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Purpose: To assess the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with pseudoexfoliation syndrome (PEX) and to compare the NLR and PLR results of patients with PEX, PEX glaucoma (PXG), and healthy controls.Methods: In total, 34 patients with PEX, 29 patients with PXG, and 42 healthy subjects were enrolled in this retrospective study. Complete ophthalmologic examination and complete blood count measurements were performed of all subjects. Complete blood counts were performed within 2 h of blood collection.Results: There was a significant difference in NLR between PEX and control groups (p = 0.012) and PXG and control groups (p = 0.003). Also, a significant difference was found in PLR values between control and PXG groups (p = 0.024).Conclusions: Our study for the first time provides evidence that PLR and NLR may be useful for predicting the prognosis of PEX patients and progression to PXG.

We read with great interest the recently published article by Wu et al1 in which the authors investigated the associations of circulating omega-6 (ω-6) polyunsaturated fatty acids (PUFAs), including linoleic acid, γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in a community-based US cohort. They concluded that high circulating linoleic acid, but not other ω-6 PUFAs, was inversely associated with total and coronary heart disease mortality in older adults. However, we think that there are some points that should be emphasized about this …

Sir,We read with great interest the recently published article “Alcohol consumption and visual impairment in a rural northern Chinese population” by Li and co-authors.1 In this study, researchers i...

We read with great interest the recently published article by Seo et al. [1] in which the authors evaluated the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with idiopathic sudden sensorineural hearing loss (ISSNHL) and its possibility of emerging as a cheap, reliable, and independent prognostic marker of ISSNHL. They found that NLR and PLR values were significantly high in ISSNHL patients. Moreover, they recommended NLR level as a novel potential marker to predict the patients' prognosis in terms of recovery. However, we think that there are some points that should be discussed about the study. First, NLR, which integrates the detrimental effects of neutrophilia (an indicator of inflammation) and lymphopenia (an indicator of physiologic stress), has emerged as a useful prognostic marker in many studies, as well as studies evaluating patients with idiopathic sudden sensorineural hearing loss [2, 3]. In the original study, despite indicating the presence of any acute inflammation and infection as an exclusion criteria, clinical characteristics provided in Tables 2 and 3 of the original study seem not to be consistent with this information. On the basis of general reference ranges, white blood cell (WBC), neutrophil, and lymphocyte counts of some subjects seem to be compatible with the presence of infection [4]. In such studies aimed at determining predictive markers by using laboratory results, it should be better to identify a specific WBC count range within the exclusion criteria. Determining specific WBC count range as well as clinical conditions likely to affect WBC count could avoid a possible bias in patient selection. Moreover, NLR itself alone without other inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, tumor necrosis factor-alpha, interleukin 6, etc.) has led to the insufficiency of evidence confirming the presence of inflammation and may not accurately provide information about the prognosis of the patients. Second, although presence of diabetes mellitus (DM) was also specified as another exclusion criterion, as understood from the glucose values presented in Tables 2 and 3 of the original study, some patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) were also included in the original study. As is known, NLR values can easily be affected by the existence of inflammation in patients with DM and prediabetes (IFG/IGT) [5]. In a study evaluating the association of NLR with different grades of glucose tolerance and insulin resistance in Asian Indians, it is concluded that NLR can be used as an adjuvant prognostic marker for macro- and microvascular complications in patients with glucose intolerance [6]. Excluding patients with metabolic confounders like IFG and/or IGT, more commonly known as prediabetes, should provide more specific results in the original study. Third, in the original study, it is noted that binary logistic regression model was used to evaluate these values as independent risk factors for recovery of ISSNHL (Table 4 in the original study). In this model authors evaluated lymphocyte, monocyte, NLR, PLR, and glucose. However, before performing the binary logistic regression analysis, univariate logistic regression analysis and correlation analysis should be performed due to the probable associations among the lymphocyte, NLR, and PLR; then significant parameters derived therefrom should be evaluated by binary logistic regression analysis. As is known, correlation of parameters with each other is very important in binary logistic regression analysis. In conclusion, we think that the findings of the present study may be affected by confounding factors mentioned above and additional statistical analysis taking all these factors into account should be performed. In such studies aiming at determining a disease-specific cut-off value, being more discerning in patient selection will provide more accurate results. In this way, further information can be obtained about the association between NLR and sudden sensorineural hearing loss.

