Thiamine Administration Research Articles

Early treatment with thiamine and mortality among patients with alcohol use disorder who are hospitalized for pneumonia.

The paucity of research linking thiamine treatment with improved outcomes may be driving its underutilization among patients at risk for Wernicke encephalopathy. To assess relationships of thiamine usage to outcomes of patients hospitalized with alcohol use disorder and pneumonia. DESIGN, SETTINGANDPARTICIPANTS: This is a retrospective cohort study of adult patients hospitalized with pneumonia who also have alcohol use disorder and were treated with benzodiazepines during the initial two hospital days, between 2010 and 2015 at hospitals participating in the Premier Healthcare Database. Any thiamine treatment, and, among those treated, high-dose thiamine treatment, during the initial two hospital days. Death on days 3-14 of hospitalization (primary); discharge home; transfer to intensive care unit; length of stay (LOS). We used propensity-weighted models to estimate treatment effects. Among 36,732 patients from 625 hospitals, 26,520 (72.2%) patients received thiamine, with mortality of 6.5% and 8.1% among recipients and nonrecipients, respectively. With propensity score adjustment, thiamine was associated with reduced mortality (odds ratio [OR]: 0.80, 95% confidence interval [CI]:0.75-0.85) and more frequent discharges to home (OR: 1.10, 95% CI: 1.06-1.14). Other outcomes were similar. Relative to low-dose thiamine, high-dose thiamine was not associated with mortality (adjusted OR: 0.99, 95% CI: 0.89-1.10), but LOS was longer (ratio of means: 1.06, 95% CI: 1.04-1.08), and discharges to home were less frequent (OR: 0.92, 95% CI: 0.87-0.97). Thiamine is not reliably given to patients with pneumonia and alcohol use disorder receiving benzodiazepines. Improving thiamine administration may represent an opportunity to save lives in this high-risk group of inpatients.

Vitamin C and its therapeutic potential in the management of COVID19.

COVID19 has emerged as one of the worst pandemics in the history of mankind. Several vaccines have been approved by different government agencies worldwide, but data on their efficacy and safety are limited, and distribution remains a massive challenge. As per WHO, personal immunity is vital for protection against COVID19. Earlier, Vitamin C-mediated pathways have been shown to play critical role in boosting immunity attributed to its antioxidant properties. Recently, the involvement of such pathways in protection against COVID19 has been suggested. The controlled doses of Vitamin C administered through intravenous (IV) injections are being studied for determining its role in the prognosis of COVID19. In this article, we have discussed the potential role of Vitamin C in the management in COVID19 patients and presented recent clinical trials data. Additionally, we have elaborated the possibility of administering Vitamin C through inhalers in order to achieve local high concentration and the challenges of such approach.

Korsakoff Syndrome: A Chronic Nutritional Deficiency Neuropsychiatric condition

In this review we have focused on Korsakoff syndrome, which is an aftermath of Wernicke encephalopathy (WE). Wernicke-Encephalopathy is neuropathologically marked by thiamine or vitamin B1 deficiency, typically induced by excessive alcohol use over an extended period of time in alcoholic patients, while in Nonalcoholic patients, it may be due to impaired utilization or accelerated usage of thiamine. Wernicke-Korsakoff syndrome (WKS) affects the brain region such as the mammillary bodies, periaqueductal and periventricular grey matter, colliculi bodies, and thalamus. The classic triads of WE are ophthalmoplegia, Nystagmus, and ataxia. The brain is examined using MRI and shows damage to the nuclei or memory transit- papez circuit that connects mamillary bodies to the anterior thalamus using the mammillothalamic tract responsible for the recollective memory in the diencephalon. Patients can be treated by parenteral thiamine administration and by abstinence of alcohol within their lifestyle. Keywords: Korsakoff Syndrome, alcoholic, non-alcoholic, Alzheimer's, memory-loss Wernicke encephalopathy, Wernicke-Korsakoff syndrome

What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke-Korsakoff syndrome? Results of a randomized controlled trial.

BackgroundThe primary cause of Wernicke–Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol‐dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS‐related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose.MethodsTwo double‐blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but “at‐risk” alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At‐Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow‐up.ResultsNo significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real‐world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross‐cultural assessment is likely to complicate RCT findings.ConclusionsThe results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high‐dose thiamine supports a recommendation for patient‐specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.

Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275–675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.

