Publications by authors named "Tomas Salek"

28 Publications

  • Page 1 of 1

The first cancer patient with COVID-19 in Slovakia.

Klin Onkol 2020 ;33(5):386-389

Background: In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection.

Case: In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease.

Results: On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG.

Conclusion: An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.
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http://dx.doi.org/10.14735/amko2020386DOI Listing
November 2020

Extreme diet without calcium may lead to hyperoxaluria and kidney stone recurrence-A case study.

Authors:
Tomáš Šálek

J Clin Lab Anal 2020 Dec 5;34(12):e23512. Epub 2020 Aug 5.

Department of Biomedical Sciences, Medical Faculty, University of Ostrava, Ostrava, The Czech Republic.

Background: The aim of the study was to present a case study of a 56-year-old woman with hyperoxaluria induced by calcium-free diet that resulted in kidney stone recurrence.

Methods: A 24-hour urine collection and serum tests for kidney stone risk factors identification were performed. The monitoring of urine risk factors was done by untimed urine samples and 24-hour urine collections. Polarized light microscopy was performed for kidney stone analysis.

Results: The results of urine collection showed hyperoxaluria of 0.551 mmoL per 24 hours. After adding calcium-containing products to the diet the oxaluria decreased to reference range value of 0.352 mmoL/24 hours and all untimed oxalate to creatinine ratios returned to reference ranges. Polarized light microscopy revealed 100% calcium oxalate kidney stone composition (It was 50% Weddellite and 50% Whewellite).

Conclusions: The case study shows the importance of calcium intake in the prevention of calcium oxalate kidney stone recurrence. Particularly, unsuitable diet without calcium can induce kidney stone recurrence. Knowledge of diet habits is important for interpretation of kidney stone risk factors and their inhibitors excreted in urine.
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http://dx.doi.org/10.1002/jcla.23512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755765PMC
December 2020

Cystatin C may be better than creatinine for digoxin dosing in older adults with atrial fibrillation.

J Clin Lab Anal 2020 Oct 17;34(10):e23427. Epub 2020 Jun 17.

Department of Internal Medicine, The Tomas Bata Hospital in Zlín, Zlín, Czech Republic.

Background: Patients taking digoxin are older with high probability of having low muscle mass, and current clinical practice in digoxin dosing relies only on estimated glomerular filtration rate from serum creatinine (eGFRcrea). The aim of the study is to compare eGFRcrea and estimated glomerular filtration rate from serum cystatin C (eGFRcys) in older adult patients with atrial fibrillation (AF) overdosed with digoxin.

Methods: A total of 80 consecutive patients overdosed with digoxin and 33 controls with AF from Department of Internal Medicine were included in the prospective observational study. The median of age of participants was 81 years in both the overdosed and the control group. The eGFRs were calculated using The Chronic Kidney Disease Epidemiology (CKD- EPI) equations using standardized methods for serum creatinine and cystatin C measurement.

Results: The median (IQR) of eGFRcrea was higher than that of eGFRcys (45 mL/min/1.73 m (35-59) vs 30 (21-38), respectively; P < .0001) in overdosed patients. The median (IQR) of eGFRcrea was higher than that of eGFRcys (61 mL/min/1.73 m (49-72) vs 40 (30-56), respectively; P < .0001) in control group of patients. Serum predose digoxin concentration in overdosed patients was inversely associated with eGFRcys (ρ = -0.26, P < .05).

Conclusion: Physicians should consider GFR when changing digoxin dosing. eGFRcys was lower in both the overdosed and the control group. eGFRcys would lead to lower digoxin doses and thus prevent overdose.
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http://dx.doi.org/10.1002/jcla.23427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595907PMC
October 2020

Survey on request form content and result reporting in therapeutic drug monitoring service among laboratories in Czechia and Slovakia.

Biochem Med (Zagreb) 2020 Jun;30(2):020706

Institute of Environmental and Chemical Engineering, University of Pardubice, Czech Republic.

Introduction: The aim of the study was to investigate current practice and policies of therapeutic drug monitoring (TDM) service requesting and result reporting in Czechia and Slovakia.

Materials And Methods: All 149 laboratories that measure plasma drug concentrations were given an online questionnaire during a regular external quality assessment TDM cycle. The questionnaire consisted of 17 questions. The optimal TDM practice was defined as the application of all elements (age, body weight, time of sampling, date of the first administration, time of the last dose administration, the dose, the dosing interval, the route of administration, information on reason of testing, and information on other co-administered drugs) needed for reporting a recommendation for further drug dosing (positive response to question number 16).

Results: The response rate was 69%, 103 out of 149 laboratories measuring drug concentrations. Only 12% (12 out of 103 laboratories) of the laboratories implemented all elements needed for optimal TDM practice and reported a recommendation. Both paper and electronic request forms were used by 77 out of 103 (75%) laboratories. A total of 69 out of 103 laboratories (67%) specified the type of sampling tube on their request form. Cystatin C was used for prediction of renal drug elimination by 24% (25 out of 103) of participants.

