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Sergey Zakharov - One of the best experts on this subject based on the ideXlab platform.

  • Estimation of long-term costs of postacute care in survivors of the Methanol Poisoning outbreak
    'BMJ', 2021
    Co-Authors: Miroslav Barták, Sergey Zakharov, Benjamin Petruželka, Vladimír Rogalewicz, Jaroslav Doubek, Jaroslav Šejvl, Michal Miovský
    Abstract:

    Objectives To fill the existing research gap related to long-term costs of postacute care in Methanol Poisoning survivors, healthcare cost for 6 years after the outbreak has been modelled and estimated.Design In a prospective longitudinal cohort study, data collected from 55 survivors of the Czech Methanol mass Poisoning outbreak in 2012 were collected in four rounds (5 months, then 2, 4 and 6 years after the discharge) in the General University Hospital in Prague according to the same predefined study protocol. The collected data were used to inform the cost model.Setting and participants All 83 patients discharged from a hospital Poisoning treatment after the 2012 Methanol outbreak were informed about the study and invited to participate. Fifty-five patients (66%) gave their written informed consent and were followed until their death or the last follow-up 6 years later. The costs were modelled from the Czech healthcare service (general health insurance) perspective.Main outcome measures Long-term national budget impact of the Methanol Poisoning outbreak, frequencies of sequelae and their average costs.Results The postacute cost analysis concentrated on visual and neurological sequelae that were shown to be dominant. Collected data were used to create process maps portraying gradual changes in long-term sequelae over time. Individual process maps were created for the central nervous system, peripheral nervous system, sequelae detected during eye examinations and sequelae concerning the visual evoked potentials. Based on the process maps the costs of the postacute outpatient care were estimated.Conclusions In 2013–2019 the highest costs per patient related to postacute care were found in the first year; the average costs decreased afterwards, and remained almost constant for the rest of the studied period of time. These costs per patient ranged from CZK4142 in 2013 to CZK1845 in 2018, when they raised to CZK2519 in 2019 again

  • mri based brain volumetry and retinal optical coherence tomography as the biomarkers of outcome in acute Methanol Poisoning
    Neurotoxicology, 2020
    Co-Authors: Jiri Hlusicka, Tomas Navratil, Katerina Kotikova, Josef Mana, Manuela Vaneckova, Pavel Urban, Pavel Diblik, Benedicte Marechal, Tobias Kober, Sergey Zakharov
    Abstract:

    Abstract Background Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute Methanol Poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute Methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss. Objectives To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute Methanol Poisoning. Methods MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of Poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8−OHdG, 8−OHG, 5−OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute Methanol Poisoning (Group I) and in 28 survivors of Poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without Methanol Poisoning. Results The survivors of acute Methanol Poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of Methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p  The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p  Conclusion In survivors of acute Methanol Poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of Poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of Methanol Poisoning.

  • the impact of co morbidities on a 6 year survival after Methanol mass Poisoning outbreak possible role of metabolic formaldehyde
    Clinical Toxicology, 2020
    Co-Authors: Sergey Zakharov, Tomas Navratil, Jan Rulisek, Katerina Kotikova, Manuela Vaneckova, Zdenek Seidl, Pavel Diblik, Jiri Hlusicka, Martin Komarc, Jan Bydzovsky
    Abstract:

    Context: The influence of co-morbid conditions on the outcome of acute Methanol Poisoning in mass Poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden ...

  • aldehyde dehydrogenase 2 polymorphism affects the outcome of Methanol Poisoning in exposed humans
    Clinical Genetics, 2018
    Co-Authors: Jaroslav A Hubacek, Daniela Pelclova, M Jirsa, Martin Bobak, Sergey Zakharov
    Abstract:

    As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute Methanol exposure. To evaluate the role of genetic variants of enzymes involved in Methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute Methanol Poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among Methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) than among healthy controls (90%) (P = 0.08 and < 0.001, respectively). Minor C allele carriers of the ALDH2 were significantly more common among Methanol-poisoned persons (46%) than among patients with alcoholic liver cirrhosis or healthy controls (31% in both groups, P < 0.05 and 0.025, respectively); the odds ratios were 1.89 (95% CI 1.02-3.52) and 1.94 (1.08-3.48), respectively. As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to Methanol Poisoning. By contrast, the genetic variant of the ALDH2 enzyme seems to specifically affect the susceptibility to Methanol in acutely exposed humans and potentially plays a role in the outcome of Methanol Poisoning.

