Age-adjusted Reference Values Research Articles

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults.

The aim of this study was to investigate age-related changes in corneal nerves and corneal epithelial cell parameters and to establish age-adjusted reference values. A total of 7025 corneal nerve images and 4215 corneal epithelial images obtained using in vivo confocal microscopy from 281 eyes of 143 healthy participants were included. Seven corneal nerve parameters and 3 corneal epithelial cell parameters were quantified using 2 automatic analytic software and analyzed across 6 age groups ranging from 21 to 80 years. There was a declining trend in all 7 nerve parameters with advancing age. In particular, corneal nerve fiber length and corneal nerve fiber density demonstrated a significant decrease in subjects aged 65 years or older compared with subjects younger than 65 years (10.8 ± 2.6 mm/mm 2 vs. 9.9 ± 2.0 mm/mm 2 , P = 0.011 in corneal nerve fiber length; 15.8 ± 5.2 fibers/mm 2 vs. 14.4 ± 4.3 fibers/mm 2 , P = 0.046 in corneal nerve fiber density), whereas corneal nerve fractal dimension demonstrated a borderline significant decrease ( P = 0.057). Similarly, there was a general declining trend in all epithelial cell parameters with advancing age. Corneal epithelial cell circularity was significantly lower in subjects aged 65 years and older as compared to subjects younger than 65 years (0.722 ± 0.021 μm 2 vs. 0.714 ± 0.021 μm 2 ; P = 0.011). Advancing age results in reduced corneal nerve metrics and alteration of corneal cell morphology. Aging effects should be considered when evaluating patients with corneal neuropathy.

Serum neurofilament light chain reference database for individual application in paediatric care: a retrospective modelling and validation study

Neurological conditions represent an important driver of paediatric disability burden worldwide. Measurement of serum neurofilament light chain (sNfL) concentrations, a specific marker of neuroaxonal injury, has the potential to contribute to the management of children with such conditions. In this context, the European Medicines Agency recently declared age-adjusted reference values for sNfL a top research priority. We aimed to establish an age-adjusted sNfL reference range database in a population of healthy children and adolescents, and to validate this database in paediatric patients with neurological conditions to affirm its clinical applicability. To generate a paediatric sNfL reference dataset, sNfL values were measured in a population of healthy children and adolescents (aged 0-22 years) from two large cohorts in Europe (the Coronavirus Antibodies in Kids from Bavaria study, Germany) and North America (a US Network of Paediatric Multiple Sclerosis Centers paediatric case-control cohort). Children with active or previous COVID-19 infection or SARS-CoV-2 antibody positivity at the time of sampling, or a history of primary systemic or neurological conditions were excluded. Linear models were used to restrospectively study the effect of age and weight on sNfL concentrations. We modelled the distribution of sNfL concentrations as a function of age-related physiological changes to derive reference percentile and Z score values via a generalised additive model for location, scale, and shape. The clinical utility of the new reference dataset was assessed in children and adolescents (aged 1-19 years) with neurological diseases (epilepsy, traumatic brain injury, bacterial CNS infections, paediatric-onset multiple sclerosis, and myelin oligodendrocyte glycoprotein antibody-associated disease) from the paediatric neuroimmunology clinic at the University of California San Francisco (San Francisco, CA, USA) and the Children's Hospital of the University of Regensburg (Regensburg, Germany). Samples from 2667 healthy children and adolescents (1336 [50·1%] girls and 1331 [49·9%] boys; median age 8·0 years [IQR 4·0-12·0]) were used to generate the reference database covering neonatal age to adolescence (target age range 0-20 years). In the healthy population, sNfL concentrations decreased with age by an estimated 6·8% per year until age 10·3 years (estimated multiplicative effect per 1 year increase 0·93 [95% CI 0·93-0·94], p<0·0001) and was mostly stable thereafter up to age 22 years (1·00 [0·52-1·94], p>0·99). Independent of age, the magnitude of the effect of weight on sNfL concentrations was marginal. Samples from 220 children with neurological conditions (134 [60·9%] girls and 86 [39·1%] boys; median age 14·7 years [IQR 10·8-16·5]) were used to validate the clinical utility of the reference Z scores. In this population, age-adjusted sNfL Z scores were higher than in the reference population of healthy children and adolescents (p<0·0001) with higher effect size metrics (Cohen's d=1·56) compared with the application of raw sNfL concentrations (d=1·28). The established normative sNfL values in children and adolescents provide a foundation for the clinical application of sNfL in the paediatric population. Compared with absolute sNfL values, the use of sNfL Z score was associated with higher effect size metrics and allowed for more accurate estimation of the extent of ongoing neuroaxonal damage in individual patients. Swiss National Science Foundation, US National Institutes of Health, and the National Multiple Sclerosis Society.