Conclusions: Small number of laboratories implemented all elements needed for optimal TDM practice and report a recommendation on further dosing. Further efforts in education on optimal TDM practice as well as harmonization of service are desirable.
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http://dx.doi.org/10.11613/BM.2020.020706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271755PMC
June 2020

Rosuvastatin-induced rhabdomyolysis due to medication errors.

Ceska Slov Farm 2020 ;69(2):100-102

Case (description): A 74 years old Caucasian suffering from chronic kidney disease presented with progressive asthenia and diffuse myalgia. It was revealed that the patient used three different rosuvastatin-containing preparations in a total daily dose of 120 mg for 76 days. Laboratory investigations revealed a marked elevation of serum urea, creatinine, myoglobin, creatine kinase (CK) and transaminases. Two serious medication errors have been identified as possible major factors that synergistically contributed to the development of rosuvastatin-induced rhabdomyolysis. First, 40 mg of rosuvastatin dose was prescribed to the patient, although the estimation of glomerular filtration rate (eGFR) declined below 40 ml/min/1.73 m2. Moreover, the patient used 3 different rosuvastatin formulations simultaneously in a total dose of 120 mg/day. The heterozygous CYP2C9*1/*3 genotype and warfarin co-administration could further contribute to the development of rhabdomyolysis. A number of preventive measures, notably in drug policy, are suggested to overcome unintended intoxications. Conclusion: Rosuvastatin-induced myopathy is a rare, but serious adverse effect. This case report highlights the need for a proper treatment and dose adjustment during chronic medical therapy, the need for adequate patient education and application of adequate drug policy measures in the era of fragmented health care delivery and polypragmasia.
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September 2020

The fat mass, estimated glomerular filtration rate, and chronic inflammation in type 2 diabetic patients.

J Clin Lab Anal 2020 Jun 11;34(6):e23229. Epub 2020 Feb 11.

Department of Physics & Material Engineering, Faculty of Technology, Tomas Bata University in Zlín, Zlín, Czech Republic.

Background: The aim of the study was to analyze the degree of obesity and its associations with age, gender, inflammation, an estimated glomerular filtration rate (eGFR), and liver function in type 2 diabetes mellitus (T2DM) patients.

Methods: A total of 874 consecutive adult Caucasian T2DM patients from outpatient diabetic clinic were included in the study. The relative fat mass (RFM) and body mass index (BMI) were used as obesity markers. Serum creatinine and cystatin C were used for the GFR estimation. Serum high-sensitive C-reactive protein (hsCRP) was used as the indicator of inflammation.

Results: The median, interquartile range (IQR) of RFM in females was higher than that in males (44.8 (42.3-47.2) % vs 31.3 (28.8-34.1) %, respectively; P < .0001). The median (IQR) of BMI in females was no higher than that in males (30 (27-34) kg/m vs 30 (27-34), respectively; P = .5152). The obesity prevalence was 99% in males and 98% in females according to RFM. BMI recognized obesity in 51% males and 53% females. RFM was positively associated with hsCRP in both males (r  = .296, P < .0001) and females (r  = .445, P < .0001). ALT was positively correlated with eGFRcys in both males (r  = .379, P < .0001) and females (r  = .308, P < .0001).

Conclusion: The RFM equation leads to higher obesity prevalence compared to BMI. Women have higher RFM compared to men. The kidney function was positively correlated with ALT serum concentrations.
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http://dx.doi.org/10.1002/jcla.23229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307376PMC
June 2020

Assessment of the degree of adherence of medical laboratories to KDIGO 2012 guideline for evaluation and management of CKD in Czechia and Slovakia.

Biochem Med (Zagreb) 2019 Oct 5;29(3):030704. Epub 2019 Aug 5.

SEKK, spol. s.r.o., Pardubice, Czech Republic.

Introduction: The aim of the study is to assess the degree of adherence of medical laboratories to Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) in laboratory practice in Czechia and Slovakia.

Materials And Methods: An electronic questionnaire on adherence to KDIGO 2012 guideline was designed by an external quality assessment (EQA) provider SEKK spol. s.r.o. The questionnaire was placed and distributed through website to all medical biochemistry laboratories in Czechia and Slovakia (N = 396).

Results: A total of 212 out of 396 laboratories responded to the questions, though some laboratories only answered some questions, those applicable to their practice. A total of 48 out of 212 laboratories adopted the KDIGO 2012 guideline in full extent. The metrological traceability of creatinine measurement to standard reference material of SRM 967 was declared by 180 out of 210 laboratories (two of the responding laboratories did not measure creatinine). Thirty laboratories are not well educated on traceability of creatinine measurement and seven laboratories do not calculate estimated glomerular filtration rate (eGFR). Both urinary albumin concentration and albumin to creatinine ratio are reported by 144 out of 175 laboratories (37 of the responding laboratories did not measure urinary albumin).

Conclusion: Majority of laboratories in Czechia and Slovakia adopted some parts of the KDIGO 2012 guideline in their practice, but only 23% of the laboratories apply them completely. Thus, further education and action should be conducted to improve its implementation.
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http://dx.doi.org/10.11613/BM.2019.030704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610673PMC
October 2019

Consensus statements on the approach to patients in a methanol poisoning outbreak.

