scholarly journals Biomarkers of Systemic Inflammation and Growth in Early Infancy are Associated with Stunting in Young Tanzanian Children

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1158 ◽  
Author(s):  
Sana Syed ◽  
Karim Manji ◽  
Christine McDonald ◽  
Rodrick Kisenge ◽  
Said Aboud ◽  
...  

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone–insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores < −2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72; p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93; p for trend = 0.019); a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12; p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.

2018 ◽  
Vol 3 (1) ◽  
pp. 46 ◽  
Author(s):  
Fred Richard Sattler ◽  
Daniel Chelliah ◽  
Xingye Wu ◽  
Alejandro Sanchez ◽  
Michelle A. Kendall ◽  
...  

Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death.Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3. The case-cohort sample consisted of 51 randomly selected participants, whose stored plasma was tested for C-reactive protein, cytokines, chemokines, and nutritional markers. Cox proportional hazards models were used to assess the association of nutritional, inflammatory, and immunomodulatory markers for survival.Results: The case-cohort sample was similar to the 282 participants within the parent cohort with CD4 < 50 cells/mm3. In the case cohort, 7 (14%) had BMI < 16.5 (kg/m2) and 17 (33%) had BMI 16.5-18.5(kg/m2). Risk of death was increased per 1 IQR width higher of log10 transformed level of C-reactive protein (adjusted hazard ratio (aHR) = 3.42 [95% CI = 1.33-8.80],P = 0.011), interferon gamma (aHR = 2.46 [CI = 1.02-5.90], P = 0.044), MCP-3 (3.67 [CI = 1.08-12.42], P = 0.037), and with IL-15 (aHR = 2.75 [CI = 1.08-6.98], P = 0.033) and IL-17 (aHR = 3.99 [CI = -1.06-15.07], P = 0.041). BMI, albumin, hemoglobin, and leptin levels were not associated with risk of death.Conclusions: Unlike patients only infected with M. tuberculosis for whom malnutrition and low BMI increase the risk of death, this relationship was not evident in our dually infected patients. Risk of death was associated with significant increases in markers of global inflammation along with soluble biomarkers of innate and adaptive immunity.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1040
Author(s):  
Valérie Gounant ◽  
Michael Duruisseaux ◽  
Ghassen Soussi ◽  
Sylvie Van Hulst ◽  
Olivier Bylicki ◽  
...  

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.


Author(s):  
Jonathan D Cogen ◽  
Frankline M Onchiri ◽  
Nicole Mayer Hamblett ◽  
Ronald L Gibson ◽  
Wayne J Morgan ◽  
...  

Abstract Background While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection. Methods We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics or ever versus never treatment with intravenous antipseudomonal antibiotics during the 18 months of EPIC CT participation. Primary outcomes were risks of acquisition of several respiratory organisms during 5 years of follow-up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism. Results Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR, 1.24; 95% CI: 1.02–1.50; P = .03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR, 2.47; 95% CI: 1.28–4.78; P = .01) and MRSA (HR, 1.57; 95% CI: 1.03–2.40; P = .04). Conclusions Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing risk of acquisition of drug-resistant organisms.


2020 ◽  
Vol 9 (11) ◽  
pp. 3616
Author(s):  
Carolina Gracia-Iguacel ◽  
Emilio González-Parra ◽  
Ignacio Mahillo ◽  
Alberto Ortiz