Thiamine Level in Out-of-hospital Cardiac Arrest Patients

BACKGROUND: Thiamine deficiency is more common in critically ill patients. Administration of thiamine in cardiac arrest mice has improved survival and neurological outcomes. Evidence for thiamine deficiency in cardiac arrest humans is insufficient to support routine use of thiamine in cardiac arrest patients. AIM: This study aimed to determine thiamine blood levels in cardiac arrest patients to understand whether the presence of thiamine deficiency is common in cardiac arrest patients. METHODS: A prospective descriptive study from April 2017 to March 2018, on 24 adult out-of-hospital cardiac arrest patients. We used the high-performance liquid chromatography technique to determine whole blood thiamine pyrophosphate levels in cardiac arrest patients who arrived at the emergency department within 1 h of the onset of a cardiac arrest. RESULTS: The mean thiamine pyrophosphate level within 1 h of the onset of a cardiac arrest was 170.9 ± 56.7 nmol/L. Only one participant had thiamine deficiency according to the cut-off level for thiamine pyrophosphate in whole blood of &lt;70 nmol/L. Fourteen patients had spontaneous return of circulation. Thiamine pyrophosphate levels were not different between the two groups of patients who had and did not have the return of spontaneous circulation at the emergency department. CONCLUSION: Little evidence was found to support thiamine deficiency as a feature among our cardiac arrest patients. A study with a larger population is required for more meaningful statistical analysis. As there is no consensus on cut-off level for thiamine deficiency diagnosis, the level of thiamine pyrophosphate in specific populations should be evaluated to establish reference values.

Evaluation of the safety of 500 mg intravenous push thiamine at a tertiary academic medical center.

Background: Thiamine, also known as vitamin B1, is an essential water-soluble micronutrient. Although thiamine has minimal safety concerns, parenteral administration has been associated with rare cases of anaphylactic shock, cardiac arrest, and injection site reaction. The objective of this analysis is to evaluate the incidence of anaphylaxis and injection site reactions associated with the administration of thiamine 500 mg as an intravenous (IV) push in adult patients. Method: This single-center, retrospective analysis was performed at Brigham and Women's Hospital in Boston, Massachusetts. Electronic health records were used to identify all adult patients who were ordered for thiamine 500 mg IV push between July 1, 2020, and December 31, 2020. For the major and minor endpoints, anaphylaxis and injection site reactions were assessed, respectively. Descriptive statistics were used as appropriate. Results: A total of 463 doses of thiamine in 69 patients were evaluated. Thiamine was administered peripherally for 392 (84.7%) doses and centrally for 68 (14.7) doses. No anaphylactic reactions were observed. A total of 4 injection site reactions (0.86%) were noted with 4 unique doses. All reactions were classified as low-grade based on our institutional grading system. All injection site reactions were classified as "possible" (Naranjo score of 1-4). Conclusion: Administration of IV push 500 mg thiamine was not associated with anaphylactic events and was associated with a low rate of injection site reactions.

LENCEPHALOPATHIE DE GAYET-WERNICKE CHEZ UNE PATIENTE SUIVIE POUR PANCREATITE: A PROPOS DUN CAS

Gayet-Wernicke encephalopathy is a serious complication of thiamine deficiency characterized by a clinical triad: confusional state, oculomotor disturbances, and cerebellar ataxia. Alcoholism is the main cause of thiamine deficiency. Severe pancreatitis through prolonged fasting and vomiting may exceptionally give a similar clinical picture which sometimes poses diagnostic difficultiesDiagnosis is based on brain imaging by showing on MRI a T2 or FLAIR hypersignal affecting the peri-aqueductal region, the medial part of the thalamus, the floor of the fourth ventricle, the vermis, the mammillary bodies and, sometimes, the cortex. Treatment consists of rapid intravenous administration of thiamine. We report a case of 66-year-old patient followed for severe pancreatitis whose evolution was marked by the onset of a consciousness disorder whose investigations returned in favor of Gayet-Wernicke encephalopathy.

Thiamine-dependent regulation of mammalian brain pyridoxal kinase in vitro and in vivo.

