scholarly journals EPID-11. A MULTI-INSTITUTIONAL COMPARATIVE ANALYSIS OF THE CLINICAL, GENOMIC, AND SURVIVAL CHARACTERISTICS OF PEDIATRIC, YOUNG ADULT AND OLDER ADULT PATIENTS WITH IDH-MUTANT GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii80-ii81
Author(s):  
Mary Jane Lim-Fat ◽  
Jayne Vogelzang ◽  
Eleanor Woodward ◽  
Alana McGovern ◽  
Clement Ma ◽  
...  

Abstract BACKGROUND Prognostic significance of IDH-mutation in glioma is incompletely understood in children and adolescents/young adults (YAs). We compared the clinico-genomic features, outcomes and prognostic factors observed in IDH-mutant gliomas across age groups. METHODS Clinical, histologic and molecular data of patients with IDH-mutant gliomas from 8 pediatric institutions (spanning twenty years) and adult patients from two institutions (from 2013–2019) were identified. Patients were grouped as pediatric (< 19y), YA (19y to < 40y) or older adult (≥ 40y). Genomic alterations, including somatic mutations and copy number variants, were captured with institutional next generation sequencing. Factors were compared across age categories using Fisher’s exact test or analysis-of-variance. Cox proportional-hazards regression tested factors for association with overall (OS) and progression-free survival (PFS). RESULTS Of 379 patients, 48(13%) were pediatric, 204(54%) YA and 127(33%) older adult. Histological subtype differed significantly by age group (p< 0.0001). YAs had higher rates of malignant transformation (p=0.01) and shorter time-from-diagnosis-to-malignant transformation (p=0.01) compared to other age groups. Analysis of genomic alterations revealed an age-related difference in distribution in ATRX mutations only (p=0.0018). Median PFS and OS for the entire cohort were 4.62 and 17.19 years. In univariate models, PFS differed by age group (p=0.0012), with YAs having the worst outcomes. Lack of MGMT methylation (p=0.024) predicted poorer OS. Upfront observant management was predictive of poorer PFS. Gene mutations were not associated with PFS. In multi-variable models, YAs had shorter PFS compared to pediatric (hazard ratio [HR]=2.03, p=0.01) and older adults (HR=1.59, p=0.003) after adjusting for histology, extent of resection, and initial therapy. Age at diagnosis was not associated with OS in multi-variable analysis. CONCLUSIONS Within our cohort, YA with IDH-mutant tumors progressed more quickly compared to their pediatric counterparts. Further study of YA patients with IDH-mutant glioma is critical to better define best practices for this group.

Author(s):  
Ljupcho Efremov ◽  
Semaw Ferede Abera ◽  
Ahmed Bedir ◽  
Dirk Vordermark ◽  
Daniel Medenwald

Abstract Introduction Glioblastoma multiforme (GBM) is a primary malignant brain tumour characterized by a very low long-term survival. The aim of this study was to analyse the distribution of treatment modalities and their effect on survival for GBM cases diagnosed in Germany between 1999 and 2014. Methods Cases were pooled from the German Cancer Registries with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes for GBM or giant-cell GBM. Three periods, first (January 1999–December 2005), second (January 2006–December 2010) and a third period (January 2011–December 2014) were defined. Kaplan–Meier plots with long-rank test compared median overall survival (OS) between groups. Survival differences were assessed with Cox proportional-hazards models adjusted for available confounders. Results In total, 40,138 adult GBM cases were analysed, with a mean age at diagnosis 64.0 ± 12.4 years. GBM was more common in men (57.3%). The median OS was 10.0 (95% CI 9.0–10.0) months. There was an increase in 2-year survival, from 16.6% in the first to 19.3% in the third period. When stratified by age group, period and treatment modalities, there was an improved median OS after 2005 due to treatment advancements. Younger age, female sex, surgical resection, use of radiotherapy and chemotherapy, were independent factors associated with better survival. Conclusion The inclusion of temozolomide chemotherapy has considerably improved median OS in the older age groups but had a lesser effect in the younger age group of cases. The analysis showed survival improvements for each treatment option over time.