Clin Toxicol (Phila) 2019 12 22;57(12):1129-1136. Epub 2019 Jul 22.

The Norwegian CBRNE Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages. We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.e., dialysis), and indications for transferring patients in the context of an MPO. We convened a group of experts from across the world to explore geographical, socio-cultural and clinical considerations in the management of an MPO. The experts answered specific open-ended questions based on themes aligned to the goals of this project. This project used a modified Delphi process. The discussion continued until there was condensation of themes. We defined MPO as a sudden increase in the number of cases of methanol poisoning during a short period of time above what is normally expected in the population in that specific geographic area. Prompt initiation of an antidote is necessary in MPOs. Scarce hemodialysis resources require triage to identify patients most likely to benefit from this treatment. The sickest patients should not be transferred unless the time for transfer is very short. Transporting extracorporeal treatment equipment and antidotes may be more efficient. We have developed consensus statements on the response to a methanol poisoning outbreak. These can be used in any country and will be most effective when they are discussed by health authorities and clinicians prior to an outbreak.
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http://dx.doi.org/10.1080/15563650.2019.1636992DOI Listing
December 2019

The prevalence of maternal hypothyroidism in first trimester screening from 11 to 14 weeks of gestation.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2019 Sep 6;163(3):265-268. Epub 2018 Nov 6.

Department of Obstetrics and Gynecology, Tomas Bata Hospital in Zlin a. s., Havlickovo nabrezi 600, 76275 Zlin, Czech Republic.

Aim: The aim of this study was to determine the prevalence of maternal hypothyroidism in the first trimester from 11 to 14 weeks of gestation according to the American Thyroid Association (ATA) guidelines from 2017 and to compare the rates for singleton and twin pregnancies.

Methods: A total of 4965 consecutive Caucasian singleton pregnancies and 109 Caucasian twin pregnancies were included in the investigation. Patients with a history of thyroid gland disorder were excluded. Subclinical maternal hypothyroidism was defined as a thyroid stimulating hormone (TSH) concentration above the 97.5 percentile and free thyroxine (fT4) within the range of a reference population of women at 11-14 weeks of gestation. Overt maternal hypothyroidism was defined as a TSH concentration above the 97.5 percentile and an fT4 below the 2.5 percentile of the reference population.TSH, fT4, and anti thyroid peroxidase antibody (TPOAb) were measured by immunochemiluminescent assays on an 16200 Abbott Architect analyzer.

Results: The prevalence of hypothyroidism for twin pregnancies was no higher than that for singleton pregnancies; 6.42% (7/109) vs. 5.32% (264/4965), respectively; P=0.61. All twin pregnancies were subclinical. Singleton hypothyroid pregnancies included 4.91% (244 cases) of subclinical and 0.41% (20 cases) of overt hypothyroidism. The prevalence of TPOAb positive hypothyroid women for twin pregnancies and singleton pregnancies was 71% (5/7) vs. 52% (137/264 cases), respectively but the differences were not statistically significant; P=0.31.

Conclusion: Each first trimester screening center should establish its TSH and fT4 reference ranges. Our center had higher upper reference limits of TSH than that of the universally fixed limit of 2.5 mU/L, which led to a lower measured prevalence of maternal hypothyroidism. A large number of hypothyroid women were TPOAb positive.
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http://dx.doi.org/10.5507/bp.2018.063DOI Listing
September 2019

Selective coronary angiography, percutaneous coronary intervention and asymptomatic peri-procedural myocardial injury.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2019 Dec 6;163(4):324-330. Epub 2018 Nov 6.

Department of Internal Medicine I - Cardiology, University Hospital Olomouc, Czech Republic.

Background: While there have been a number of studies reporting the incidence and implications of elevated troponin levels after percutaneous coronary intervention (PCI), the body of information about the incidence, associations, and implications of elevated troponin levels following coronary angiography (CAG) is limited.

Materials And Methods: A total of 220 consecutive patients with stable coronary artery disease or intermediate or low-risk acute coronary syndrome without persistent ST-segment elevation (NSTE-ACS) were included in our study. High-sensitivity cardiac troponin I (hs-cTnI) levels were measured before and after coronary angiography (CAG) in patients with or without PCI and correlated with a number of clinical variables.

Results: Hs-cTnI elevations above the 99 percentile upper reference limit (URL), or above 20% of the initially positive, yet already declining values, were found in 60 (37.2%) patients after CAG and in 45 (76.2%) patients undergoing PCI. Significant correlations of hs-cTnI elevation were found with the following variables: volume of contrast, fluoroscopy time, dose-area product, amount of contrast agent injected directly into the coronary arteries, total time of balloon dilation and the number and total length of implanted stents (P<0.001 for all).

Conclusion: While an asymptomatic elevation of hs-cTnI is a common finding after PCI, it does occur, quite surprisingly, also after CAG. Despite contradictory views regarding the clinical relevance of asymptomatic post-procedural elevated hs-cTnI levels, it is generally believed that a mild elevation is not associated with an increased risk. Still, it may pose a diagnostic quandary following a successful interventional procedure and even more so after an uncomplicated CAG.

