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Serum pentraxin-3 follows a logarithmic distribution particularly at low expected levels

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L E T T E R T O T H E E D I T O R

Serum pentraxin-3 follows a logarithmic distribution particularly

at low expected levels

Dear Editors,

We read the article by Ozer Balin et al

1

with interest and would

like to comment on the results, focusing on data expression and

statistical evaluation regarding serum pentraxin-3 (PTX3) levels.

PTX3, a soluble pattern recognition receptor, is an acute-phase

protein, and its level in systemic circulation was proposed as a

marker for the prediction and/or prognostication of

cardiovascu-lar, metabolic, infectious, and inflammatory disorders as in the

present study.

1

As in the case of C-reactive protein (CRP),

dis-tribution of serum PTX3 is skewed to the right (positive

skew-ness) in healthy population,

1-6

but unlike CRP, it may increase

by up to 1000 to 10 000 times in case of disease, and its range

F I G U R E 1 Histograms (A,B) and Q–Q plots (C,D) showing distribution of serum pentraxin-3 (PTX3) and deviation from normal before (A,C) and after (B,D) logarithmic transformation. Frequencies of measurements in 0 to 5000 pg/mL band were provided as an inner histogram (A). Note that the histogram appeared normal, and skewness and kurtosis were around zero with a Shapiro-Wilk statistic of 0.968 (P = .11) after transformation. Modified with permission.4International League of Associations for Rheumatology (ILAR): Springer Nature ©2016

Received: 16 July 2019 Accepted: 28 July 2019

DOI: 10.1111/iwj.13184

© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd

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is quite wide in healthy population.

4-6

Based on our previous

findings in a healthy control group,

4

we tested the hypothesis

if logarithmic transformation could yield a normal distribution

in these wide-ranging and skewed data. After transformation,

the histogram appeared to be normal and skewness and

kurtosis were around zero with a Shapiro

–Wilk statistic of

0.968 (P = .11) (Figure 1). Similarly, logarithmic

transforma-tion resulted in near-normal distributransforma-tions in disease groups

too (Figure 2). In studies with higher numbers of

parti-cipants, healthy or with disease, it is the logarithmic

distribu-tion of serum PTX3 that made the researchers use

logarithmic/exponential scales when reporting their data.

5-7

In

the case of a small sample size and high expected serum

PTX3 levels, it is depicted in Figure 3 how the data

distribu-tion may appear normal, particularly after excluding the

extreme values (ie, the outliers), which is a common statistical

practice. This was possibly the case in many previous

stud-ies.

8-11

However, extreme values in a linear scale are an

integral feature of a logarithmic/exponential distribution

5-7

and should not be missed.

In conclusion, logarithmic transformation of serum

PTX3 levels may yield normal distribution, particularly at

low expected levels, and makes parametric analysis of

vari-ance possible. Beside an easier data expression and more

powerful statistical analysis, this may enable logarithmic/

exponential, instead of linear cut-offs to be used in

discrim-inating between potential diagnostic and/or prognostic

groups in future studies.

C O N F L I C T O F I N T E R E S T

The authors declare no potential conflict of interest.

O R C I D

Ufuk _llgen

https://orcid.org/0000-0001-6443-6426

Ufuk _llgen

1

Müçteba Enes Yayla

2

Cenk Gökalp

3

Hakan Emmungil

1

Nurs¸en Düzgün

4 1

Department of Rheumatology, Trakya University Medical

School, Edirne, Turkey

2

Department of Rheumatology, Ankara University Medical

School, Ankara, Turkey

3

Department of Nephrology, Trakya University Medical

School, Edirne, Turkey

4

Department of Rheumatology, Ufuk University Medical

School, Ankara, Turkey

Correspondence

Ufuk _Ilgen, MD, Department of Rheumatology, Trakya

University Hospital, 22100 Edirne, Turkey.

Email: ufukilgen@gmail.com

F I G U R E 2 Logarithmic transformation of serum pentraxin-3

(PTX3) in disease groups (ie, systemic sclerosis and systemic lupus erythematosus) yielded near-normal distributions as in the case of healthy population. Modified with permission.4International League of Associations for Rheumatology (ILAR): Springer Nature ©2016

0 100 200 300 400 500 600 1 2 3 4 5 6 7 8 9 10 Fr equency

Serum pentraxin-3 quantiles

Low-expected High-expected High-expected with a small sample size

F I G U R E 3 Distribution of serum pentraxin-3 at low and high expected levels. Note that the decrease in skewness at high expected levels may result in a normal-like distribution, particularly if the quantiles 8 to 10 with a low number of cases were considered outliers. At high expected levels with a small sample size, the tail of the histogram may automatically disappear, again leaving a normal-like distribution

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R E F E R E N C E S

1. Ozer Balin S, Sagmak Tartar A, Ugur K, et al. Pentraxin-3: a new parameter in predicting the severity of diabetic foot infection? Int Wound J. 2019;16:659-664.

2. Rifai N, Ridker PM. Population distributions of C-reactive protein in apparently healthy men and women in the United States: impli-cation for clinical interpretation. Clin Chem. 2003;49:666-669. 3. Imhof A, Fröhlich M, Loewel H, et al. Distributions of C-reactive

protein measured by high- sensitivity assays in apparently healthy men and women from different populations in Europe. Clin Chem. 2003;49:669-672.

4. _llgen U, Yayla ME, Düzgün N. Low serum fibroblast growth factor 2 levels not accompanied by increased serum pentraxin 3 levels in patients with systemic sclerosis. Clin Rheumatol. 2017;36:367-372. 5. Hamed S, Behnes M, Pauly D, et al. Diagnostic value of

Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions. BMC Infect Dis. 2017;17:554. 6. Yamasaki K, Kurimura M, Kasai T, Sagara M, Kodama T, Inoue K.

Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations. Clin Chem Lab Med. 2009;47:471-477.

7. Kontny F, Andersen T, Ueland T, et al. Pentraxin-3 vs C-reactive protein and other prognostic biomarkers in acute coronary syn-drome: a substudy of the Platelet Inhibition and Patients Outcomes (PLATO) trial. Eur Heart J Acute Cardiovasc Care. 2019. In press. https://doi.org/10.1177/2048872619846334.

8. Oztan MO, Aksoy Gokmen A, Ozdemir T, Müderris T, Kaya S, Koyluoglu G. Pentraxin-3: a strong novel biochemical marker for appendicitis in children. Am J Emerg Med. 2019. In press. https:// doi.org/10.1016/j.ajem.2019.01.010.

9. Gokdemir MT, Nas C, Gokdemir GS. Pentraxin 3 level in acute migraine attack with aura: patient management in the emergency department. Am J Emerg Med. 2019. In press. https://doi.org/10. 1016/j.ajem.2019.04.004.

10. Yang H, Zhang J, Huan Y, Xu Y, Guo R. Pentraxin-3 levels relate to the Wells score and prognosis in patients with acute pulmonary embolism. Dis Markers. 2019;2019:1-6. https://doi.org/10.1155/ 2019/2324515.

11. Leira Y, Ameijeira P, Domínguez C, et al. Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs. Clin Oral Investig. 2019. In press. https://doi. org/10.1007/s00784-019-02950-9.

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