  • the hypothesis of circulus hypoxicus and its clinical relevance in patients with Methanol Poisoning an observational study of 35 patients
    Basic & Clinical Pharmacology & Toxicology, 2018
    Co-Authors: Elise Drangsholt, Sergey Zakharov, Knut Erik Hovda, Dag Jacobsen, Marie Vangstad
    Abstract:

    Methanol mass Poisoning is a global problem with high fatality rates and often severe sequelae in survivors. Patients typically present late to the hospital with severe metabolic acidosis followed by a rapid deterioration in their clinical status. The hypothesis 'Circulus hypoxicus' describes the metabolic acidosis following Methanol Poisoning as a self-enhancing hypoxic circle responsible for Methanol toxicity. We wanted to test the validity of this hypothesis by an observational study based on 35 patients from the Methanol outbreaks in Norway (2004) and the Czech Republic (2012). Comprehensive laboratory values, including S(serum)-Methanol, S-formate, S-lactate, arterial blood gases, anion and osmolal gaps, were used in the calculations. Laboratory values and calculated gaps were compared to each other using linear regression. S-lactate and S-formate correlated better with the increased base deficit and anion gap than did S-formate alone. Base deficit rose to about 20 mmol/L and S-formate rose to 12 mmol/L prior to a significant rise in S-lactate - most likely caused by formate inhibition of mitochondrial respiration (type B lactacidosis). The further rise in S-lactate was not linear to S-formate most likely due to the self-enhancing pathophysiology, but may also be associated with hypotension in critically ill patients and variable ethanol drinking habits. Our study suggests that the primary metabolic acidosis leads to a secondary lactic acidosis mainly due to the toxic effects of formate. The following decline in pH will further increase this toxicity. As such, a vicious and self-enhancing acidotic circle may explain the pathophysiology in Methanol Poisoning, namely the 'Circulus hypoxicus'.

Daniela Pelclova - One of the best experts on this subject based on the ideXlab platform.

  • Methanol Poisoning as an acute toxicological basal ganglia lesion model evidence from brain volumetry and cognition
    Alcoholism: Clinical and Experimental Research, 2019
    Co-Authors: Josef Mana, Daniela Pelclova, Manuela Vaneckova, Jiři Klempiř, Irena Liskova, Hana Brožova, Kamila Polakova, Z Seidl, Michal Miovský, Kateřina Bukacova
    Abstract:

    BACKGROUND Acute Methanol Poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of Methanol Poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of Methanol Poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of Methanol Poisoning and the volume of the brain structures that are selectively vulnerable to Methanol. METHODS We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute Methanol Poisoning during Methanol mass Poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software. RESULTS In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01). CONCLUSIONS Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in Methanol Poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in Methanol Poisoning.

  • aldehyde dehydrogenase 2 polymorphism affects the outcome of Methanol Poisoning in exposed humans
    Clinical Genetics, 2018
    Co-Authors: Jaroslav A Hubacek, Daniela Pelclova, M Jirsa, Martin Bobak, Sergey Zakharov
    Abstract:

    As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute Methanol exposure. To evaluate the role of genetic variants of enzymes involved in Methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute Methanol Poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among Methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) than among healthy controls (90%) (P = 0.08 and < 0.001, respectively). Minor C allele carriers of the ALDH2 were significantly more common among Methanol-poisoned persons (46%) than among patients with alcoholic liver cirrhosis or healthy controls (31% in both groups, P < 0.05 and 0.025, respectively); the odds ratios were 1.89 (95% CI 1.02-3.52) and 1.94 (1.08-3.48), respectively. As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to Methanol Poisoning. By contrast, the genetic variant of the ALDH2 enzyme seems to specifically affect the susceptibility to Methanol in acutely exposed humans and potentially plays a role in the outcome of Methanol Poisoning.