Trial Registration: Clinicaltrials.gov - NCT02960321.
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http://dx.doi.org/10.5507/bp.2018.066DOI Listing
December 2019

Cystatin C measurement leads to lower metformin dosage in elderly type 2 diabetic patients.

Basic Clin Pharmacol Toxicol 2019 Mar 17;124(3):298-302. Epub 2018 Oct 17.

Diabetes Center, Tomas Bata Hospital in Zlín, a. s., Zlín, Czech Republic.

The aim of this study was to provide evidence for the hypothesis that estimated glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be determined for all elderly type 2 diabetes mellitus (T2DM) patients based on eGFRcys upward and downward reclassification rate for hypothetical metformin dose reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m . A total of 265 consecutive T2DM elderly patients (age range 65-91 years) from outpatient diabetic clinic were included in the study. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines for metformin dosing were strictly followed. Estimated glomerular filtration rate from serum creatinine (eGFRcrea) led to results of metformin eligibility. Each of the results of eGFRcrea-based eligibility was further compared to eGFRcys-based eligibility. Creatinine was measured by enzymatic method standardized against international reference material SRM 967. Cystatin C was determined by method traceable to DA ERM 471 international standard. eGFRcrea and eGFRcys were calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. A downward reclassification rate was higher than upward reclassification rate (31 vs 3, respectively; P < 0.0001). The median (IQR) eGFRcrea was higher than eGFRcys (73 (58-85) vs 63 (50-75) mL/min/1.73 m , respectively; P < 0.0001). eGFRcys reclassified significant proportion of patients with T2DM from metformin eligible CKD stages to less or non-eligible stages. The downward reclassification was more frequent in patients older than 80 years (P < 0.01). Cystatin C-based eGFR selects more complicated patients, where lower doses of metformin are possibly advisable. We recommend calculating both eGFRcrea and eGFRcys for metformin dosing in elderly patients with T2DM.
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http://dx.doi.org/10.1111/bcpt.13132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379635PMC
March 2019

Pseudohyperkalemia - Potassium released from cells due to clotting and centrifugation - a case report.

Authors:
Tomáš Šálek

Biochem Med (Zagreb) 2018 Feb 10;28(1):011002. Epub 2018 Jan 10.

Department of biomedical sciences, Medical Faculty of the University of Ostrava, Ostrava - Zábřeh, Czech Republic.

Hyperkalemia is a potentially lethal condition. Pseudohyperkalemia should be always excluded before implementing treatment to prevent inappropriate cause of hypokalemia - equally a potentially lethal condition. Here we present a case report of a 62 year female with chronic myeloproliferative disorder, essential thrombocythemia. The laboratory test results for potassium concentration were 6.3 mmol/L, for platelet count 1305 x10/L and for leukocyte count 39.8 x10/L. This was due to a temporary drug withdrawal after a surgical intervention for gastric bleeding. Potassium concentration in lithium heparin plasma collected in a vacuum tube without gel separator and in whole blood syringe were 4.6 mmol/L and 3.4 mmol/L, respectively. It means that mechanical stress such as centrifugation can contribute to spurious hyperkalemia.
Prior to reporting unexpected hyperkalemia result, pseudohyperkalemia should always be considered by the laboratory. Such potassium results require investigation in case it is pseudohyperkalemia, which may be due to thrombocytosis and leukocytosis. In cases where thrombocytosis or leukocytosis exists, an interpretative comment indicating these conditions inserted with the results of the potassium concentration can increase awareness for more accurate patient care decisions.
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http://dx.doi.org/10.11613/BM.2018.011002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806620PMC
February 2018

Maternal thyroid-stimulating hormone reference ranges for first trimester screening from 11 to 14 weeks of gestation.

J Clin Lab Anal 2018 Jul 3;32(6):e22405. Epub 2018 Feb 3.

Department of Obstetrics and Gynecology, Tomas Bata Hospital in Zlín, Zlín, Czech Republic.

Background: To establish maternal thyroid-stimulating hormone (TSH) reference ranges for first trimester screening from 11 + 0 to 13 + 6 weeks of gestation.

Methods: A total of 10 592 singleton and 201 twin consecutive Caucasian pregnant women who underwent simultaneously prenatal first trimester Down's syndrome screening and thyroid function screening from January 2010 to November 2017 were included in the study. Women with positive antithyroid peroxidase antibody (TPOAb) and positive personal history of thyroid disease were previously excluded. TSH was measured by immunochemiluminescent assay on ci 16200 Abbott Architect analyzer. Nonparametric percentile method (also known as CLSI C28.A3) was used for the determination of reference ranges.

Results: We established reference ranges of TSH for the period of gestation from 11 + 0 to 13 + 6 weeks of pregnancy as 0.16-3.43 mU/L for singleton Caucasian pregnancies and 0.02-2.95 mU/L for twin Caucasian pregnancies. The median (IQR) of TSH for singleton pregnancies was higher than that for twin pregnancies (1.25 mU/L (0.83-1.81) vs 0.84 (0.37-1.47), respectively; P < .0001).