Blood gas analyzers (BGAs) are important in assessing and monitoring critically ill patients. However, the random use of BGAs to measure blood gases, electrolytes and metabolites increases the variability in test results. Therefore, this study aimed to investigate the correlation of blood gas, electrolyte and metabolite results measured with two BGAs and a core laboratory analyzer.A total of 40 arterial blood gas samples were analyzed with two BGAs [(Nova Stat Profile Critical Care Xpress (Nova Biomedical, Waltham, MA, USA) and Siemens Rapidlab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA)) and a core laboratory analyzer [Olympus AU 2700 autoanalyzer (Beckman-Coulter, Inc., Fullerton, CA, USA)]. The results of pH, pCO₂, pO₂, SO₂, sodium (Na⁺), potassium (K⁺), calcium (Ca⁺²), chloride (Cl⁻), glucose, and lactate were compared by Passing-Bablok regression analysis and Bland-Altman plots.The present study showed that there was negligible variability of blood gases (pCO₂, pO₂, SO₂), K⁺ and lactate values between the blood gas and core laboratory analyzers. However, the differences in pH were modest, while Na⁺, Cl⁻, Ca²⁺ and glucose showed poor correlation according to the concordance correlation coefficient.BGAs and core laboratory autoanalyzer demonstrated variable performances and not all tests met minimum performance goals. It is important that clinicians and laboratories are aware of the limitations of their assays.

Liver fibrosis may be due to a variety of chronic liver diseases and may occur as a result of the healing process of liver damage. Although liver biopsy is accepted as the gold standard method in diagnosis and follow-up of patients with fibrosis currently, due to the serious complications like severe pain, internal bleeding, pneumothorax, and rarely death and even fault in the diagnostic accuracy like sampling error, various assessments by different pathologists and even by the same pathologist, interest in alternative methods is increasing day by day. In the light of these improvements, many studies have been performed on indirect non-invasive biochemical markers that can be used instead of liver biopsy, in the last decade. APRI, Forns index, FIB-4, AST-ALT ratio, age-platelet index, hepascore, fibrotest, fibroindex, fibrometer and fibrosis index are the most commonly used ones of these tests. While having some advantages like ease of accessibility, low complication rate, and lower costs, these tests cannot be used as the gold standard method due to the unsatisfactory diagnostic accuracy values. However, these indices have a high diagnostic value especially in the diagnosis and exclusion of significant fibrosis (METAVIR F2-4) and cirrhosis (METAVIR F4)., Karaciğer fibrozisi karaciğerin çeşitli kronik hastalıklarına bağlı olarak ve karaciğer hasarının iyileşme sürecinin bir sonucu olarak gelişebilir. Hastalardaki fibrozisin tanı ve takibinde günümüzde kullanılan altın standart metot karaciğer biyopsisi olarak kabul görmekle birlikte şiddetli ağrı, kanama, pnömotoraks ve hatta ölüm gibi çok ciddi komplikasyonlara neden olabildiği ve örnekleme hatası, farklı patolog ve hatta aynı patolog tarafından farklı değerlendirmelerin yapılabilmesi gibi tanısal doğruluk sapmalarından dolayı alternatif tanı ve takip yöntemlerine yönelim gün geçtikçe artmıştır. Bu gelişmeler ışığında son on yılda karaciğer biyopsisi yerine kullanılabilecek invazif olmayan dolaylı biyokimyasal belirteçler üzerine çok sayıda araştırma yapılmıştır. APRI, Forns indeks, FIB-4, AST-ALT oranı, yaş-platelet indeksi, hepaskor, fibrotest, fibroindeks, fibrometre ve fibrozis indeksi bu testlerden en çok kullanılanlarıdır. Bu testler kolay ulaşılabilirlik, düşük maliyet ve minimum komplikasyon riskleri gibi avantajlara sahip olsa da ortalama tanısal doğruluk değerlerinin istenen düzeyde olmaması nedeni ile altın standart test olarak kullanılabilmeleri şu an için mümkün değildir. Ancak özellikle belirgin fibrozis (METAVIR F2-4) ve sirozun (METAVIR F4) tanısı ve dışlanmasında bu indekslerin tanısal değeri yüksektir.