Age-adjusted reference values and influencing factors of cystatin C in healthy Chinese population.

Normative distribution of serum cystatin C and relationship with sex and age in healthy adult Chinese population is unknown. This is a prospective cohort study. Adult subjects (18years of age and older) who underwent annual health examination at the Health Management Center in Sir Run Run Hospital were eligible. Subjects with major diseases, e.g., hypertension, diabetes, chronic kidney disease, obesity (body mass index ≥ 28kg/m2) were excluded from the analysis. Multivariate logistic regression analysis was conducted to identify risk factors of elevated cystatin C (> 1.03mg/L). Data are shown as median and 95% confidence interval (CI). The final analysis included a total of 10,640 subjects (40 ± 12years, 52% men). The median serum cystatin C concentration was 0.73mg/L (95% CI 0.52-1.03mg/L) in the overall analysis, 0.79 (95% CI 0.59-1.07mg/L) in men, and 0.67 (95% CI 0.49-0.95mg/L) in women. In the multivariate regression analysis, elevated cystatin C was independently associated with the male sex (odds ratio 1.94; 95% CI 1.07-3.52), older age (odds ratio 1.04 every year; 95% CI 1.02-1.06), higher body mass index (odds ratio 1.70; 95% CI 1.01-2.83), uric acid (odds ratio 1.00; 95% CI 1.00-1.01), and β2-microglobulin (odds ratio 39.35; 95% CI 22.90-67.64). The median serum cystatin C concentration was 0.73 (95% CI 0.52-1.03mg/L) in healthy adult Chinese population, 0.79 (95% CI 0.59-1.07mg/L) in men, and 0.67 (95% CI 0.49-0.95mg/L) in women. Elevated cystatin C was associated with the male sex, older age and higher body mass index.

An adrenal incidentaloma that had appeared to produce dehydroepiandrosterone-sulfate in excess before immunohistochemical study of the tumor.

Adrenal incidentaloma is a clinically unapparent adrenal mass more than one cm in diameter detected during imaging performed not for adrenal disease. A 34-year-old man was evaluated for AI with a diameter of 3.5 cm in the left adrenal. He was obese with body mass index of 33,9. Blood pressure was 110-120/90 mmHg. The general laboratory tests were unremarkable. An adrenal hormone screening set revealed that ACTH was 6.9 pg/mL, cortisol 14.9 μg/dL, renin activity 0.9 ng/mL/h, aldosterone 79.4 pg/mL, dehydroepiandrosterone-sulfate (DHEA-S) measured on two occasions 5,217 ng/mL and 6,477 ng/mL (gender- and age-adjusted reference values, 1,060-4,640 ng/mL). The levels of metanephrine and normetanephrine were normal. The tumor was thought to produce solely DHEA-S. The excised left adrenal tissue contained a tumor with a diameter of 26 mm and neighboring adrenal tissue. The tumor consisted mostly of acidophil cells without necrosis, capsular or vascular invasion, and mitosis. Immunohistochemical study revealed followings: the cells of the tumors were stained positive for 3β-hydroxysteroid dehydrogenase, and 17α-hydroxylase, and 11β-hydroxylase, weakly positive for DHEA sulphotransferase, and negative for aldosterone synthetase. The atrophy of neighboring tissue was presumably caused by excess cortisol production. Four months after surgery, the cortisol level was 11.2 μg/dL and DHEA-S level 1,462 ng/mL. The tumor is considered to be a cortisol-producing adenoma with modestly excessive DHEA-S production rather than isolated DHEA-S-producing adenoma. Immunohistochemical study of steroidogenic enzymes is a valuable addition to blood hormone measurement to clarify steroid production profile.

Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development.

Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development.

Cardiorespiratory Fitness Levels In Adolescent And Young Adult Cancer Survivors

PURPOSE: Adolescent and young adult (AYA) cure rates have greatly improved, leading to a growing population of survivors that are at risk for competing causes of death, notably cardiovascular disease (CVD). The purpose of this study was to assess levels of cardiorespiratory fitness, a prognostic indicator of CVD, among AYA survivors. METHODS: We studied 37 AYA cancer survivors presenting to the University of Texas MD Anderson Healthy Heart Program between 2017-2019 for cardiorespiratory fitness and heart risk factor assessment. All patients underwent a symptom-limited exercise treadmill testing with metabolic gas exchange to assess peak oxygen consumption (VO2peak). RESULTS: At the time of the clinic assessment, the mean age was 28.8 ± 5.9 years and mean time from diagnosis was 9.3 ± 7.1 years. Breast cancer (27.0%), sarcoma (24.3%), and Hodgkin’s Lymphoma (13.5%) were the most common cancer diagnoses and 94.5% had been treated with anthracycline-based chemotherapy. The mean BMI was 28.2 ± 5.4 kg/m2. 2D echocardiographic assessment of left ventricular ejection fraction (LVEF) performed within 2.5 years of clinic assessment was available in 29 participants and was 59% ± 0.3%. The mean VO2peak was 27.9 ± 7.8 ml · kg-1 · min-1, the equivalent of 35.6% below healthy, age-adjusted reference values. Mean VO2peak of the males (n = 19) was 30.7 ± 8.2 ml · kg-1 · min-1and 25.0 ± 4.6 for ml · kg-1 · min-1 for the females (n = 18). CONCLUSIONS: The large and growing population of AYA cancer survivors is at increased risk for CVD late effects. In the current study, cardiorespiratory fitness, an important marker of CVD risk, was markedly reduced among AYA cancer survivors. Strategies to promote exercise and fitness and cardiovascular health in this population are needed.

Duplex ultrasound for assessing vascular impairment after supracondylar humerus fractures.

Background:Supracondylar humerus fractures (SHF) are the second most common fracture in children and the most common fracture in children under seven years. Subtle neurovascular lesions in displaced SHF may be underdiagnosed clinically, but their sequelae can mean life-long symptoms. Here we show that color-coded duplex ultrasound (DUS) could help to identify these patients.Methods:We reviewed records of 229 children who had recovered from SHF. Ninety patients were available for detailed questionnaires, in-depth neurovascular examinations, and DUS.Results:In 90 examined patients, only two had been known to have suffered from vascular complications before our study. Only one still complained spontaneously about perfusion-induced symptoms. Qualitative changes in blood flow in duplex-sonography were detectable in both. Another two patients showed similar changes in blood flow at the fracture site. Both reported load-induced pain and paresthesia on detailed inquisition when no vascular impairments had been known before. Thus, duplex-sonography identified two patients with vascular affections that had not been noticed before in routine clinical examinations.Conclusion:DUS can be a sensitive tool in diagnosing vascular impairments in patients with SHF. It could reduce diagnostic insecurity, especially in anesthetized or otherwise hard to examine children, and thus help avoid the therapeutic delay that otherwise might foster life-long sequelae for the patients. More studies are needed to establish age-adjusted reference values for duplex-sonography of children's arms. Level of Evidence: Level III, Study of nonconsecutive patients (without consistently applied reference).

Age-Adjusted Reference Values for Prostate Specific Antigen - A Systematic Review and Meta-Analysis.

