age of 10 was associated with a higher risk of MS (OR = 1.42; 95% CI: 1.24–1.61). Individuals getting very tanned or moderately tanned were at higher risk of MS compared with individuals that never tan or get mildly to occasionally tanned (OR = 0.86; 95% CI: 0.79–0.94). The MR analysis supported the association of age at menarche and childhood body mass index (BMI) without presence of pleiotropic effects. In the multivariable MR analysis, the association of age at menarche was not statistically significant after adjusting for childhood BMI. The MR analysis for ease of tanning did not reveal a statistically significant association. In multiple scenarios, the power of MR-EWAS approach was larger than the power of a hypothesis-free MR approach. <b><i>Conclusions:</i></b> We introduced the MR-EWAS, a 2-step approach that is more powerful compared with the hypothesis-free MR approach under certain scenarios, to test potential causal signals. Our comprehensive assessment of early-life risk factors of MS highlighted a potential causal role of early menarche and elevated childhood BMI for risk of MS.

Aortic aneurysms after correction of aortic coarctation: A systematic review

VASA ◽  
2010 ◽  
Vol 39 (1) ◽  
pp. 3-16 ◽  
Author(s):  
von Kodolitsch ◽  
Aydin ◽  
Bernhardt ◽  
Habermann ◽  
Treede ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Aortic Coarctation ◽  
Significant Risk ◽  
Coarctation Of The Aorta ◽  
Aortic Aneurysms ◽  
Percutaneous Therapy ◽  
Presenting Symptoms

Despite advanced techniques for surgical or percutaneous therapy coarctation of the aorta continues to carry a high risk of aneurysmal formation. Mortality of these aneurysms ranges between <1 and >90%, reflecting remarkable differences in surgical strategies and the follow-up management of coarctation. We review the frequency, anatomical types, risk factors and mechanisms of aortic aneurysm forming late after surgical or percutaneous therapy of aortic coarctation. We emphasize that aneurysms do not form exclusively at the site of previous intervention, but also at remote locations such as the ascending aorta. Moreover, aneurysm formation may only in part be attributed to a specific technique of coarctation therapy, and we emphasize the role of a bicuspid aortic valve and inherent weakness of the aortic wall as significant risk factors for aneurysm after aortic coarctation. We report the presenting symptoms, follow-up protocols, and imaging criteria for local and proximal aneurysms. Finally, we discuss criteria for prophylactic intervention at the site of such aneurysms, and present therapeutic options for different types of aneurysms. With this systematic review, we wish to provide data for establishing more uniform strategies for preventing, diagnosing and treating aneurysms associated with aortic coarctation.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

The combined impact of Type D personality and depression on cardiovascular events after acute myocardial infarction

2021 ◽  
pp. 1-11
Author(s):  
Yini Wang ◽  
Xueqin Gao ◽  
Zhenjuan Zhao ◽  
Ling Li ◽  
Guojie Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Significant Risk ◽  
Type D Personality ◽  
Adverse Outcomes ◽  
Combined Effect ◽  
Continuous Variables ◽  
Type D

Abstract Background Type D personality and depression are the independent psychological risk factors for adverse outcomes in cardiovascular patients. The aim of this study was to examine the combined effect of Type D personality and depression on clinical outcomes in patients suffering from acute myocardial infarction (AMI). Methods This prospective cohort study included 3568 patients diagnosed with AMI between February 2017 and September 2018. Type D personality and depression were assessed at baseline, while the major adverse cardiac event (MACE) rate (cardiac death, recurrent non-fatal myocardial infarction, revascularization, and stroke) and in-stent restenosis (ISR) rate were analyzed after a 2-year follow-up period. Results A total of 437 patients developed MACEs and 185 had ISR during the follow-up period. The Type D (+) depression (+) and Type D (+) depression (−) groups had a higher risk of MACE [95% confidence interval (CI) 1.74–6.07] (95% CI 1.25–2.96) and ISR (95% CI 3.09–8.28) (95% CI 1.85–6.22). Analysis of Type D and depression as continuous variables indicated that the main effect of Type D, depression and their combined effect were significantly associated with MACE and ISR. Moreover, Type D (+) depression (+) and Type D (+) depression (−) emerged as significant risk factors for MACE and ISR in males, while only Type D (+) depression (+) was associated with MACE and ISR in female patients. Conclusions These findings suggest that patients complicated with depression and Type D personality are at a higher risk of adverse cardiovascular outcomes. Individual assessments of Type D personality and depression, and comprehensive interventions are required.