  • gait and balance impairment after acute Methanol Poisoning
    Basic & Clinical Pharmacology & Toxicology, 2018
    Co-Authors: Kamila Peterova, Daniela Pelclova, Jiři Klempiř, Irena Liskova, Hana Brožova, Ondřej Bezdicek, Petr Ridzoň, Manuela Vaněckova, Sergej Zakharov, Michal Miovský
    Abstract:

    Neurological sequelae including gait impairment were reported in survivors after Methanol intoxication; however, no systematic study has been published so far. We aimed to analyse gait and balance impairment in a group of Czech Methanol Poisoning survivors. We examined 43 patients (age 46 ± 13 years) 2-8 months after Methanol Poisoning and 43 healthy controls. Investigations contained a shortened version of Falls Efficacy Scale (FES), clinical tests of gait and balance including Timed Up and Go test (TUG) and gait analysis using GaitRite® system, neurological and neuropsychological examination, brain imaging, EMG and tests of alcohol consumption. Nineteen patients admitted balance and gait impairment according to FES. Mild to moderate parkinsonian signs showed seven patients. Patients were slower (8.8 versus 5.7 s, p < 0.001) and performed more steps (11.1 versus 7.9, p < 0.001) in TUG compared with the controls. Gait analysis revealed shorter step length (76.5 versus 88.7 cm, p < 0.001), increased double support phase (18.8 versus 15.5%, p < 0.001) and wider base of support (11.3 versus 9.6 cm, p = 0.006) in patients. Eleven patients had deficit of executive function and performed higher cadence compared to the patients with normal execution (122.7 versus 115.0 step/min., p = 0.025). Lower limb polyneuropathy was verified in nine patients, without relation with gait or balance parameters. Neuroimaging revealed lesions mainly in the basal ganglia. Methanol Poisoning survivors presented slower wide-based gait with shortened steps corresponding with frontal gait disorder. Higher stepping cadence associated with executive deficit supported the evidence of frontal lobe dysfunction related to impairment of basal ganglia and connections in frontal cortico-basal ganglia loops.

  • intermittent versus continuous renal replacement therapy in acute Methanol Poisoning comparison of clinical effectiveness in mass Poisoning outbreaks
    Annals of Intensive Care, 2017
    Co-Authors: Sergey Zakharov, Daniela Pelclova, Tomas Navratil, Jan Rulisek, Olga Nurieva, Katerina Kotikova, Martin Komarc, Knut Erik Hovda
    Abstract:

    Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute Methanol Poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass Methanol Poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute Methanol Poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p   0.05). In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of Poisoning on admission. These findings support the strategy of “use what you have” in situations with large outbreaks and limited dialysis capacity.

  • cost effectiveness of hospital treatment and outcomes of acute Methanol Poisoning during the czech republic mass Poisoning outbreak
    Journal of Critical Care, 2017
    Co-Authors: Jan Rulisek, Daniela Pelclova, Petr Waldauf, Jan Belohlavek, Martin Balik, Ferdinand Polak, Sergey Zakharov
    Abstract:

    Abstract Purpose During an outbreak of mass Methanol Poisoning in the Czech Republic in 2012–2014, we compared the total hospital costs and one-year medical costs in the patients treated with different antidotes (fomepizole versus ethanol) and modalities of hemodialysis (intermittent hemodialysis, IHD, versus continuous renal replacement therapy, CRRT). Methods Cross-sectional study in 106 patients with confirmed diagnosis treated in 30 ICU settings. For each patient, the following data were analyzed: admission laboratory data, GCS, PSS, ICU length of stay, organ failures, treatment, outcome, and total hospital costs. Of 83 survivors, in 54 (65%) patients the follow-up examination, quality of life measurement with SF36 questionnaire two years after discharge, and one-year medical costs analysis were performed. Results The median total hospital costs were 7200 (IQR 1500–10,900) euros and the median one-year medical costs were 1447 (IQR 133–1163) euros in the study population. The total hospital costs were higher in the patients treated with fomepizole comparing to ethanol: 12,890 (IQR 6910–16,210) versus 5590 (IQR 1430–6940) euros (p versus 12,410 (IQR 5380–16,960) euros in the patients with CRRT (p=0.317). The geometric mean ratio for increased hospital costs in the patients treated with fomepizole versus ethanol adjusted for the severity of Poisoning was 3.30 (1.70–3.80 CI 95%), p versus CRRT - 0.70 (0.60–0.99 CI 95%), p=0.047. The patients with visual sequelae had higher total hospital costs than those without sequelae: 10,419 (IQR 2984–14,355) versus 4605 (IQR 1303–4505) euros (p=0.009). The patients with GCS≤13 on admission had higher one-year medical costs as well (p 0.05). Conclusion The total hospital costs in the patients with acute Methanol Poisoning were more than three times higher in the patients treated with fomepizole than in the patients treated with ethanol after adjustment for the severity of Poisoning. The dialysis modality did not affect the total hospital costs, but the trend to lower costs was present in IHD-group.

Manuela Vaneckova - One of the best experts on this subject based on the ideXlab platform.

  • mri based brain volumetry and retinal optical coherence tomography as the biomarkers of outcome in acute Methanol Poisoning
    Neurotoxicology, 2020
    Co-Authors: Jiri Hlusicka, Tomas Navratil, Katerina Kotikova, Josef Mana, Manuela Vaneckova, Pavel Urban, Pavel Diblik, Benedicte Marechal, Tobias Kober, Sergey Zakharov
    Abstract:

    Abstract Background Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute Methanol Poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute Methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss. Objectives To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute Methanol Poisoning. Methods MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of Poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8−OHdG, 8−OHG, 5−OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute Methanol Poisoning (Group I) and in 28 survivors of Poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without Methanol Poisoning. Results The survivors of acute Methanol Poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of Methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p  The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p  Conclusion In survivors of acute Methanol Poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of Poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of Methanol Poisoning.

  • the impact of co morbidities on a 6 year survival after Methanol mass Poisoning outbreak possible role of metabolic formaldehyde
    Clinical Toxicology, 2020
    Co-Authors: Sergey Zakharov, Tomas Navratil, Jan Rulisek, Katerina Kotikova, Manuela Vaneckova, Zdenek Seidl, Pavel Diblik, Jiri Hlusicka, Martin Komarc, Jan Bydzovsky
    Abstract:

    Context: The influence of co-morbid conditions on the outcome of acute Methanol Poisoning in mass Poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden ...

  • health related quality of life determinants in survivors of a mass Methanol Poisoning outbreak six year prospective cohort study
    Clinical Toxicology, 2020
    Co-Authors: Jan Rulisek, Katerina Kotikova, Manuela Vaneckova, Zdenek Seidl, Pavel Diblik, Jiri Hlusicka, Petr Waldauf, Jan Belohlavek, Martin Balik, Jan Bydzovsky
    Abstract:

    Purpose: The effect of acute Methanol Poisoning on the follow-up quality of life of survivors in mass Poisoning outbreaks is not known. The objective of this is to study the impact of visual and ce...

  • Methanol Poisoning as an acute toxicological basal ganglia lesion model evidence from brain volumetry and cognition
    Alcoholism: Clinical and Experimental Research, 2019
    Co-Authors: Josef Mana, Daniela Pelclova, Manuela Vaneckova, Jiři Klempiř, Irena Liskova, Hana Brožova, Kamila Polakova, Z Seidl, Michal Miovský, Kateřina Bukacova
    Abstract:

    BACKGROUND Acute Methanol Poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of Methanol Poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of Methanol Poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of Methanol Poisoning and the volume of the brain structures that are selectively vulnerable to Methanol. METHODS We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute Methanol Poisoning during Methanol mass Poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software. RESULTS In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01). CONCLUSIONS Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in Methanol Poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in Methanol Poisoning.