Author(s):  
Alejandro Márquez-Salinas ◽  
Carlos A Fermín-Martínez ◽  
Neftalí Eduardo Antonio-Villa ◽  
Arsenio Vargas-Vázquez ◽  
Enrique C. Guerra ◽  
...  

Abstract Background Chronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Methods In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.


Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 100833
Author(s):  
Graziana Colaianni ◽  
Lorenzo Sanesi ◽  
Giuseppina Storlino ◽  
Roberta Zerlotin ◽  
Patrizia Pignataro ◽  
...  

2001 ◽  
Vol 8 (3) ◽  
pp. 556-559 ◽  
Author(s):  
Jaime Inostroza ◽  
Ana Maria Vinet ◽  
Gloria Retamal ◽  
Pedro Lorca ◽  
Gonzalo Ossa ◽  
...  

ABSTRACT All clinical S. pneumoniae specimens isolated from patients with invasive or sterile-site infections admitted to one regional general hospital in southern Chile were collected during a 5-year period (February 1994 to September 1999). A total of 247 strains belonging to 50 serotypes were isolated in this survey: 69 in patients under 5 years of age, 129 in patients 5 to 64 years old, and 49 from patients 65 years and older. Eight serotypes were identified in all age groups, while all other serotypes were found exclusively in one age group or in patients over 4 years of age. Serotype 3 was never found in patients under 5 years old, and serotype 14 was not found in patients >64 years of age. There was no difference in the serotypes causing infection in each one of the 5 years of the survey. Our results suggest that both bacterial virulence factors and host factors play an important role in the selection of S. pneumoniae serotypes causing invasive infection. Possible host factors include age-related differences in the immune response. Comparative studies with other areas of the world may help to further understanding of our observations in southern Chile.


1996 ◽  
Vol 85 (3) ◽  
pp. 410-418 ◽  
Author(s):  
Giuseppe Lanzino ◽  
Neal F. Kassell ◽  
Teresa P. Germanson ◽  
Gail L. Kongable ◽  
Laura L. Truskowski ◽  
...  

✓ Advanced age is a recognized prognostic indicator of poor outcome after subarachnoid hemorrhage (SAH). The relationship of age to other prognostic factors and outcome was evaluated using data from the multicenter randomized trial of nicardipine in SAH conducted in 21 neurosurgical centers in North America. Among the 906 patients who were studied, five different age groups were considered: 40 years or less, 41 to 50, 51 to 60, 61 to 70, and more than 71 years. Twenty-three percent of the individuals enrolled were older than 60 years of age. Women outnumbered men in all age groups. Level of consciousness (p = 0.0002) and World Federation of Neurological Surgeons grade (p = 0.0001) at admission worsened with advancing age. Age was also related to the presence of a thick subarachnoid clot (p = 0.0001), intraventricular hemorrhage (p = 0.0003), and hydrocephalus (p = 0.0001) on an admission computerized tomography scan. The rebleeding rate increased from 4.5% in the youngest age group to 16.4% in patients more than 70 years of age (p = 0.002). As expected, preexisting medical conditions, such as diabetes (p = 0.028), hypertension (p = 0.0001), and pulmonary (p = 0.0084), myocardial (p = 0.0001), and cerebrovascular diseases (p = 0.0001), were positively associated with age. There were no age-related differences in the day of admission following SAH, timing of the surgery and/or location, and size (small vs. large) of the ruptured aneurysm. During the treatment period, the incidence of severe complications (that is, those complications considered life threatening by the reporting investigator) increased with advancing age, occurring in 28%, 33%, 36%, 40%, and 46% of the patients in each advancing age group, respectively (p = 0.0002). No differences were observed in the reported frequency of surgical complications. No age-related differences were found in the overall incidence of angiographic vasospasm; however, symptomatic vasospasm was more frequently reported in the older age groups (p = 0.01). Overall outcome, assessed using the Glasgow Outcome Scale at 3 months post-SAH, was poorer with advancing age (p < 0.001). Multivariate analysis of overall outcome, adjusting for the different prognostic factors, did not remove the age effect, which suggests that the aging brain has a less optimal response to the initial bleeding. Age as a risk factor is a continuum; however, there seems to be a significant increased risk of poor outcome after the age of 60 years.