Women diagnosed with gestational diabetes mellitus have an increased risk of developing diabetes mellitus, which is a known risk factor for cardiovascular disease and insulin resistance. In the recently published article by Zajdenverg et al., they aimed to identify endothelial dysfunction and cardiovascular risk factors in women with previous gestational diabetes mellitus. However, authors did not evaluate the role of total homocysteine, which has important effects for endothelial dysfunction. Vitamin B12 and folic acid are important vitamins since their deficiency may lead to the probable microvascular abnormalities by increasing the tHcy, which is an independent risk factor for endothelial dysfunction.

We read with great interest the recently published article by Malaguarnera et al. [1]. This study was aimed at evaluating the plasma total homocysteine (tHcy) levels in diabetic patients with and without retinopathy for the progression of diabetic retinopathy. In conclusion, higher plasma levels of tHcy have been found in diabetic patients with proliferative diabetic retinopathy compared to both nonproliferative diabetic retinopathy (DR) and diabetics without retinopathy. However, we would like to share our thoughts and contributions to the original study. First, there was a significant difference between patient groups in terms of age, in the original study. However, there are age specific normal ranges for total homocysteine (tHcy) levels [2]. This is critical because comparison of patient groups with different age distributions may lead to a bias in tHcy results arising from different normal values by age. It should be better to select age-matched patient groups in such studies evaluating parameters with age specific normal values. Second, specimens for tHcy analysis may be fresh or frozen plasma. Since red blood cells continue to produce and release homocysteine after blood sample has been obtained, plasma must be separated promptly [3]. Freshly drawn K2EDTA tubes must be kept in ice water, and plasma should be harvested within 30 min after drawing. Although this may affect the results directly, adding these details about sampling and storage procedure increases the quality of the original study. Third, elevated tHcy levels cause inflammation by increasing arachidonic acid and the proinflammatory prostaglandin E2 [4]. However, tHcy levels in the blood are strongly influenced by diet. Dietary folic acid and vitamins B6 and B12 have the greatest effects [5]. However, none of these vitamins' levels were evaluated in the original study. Moreover, tHcy itself alone without other inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, tumor necrosis factor-alpha, interleukin 6, etc.) may not accurately provide information about the presence of inflammation. In conclusion, plasma total homocysteine (tHcy) levels are important in patients with diabetic retinopathy.

Cytokines released from the adipose tissue and fatty acids (FAs) derived from lipolysis or uptake of fats go in to competition with glucose to be uptaken from the liver leads to insulin resistance (IR). We aimed to show the associations among serum lipid profile, FA compositions and IR.Anthropometrical measurements, biochemical parameters and erythrocyte membrane (EM) FA levels of 95 obese adolescents (41 with IR) and 40 healthy controls were compared.LDL-C, fasting insulin levels, HOMA-IR were significantly higher and HDL-C levels were significantly lower in obese patients than in controls (p=0.013, p0.001, p0.001 and p0.001, respectively). EM C 24:0, C 16:1 ω7 and C 22:1 ω9 FA levels were significantly higher, while C 20:5 ω3 (EPA) levels were significantly lower in obese subjects than in controls (p0.001, p=0.018, p0.001, p=0.043 and p0.001, respectively). Moreover, when obese subjects divided into two groups according to the presence of IR; EM C 16:1 ω7 levels were still significantly higher and EPA levels were still significantly lower in both obese subjects with and without IR compared to controls (p0.001 for both).Saturated FA intake should be decreased because of its role in the development of obesity and IR, and ω-3 group FA intake should be increased.