Vitamins B1 (thiamine) and B6 (pyridox (al/ine/amine)) are crucial for central nervous system (CNS) function and neurogenesis due to the coenzyme action of their phosphorylated derivatives in the brain metabolism of glucose and neurotransmitters. Here, the non-coenzyme action of thiamine on the major mammalian producers of pyridoxal-5'-phosphate (PLP), such as pyridoxal kinase (PdxK) and pyridoxine 5'-phosphate oxidase (PNPO), is characterized. Among the natural thiamine compounds, thiamine triphosphate (ThTP) is the best effector of recombinant human PdxK (hPdxK) in vitro, inhibiting hPdxK in the presence of Mg2+ but activating the Zn2+ -dependent reaction. Inhibition of hPdxK by thiamine antagonists decreases from amprolium to pyrithiamine to oxythiamine, highlighting possible dysregulation of both the B1 - and B6 -dependent metabolism in the chemical models of thiamine deficiency. Compared with the canonical hPdxK, the D87H and V128I variants show a twofold increase in Kapp of thiamine inhibition, and the V128I and H246Q variants show a fourfold and a twofold decreased Kapp of thiamine diphosphate (ThDP), respectively. Thiamine administration changes diurnal regulation of PdxK activity and phosphorylation at Ser213 and Ser285, expression of the PdxK-related circadian kinases/phosphatases in the rat brain, and electrocardiography (ECG). In contrast to PdxK, PNPO is not affected by thiamine or its derivatives, either in vitro or in vivo. Dephosphorylation of the PdxK Ser285, potentially affecting mobility of the ATP-binding loop, inversely correlates with the enzyme activity. Dephosphorylation of the PdxK Ser213, which is far away from the active site, does not correlate with the activity. The correlations analysis suggests the PdxK Ser213 to be a target of kinase MAP2K1 and phosphatase Ppp1ca. Diurnal effects of thiamine administration on the metabolically linked ThDP- and PLP-dependent enzymes may support the brain homeostatic mechanisms and physiological fitness.

Association of Thiamine Use with Outcomes in Patients with Sepsis and Alcohol Use Disorder: An Analysis of the MIMIC-III Database.

IntroductionThe association between thiamine use and clinical outcomes among patients with sepsis and alcohol use disorder (AUD) is unclear.MethodsIn this retrospective cohort study of patients from Medical Information Mart for Intensive Care III (MIMIC-III, version 1.4), we evaluated the association of thiamine use with clinical outcomes in patients with AUD and sepsis. The primary outcome was 28-day survival, and secondary outcomes included ICU, in-hospital, and 90-day mortality, ICU and hospital length of stay, duration of vasopressor use, need and duration of continuous renal replacement therapy (CRRT), and dynamic changes for variables up to day 7 after ICU admission.ResultsA total of 944 patients with sepsis and AUD were included in this cohort [median age, 53.1 years; women, 26.0% (245 of 944)]. Among all patients, 24.6% (233 of 944) received thiamine with a dose of 200 mg (IQR 100–345 mg). The 28-day mortality was 11.2% (26 of 233) in the thiamine use group compared with 18.6% (132 of 711) in the no thiamine use group (P = 0.009). After adjustment for a series of confounders, the mixed-effects Cox proportional hazards models showed that administration of thiamine was associated with a lower risk of 28-day mortality compared with no administration of thiamine.ConclusionsIn critically ill patients with alcohol use disorder admitted for sepsis, treatment with thiamine may be associated with a decreased risk of death. However, the present results should be interpreted with caution due to the limitations of retrospective design. Additional larger, multicenter randomized controlled trials are needed to confirm our findings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00603-1.

Synthesis, physico-chemical properties and effect of adenosine thiamine triphosphate on vitamin B1 metabolism in the liver of alloxan diabetic rats

BackgroundAdenosine thiamine triphosphate (AThTP) is a nucleotide discovered in bacteria and some other living organisms more than a decade ago. No biochemical function for AThTP has been established yet, however, experimental data available indicate its possible involvement in metabolic regulation or cell signaling. Metabolism of AThTP in mammals, as well as the feasibility of its pharmacological application, is essentially unstudied. MethodsPreparative low-pressure chromatography was employed to purify chemically synthesized AThTP with its further analysis by mass spectrometry, HPLC, UV and fluorescence spectroscopy. Enzyme activity assays along with HPLC were used to examine the effects of AThTP and thiamine on vitamin B1 metabolism in the liver of alloxan-induced diabetic rats. ResultsAn improved procedure for AThTP synthesis and purification is elaborated. Solution stability, optical spectral properties and the molar absorption coefficient for AThTP were determined. The levels of thiamine compounds were found to be increased in the liver of diabetic rats. Neither AThTP nor thiamine treatment affected hepatic vitamin B1 metabolism. Fasting blood glucose concentration was also unchangeable after AThTP or thiamine administration. General significanceContrast to the widespread view about thiamine deficiency in diabetes, our results clearly shows an adaptive increase in the level of B1 vitamers in the liver of alloxan diabetic rats with no further rising after AThTP or thiamine treatment at a moderate dose. Neither AThTP nor thiamine is effective in glycaemic control. These findings are to be considered in future studies dealing with thiamine or its analogues application to correct metabolic disturbances in diabetes.