Background: In hemodialysis patients, extracellular water (ECW) overload predicts all-cause and cardiovascular mortality. The primary aim of the present study was to analyze changes in post-dialysis (i.e., following removal of excess ECW) ECW, intracellular water (ICW), and the overhydration (OH) parameter over time. Additionally, the association of these parameters with mortality was explored. Patients and methods: Prospective study of prevalent hemodialysis patients (n = 124) followed for a median of 20 (interquartile range (IQR) 8–31) months. In three visits, inflammation (C-reactive protein) and post-dialysis fluid status (bioimpedance, BIS) were assessed. Results: During follow-up, the overhydration (OH) parameter increased (−0.696 ± 1.6 vs. 0.268 ± 1.7 L; p = 0.007) at the expense of a decrease in intracellular water (ICW) (19.90 ± 4.5 vs. 18.72 ± 4.1 24 L; p = 0.006) with a non-significant numerical increase in ECW/ICW ratio (0.795 ± 0.129 vs. 0.850 ± 0.143; p = 0.055). Baseline ICW positively correlated with muscle mass and energy intake and negatively with C-reactive protein and it was lower in those who died than in survivors (15.09 ± 2.36 vs. 18.87 ± 4.52 L; p = 0.004). In Kaplan–Meier analysis, patients with low baseline ICW (≤17 L) and high ECW/ICW ratio (≥0.84) were at an increased risk of death. Baseline ICW was also associated with the risk of death in adjusted Cox proportional hazards models (HR 0.62 (0.40–0.98) p = 0.04). Conclusions: In hemodialysis patients, the post-dialysis OH parameter increased over time while ICW decreased, without changes in ECW. Low baseline post-dialysis ICW correlated with muscle wasting and inflammation and was an independent risk factor for mortality.


2021 ◽  
Vol 12 ◽  
pp. 215145932110377
Author(s):  
Arkan Sayed-Noor ◽  
Bariq Al-Amiry ◽  
Alan Alwan ◽  
Björn Knutsson ◽  
Björn Barenius

Introduction The mortality of femoral neck fracture (FNF) is high and every effort should be made to identify and manage any possible risk factors. The aim of this study was to evaluate whether on-admission hemoglobin (Hb) level, C-reactive protein (CRP), and serum creatinine were associated with 2-year mortality after FNF. Patients and Methods In this retrospective observational cohort study, we considered for inclusion all displaced FNF patients 65 years and above treated with hemi-arthroplasty between February 2011 and May 2015. We documented the age, sex, cognitive status, and American Society of Anesthesiologists (ASA) classification. The Hb level, CRP, and serum creatinine were measured. The medical records were followed up for 2 years. We fitted different crude and adjusted Cox proportional hazards models to examine whether Hb level <100 g/L, CRP >20 mg/L, and serum creatinine >100 μmol/L were associated with the 2-year mortality, adjusted for age, sex, and ASA class. Results A total of 290 patients [208 females (72%), mean age 84 years] were included in the study. More than 50% of patients had impaired cognition and ASA class 3–4. Of the 290 patients, 38.3% ( n = 111) had died within 2 years after surgery. Mortality among males was 46.3% ( n = 38) while mortality among females was 35,1% ( n = 73), p = 0.07. We found that on-admission Hb level <100 g/L was associated with 2-year mortality (HR = 3.3, 95% CI: 1.3–8.3, p < 0.01) while CRP >20 mg/L and serum creatinine >100 μmol/L were not associated with 2-year mortality ( p = 0.89 and p = 0.31, respectively). Conclusion On-admission Hb level <100 g/L, but not CRP >20 mg/L and serum creatinine >100 μmol/L, was associated with 2-year mortality. These results can help healthcare providers identify high-risk FNF patients who probably would benefit from optimized perioperative medical management.


2020 ◽  
Author(s):  
Zhao-Yan Liu ◽  
Dinuerguli Yishake ◽  
Ai-Ping Fang ◽  
Dao-Ming Zhang ◽  
Gong-Cheng Liao ◽  
...  

Abstract Background: Higher choline/betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival. Methods: 866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Both LCSS (T3 vs. T1: HR=0.69, 95% CI: 0.51-0.94; P-trend <0.05) and OS (T3 vs. T1: HR=0.73, 95% CI: 0.54-0.99; P-trend <0.05) were better with sex-specific tertiles of serum choline levels. The associations were not significantly modified across strata of selected prognostic factors, except in the different C-reactive protein (CRP) levels, the favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS. Conclusions: This study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our finding might open new prospect in understanding the benefits of choline on HCC survival. Registration: The Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT 03297255.


2019 ◽  
pp. 1-11 ◽  
Author(s):  
Ping Zhu ◽  
Xianglin L. Du ◽  
Angel I. Blanco ◽  
Leomar Y. Ballester ◽  
Nitin Tandon ◽  
...  