We read with great interest the recently published article by Kilincalp et al. (2014) in which the authors aimed to elucidate the efficiency of the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the mean platelet volume (MPV) as tools for the preoperative diagnosis of colorectal cancer (CRC) and their usefulness in the follow-up of CRC. They concluded that surgical tumor resection resulted in a significant decrease in NLR, PLR, and MPV. Their results suggest that NLR, PLR, and MPV may be used as easily available additional biomarkers for CRC in screening the general population as well as in postoperative follow-up (Kilincalp et al., 2014). However, we would like to share our thoughts and experiences with Kilincalp et al. (2014). First, as indicated in the original study, some clinical conditions that may affect the total and differential white blood cell (WBC) count were excluded to avoid possible confounders for NLR. As is known, diabetes mellitus (DM) and hypertension (HT) are the most common chronic diseases frequently observed in the current study population evaluated in the original study (CDC Diabetes Public Health Resource). There are several studies indicating that a high level of NLR may reflect ongoing vascular inflammation and play an important role in the pathophysiology of HT, DM, and even prediabetes. Similarly, NLR results can be affected by these metabolic confounders (Pusuroglu et al., 2014; Sefil et al., 2014; Shiny et al., 2014). However, patients included in the original study were not evaluated in terms of DM and HT. In addition, in such studies aimed to determine predictive markers by using laboratory results, it would be better to identify a specific WBC count range within the exclusion criteria (Sertoglu et al., 2014). It is well known that the WBC reference ranges may vary depending on many factors such as the population studied, the individual laboratory, and the instruments (e.g. types of collection tubes) or measurement methods used (e.g. waiting period before analysis) (Sertoglu and Uyanik, 2014). Determining the specific WBC count range as well as clinical conditions likely to affect the WBC count could avoid a possible bias in patient selection. Second, NLR integrates the detrimental effects of neutrophilia (an indicator of inflammation) and lymphopenia (an indicator of physiological stress) and has emerged as a useful prognostic marker in many studies, which claim inflammation as the main cause of pathology (Kayadibi et al., 2014). To assess the value of the NLR in this patient group, it is important to determine whether the increase in NLR is a result of a low count of lymphocytes or a high neutrophil count. However, neutrophil and lymphocyte counts were not provided in the original study. Therefore, it cannot be stated that inflammation alone is responsible for this increase in NLR. Moreover, the lack of data on other inflammatory markers has led to the lack of any evidence confirming the presence of inflammation in these patients. As is known, decreased lymphocyte count has been associated with malnutrition and lymphopenia and it is used as an indicator of malnutrition (Omran and Morley, 2000). As a result, a decrease in the lymphocyte count increases NLR. However, the nutritional status of participants was not evaluated and there is no effective laboratory indicator identifying malnutrition as the cause of lymphopenia in the original study (White et al., 2012). As is known, serum proteins, particularly albumin, have often been used to assess malnutrition. Albumin has a relatively long half-life, ∼14–20 days, and because of this, has been considered a marker of chronic nutritional status (Banh, 2006). Therefore, it would be better to assess at least albumin levels to evaluate the correlation between albumin levels and nutritional status in the current study. In conclusion, NLR itself, alone without other inflammatory markers as well as neutrophil and lymphocyte counts, may not accurately provide information on the presence of inflammation in these patients, and excluding patients with metabolic confounders with an effect on NLR could avoid a possible bias in patient selection.

Sir: In a recent issue of The Scandinavian Journal of Clinical & Laboratory Investigation, Wium and colleagues [1] investigated the relationship between diabetes and adipose tissue distribution in ...

We aimed to investigate the diagnostic utility of serum DPP-IV enzyme activity, urinary GAG/Cre ratio, chitotriosidase activity, total adenosine deaminase (ADA) and ADA-1 isoenzyme activity in the diagnosis of MPS. 31 MPS patients which were previously diagnosed by clinical and enzymatic analysis and 31 healthy controls matched with age and gender were included in this study. Serum DPP-IV enzyme activity, urinary GAG/Cre ratio, total ADA and ADA-1 isoenzyme activity were significantly higher in patients than in controls (p0.001, p0.001, p=0.038 and p=0.006, respectively). There were significant correlations between serum DPP-IV enzyme activity and urinary GAG/Cre ratios, ADA-1 activity, ADA-1/total ADA (r=0.498, p0.001; r=0.348, p=0.006; r=0.270, p=0.034, respectively). Area under ROC curve for DPP-IV enzyme activity was 0.988, p0.001 and for urinary GAG/Cre ratio was 0.986, p0.001. DPP-IV enzyme activity and urinary GAG/Cre ratio were the most significant parameters according to the univariate logistic regression analysis (p=0.001 and p0.001, respectively). The measurement of serum DPP-IV enzyme activity can be used complementary to the urinary GAG/Cre ratio for first-line MPS screening, since it is more less prone to age and hydration related interferences.