2016 ◽  
Vol 175 (1) ◽  
pp. 49-54 ◽  
Author(s):  
David Strich ◽  
Gilad Karavani ◽  
Shalom Edri ◽  
David Gillis

ObjectiveWe previously reported increasing free T3 (FT3) to free T4 (FT4) ratios as thyroid-stimulating hormone (TSH) increases within the normal range in children. It is not known if this phenomenon is age-related among humans, as previously reported in rats. This study examines the relationships between TSH and FT3/FT4 ratios in different ages.DesignRetrospective examination of thyroid tests from patients without thyroid disease from community clinics.MethodsFree T3, free T4, and TSH levels from 527 564 sera collected from patients aged 1 year or greater were studied. Exclusion criteria were the following: missing data, TSH greater than 7.5mIU/L, and medications that may interfere with thyroid hormone activity. A total of 27 940 samples remaining after exclusion were stratified by age. Samples with available anthropometric data were additionally stratified for body mass index (BMI). Correlations of TSH to FT4, FT3, and FT3/FT4 ratios by age group were examined.ResultsUp to age 40, for each increasing TSH quartile, FT3 and the FT3/FT4 ratio increased and FT4 decreased significantly (for both FT3, FT4 and FT3/FT4 ratio,P<0.05 for every TSH quartile when compared with the 1st quartile, except FT3 in the 30–40 age group). In older age groups, increasing TSH was not associated with increased FT3/FT4 ratio.ConclusionAs TSH levels increase, FT3/FT4 ratios increase until age 40, but this differential increase does not occur in older age groups. This may reflect a decrease in thyroxine (T4) to triiodothyronine (T3) conversion with age, which may be part of the aging process.


1999 ◽  
Vol 175 (6) ◽  
pp. 576-580 ◽  
Author(s):  
Janet Munro ◽  
Desmond O'Sullivan ◽  
Christopher Andrews ◽  
Alejandro Arana ◽  
Ann Mortimer ◽  
...  

BackgroundPeople prescribed clozapine for treatment-resistant schizophrenia have mandatory haematological monitoring through a case register for identifying reversible neutropenia.AimsTo quantify risk factors for agranulocytosis in subjects receiving clozapine.MethodData from 12 760 subjects registered to receive clozapine from January 1990 to April 1997 were analysed. Risk factors for agranulocytosis were quantified using a Cox proportional-hazards regression analysis.ResultsThe risk for agranulocytosis in Asian subjects was 2.4 times that in Caucasians (P=0.03). There was an age-related increase in risk of 53% per decade (P=0.0001).ConclusionsThe case register yielded valuable information for guiding research into the causes of the haematological reactions.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Zuber S Ali ◽  
Danielle M Greere ◽  
Robyn L Shearer ◽  
Syed Ali Gardezi ◽  
Arshad Jahangir

Introduction: Androgen suppression therapy for prostate cancer is controversial due to adverse fatal and non-fatal cardiovascular outcomes reported in some studies. However, effects of androgen suppression on stroke have not been fully assessed in the elderly. Methods: Patients diagnosed with prostate cancer during 2007-2013 in a large community-based healthcare system were identified from the Cancer Registry, electronic records, and billing codes. Those who underwent androgen suppression therapy with Gonadotropin-releasing hormone agonist (GnRH) were propensity-matched to patients treated without androgen suppression therapy by age at cancer diagnosis, race/ethnicity, disease stage and outcome, body mass index and use of surgery, radiation, and chemotherapy. Tests of independence and Cox proportional hazards models were used to examine effects of hormone therapy on acute myocardial infarction (AMI), stroke, and mortality outcomes. Models also adjusted for patient comorbidities. Results: A total of 1282 patients and 641 matched-pairs were identified, with mean diagnosis age of 69 yr and follow-up period of 3.05 yr. Effects of androgen suppression therapy on AMI (P=0.051) and stroke (P=0.062) were of marginal to non-significance, but adjusted-odds of death and combined AMI, stroke, and death were 1.61 times (P=0.002; odds ratio [OR] 95% CI: 1.19-2.18) and 1.70 times (P<0.001; OR 95% CI: 1.26-2.28) greater, respectively, for men with than without androgen suppression. An interaction of androgen suppression and age-group (<65 yr, 65-74 yr, >74 yr) was discovered for combined outcomes, suggesting increased probability of AMI, stroke, and/or death with age (8.6-20.0%; P=0.003) for patients without androgen suppression but elevated risk of outcomes across all age groups (18.3-22.4%; P=0.546) for men treated with androgen suppression therapy. Conclusion: Endogenous androgen suppression presents elevated risk of combined cardiovascular and death outcomes, especially for men <65 yr.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Smith-Simpson ◽  
Lisa Fries ◽  
Carolyn Ross