Changes in the Levels of Neurospecific Proteins and Indices of Apoptosis in the Rat Cornea at Chronic Ethanol Consumption: Protective Effects of Thiamine Administration

Changes in the Levels of Neurospecific Proteins and Indices of Apoptosis in the Rat Cornea at Chronic Ethanol Consumption: Protective Effects of Thiamine Administration

Marchiafava- Bignami disease (MBD): A rare case report

Marchiafava-Bignami disease (MBD) is a rare neuro degenerative disease characterized by demyelination of corpus callosum. Clinical diagnosis of MBD is challenging due to its nonspecific neurological manifestations. It’s promptly diagnosed by brain Magnetic Resonance Imaging (MRI). Prompt treatment with high dose thiamine could be lifesaving. Here we report a 68 year old male with chronic alcoholism who was diagnosed to have MBD and successfully treated with high doses of intravenous thiamine administration.

Thiamine Supplementation in Patients With Alcohol Use Disorder Presenting With Acute Critical Illness : A Nationwide Retrospective Observational Study.

Thiamine supplementation is recommended for patients with alcohol use disorder (AUD). The authors hypothesize that critically ill patients with AUD are commonly not given thiamine supplementation. To describe thiamine supplementation incidence in patients with AUD and various critical illnesses (alcohol withdrawal, septic shock, traumatic brain injury [TBI], and diabetic ketoacidosis [DKA]) in the United States. Retrospective observational study. Cerner Health Facts database. Adult patients with a diagnosis of AUD who were admitted to the intensive care unit with alcohol withdrawal, septic shock, TBI, or DKA between 2010 and 2017. Incidence and predicted probability of thiamine supplementation in alcohol withdrawal and other critical illnesses. The study included 14998 patients with AUD. Mean age was 52.2 years, 77% of participants were male, and in-hospital mortality was 9%. Overall, 7689 patients (51%) received thiamine supplementation. The incidence of thiamine supplementation was 59% for alcohol withdrawal, 26% for septic shock, 41% for TBI, and 24% for DKA. Most of those receiving thiamine (n= 3957 [52%]) received it within 12 hours of presentation in the emergency department. The predominant route of thiamine administration was enteral (n= 3119 [41%]). Specific dosing and duration were not completely captured. Thiamine supplementation was not provided to almost half of all patients with AUD, raising a quality-of-care issue for this cohort. Supplementation was numerically less frequent in patients with septic shock, DKA, or TBI than in those with alcohol withdrawal. These data will be important for the design of quality improvement studies in critically ill patients with AUD. National Institutes of Health.

Clinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospital

Acute thiamine deficiency can occur in patients with or without history of alcohol abuse and can lead to life-threatening complications. Clinical diagnosis is challenging, often resulting in delayed recognition and treatment. Patients may present with heterogenous symptoms, more diverse than the historical neurological description. Cerebral MRI can contribute to the diagnosis in patients with neurological signs but it is not always feasible in emergency settings. Prompt parenteral supplementation is required to obtain the improvement of symptoms and avoid chronic complications. To describe the clinical presentation of reported cases of thiamine deficiency, assess prescription and results of cerebral imaging, review treatments that had been prescribed in accordance or not with available guidelines, and study the short-term outcome of these patients. This is a monocentric retrospective analysis of all reported cases of thiamine deficiency in a French tertiary hospital between January 1st 2008 and December 31st 2018. Fifty-six cases were identified during the study period. Forty-five (80%) patients had a history of alcohol abuse. Most patients were diagnosed based on neurological symptoms but non-specific and digestive symptoms were frequent. Thirty-four percent of patients fulfilled clinical criteria for malnutrition. A brain MRI was performed in 54% of patients and was abnormal in 63% of these cases. Eighty-five percent of patients were treated by parenteral thiamine administration and the supplementation was continued orally in 55% of them. The majority of patients initially received 1000mg daily of IV thiamine but the dose and duration of thiamine supplementation were variable. At the time of discharge, partial or complete improvement of symptoms was noted in 59% of patients. This study highlights the clinical and radiological heterogeneity of thiamine deficiency. These observations should encourage starting thiamine supplementation early in patients with risk factors or suggestive symptoms even in non-alcoholic patients, and underline the importance of early nutritional support.