  • role of activation of lipid peroxidation in the mechanisms of acute Methanol Poisoning
    Clinical Toxicology, 2018
    Co-Authors: Jiri Hlusicka, Tomas Navratil, Manuela Vaneckova, Zdenek Seidl, Pavel Urban, Pavel Diblik, Tomas Loster, Lucie Lischkova, Pavel Kuthan, Petr Kacer
    Abstract:

    AbstractContext: The role of activation of lipid peroxidation in the mechanisms of acute Methanol Poisoning has not been studied.Objective: We measured the concentrations of lipid peroxidation markers in acutely intoxicated patients with known serum concentrations of Methanol and leukotrienes.Methods: Blood serum samples were collected from 28 patients hospitalized with acute intoxication and from 36 survivors 2 years after discharge. In these samples, concentrations of 4-hydroxy-trans-2-hexenal (HHE), 4-hydroxynonenal (HNE), and malondialdehyde (MDA) were measured using the method of liquid chromatography-electrospray ionization-tandem mass spectrometry.Results: The maximum acute serum concentrations of all three lipid oxidative damage markers were higher than the follow-up serum concentrations: HNE 71.7 ± 8.0 ng/mL versus 35.4 ± 2.3 ng/mL; p < .001; HHE 40.1 ± 6.7 ng/mL versus 17.7 ± 4.1 ng/mL; p < .001; MDA 80.0 ± 7.2 ng/mL versus 40.9 ± 1.9 ng/mL; p < .001. The survivors without Methanol Poisoning seq...

Tomas Navratil - One of the best experts on this subject based on the ideXlab platform.

  • mri based brain volumetry and retinal optical coherence tomography as the biomarkers of outcome in acute Methanol Poisoning
    Neurotoxicology, 2020
    Co-Authors: Jiri Hlusicka, Tomas Navratil, Katerina Kotikova, Josef Mana, Manuela Vaneckova, Pavel Urban, Pavel Diblik, Benedicte Marechal, Tobias Kober, Sergey Zakharov
    Abstract:

    Abstract Background Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute Methanol Poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute Methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss. Objectives To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute Methanol Poisoning. Methods MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of Poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8−OHdG, 8−OHG, 5−OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute Methanol Poisoning (Group I) and in 28 survivors of Poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without Methanol Poisoning. Results The survivors of acute Methanol Poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of Methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p  The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p  Conclusion In survivors of acute Methanol Poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of Poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of Methanol Poisoning.

  • the impact of co morbidities on a 6 year survival after Methanol mass Poisoning outbreak possible role of metabolic formaldehyde
    Clinical Toxicology, 2020
    Co-Authors: Sergey Zakharov, Tomas Navratil, Jan Rulisek, Katerina Kotikova, Manuela Vaneckova, Zdenek Seidl, Pavel Diblik, Jiri Hlusicka, Martin Komarc, Jan Bydzovsky
    Abstract:

    Context: The influence of co-morbid conditions on the outcome of acute Methanol Poisoning in mass Poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden ...

  • role of activation of lipid peroxidation in the mechanisms of acute Methanol Poisoning
    Clinical Toxicology, 2018
    Co-Authors: Jiri Hlusicka, Tomas Navratil, Manuela Vaneckova, Zdenek Seidl, Pavel Urban, Pavel Diblik, Tomas Loster, Lucie Lischkova, Pavel Kuthan, Petr Kacer
    Abstract:

    AbstractContext: The role of activation of lipid peroxidation in the mechanisms of acute Methanol Poisoning has not been studied.Objective: We measured the concentrations of lipid peroxidation markers in acutely intoxicated patients with known serum concentrations of Methanol and leukotrienes.Methods: Blood serum samples were collected from 28 patients hospitalized with acute intoxication and from 36 survivors 2 years after discharge. In these samples, concentrations of 4-hydroxy-trans-2-hexenal (HHE), 4-hydroxynonenal (HNE), and malondialdehyde (MDA) were measured using the method of liquid chromatography-electrospray ionization-tandem mass spectrometry.Results: The maximum acute serum concentrations of all three lipid oxidative damage markers were higher than the follow-up serum concentrations: HNE 71.7 ± 8.0 ng/mL versus 35.4 ± 2.3 ng/mL; p < .001; HHE 40.1 ± 6.7 ng/mL versus 17.7 ± 4.1 ng/mL; p < .001; MDA 80.0 ± 7.2 ng/mL versus 40.9 ± 1.9 ng/mL; p < .001. The survivors without Methanol Poisoning seq...