OBJECTIVEThe object of this study was to investigate the impact of facility type (academic center [AC] vs non-AC) and facility volume (high-volume facility [HVF] vs low-volume facility [LVF]) on low-grade glioma (LGG) outcomes.METHODSThis retrospective cohort study included 5539 LGG patients (2004–2014) from the National Cancer Database. Patients were categorized by facility type and volume (non-AC vs AC, HVF vs LVF). An HVF was defined as the top 1% of facilities according to the number of annual cases. Outcomes included overall survival, treatment receipt, and postoperative outcomes. Kaplan-Meier and Cox proportional-hazards models were applied. The Heller explained relative risk was computed to assess the relative importance of each survival predictor.RESULTSSignificant survival advantages were observed at HVFs (HR 0.67, 95% CI 0.55–0.82, p < 0.001) and ACs (HR 0.84, 95% CI 0.73–0.97, p = 0.015), both prior to and after adjusting for all covariates. Tumor resection was 41% and 26% more likely to be performed at HVFs vs LVFs and ACs vs non-ACs, respectively. Chemotherapy was 40% and 88% more frequently to be utilized at HVFs vs LVFs and ACs vs non-ACs, respectively. Prolonged length of stay (LOS) was decreased by 42% and 24% at HVFs and ACs, respectively. After tumor histology, tumor pattern, and codeletion of 1p19q, facility type and surgical procedure were the most important contributors to survival variance. The main findings remained consistent using propensity score matching and multiple imputation.CONCLUSIONSThis study provides evidence of survival benefits among LGG patients treated at HVFs and ACs. An increased likelihood of undergoing resections, receiving adjuvant therapies, having shorter LOSs, and the multidisciplinary environment typically found at ACs and HVFs are important contributors to the authors’ finding.


2019 ◽  
Vol 6 (11) ◽  
Author(s):  
Katelyn A Pastick ◽  
Ananta S Bangdiwala ◽  
Mahsa Abassi ◽  
Andrew G Flynn ◽  
Bozena M Morawski ◽  
...  

Abstract Background Seizures commonly occur in patients with cryptococcal meningitis, yet risk factors and outcomes related to seizures are not well described. Methods We performed post hoc analyses on participants prospectively enrolled in 3 separate human immunodeficiency virus (HIV)-associated cryptococcal meningitis clinical trials during 2010–2017. Documentation of seizures at presentation or during hospitalization and antiseizure medication receipt identified participants with seizures. We summarized participant characteristics by seizure status via Kruskal-Wallis and χ 2 tests. Cox proportional hazards models analyzed the relationship between seizures and mortality. We compared mean quantitative neurocognitive performance Z (QNPZ-8) scores, and individual domain z-scores, at 3-months using independent t tests. Results Among 821 HIV-infected cryptococcal meningitis participants, 28% (231 of 821) experienced seizures: 15.5% (127 of 821) experienced seizures at presentation, and 12.7% (104 of 821) experienced incident seizures. Participants with seizures at presentation had a significantly lower Glasgow coma scale ([GCS] &lt;15; P &lt; .001), CD4 count (&lt;50 cells/mcL; P = .02), and higher cerebrospinal fluid (CSF) opening pressure (&gt;25 cm H2O; P = .004) when compared with participants who never experienced seizures. Cerebrospinal fluid fungal burden was higher among those with seizures at presentation (125 000 Cryptococcus colony-forming units [CFU]/mL CSF) and with seizures during follow-up (92 000 CFU/mL) compared with those who never experienced seizures (36 000 CFU/mL, P &lt; .001). Seizures were associated with increased 10-week mortality (adjusted hazard ratio = 1.45; 95% confidence interval, 1.11–1.89). Participants with seizures had lower neurocognitive function at 3 months (QNPZ-8 = −1.87) compared with those without seizures (QNPZ-8 = −1.36; P &lt; .001). Conclusions Seizures were common in this HIV-associated cryptococcal meningitis cohort and were associated with decreased survival and neurocognitive function.


JAMIA Open ◽  
2020 ◽  
Author(s):  
Spiros Denaxas ◽  
Anoop D Shah ◽  
Bilal A Mateen ◽  
Valerie Kuan ◽  
Jennifer K Quint ◽  
...  

Abstract Objectives The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1177
Author(s):  
In Young Choi ◽  
Sohyun Chun ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Keun Hye Jeon ◽  
...  

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.


Sign in / Sign up

Export Citation Format

Share Document