HYDROCORTISONE, VITAMIN C, AND THIAMINE SUPPLEMENTATION VS PLACEBO IN PATIENTS WITH SEPSIS

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: While retrospective studies have shown conflicting outcomes in septic patients who received hydrocortisone, vitamin C, and thiamine compared to placebo, randomized controlled trials (RCTs) failed to show significant differences between the two groups in 30-day and in hospital mortality, hospital length of stay, and change in sequential organ failure (SOFA) score. We conducted a systematic review and meta-analysis to evaluate the beneficial effect of hydrocortisone, vitamin C, and thiamine compared to placebo in septic patients. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane databases from inception through March 2021 for RCTs comparing hydrocortisone, vitamin C, and thiamine vs placebo in septic patients. Outcome of interests were 30-day and in hospital mortality, hospital length of stay, and change in SOFA score from hospital presentation and day 3 or day 4. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The random-effects model was used for all variables, and publication bias was assessed using Egger's test. RESULTS: Three RCTs published between April 2020 and February 2021 examining 717 patients were included in our analysis. The outcomes of these studies evaluated 30-day and in hospital mortality, hospital length of stay, and change in SOFA score from hospital presentation. Our analysis showed no significant difference in 30-day and in hospital mortality rates between the treatment group and placebo group with relative risk ratio of 0.975 (95% CI 0.766 to 1.241) (I2 =0.000) and 1.066 (95% CI 0.724 to 1.571) (I2=0.000) respectively. Our analysis also suggested no difference in the length of hospital stay and change is SOFA score from hospital presentation to day 3 or day 4 in the two groups with standardized mean difference of -0.031 (95% CI -0.204 to 0.141, P-value = 0.722) and 0.074 (95% CI -0.234 to 0.381, P-value = 0.639). CONCLUSIONS: Our analysis suggests no significant improvement in 30-day and in hospital mortality rate, hospital length of stay, or change in SOFA score in septic patients treated with hydrocortisone, vitamin C and thiamine compared to placebo. CLINICAL IMPLICATIONS: Hydrocortisone, vitamin C and thiamine administration provides no mortality benefit, decrease in hospital stay, or improvement in SOFA scores in patients with sepsis. DISCLOSURES: No relevant relationships by Mohammad Darweesh, source=Web Response No relevant relationships by chris haas, source=Web Response No relevant relationships by Ibrahim Haddad, source=Web Response No relevant relationships by Metri Haddaden, source=Web Response

Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine in Septic Shock: A Post-Hoc Study of the ATESS Trial.

We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock. This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multicenter, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate. Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve. Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β. NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220.

Wernicke's encephalopathy in a child with abdominal tuberculosis

Wernicke's encephalopathy (WE) is an acute neurological disorder, potentially fatal if untreated, caused by thiamine deficiency. A 15-year-old female patient with choledocholithiasis, cholecystitis and abdominal tuberculosis on antitubercular therapy presented with poor oral intake, bilious vomiting and encephalopathy. A prompt diagnosis of WE was made and confirmed by brain magnetic resonance imaging. The patient recovered completely after the administration of thiamine.

Associations between early thiamine administration and clinical outcomes in critically ill patients with acute kidney injury.

The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.

Thiamine deficiency in rats affects thiamine metabolism possibly through the formation of oxidized thiamine pyrophosphate

BackgroundThiamine deficiency (TD) has a number of features in common with the neurodegenerative diseases development and close relationship between TD and oxidative stress (OS) has been repeatedly reported in the literature. The aim of this study is to understand how alimentary TD, accompanied by OS, affects the expression and level of two thiamine metabolism proteins in rat brain, namely, thiamine transporter 1 (THTR1) and thiamine pyrophosphokinase (TPK1), and what factors are responsible for the observed changes. MethodsThe effects of OS caused by TD on the THTR1and TPK1 expression in rat cortex, cerebellum and hippocampus were examined. The levels of active and oxidized forms of ThDP (enzymatically measured) in the blood and brain, ROS and SH-groups in the brain were also analyzed. ResultsTD increased the expression of THTR1 and protein level in all studied regions. In contrast, expression of TPK1 was depressed. TD-induced OS led to the accumulation of ThDP oxidized inactive form (ThDPox) in the blood and brain. In vitro reduction of ThDPox by dithiothreitol regenerates active ThDP suggesting that ThDPox is in disulfide form. A single high-dose thiamine administration to TD animals had no effect on THTR1 expression, partly raised TPK1 mRNA and protein levels, but is unable to normalize TPK1 enzyme activity. Brain and blood ThDP levels were increased in these conditions, but ThDPox was not decreased. General significanceIt is likely, that the accumulation of ThDPox in tissue could be seen as a potential marker of neurocellular dysfunction and thiamine metabolic state.