  • intermittent versus continuous renal replacement therapy in acute Methanol Poisoning comparison of clinical effectiveness in mass Poisoning outbreaks
    Annals of Intensive Care, 2017
    Co-Authors: Sergey Zakharov, Daniela Pelclova, Tomas Navratil, Jan Rulisek, Olga Nurieva, Katerina Kotikova, Martin Komarc, Knut Erik Hovda
    Abstract:

    Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute Methanol Poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass Methanol Poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute Methanol Poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p   0.05). In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of Poisoning on admission. These findings support the strategy of “use what you have” in situations with large outbreaks and limited dialysis capacity.

  • positive serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in acute Methanol Poisoning
    Monatshefte Fur Chemie, 2017
    Co-Authors: Sergey Zakharov, Tomas Navratil, Jaromir Belacek, Olga Nurieva, Katerina Kotikova, Daniela Pelclova
    Abstract:

    Mass Methanol Poisonings present a serious problem for health systems worldwide, with poor outcome associated with delayed treatment. Positive pre-hospital serum ethanol concentration may have predictive value as the prognostic factor of the treatment outcome. We studied the effect of positive serum ethanol level on admission to hospital on survival in patients treated during the Czech Methanol outbreak during 2012–2014. Cross-sectional cohort study was performed in 100 hospitalized patients with confirmed Methanol Poisoning. Pre-hospital ethanol was administered in 42 patients (by paramedic/medical staff to 30 patients and self-administered by 12 patients before admission); 58 patients did not receive pre-hospital ethanol. Forty-two patients had detectable serum ethanol concentration on admission to hospital [median 18.3 (IQR 6.6–32.2) mmol dm−3]. Pre-hospital ethanol administration by paramedic/medical staff had a significant effect on survival without visual and CNS sequelae when adjusted for arterial blood pH on admission (OR 8.73; 95 % CI 3.57–21.34; p < 0.001). No patients receiving pre-hospital ethanol died compared with 21 not receiving (p < 0.001). Positive serum ethanol concentration on admission to hospital was a predictor for survival without health sequelae when adjusted for arterial blood pH (OR 8.10; 95 % CI 2.85–23.02; p < 0.001). The probability of visual and CNS sequelae in survivors reduced with increasing serum ethanol concentration on admission.

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  • formate test for bedside diagnosis of Methanol Poisoning
    Basic & Clinical Pharmacology & Toxicology, 2021
    Co-Authors: Knut Erik Hovda, Yvonne Elisabeth Lao, Gaut Gadeholt, Dag Jacobsen
    Abstract:

    Methanol Poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of Methanol. We hereby present the first clinical Methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect Methanol Poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a Methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of Methanol Poisoning.

  • the hypothesis of circulus hypoxicus and its clinical relevance in patients with Methanol Poisoning an observational study of 35 patients
    Basic & Clinical Pharmacology & Toxicology, 2018
    Co-Authors: Elise Drangsholt, Sergey Zakharov, Knut Erik Hovda, Dag Jacobsen, Marie Vangstad
    Abstract:

    Methanol mass Poisoning is a global problem with high fatality rates and often severe sequelae in survivors. Patients typically present late to the hospital with severe metabolic acidosis followed by a rapid deterioration in their clinical status. The hypothesis 'Circulus hypoxicus' describes the metabolic acidosis following Methanol Poisoning as a self-enhancing hypoxic circle responsible for Methanol toxicity. We wanted to test the validity of this hypothesis by an observational study based on 35 patients from the Methanol outbreaks in Norway (2004) and the Czech Republic (2012). Comprehensive laboratory values, including S(serum)-Methanol, S-formate, S-lactate, arterial blood gases, anion and osmolal gaps, were used in the calculations. Laboratory values and calculated gaps were compared to each other using linear regression. S-lactate and S-formate correlated better with the increased base deficit and anion gap than did S-formate alone. Base deficit rose to about 20 mmol/L and S-formate rose to 12 mmol/L prior to a significant rise in S-lactate - most likely caused by formate inhibition of mitochondrial respiration (type B lactacidosis). The further rise in S-lactate was not linear to S-formate most likely due to the self-enhancing pathophysiology, but may also be associated with hypotension in critically ill patients and variable ethanol drinking habits. Our study suggests that the primary metabolic acidosis leads to a secondary lactic acidosis mainly due to the toxic effects of formate. The following decline in pH will further increase this toxicity. As such, a vicious and self-enhancing acidotic circle may explain the pathophysiology in Methanol Poisoning, namely the 'Circulus hypoxicus'.

  • intermittent versus continuous renal replacement therapy in acute Methanol Poisoning comparison of clinical effectiveness in mass Poisoning outbreaks
    Annals of Intensive Care, 2017
    Co-Authors: Sergey Zakharov, Daniela Pelclova, Tomas Navratil, Jan Rulisek, Olga Nurieva, Katerina Kotikova, Martin Komarc, Knut Erik Hovda
    Abstract:

    Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute Methanol Poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass Methanol Poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute Methanol Poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p   0.05). In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of Poisoning on admission. These findings support the strategy of “use what you have” in situations with large outbreaks and limited dialysis capacity.

  • a novel bedside diagnostic test for Methanol Poisoning using dry chemistry for formate
    Scandinavian Journal of Clinical & Laboratory Investigation, 2015
    Co-Authors: Knut Erik Hovda, Gaut Gadeholt, Vladimir Evtodienko, Dag Jacobsen
    Abstract:

    AbstractBackground. The standard diagnostic approach to Methanol Poisoning is chromatographic measurement of Methanol on centrally placed stationary equipment. Methanol Poisoning in places where such equipment is unavailable is thus often not diagnosed. Methanol is metabolized to a toxic metabolite, formate; the presence of this compound indicates Methanol Poisoning. We have developed an enzymatic test for formate and modified it into a portable dry chemistry system that could be used anywhere. Methods. The method consists of two enzymatic steps: Formation of NADH from NAD by formate dehydrogenase, and subsequent use of NADH as a reductant of a tetrazolium into a formazan dye that can be quantified photometrically or visually. Results. The photometer gave a good correlation of R2 = 0.9893 in serum and R2 = 0.9949 in whole blood, showing an instrumental detection limit of less than 1 mM (4.5 mg/dL). The visual readings showed a correlation of R2 = 0.8966. Users experienced some difficulty in separating the...

  • fomepizole versus ethanol in the treatment of acute Methanol Poisoning comparison of clinical effectiveness in a mass Poisoning outbreak
    Clinical Toxicology, 2015
    Co-Authors: Sergey Zakharov, Daniela Pelclova, Tomas Navratil, Jaromir Belacek, Michael Eddleston, Martin Komarc, Knut Erik Hovda
    Abstract:

    AbstractContext. Mass or cluster Methanol Poisonings are frequently reported from around the world. The comparative effectiveness of ethanol and fomepizole as antidotes for Methanol Poisoning is unknown due to the difficulty of performing a randomized controlled trial. Objective. During an outbreak of mass Poisonings in the Czech Republic in 2012–2014, we compared the effects of antidotes on the frequency of health sequelae and mortality. Methods. The study was designed as a cross-sectional case series and quasi-case–control study. Patients with a diagnosis of Methanol Poisoning on admission to hospitals were identified for the study. Diagnosis was established when (i) a history of recent ingestion of illicit spirits was available and serum Methanol was higher than 6.2 mmol/L (20 mg/dL), or (ii) there was a history/clinical suspicion of Methanol Poisoning, and serum Methanol was above the limit of detection with at least two of the following: pH < 7.3, serum bicarbonate < 20 mmol/L, and anion gap or AG ≥ ...