Conclusions: Each first trimester screening center should be aware of which type of immunoassay their laboratory uses. TSH reference ranges in women during the first trimester of pregnancy are lower than those for general population. Twin pregnancies have lower TSH than singleton pregnancies.
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http://dx.doi.org/10.1002/jcla.22405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817144PMC
July 2018

Adherence with perindopril therapy: a pilot study using therapeutic drug monitoring of perindoprilat and an evaluation of the clearance estimation.

Int J Clin Pharm 2017 Oct 8;39(5):1095-1100. Epub 2017 Aug 8.

Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Background Although measurement of drug serum levels is an objective direct method for testing compliance, it can be distorted by "white-coat compliance" or by variations in drug elimination. Objective The aim of this prospective study was to evaluate the prevalence of noncompliance with perindopril therapy in adult out-patients using pharmacokinetic simulations. The additional aim was to compare the predictive performance of two glomerular filtration rate markers-creatinine and cystatin C. Setting Department of Cardiology, Tomas Bata Regional Hospital in Zlín, Czech Republic. Method Perindoprilat pharmacokinetic models individualized according to patient characteristics were compared with measured perindoprilat serum concentrations to document compliance. Linear regression was used to evaluate the relations between perindoprilat clearance and glomerular filtration rate estimated using creatinine and cystatin C. Main outcome measure Assessment of non-compliance with medication using drug concentration measurements reinforced with therapeutic drug monitoring. Results Non-detectable perindoprilat levels were observed in 26.1% of patients. Another 21.7% were classified as non-compliant based on therapeutic drug monitoring pharmacokinetic simulations. Volume of distribution, clearance and half-life median value (interquarti°range) for perindoprilat were 408.3 (360.4-456.8) L, 10.1 (4.9-17.0) L h and 24.7 (19.4-62.7) h, respectively. Linear regression models showed tight relationship between cystatin C and perindoprilat clearance. Conclusions Assessment of adherence with medication reinforced with therapeutic drug monitoring and pharmacokinetic simulations is proposed as an optimal method reducing disadvantages of simple drug concentration measurements. Cystatin C proves to be better surrogate marker for perindoprilat elimination than creatinine.
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http://dx.doi.org/10.1007/s11096-017-0522-7DOI Listing
October 2017

Topiramate induced metabolic acidosis and kidney stones - a case study.

Biochem Med (Zagreb) 2017 Jun;27(2):404-410

Department of Clinical Biochemistry, Tomas Bata Hospital in Zlín a. s., Zlín, Czech Republic.

Introduction: The aim of this study is to present a case of 44 years old woman with topiramate induced metabolic acidosis and kidney stones.

Materials And Methods: The laboratory features of topiramate caused renal tubular acidosis in blood and urine during topiramate treatment, with correction of metabolic acidosis by potassium citrate, and after topiramate withdrawal are presented. Differential diagnosis of all possible causes of metabolic acidosis is discussed.

Results: The results revealed negative base excess in extracellular fluid of - 9.2 mmol/L, low serum HCO concentration (18.6 mmol/L), trend to alkaline urine (pH 6.39) and low urine citrate concentration (0.3 mmol/24h). After topiramate withdrawal, all parameters of the internal environment normalized.

Conclusions: This study has shown that long-term topiramate administration could induce metabolic acidosis and consequently urholithiasis. Thus, we could recommend testing blood acid base balance, urinary pH and citrates in patients taking topiramate and suffering from kidney stones.
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http://dx.doi.org/10.11613/BM.2017.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493179PMC
June 2017

Incorporating thyroid markers in Down syndrome screening protocols.

Prenat Diagn 2017 May 24;37(5):510-514. Epub 2017 Apr 24.

Department of Obstetrics and Gynaecology, Columbia University Medical Centre, New York, NY, USA.

Objective: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols.

Methods: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome.

Results: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%.

Conclusions: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.5047DOI Listing
May 2017

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES).

Clin Colorectal Cancer 2017 06 7;16(2):103-114.e3. Epub 2016 Sep 7.

Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Sciences University, Portland, OR.

Background: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]).

Patients And Methods: Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period.

Results: A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300).

Conclusion: Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.
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http://dx.doi.org/10.1016/j.clcc.2016.08.008DOI Listing
June 2017

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning.

Clin Toxicol (Phila) 2017 Feb 7;55(2):123-132. Epub 2016 Nov 7.

u Department of Acute Medicine , The Norwegian CBRNe Centre of Medicine, Oslo University Hospital , Oslo , Norway.

Context: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined.

Objective: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning.

Methods: The study was designed as observational cohort study. The mean time for an increase of 1 mmol/L HCO, 0.01 unit arterial blood pH, and the total time for correction of HCO were determined in IHD- and CRRT-treated patients.

Results: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79 ± 0.10 versus 7.05 ± 0.10; p = 0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO correction correlated with arterial blood pH (r= -0.511; p = 0.003) and creatinine (r = 0.415; p = 0.020). There was association between the time to HCO correction and dialysate/effluent and blood flow rates (r= -0.738; p < 0.001 and r= -0.602; p < 0.001, correspondingly). The mean time for HCO to increase by 1 mmol/L was 12 ± 2 min for IHD versus 34 ± 8 min for CRRT (p < 0.001), and the mean time for arterial blood pH to increase 0.01 was 7 ± 1 mins for IHD versus 11 ± 4 min for CRRT (p = 0.024). The mean increase in HCO was 5.67 ± 0.90 mmol/L/h for IHD versus 2.17 ± 0.74 mmol/L/h for CRRT (p < 0.001).