Post-Bariatric Abdominoplasty: Analysis of 406 Cases With Focus on Risk Factors and Complications

2020 ◽  
Vol 41 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Torsten Schlosshauer ◽  
Marcus Kiehlmann ◽  
Diana Jung ◽  
Robert Sader ◽  
Ulrich M Rieger
Keyword(s):  
Risk Factors ◽  
Wound Healing ◽  
Surgical Technique ◽  
Significant Risk ◽  
Level Of Evidence ◽  
Increased Risk ◽  
Potential Risk Factors ◽  
Wound Healing Problems ◽  
Bariatric Patients

Abstract Background Post-bariatric patients present a surgical challenge within abdominoplasty because of residual obesity and major comorbidities. In this study, we analyzed complications following abdominoplasty in post-bariatric patients and evaluated potential risk factors associated with these complications. Objectives The authors sought to determine the complications and risk factors following abdominoplasty in post-bariatric patients. Methods A retrospective study of patients who underwent abdominoplasty was performed from January 2009 to December 2018 at our institution. Variables analyzed were sex, age, body mass index (BMI), smoking, surgical technique, operative time, resection weight, drain output, and complications. Results A total of 406 patients were included in this study (320 female and 86 male) with a mean age of 44.4 years and a BMI of 30.6 kg/m2. Abdominoplasty techniques consisted of traditional (64.3%), fleur-de-lis technique (27.3%), and panniculectomy without umbilical displacement (8.4%). Overall complications recorded were 41.9%, the majority of these being wound-healing problems (32%). Minor and major complications were found in 29.1% and 12.8% of patients, respectively. A BMI value of ≥30 kg/m2 was associated with an increased risk for wound-healing problems (P = 0.001). The frequency of total complications was significantly related to age (P = 0.007), BMI (P = 0.004), and resection weight (P = 0.001). Abdominoplasty technique tended to influence total complications. Conclusions This study demonstrates in a fairly large sample of post-bariatric patients (n = 406) that abdominoplasty alone can be performed safely, with an acceptable complication rate. Age, BMI, and resection weight are shown to be significant risk factors for total complications. The role of surgical technique needs to be evaluated further. Level of Evidence: 4

scholarly journals Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

2021 ◽  
Vol 11 (5) ◽  
pp. 335
Author(s):  
María José Zarzuelo Romero ◽  
Cristina Pérez Ramírez ◽  
María Isabel Carrasco Campos ◽  
Almudena Sánchez Martín ◽  
Miguel Ángel Calleja Hernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mechanism Of Action ◽  
Dimethyl Fumarate ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
New Therapies ◽  
Therapeutic Value ◽  
The Impact

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

FC 059EARLY LIFE FACTORS AND ADULT KIDNEY FUNCTION ESTIMATED BY CYSTATIN C AND CREATININE GLOMERULAR FILTRATION RATE EQUATIONS AND ALBUMINURIA: A SWEDISH COHORT STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Agne Laucyte-Cibulskiene ◽  
Shantanu Sharma ◽  
Peter M Nilsson ◽  
Anders Christensson
Keyword(s):  
Regression Analysis ◽  
Birth Weight ◽  
Kidney Function ◽  
Cystatin C ◽  
Early Life ◽  
Postnatal Growth ◽  
Lower Birth Weight ◽  
Adult Kidney ◽  
Early Life Factors