There is increasing evidence that neutrophil-lymphocyte ratio (NLR) may play a role in predicting recurrence in patients with hepatitis B virus-related hepatocellular carcinoma (HCC) after liver transplantation. In the original study by Yan et al, it was aimed to determine whether an elevated NLR is associated with tumor recurrence. Total tumor size (> 9 cm) and macro-vascular invasion were found to be more significant than NLR according to the multivariate logistic regression analysis. Therefore, substantive significance should be emphasized rather than NLR because total tumor size and macro-vascular invasion are easier and more expressive than NLR in assessing HCC recurrence. NLR and platelet-lymphocyte ratio (PLR) are markers which are easy to obtain and can be used as inflammation indicators. Moreover, assessment of both NLR and PLR may add some value as a good predictor of risk for post-liver transplantation HCC recurrence. However, while the study was constructed on whole blood analysis, further details about the features and performance characteristics of the whole-blood analyzer, and preanalytical/analytical variables should also be mentioned.

Objective Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. Methods The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima-media thickness (cIMT) was assessed by high-resolution ultrasonography. Results Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P = 0·004, P

Aims Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease. Asymmetric dimethylarginine (ADMA) is a novel marker of endothelial dysfunction and atherosclerosis. We aimed to investigate circulating ADMA concentrations in biopsy proven NAFLD and also to search its association with carotid atherosclerosis. Methods Sixty-seven nondiabetic and normotensive patients with NAFLD and 35 healthy controls were enrolled. Plasma ADMA was measured along with glucose, lipids and insulin levels. Insulin resistance (IR) was assessed by homeostasis model assessment-estimated insulin resistance (HOMA-IR) method. Carotid atherosclerosis was evaluated by carotid artery intima-media thickness (CIMT) using carotid ultrasonography. Results ADMA levels and CIMT measurements were significantly higher in NAFLD group than the controls. However, the difference regarding the CIMT disappeared when the findings were adjusted according to the metabolic parameters and insulin sensitivity. In contrast, the difference for ADMA remained significant between two groups. No significant association was found between ADMA, CIMT and histopathological findings. Conclusions Plasma ADMA levels are increased in subjects with NAFLD. This increase seems to be independent from traditional cardiovascular risk factors, insulin resistance and liver histology. Circulating ADMA may be an earlier marker of vascular damage with respect to CIMT in subjects with NAFLD.

We read with great interest the recently published article “Assessment of neutrophil/lymphocyte ratio in patients with age-related macular degeneration” by Ilhan et al.1 In this study, researchers ...

5-Fluorouracil (5-FU), acting as a pyrimidine antagonist, is a major chemotherapy drug used for the treatment of tumors such as gastrointestinal, breast, ovary, and head and neck cancers. The key and rate-limiting enzyme in 5-FU catabolism is dihydropyrimidine dehydrogenase (DHPDH), whose partial or complete deficiency exposes to a severe 5-FU toxicity in patients. The determination of DHPDH activity in patients before the treatment and setting up a personalized therapy for each patient receiving the drug can help us to prevent the possible risk of toxicity. To isolate peripheral blood mononuclear cells (PBMCs), EDTA-anticoagulated blood samples were collected from randomly selected 47 patients and examined for 5-FU and its metabolite dihydrofluorouracil (FUH2) by using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) to observe DHPDH activity at different intervals (0 and 4th hour) indirectly. Intra-assay and interassay CV % values of samples from the measurements of the modified methods are found 1.3–11.9, 2.3–9.4 for 5-FU and 3.1–14.4, 3.3–12.6 for FUH2, respectively. The reference values derived from 45 patients treated with 5-FU are 1.84 ± 0.34 ug/gr protein for 5-FU, 40.15 ± 11.43 ng/gr protein for FUH2, respectively. FUH2/5-FU ratio is 21.9 ± 3.72. In addition, the results determined from two patients, in which the lack of DHPDH is considered, were 3.24 and 4.16 ug/gr protein for 5-FU, 4.1 and 6.7 ng/gr protein for FUH2. FUH2/5-FU ratio is 1.26 and 1.61. The measurements of 5-FU, FUH2, and especially their ratio (FUH2/5-FU) by the modified LC–MS/MS method could be used to determine DHPDH enzyme activity.