Conclusions: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.
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http://dx.doi.org/10.1080/15563650.2016.1250901DOI Listing
February 2017

Comparison of biochemical response between the minimally invasive and standard open posterior lumbar interbody fusion.

Neurol Neurochir Pol 2016 6;50(1):16-23. Epub 2015 Nov 6.

Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic.

Background: The mini-invasive open posterior lumbar fusion procedure (mini PLIF) procedure is an alternative to standard open procedure (open PLIF) and is intended to reduce surgery-related trauma. The measuring of suitable biochemical factors enables objective comparison of the invasiveness of spinal surgery procedures.

Methods: Prospectively collected data on myoglobin, creatine kinase, interleukin-6, C-reactive protein levels and intensity of low back pain and radicular pain in one-level mini PLIF and open PLIF procedures were analysed. The mini PLIF and the open PLIF groups included 27 and 23 patients, respectively. The collection of blood samples and clinical data were performed preoperatively and on postoperative days 1, 3 and 7. The non-paired t-test was used for statistical evaluation.

Results: We did not found any statistically significant differences of myoglobin and creatine kinase levels between the groups. In the open PLIF group the IL-6 levels were significantly higher than in the mini PLIF group on postoperative day 3. CRP levels showed significant lower stress response in favour of the mini PLIF group on postoperative days 3 and 7. Levels of post-op low back pain on day 3 were significantly lower in mini PLIF group. Also intensity of radicular pain on day 1 and 3 were lower also mini PLIF group.

Conclusion: The extent of myonecrosis was comparable in both techniques. The analysis of the IL-6 and CRP levels showed significantly lower systemic inflammatory response in mini PLIF technique. The mini PLIF technique provides transiently lower postoperative pain levels.
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http://dx.doi.org/10.1016/j.pjnns.2015.10.008DOI Listing
June 2016

Reply to the letter to editor.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014 Dec;158(4):640

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December 2014

Comparison of Biochemical Markers of Muscle Damage and Inflammatory Response Between the Open Discectomy, Microsurgical Discectomy, and Microsurgical Discectomy Using Tubular Retractor.

J Neurol Surg A Cent Eur Neurosurg 2015 Sep 29;76(5):384-91. Epub 2015 May 29.

Institute of Biostatistics and Analyses, Masaryk University Brno, Brno, Czech Republic.

Background: One of the methods to compare the invasiveness of different surgical techniques objectively is to measure the levels of biochemical markers of systemic inflammatory response and muscle damage.

Methods: A total of 120 patients undergoing surgery for symptomatic disc herniation at L4-L5 and L5-S1 were enrolled in the study. Patients were operated on using open discectomy (OD), microsurgical discectomy (MD), or microsurgical discectomy with tubular retractor (MD-TUB). Myoglobin (MYO) and creatine kinase (CK) levels were used as indicators of muscle damage, and interleukin-6 (IL-6) and C-reactive protein (CRP) levels were used as indicators of systemic inflammatory response. Sampling and analysis of samples were performed preoperatively and on postoperative days 1, 3, and 7. Levels of postoperative low back pain and radicular pain were recorded on a 10-grade visual analog scale. Statistical evaluation was performed using the analysis of variance test.

Results: MYO concentrations in the MD-TUB group on postoperative day 1 were significantly lower than in the MD and OD groups. CK values on postoperative day 1 were significantly lower in microsurgical techniques (MD and MD-TUB) than in the OD group. The lowest IL-6 levels were found in the MD-TUB group, followed by the MD and OD groups. Differences in the IL-6 levels were significant between the groups on postoperative day 1. On all postoperative days that were monitored, values of CRP in the MD-TUB group were significantly lower compared with the MD and OD groups. Lower values in the MD group versus OD group were not statistically significant.

Conclusion: All studied techniques showed similar efficacy in reducing radicular pain. The microsurgical diskectomy using a retractor in comparison with MD and OD is friendlier toward the paraspinal muscles, but the difference is significant only for the MYO levels. The total stress inflammatory response exhibited by patients undergoing the MD-TUB technique is significantly lower compared with the MD and OD techniques.
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http://dx.doi.org/10.1055/s-0034-1393929DOI Listing
September 2015

Fluctuations in serum ethanol concentration in the treatment of acute methanol poisoning: a prospective study of 21 patients.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015 Dec 1;159(4):666-76. Epub 2015 Mar 1.

Toxicological information center, Department of Occupational Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.

Objective: During the 2012 outbreak of mass methanol poisonings in the Czech Republic, ethanol, in the main, was used as an antidote. The complex pharmacokinetics of ethanol made it difficult to maintain the requisite 1000-1500 mg/L serum ethanol levels (S-EtOH). The aim of this study was to measure the fluctuations in S-EtOH during the treatment.

Methods: A prospective case series in 21 patients, median age 52 (27-79 years), 13 males and 8 females. Serum ethanol, methanol and formate were measured every 2-6 hours during the treatment. Follow-up clinical examination was carried out in 15/18 survivors.