Abstract Background and Aims Renal functional capacity is influenced by factors acting early in life, such as intrauterine environment, maturity, birth weight, length at birth, placental weight etc. Early life factors are responsible for the number of nephrons a person starts life with, and the consequence of a low nephron number is earlier kidney ageing and chronic kidney disease (CKD). Notably, most reports addressing early life factors in the context of adult kidney function use creatinine-based eGFR equations and/or albuminuria and lack longer follow-up (&lt;30 years). Therefore, we aimed to identify early life factors associated with kidney function, determined by different creatinine and cystatin C equations and urinary albumin-to-creatinine ratio (UACR), more than 40 years later. Method 94 women and 494 men, born 1923-50, who participated in The Malmo Diet and Cancer (MDC) study were analyzed. Perinatal data records including birth weight (BW), birth length, head circumference, gestational age, placenta weight (PW) and mother related risk factors were collected from hospital and regional state archives. After a follow-up of 46 to 67 years study subjects underwent physical examination, blood pressure measurements and estimation of glomerular filtration rate (eGFR) using 4 different equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2012 creatinine and cystatin C formula (CKD-EPI_creatinine, CKD-EPI_cystatin C), cystatin C eGFR equation based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised creatinine based eGFR equation (LM_rev). Urinary albumin-to-creatinine ratio (UACR) was measured in morning urine samples, albuminuria was defined as UACR ⩾3 mg/mmol. Birth weight z-scores (gender specific BWz and combined BWz) acquired by using the equation as reported by Marsal et al.(1996). Four growth mismatch phenotypes defined by combining low or high BW z-score (lowBWz or hiBWz respectively) with lower or higher body mass index at 20 years of age (lowBMI20 ir hiBMI20 respectively). Results Linear regression analysis of early life factors indicated that in females birth weight was positively associated with kidney function measured by both CAPA and CKD-EPI_cystatin C. In the whole population, birth weight adjusted for gestational age and sex, together with prematurity were independently associated to CKD-EPI_cystatin C, while BW/PW ratio was related to LM_rev. Logistic regression analysis showed that only gender specific BWz and combined BWz shared the same odds ratios for age and pulse pressure adjusted albuminuria in males (OR 0,75 (95%CI [0,58; 0,96]). While analyzing postnatal growth mismatch we found that females with hiBWz/lowBMI20 phenotype had significantly worse kidney function acquired by both cystatin C equations compared to those with lowBWz/lowBMI20 phenotype (p=0.044 for CAPA, p=0.040 for CKD-EPI_cystatin C). The logistic regression analysis revealed that hiBWz/hiBMI20 phenotype was related to lower risk of age and pulse pressure adjusted albuminuria (OR 0,35 (95%CI[0,12;0,93]) Conclusion Here we report that lower birth weight in females is associated with worse kidney function determined by cystatin C eGFR equations, while in males lower birth weight z-score is a risk factor for albuminuria in adulthood. Postnatal growth catch-up is not related to worse kidney function. We identified the protective phenotype (hiBWz/hiBMI20) for albuminuria in males and the unfavorable phenotype (hiBWz/lowBMI20) for kidney function in females. This suggests that lower birth weight and postnatal growth curve have a potential sex specific effect to kidney function and development of CKD in middle-aged Swedish subjects. Further studies are warranted to address early life factor prognostic accuracy in kidney function and outcomes prediction later in the lifetime.

scholarly journals PREDICTORS OF AGE AT MENARCHE IN THE NEWCASTLE THOUSAND FAMILIES STUDY

2008 ◽  
Vol 40 (4) ◽  
pp. 563-575 ◽  
Author(s):  
MWENZA BLELL ◽  
TESSA M. POLLARD ◽  
MARK S. PEARCE
Keyword(s):  
Birth Weight ◽  
Early Life ◽  
Age At Menarche ◽  
Childhood Growth ◽  
Study Support ◽  
Statistical Relationships ◽  
Timing Of Menarche ◽  
Future Work