To systematically evaluates the evidence on ethnic differences in age-adjusted reference values of PSA. In concordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement, a review of English articles using Medline, Embase and Cochrane databases, from inception to December 2019 was conducted. Studies that reported the PSA upper reference value as 95th percentile of the cohort distribution, in healthy men aged 40 to 79, were included. Methodological quality was assessed with a modified version of the Agency for Healthcare Research and Quality checklist for cross-sectional studies. Forty-three studies examining 325,514 participants were included in the analysis. These were published between 1993 and 2018. Majority were prospective observational studies and reported the reference values in ten-year age intervals. Only five reports directly compared ethnic differences in PSA values. Due to missing data, six studies were not considered in the quantitative synthesis. For the remainder (37/43), heterogeneity in PSA reference values was considerable (Higgin's index=99.2%), with age and ethnicity being the sole identified significant contributors. Accordingly, the pooled upper limits for PSA reference values were 2.1, 3.2, 4.9 and 6.5 ng/ml for men in their 40 s, 50 s, 60 s, and 70 s, respectively. Moderate quality evidence suggest that upper PSA reference limits increased with age and significant ethnic differences were present.

Revisited Upper Reference Limits for Highly Sensitive Cardiac Troponin T in Relation to Age, Sex, and Renal Function.

(1) Background: Highly sensitive cardiac troponin T (hs-cTnT) plays an essential role in the diagnosis of myocardial injury. The upper reference limit of the respective assay is generally applied, irrespective of age, renal function, or sex. We aimed to identify age-adjusted and sex-adjusted upper reference limits in relation to renal function in a large population-based cohort without cardiac diseases. (2) Methods: We included 5428 subjects of the population-based LIFE-Adult cohort, free of diagnosed cardiac diseases. Sex-adjusted and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained. (3) Results: The hs-cTnT values were higher in men of all age groups. In both sexes, an increasing age positively correlated with higher hs-cTnT values. Hs-cTnT weakly correlated with serum creatinine. The three-dimensional analysis of age, creatinine, and hs-cTnT showed no relevant additional effect of creatinine on hs-cTnT. In men aged above 60 and women above 70, the calculated 99th percentiles clearly exceeded the commonly applied thresholds. (4) Conclusion: Age and sex have a major impact on the serum concentration of hs-cTnT, while renal function does not. We propose to consider age-adjusted and sex-adjusted reference values.

Age-adjusted Reference Values and Z-scores of the Coronary Sinus Diameter among Healthy Children and Adolescents in Southern Iran.

Coronary sinus dimension is an important factor for diagnosing some types of cyanosis as well as congenital heart diseases and insertion of some devices into the coronary sinus if required. This study was designed to access the diameter and Z-score of the coronary sinus among children under 18 years of age. In this cross-sectional study on 95 individuals, the coronary sinus diameter was measured by transthoracic echocardiography in the four-chamber view at the connection to the right atrium, middle part, and distal end. The linear regression equation was utilized to determine age-adjust reference values, Z-scores, and the relationship between the individuals' coronary sinus diameter age, height, and body surface area. The study was conducted from March to July 2020 in Namazi hospital clinic of Shiraz University of Medical Sciences, Shiraz, Iran. The mean age of the persons who entered this study was 5.87±4.25 years. The mean coronary sinus diameter was 4.91±1.29 mm at the site of connection to the right atrium, 4.50±1.44 mm at the middle part, and 3.74±1.32 mm at the distal end. Coronary sinus diameter correlates positively with the participants' age, weight, height, and body surface area (P<0.001). Coronary sinus diameter significantly correlates with the age, height, and body surface area of the cases. These features are useful in diagnosing some congenital heart diseases and insertion of suitable devices through it.