Results: The majority of patients (17/21) were late presenters and on admission, almost half (10/21) had suffered a severe grade of intoxication according to the Poisoning Severity Score (PSS). The mean observation time was 90±20 h. The mean period of consistent maintenance of S-EtOH within the recommended therapeutic range lasted 28±7% of the total observation time. For 29±8% of the time, S-EtOH was >1500 mg/L with "peaks" of up to 3500 mg/L. For 44±10% of the observation time, S-EtOH was <1000 mg/L. The mean duration of sub-therapeutic concentration of S-EtOH and toxic serum levels of methanol >200 mg/L or formate >20 mg/L lasted 20±10% and 18±11% of the time of observation, respectively. Complications occurred in 14 (67%) of cases including significant fluctuations of S-EtOH in 9; aspiration pneumonia in 3 and delirium tremens in 2 cases. Other complications included sepsis, bleeding, acidosis rebound, intolerance and set clotting. The outcomes were: 11 survivors free of health impairment, 7 with sequelae and 3 deaths. There was no significant difference in mean duration of sub-therapeutic and supra-therapeutic concentrations of serum ethanol in patients who survived without sequelae and those with poor outcome (P > 0.05).

Conclusion: Administration of ethanol according to the present guidelines of the AACT/EAPCCT is effective and relatively safe in the treatment of methanol poisoning during a mass outbreak(31). Physicians have to be most aware of fluctuations in serum ethanol at the end of short sessions of IHD and after changes in route from intravenous to oral. Rigorous monitoring of serum ethanol concentrations is pivotal for severely poisoned patients with PSS 3 and where there is suspected conversion of significant amounts of methanol to formic acid.
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http://dx.doi.org/10.5507/bp.2015.008DOI Listing
December 2015

Is the measurement of serum formate concentration useful in the diagnostics of acute methanol poisoning? A prospective study of 38 patients.

Basic Clin Pharmacol Toxicol 2015 May 18;116(5):445-51. Epub 2014 Nov 18.

Toxicological Information Center, Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.

The aim of this article was to study the role of serum formate (S-formate) in diagnosing methanol poisoning. A prospective study was undertaken of 38 patients from the Czech methanol mass poisoning in 2012 - median age 51 [interquartile range (IQR) 37-62] years with confirmed methanol poisoning. S-formate was measured enzymatically. The receiver operating characteristics (ROC) curve was used to examine the predictive ability of S-formate. Asymptomatic patients had median S-formate of 1.9 (IQR 1.5-2.4) mmol/L. The median S-formate was 15.2 (IQR 13.9-17.6) mmol/L in symptomatic subjects with visual disturbances, 15.4 (12.1-18.0) mmol/L in subjects with dyspnoea and 15.7 (IQR 12.8-18.5) mmol/L in comatose patients. The differences in serum formate concentrations in symptomatic patients depending on clinical features were not significant (all p > 0.05). Patients with long-term visual sequelae of poisoning had median S-formate of 16.1 (IQR 14.3-19.9) mmol/L; with central nervous system (CNS) sequelae, patients had 15.9 (IQR 14.2-19.5) mmol/L. In lethal cases, the median S-formate was 15.2 (IQR 13.8-15.9) mmol/L. The probability of a poor outcome (death or survival with sequelae) was higher than 90% in patients with S-formate ≥17.5 mmol/L, S-lactate ≥7.0 mmol/L and/or pH <6.87. The ROC analysis showed that the corresponding areas under the curve (AUC) were 0.64 (0.44-0.85 CI 95%) for S-formate, 0.75 (0.56-0.93 CI 95%) for 'S-formate+S-lactate' and only 0.54 (0.38-0.69 CI 95%) for serum methanol, which is lower than for S-formate (p < 0.05). The measurement of S-formate is an important tool in the laboratory diagnostics and clinical management of acute methanol poisoning. S-formate ≥3.7 mmol/L can lead to the first clinical signs of visual toxicity, indicating haemodialysis. S-formate ≥11-12 mmol/L is associated with visual/CNS sequelae and a lethal outcome.
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http://dx.doi.org/10.1111/bcpt.12338DOI Listing
May 2015

Comparison of approaches and measurement of continuing professional development for specialists in laboratory medicine within four European countries.

Clin Chem Lab Med 2015 Jan;53(1):35-44

Background: This study investigated approaches to continuing professional development (CPD) for specialists in laboratory medicine within four European countries: Croatia, the Czech Republic, Malta and the UK.

Methods: The research questions focussed on ascertaining if continued registration/licence was linked to CPD and if so, were there requirements for certain amounts and types of CPD and for CPD activities to meet specified accreditation criteria. The Professional Associations Research Network (PARN) model of CPD measurement was applied to each country's registration/licencing body's CPD requirements.

Results: Our results indicate a spectrum of approaches to CPD within participating countries.

Conclusions: It will be necessary for European employers to be familiar with these differences and to take them into account for this increasingly mobile European workforce.
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http://dx.doi.org/10.1515/cclm-2014-0415DOI Listing
January 2015

Chemotherapy treatment patterns and neutropenia management in gastric cancer.