SummarySeveral studies have found relationships between early life factors (birth weight, length of gestation, height, weight, duration of breast-feeding, maternal age, social class, periods of infection, presence of adverse life events, and quality of housing conditions in childhood) and age at menarche but none has considered all of these factors in the same study. The follow-up study of the Newcastle Thousand Families birth cohort, established in 1947, provided age at menarche data collected retrospectively at age 50 from 276 women who returned self-completion questionnaires in 1997. Three main independent associations were observed: girls who experienced a shorter gestation, girls whose mothers were younger when they were born, and girls who were heavier at age 9 had earlier menarche. Birth weight, standardized for gestational age, was found to have different relationships with age at menarche depending upon how heavy or light a girl was at age 9. The results of this study support the hypotheses that conditions in fetal and early life are associated with the timing of menarche and that greater childhood growth is associated with earlier menarche. It is suggested that future work should focus on illuminating the mechanisms underlying these statistical relationships.

scholarly journals The Ala/Ala genotype of PPARY Pro12 Ala polymorphism is associated with late onset of multiple sclerosis

2013 ◽  
Vol 65 (2) ◽  
pp. 447-453
Author(s):  
N. Lukic ◽  
A. Stankovic ◽  
E. Dincic ◽  
M. Bundalo ◽  
Z. Krsmanovic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Hoc ◽  
Genotype And Allele Frequencies

The function of peroxisome proliferator-activated receptor ? (PPAR?) in immune regulation, as well as in antiinflammatory and anti-proliferative actions towards T lymphocytes, has been reported. A potential role of PPARs in multiple sclerosis (MS) was suggested. The aim of this study was to investigate if there is an association of PPAR?-2 Pro12Ala polymorphism with MS in 361 patients from Serbia. The genotype and allele frequencies of Pro12Ala polymorphism were not significantly different between controls and patients, or between females and males. In contrast to controls, we detected a rare Ala/Ala genotype in patients with MS. We found that there is a significant association of Ala/Ala genotype with older age at onset (ANOVA, p=0.07; LSD post-hoc, Ala/Ala vs. Pro/Ala, p=0.03, Ala/Ala vs. Pro/Pro p=0.02). It would be useful to validate our results in other populations, as well as to perform follow-up of the disease progression in regard to PPAR? genotypes.

Risk factors for progression of articular cartilage damage after anatomical anterior cruciate ligament reconstruction

2018 ◽  
Vol 100-B (3) ◽  
pp. 285-293 ◽  
Author(s):  
A. Nakamae ◽  
N. Adachi ◽  
M. Deie ◽  
M. Ishikawa ◽  
T. Nakasa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Anterior Cruciate Ligament ◽  
Articular Cartilage ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Significant Risk ◽  
Articular Cartilage Damage ◽  
Anterior Cruciate

Aims To investigate the risk factors for progression of articular cartilage damage after anatomical anterior cruciate ligament (ACL) reconstruction. Patients and Methods A total of 174 patients who underwent second-look arthroscopic evaluation after anatomical ACL reconstruction were enrolled in this study. The graded condition of the articular cartilage at the time of ACL reconstruction was compared with that at second-look arthroscopy. Age, gender, body mass index (BMI), ACL reconstruction technique, meniscal conditions, and other variables were assessed by regression analysis as risk factors for progression of damage to the articular cartilage. Results In the medial compartment, multivariable logistic regression analysis indicated that partial medial meniscectomy (odds ratio (OR) 6.82, 95% confidence interval (CI) 2.11 to 22.04, p = 0.001), pivot-shift test grade at the final follow-up (OR 3.53, CI 1.39 to 8.96, p = 0.008), BMI (OR 1.15, CI 1.03 to 1.28, p = 0.015) and medial meniscal repair (OR 3.19, CI 1.24 to 8.21, p = 0.016) were significant risk factors for progression of cartilage damage. In the lateral compartment, partial lateral meniscectomy (OR 10.94, CI 4.14 to 28.92, p < 0.001) and side-to-side differences in anterior knee laxity at follow-up (OR 0.63, p = 0.001) were significant risk factors. Conclusion Partial meniscectomy was found to be strongly associated with the progression of articular cartilage damage despite r anatomical ACL reconstruction. Cite this article: Bone Joint J 2018;100-B:285–93.

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