Utilidad clínica de la elevación del dímero-D a la admisión en pacientes con sospecha de COVID-19

Introduction: Studies associated increased D-dimer (DD) with severe COVID-19. Methods: Retrospective cohort of patients with suspicion of COVID-19 and DD measurement. Plasma levels of DD at first consultation and the DD peak during hospitalization were recorded (expressed in ng/mL FEU or as patient/age-adjusted expected ratio-P/AA DD-). COVID-19 positive and negative groups were compared. Factors associated with severity and death were evaluated in both groups. Results: Out of 723 patients included, 162 were diagnosed with SARS-CoV2 infection. COVID-19 patients had lower levels of DD [465(226-880) vs 691(295-1823) ng/mL,p 500ng/mL at diagnosis was associated with an increased risk of severity, however it was not evidenced with P/AA DD>1. In this group, DD at admission was not different in deaths compared with survivors. Deceased COVID-19-negative patients had higher levels of DD Conclusions: DD seems not to be a specific biomarker of COVID-19 infection, and its increase is more pronounced in patients who developed pneumonia from other etiologies. Considering age-adjusted DD reference values could avoid the overestimation of its prognostic value in COVID-19 patients.

Standardized gait speed ratio in elderly patients with heart failure.

AimsAlthough aging is strongly associated with both heart failure and a decline in gait speed, a definition of slowness incorporating an age‐related decline has yet to be developed. We aimed to define an event‐driven cut‐off for the relative decline in gait speed against age‐adjusted reference values derived from the general population and evaluate its prognostic implications.Methods and resultsStandardized gait speed (SGS) was defined as the median gait speed stratified by age, sex, and height in 3777 elderly (age ≥ 65 years) individuals without a history of cardiovascular diseases (Tokyo Metropolitan Institute of Gerontology‐Longitudinal Interdisciplinary Study on Aging: general population cohort). The mortality event‐driven optimal cut‐off of the SGS ratio (actual gait speed divided by the respective SGS) was defined using FRAGILE‐HF cohort data and externally validated using Kitasato cohort data, comprising 1301 and 1247 hospitalized elderly patients with heart failure, respectively. Using FRAGILE‐HF data, the optimal SGS ratio cut‐off was determined as 0.527. In the Kitasato cohort, SGS ratio < 0.527 was associated with a higher 1 year [hazard ratio (HR): 1.70, 95% confidence interval (CI): 1.07–2.72, P = 0.024] and long‐term (HR: 1.46, 95% CI: 1.05–2.02, P = 0.024) mortality rate, independent of pre‐existing covariates.ConclusionsGait speed was significantly declined in patients with heart failure, even after taking age and sex‐related decline into account. A SGS ratio of 0.527 is a validated cut‐off for slowness independently associated with mortality in patients with heart failure age ≥65.

Age-adjusted reference values for prostate-specific antigen in a multi-ethnic population.

To establish age-adjusted reference values for prostate-specific antigen in an ethnically diverse population. Between 2009 and 2017, data were collected from all men aged 40-79years, who had a prostate-specific antigen test in the northern region of New Zealand, where the prostate-specific antigen testing service is provided by a single community laboratory and using the same assay analyzer. Men known to have prostate cancer, who developed prostate cancer during the study period, who were treated with finasteride, or who had prostate-specific antigen levels above 20ng/mL were excluded. Age-adjusted prostate-specific antigen reference values were calculated for each of the main ethnic groups in the country including: Māori (indigenous), Pacific, Asian and European. For every 5-year age interval, the 95th percentile of the log prostate-specific antigen distribution was used to define the upper limit of normal. The study cohort included 215132 apparently healthy men, with a median age and prostate-specific antigen concentration of 59years and 0.9ng/mL, respectively. Prostate-specific antigen levels for the entire cohort increased with age (Pearson correlation=0.362, P<0.001). This relationship was most prominent in Pacific men. Similarly, the upper reference limit for the entire cohort increased with age, from 1.60ng/mL for men aged 40-44years to 7.61ng/mL for those aged 75-79years. Significant ethnic differences were present within each interval, which was most apparent in the older age groups. Ethnic differences in age-adjusted prostate-specific antigen reference values are present in New Zealand. These need to be considered when prostate-specific antigen results are being interpreted in clinical practice.

Congenital Hypothyroidism: A Review of 2020 European Society for Pediatric Endocrinology and the European Society for Endocrinology Consensus Guidelines

Congenital Hypothyroidism: A Review of 2020 European Society for Pediatric Endocrinology and the European Society for Endocrinology Consensus Guidelines

Multi-center implementation of automated age-adjusted D-dimer results reduces unnecessary PE imaging.