Abstract Objectives The objective was to identify the age at which parents expose their children to different food textures and how challenging the textures were for their child to eat. It was hypothesized that older children would be exposed to a wider variety of food textures and that parents would consider a larger proportion of these textures to be easy to eat. Methods Parents (n = 365) in Grand Rapids, MI, USA with a child aged 6–36 months completed an online survey. The survey had 37 questions, including 15 unique food texture categories with food examples (Table 1). Parents were asked how difficult each texture category was for their child to eat using a 5-point scale ranging from “Very Easy” to “Very Difficult”, plus an option for “My child hasn't tried this yet”. Children were divided into 5 age groups (6-8 months, 9–12 months, 13–18 months, 19–24 months, 25–36 months) for analysis. Across texture category and age group, data were analyzed using analysis of variance, with mean separation accomplished using Fisher's LSD (P < 0.05). Results A majority of children in the youngest age group (6-8 months) had only eaten foods described as creamy, dissolvable, or pureed. All of the texture categories had been served to a majority of 9–12 month-old children, except for “hard” and “tough meat”. By 18 months of age, a majority of children had tried all food texture categories except “hard”. Across all age groups, creamy, dissolvable, and puree were rated as easy and “tough meat” was rated as difficult. The other textures showed age-related differences, with parents of older children reporting the textures as easier to eat than those of younger children. Food textures were compared within the 9–12 and 13–18 month age groups, when most new food textures are introduced, and similar trends were observed. The easiest textures were creamy, dissolvable, puree and soft, followed by lumpy and juicy, then slippery, chewy, rubbery, and sticky. The most difficult textures were leafy, with skin, hard, tough meat and combination of textures. Conclusions When considering textures of the foods that comprise a well-balanced, healthy diet, many foods are difficult for children to eat. Preparing foods such as green vegetables specifically to have age-appropriate textures could improve consumption. Funding Sources Washington State Univ College of Agricultural, Human and Natural Resource Emerging Research Issues Grant.


2019 ◽  
Vol 49 (6) ◽  
pp. 425-434 ◽  
Author(s):  
Xue Li ◽  
Jinsong Chen ◽  
Dongrui Cheng ◽  
Wei Wang ◽  
Kenan Xie ◽  
...  

Background: Transplant glomerulopathy (TG) represents a major cause of long-term allograft failure and is the leading cause of overall post-transplant proteinuria. The extent to which histopathologic features predicts prognostication is uncertain. Methods: A single-center retrospective cohort with biopsy-proven TG was investigated. Renal biopsies were scored according to Banff 2017. The primary outcome was death-censored graft failure defined as return to dialysis or estimated glomerular filtration rate (eGFR) decreased to <15 mL/min/1.73 m2. The prognostic significance of clinical and histopathologic parameters was determined using Cox proportional hazards models. Results: Data from 180 cases were available for analysis with a median follow-up of 5.0 (2.6–8.2) years. In multivariable models, ci + ct score (HR 3.1; 95% CI 2.0–4.9), cg score (HR 1.7; 95% CI 1.1–2.8), eGFR (HR 2.1; 95% CI 1.4–3.2) and proteinuria (HR 2.4; 95% CI 1.6–3.7) were independent predictors of the primary outcome. Mesangial Immunoglobulin A deposition did not significantly affect allograft survival. The only significant pathologic factors for the severity of proteinuria were cg and g + ptc (adjusted R2 = 0.46) as determined by multivariable stepwise linear regression analysis. Conclusions: Severe ci + ct and cg at biopsy were predictors of unfavorable allograft prognosis in TG patients even after taking into consideration clinical characteristics. Histologic severity of cg and g + ptc was significantly associated with clinical proteinuria.


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