Gastric Cancer 2015 Apr 5;18(2):360-7. Epub 2014 May 5.

Wojewodzki Szpital, Pabianicka 62, 93-513, Lodz, Poland,

Background: Potentially myelosuppressive doublet and triplet chemotherapy combination regimens are considered the most active treatments in gastric cancer. This multicenter prospective observational study was designed to gain insight into the chemotherapy regimens being used in Europe and to evaluate neutropenia management in patients identified as at high risk for febrile neutropenia (FN).

Methods: Eligible patients had gastric cancer, were scheduled for ≥ 3 cycles of myelosuppressive chemotherapy, and had an investigator-assessed overall FN risk ≥ 20%. Data were collected for up to ten cycles. The primary endpoint was the proportion of patients who received granulocyte colony stimulating factor (G-CSF) primary prophylaxis (defined as G-CSF initiated on days 1-7 of cycle 1). Secondary endpoints included FN incidence, chemotherapy administration, and G-CSF use.

Results: Of 199 patients who met the eligibility criteria and started at least one cycle of chemotherapy, mean age was 63 years, 76% were men, 83% had an ECOG score of 0 or 1, 54% had metastatic disease, and 24% had received prior chemotherapy. A total of 27 different backbone regimens were given; the most common regimen was modified docetaxel, cisplatin, and 5-fluorouracil (DCF). Despite all patients having been identified as having a ≥ 20% FN risk, only 70 (35%) received G-CSF primary prophylaxis. FN occurred in 14 patients overall (7%). Most FN events occurred in patients who received DCF/modified DCF (9/14 events, 64%).

Conclusions: The results of this study reveal a high use of myelotoxic treatment regimens in gastric cancer in Europe and low adherence to clinical practice guidelines for the use of primary and secondary G-CSF prophylaxis for FN.
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http://dx.doi.org/10.1007/s10120-014-0375-xDOI Listing
April 2015

Intermittent hemodialysis is superior to continuous veno-venous hemodialysis/hemodiafiltration to eliminate methanol and formate during treatment for methanol poisoning.

Kidney Int 2014 Jul 12;86(1):199-207. Epub 2014 Mar 12.

Department of Acute Medicine, The Norwegian Center for NBC Medicine, Oslo University Hospital, Ullevaal, Norway.

During an outbreak of methanol poisonings in the Czech Republic in 2012, we were able to study methanol and formate elimination half-lives during intermittent hemodialysis (IHD) and continuous veno-venous hemodialysis/hemodiafiltration (CVVHD/HDF) and the relative impact of dialysate and blood flow rates on elimination. Data were obtained from 11 IHD and 13 CVVHD/HDF patients. Serum methanol and formate concentrations were measured by gas chromatography and an enzymatic method. The groups were relatively comparable, but the CVVHD/HDF group was significantly more acidotic (mean pH 6.9 vs. 7.1 IHD). The mean elimination half-life of methanol was 3.7 and formate 1.6 h with IHD, versus 8.1 and 3.6 h, respectively, with CVVHD/HDF (both significant). The 54% greater reduction in methanol and 56% reduction in formate elimination half-life during IHD resulted from the higher blood and dialysate flow rates. Increased blood and dialysate flow on the CVVHD/HDF also increased elimination significantly. Thus, IHD is superior to CVVHD/HDF for more rapid methanol and formate elimination, and if CVVHD/HDF is the only treatment available then elimination is greater with greater blood and dialysate flow rates.
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http://dx.doi.org/10.1038/ki.2014.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080337PMC
July 2014

Metabolic disorders due to methanol poisoning.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014 Dec 27;158(4):635-9. Epub 2013 Sep 27.

Department of Clinical Biochemistry, Tomas Bata Regional Hospital in Zlin a.s., Zlin, Czech Republic.

Aim: The aim of this study is to compare markers of glomerular filtration rate (GFR), estimated GFR (eGFR), and metabolic parameters between admission and recovery in 13 patients of Tomas Bata hospital with methanol poisoning during methanol problems in the Czech Republic in 2012. The impact of methanol concentration and age on metabolic parameters were discovered at the time of admission to hospital.

Materials And Methods: The serum osmolality, methanol, ethanol, creatinine, cystatin C, Troponin I, ALT, plasma pH and lactate were measured in these 13 patients. The eGFR from serum creatinine (creatnine eGFR) and from cystatin C (cystatin C eGFR) were also determined.

Results: Increased serum osmolality and markers of metabolic acidosis are key indirect laboratory findings in patients with methanol poisoning. There were no significant changes in eGFR in our patients between admission and recovery. Increased serum troponin I concentration was confirmed as an indicator of myocardial necrosis in four patients. Two patients developed acute kidney injury (AKI) before admission.

Conclusions: We found statistically significant differences in serum osmolality concentration, plasma pH and lactate between admission and recovery. We found no changes in eGFR between admission and recovery. One patient had vision problems due to damage to the occipital lobes. Methanol poisoning may cause increase in markers of cardiac damage.
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http://dx.doi.org/10.5507/bp.2013.074DOI Listing
December 2014
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