Several previous studies have investigated the clinical utility of age-adjusted D-dimer cutoffs for diagnosing pulmonary embolism (PE). We performed a pre/post implementation study, using data from a mid-Atlantic healthcare system comprising 6 hospitals and 400,000 ED visits to determine whether implementing age adjusted D-dimer cutoffs reduced the number of imaging tests performed. Retrospective study of all patients who had a D-dimer performed during ED visits between September 2015 to September 2018. On March 21, 2017, the D-dimer upper limit of normal system-wide was increased for patients over 50 to: Age (years) x 0.01μg/mL. D-dimer results were displayed as normal or high based on automated age adjustment. EHR Chart review was performed 1.5years prior to implementation of age-adjusted D-dimer cutoffs, as well as 1.5years after to evaluate mortality and test accuracy characteristics such as false negative rates. Comparisons were made using chi-square testing. 22,302 D-dimers were performed pre-implementation of which 10,837 (48.6%) were positive resulting in 7218 (32.3%) imaging studies. After implementation of age-adjusted d-dimer, 25,082 were performed of which 10,851 (43.2%) were positive resulting in 7017 (28.0%) imaging studies. (pre: 48.6%, post: 43.2%; p<0.01). A significantly lower proportion of patients had a positive d-dimer (pre: 48.6%, post: 43.2%; p<0.01) and underwent imaging post-implementation (pre: 32.3%, post: 28.0%; p<0.05) a relative risk reduction of 13.3. This absolute risk reduction of 4.4% is associated with 1104 less scans in the post-implementation group while still increasing test accuracy from 53.7% to 59.2% (p<0.05). Implementation of an automated age-adjusted D-dimer positive reference value reduced CT and V/Q imaging in this population by 4.4% while increasing test accuracy in a regional, heterogeneous six-hospital system.

Myocardial work - correlation patterns and reference values from the population-based STAAB cohort study.

BackgroundRecently, myocardial work analysis as an echocardiographic tool to non-invasively determine LV work has been introduced and validated against invasive measurements. Based on systolic blood pressure and speckle-tracking derived longitudinal strain (GLS) during systole and isovolumic relaxation, it is considered less load-dependent than LV ejection fraction (LVEF) or GLS and to integrate information on LV active systolic and diastolic work.ObjectivesWe aimed to establish reference values for global constructive (GCW) and global wasted work (GWW) as well as of global work index (GWI) and global work efficiency (GWE) across a wide age range and to assess the association with standard echocardiography parameters to estimate the potential additional information provided by myocardial work (MyW).MethodsThe Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of the City of Würzburg, Germany, aged 30–79 years. We performed myocardial work analysis using the standardized, quality-controlled transthoracic echocardiograms of all individuals lacking any cardiovascular risk factor.ResultsOut of 4965 participants, 779 (49±10 years, 59% women) were eligible for the present analysis. Levels of GCW, GWW, and GWE were independent of sex and body mass index, and were stable until the age of 45 years. Thereafter, we observed an upward shift to further stable values of GCW and a linear increase of GWW with advancing age, resulting in lower GWE. Age-adjusted percentiles for GCW, GWW, GWI, and GWE were derived. Higher levels of blood pressure or LV mass were associated with higher GCW, GWI, and GWW, resulting in lower GWE; higher LVEF correlated with higher GCW and GWI, but lower GWW. Higher E/e´ correlated with higher GWW, higher e´ with lower GWW.ConclusionsDerived from a large sample of apparently healthy individuals from a population based-cohort, we provide age-adjusted reference values for myocardial work indices, applicable for either sex. Weak correlations with common echocardiographic parameters suggest MyW indices to potentially provide additional information, which has to be evaluated in diseased patient cohorts.

Cancer Antigen 125 Serum Level in Head and Neck Diffuse Large B-Cell Lymphoma

Background : Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of the Non-Hodgkin Lymphoma (LNH). Until now, lactate dehydrogenase (LDH) is the only tumor marker to assess DLBCL progression; however, increased LDH is a relatively non-specific biomarker. Cancer antigen 125 (CA-125) serum level have been used as a tumor marker in ovarian cancer. The aim of this study was to explore the possible role of CA-125 serum level as a tumor marker in head and neck DLBCL. Methods : This was an observational descriptive study among consecutively sampled DLBCL patients. CA-125 serum level examination was carried out (ADVIA Centaur CA-125II) and described along with the clinical characteristics of DLBCL patients. Results : DLBCL was mostly observed in males (54.05%), most often in the 55-65 year age group (51.3%), with stage 1 DLBCL was the most prevalent (71.9%). The mean CA-125 serum level was 22.9 U/ml and increased in patients with advanced DLBCL. Conclusions : Increased CA-125 serum level in DLBCL, especially at advanced stages, suggests that CA-125 serum level may be of benefit as a tumor marker in the head and neck DLBCL. Further study is in need to explore the role of CA-125. 1. Kementerian Kesehatan Republik Indonesia. Data dan kondisi penyakit limfoma di Indonesia. InfoDatin Pusat Data dan Informasi Kementerian Kesehatan RI. 2015 [cited 2020 March 18] Available from: https://www.kemkes.go.id/resources/download/pusdatin/infodatin/infodatin-limfoma.pdf 2. Dwianingsih EK, Indrawati, Hardianti MS, Malueka RG , Iswar RR, Sutapa S, et al. Histopathological features of lymphoma in Yogyakarta, Indonesia. Asian Pac J Cancer Prev. 2016;17(9):4213–16. 3. Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI. Riset Kesehatan Dasar (RISKESDAS) 2013. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI; 2013 4. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27):3059–67. 5. Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(14):2373-2380. 6. Gutiérrez A, Martínez-Serra J, Barceló B, Sampol A, Vinas L, Gonzales G, et al. Prognostic value of serum CA125 levels in diffuse large B-cell lymphoma: potential role of a new sex and age adjusted reference value. Int J Lab Hematol. 2010; 32(6 Pt 2): 582–9. 7. Dilek I, Ayakta H, Demir C, Meral C, Ozturk M. CA 125 levels in patients with Non-Hodgkin lymphoma and other hematologic malignancies. Clin Lab Haematol. 2005;27(1):51–5. 8. Memar B, Aledavood A, Shahidsales S, Ahadi M, Farzadnia, Raziee HR, et al. The prognostic role of tumor marker CA-125 in B-Cell non-Hodgkin’s Lymphoma. Iran J Cancer Prev. 2015;8(1):42–6. 9. Garg S, Goyal B. Evaluation of CA-125 as a prognostic marker in patients with Non-Hodgkin’s lymphoma. International Journal of Medical and Health Research. 2017;3(4):13–5. 10. Paoli CJ, Bach BA, Quach D, Tsai KT, Wong B, Kallich J. Performance status of real-world oncology patients before and after first course of chemotherapy. The Journal of Community and Supportive Oncology. 2014; 12(5):163–70. 11. Yadav C, Ahmad A, D’Souza B, Agarwal A, Nandini M, Prabhu KA, et al. Serum lactate dehydrogenase in Non-Hodgkin’s lymphoma: a prognostic indicator. Indian J Clin Biochem. 2016;31(2):240–2.

Heart rate variability measures for prediction of severity of illness and poor outcome in ED patients with sepsis.

This study evaluates the utility of heart rate variability (HRV) for assessment of severity of illness and poor outcome in Emergency Department (ED) patients with sepsis. HRV measures evaluated included low frequency (LF) signal, high frequency (HF) signal, and deviations in LF and HF signal from age-adjusted reference values. This was a prospective, observational study. Seventy-two adult ED patients were assessed within 6h of arrival. Severity of illness as defined by sepsis subtype correlated with decreased LF signal (sepsis: 70.68±22.95, severe sepsis: 54.00±28.41, septic shock: 45.54±23.31, p=0.02), increased HF signal (sepsis: 27.87±19.42, severe sepsis: 44.63±27.29, septic shock: 47.66±20.98, p=0.01), increasingly negative deviations in LF signal (sepsis: 0.41±24.53, severe sepsis: -21.43±30.09, septic shock -30.39±26.09, p=0.005) and increasingly positive deviations in HF signal (sepsis: -1.86±21.09, severe sepsis: 20.07±29.03, septic shock: 23.6±24.17, p=0.004). Composite poor outcome correlated with decreased LF signal (p=0.008), increased HF signal (p=0.03), large negative deviations in LF signal (p=0.004) and large positive deviations in HF signal (p=0.02). Deviations in LF and HF signal from age-adjusted reference values correlated with individual measures of poor outcome with greater consistency than LF or HF signal. Accounting for the influence of age on baseline HRV signal improves the predictive value of HRV measures in ED patients with sepsis.

Accurate discrimination of Hartnup disorder from other aminoacidurias using a diagnostic ratio

IntroductionHartnup disorder is caused by a deficiency of the sodium dependent B0 AT1 neutral amino acid transporter in the proximal kidney tubules and jejunum. Biochemically, Hartnup disorder is diagnosed via amino acid excretion patterns. However, these patterns can closely resemble amino acid excretion patterns of generalized aminoaciduria, which may induce a risk for misdiagnosis and preclusion from treatment. Here we explore whether calculating a diagnostic ratio could facilitate correct discrimination of Hartnup disorder from other aminoacidurias. Methods27 amino acid excretion patterns from 11 patients with genetically confirmed Hartnup disorder were compared to 68 samples of 16 patients with other aminoacidurias. Amino acid fold changes were calculated by dividing the quantified excretion values over the upper limit of the age-adjusted reference value. ResultsIncreased excretion of amino acids is not restricted to amino acids classically related to Hartnup disorder (“Hartnup amino acids”, HAA), but also includes many other amino acids, not classically related to Hartnup disorder (“other amino acids”, OAA). The fold change ratio of HAA over OAA was 6.1 (range: 2.4–9.6) in the Hartnup cohort, versus 0.2 (range: 0.0–1.6) in the aminoaciduria cohort (p < .0001), without any overlap observed between the cohorts. DiscussionExcretion values of amino acids not classically related to Hartnup disorder are frequently elevated in patients with Hartnup disorder, which may cause misdiagnosis as generalized aminoaciduria and preclusion from vitamin B3 treatment. Calculation of the HAA/OAA ratio improves diagnostic differentiation of Hartnup disorder from other aminoacidurias.

Higher mortality in pediatric and adult trauma patients with traumatic coagulopathy, using age-adjusted diagnostic criteria

BackgroundAcute traumatic coagulopathy has been described in adult trauma patients. Acute traumatic coagulopathy may be associated with higher mortality and morbidity in pediatric trauma patients. We aimed to (1) compare acute traumatic coagulopathy incidence among various age groups, using age-adjusted normal reference values for three tests of coagulation, and (2) compare acute traumatic coagulopathy–associated mortality by age. MethodsWe queried our institutional trauma database for all level 1 and 2 activations with an injury severity score ≥ 9 during 2012 to 2017. Demographics, injury information, and coagulation test results were collected. Coagulopathy was defined using published age-specific and assay-specific parameters. Variables were compared among age groups (children, adults, and older adults), and logistic regression was used to determine independent associations with mortality. ResultsA total of 1,983 patients were included with a median injury severity score of 17 and mortality of 12%. Prolonged partial thromboplastin time, prolonged international normalized ratio, and hypofibrinogenemia were all strongly associated with mortality among adults and children, but not among older adults (P < .001, P < .001, and P > .01, respectively). Logistic regression revealed an independent association between prolonged partial thromboplastin time and mortality (P < .001). ConclusionProlonged partial thromboplastin time/international normalized ratio and hypofibrinogenemia were common among trauma patients of all ages and were associated with mortality among children and adults, but not older adults, perhaps implicating age-related hemostatic biologic differences.