UNASSIGNED: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency.
UNASSIGNED: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine.
UNASSIGNED: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework.
UNASSIGNED: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 μg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine.
UNASSIGNED: Although ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting.
METHODS: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People\'s Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve.
RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86).
CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement.
BACKGROUND: Clinicaltrials.gov NCT03626337.

Despite guidelines and recommendations, Wernicke\'s encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.
Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.
This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.
We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.
Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Background Thiamine deficiency (TD) is an important public health problem in nutrition, occurring in 2-6% of the population in Europe and the US, whereas thiamine levels are reported to be significantly reduced by 36.6-40% in some populations of East Asia. However, there is little information available at present, regarding factors such as age, despite the continued aging of society. Further, studies such as those mentioned above have not yet been undertaken in Japan, the country in which population aging is most advanced. Objective To investigate TD in the Japanese community-dwelling individuals who are independently ambulatory. Methods We undertook an examination of TD in blood samples obtained from 270 citizens in a provincial town, aged 25-97 years, who were able to walk to the venue and provide informed consent for inclusion in this research and of whom 8.9% had a history of cancer. We summarized the demographic characteristics of the subjects. The whole-blood thiamine concentrations were measured using the high-performance liquid chromatography method. A value of 21.3 ng/ml or less was taken as low and a borderline value was set as less than 28 ng/ml. Results The mean (±SD) whole blood thiamine concentration was 47.6 ± 8.7 ng/ml. No TD was observed to exist participating in this study, with no subjects even showing show borderline values. Further, there was no significant difference in thiamine level between those aged 65 or older and those aged less than 65. Conclusions No cases of TD were observed among the subjects in this study, nor was the concentration of thiamine found to be related to age. It is possible that the frequency of TD might be very low in citizens who have a certain level of activity. In the future, it is necessary to expand the prevalence of TD to a wider range of subjects.

UNASSIGNED: Although thiamine deficiency (TD) can lead to Wernicke encephalopathy, the characteristics associated with TD in the elderly have not yet been clarified. We sought to clarify the frequency of TD among an institutionalized elderly population with a controlled dietary intake and to identify possible factors related to TD.
UNASSIGNED: We undertook a cross-sectional study of residents in three nursing homes for the elderly as of June 2020. Blood thiamine concentrations were measured using a high-performance liquid chromatography method, with TD defined as a concentration of <21.3 ng/mL. Basic data (age, sex, height, weight, and BMI), dietary intake for the previous 3 weeks, degree of care (DOC), degree of independence in daily life for elderly with dementia (DIDLED), and comorbidities were analyzed using descriptive statistical methods.
UNASSIGNED: The mean age (±SD) was 86.9 years (±8.29), with 84 residents (70.0%) being female. The DIDLED varied from total independence to long-term care level 5 (full assistance), with 89.2% suffering dementia. The mean whole blood thiamine value was 36.18 (±17.58) ng/ml, with TD confirmed in 7 (5.8%) of the 120 residents. All TD patients suffered from dementia. No TD was observed in patients with a near-normal food intake, and no related factors were observed among the other items.
UNASSIGNED: Reduced food intake may at increase the risk of TD and symptoms of TD may be overlooked in those displaying symptoms of dementia; thus, it is important for clinicians working with the elderly to remain aware of the potential for TD.

BACKGROUND: Thiamine is an essential co-factor for aerobic intracellular respiration, nerve conduction, and muscle contraction. Thiamine deficiency is common in the intensive care unit (ICU). Delirium is a frequent unwanted symptom among critical ill patients. Although the exact cause of ICU-associated delirium is unknown, abnormal nutrition and thiamine deficiency may contribute to the etiology.
OBJECTIVE: To compare the prevalence of delirium among ICU patients who received thiamine with those who did not and to compare morbidity and mortality.
METHODS: A retrospective study was conducted among ICU patients admitted 2014-2018. Routine thiamine administration began in 2016. Collected data included patient demographics, medical history, indication for ICU admission, hospital admission times, ventilation days, inotropic therapy, hemodialysis, tracheostomy, 28-day mortality, and need for anti-psychotic therapy. Group A received thiamine, group B did not. All data were statistically analyzed according to type.
RESULTS: The study included 930 patients: 465 patients in group A and 465 in group B. At admission and throughout the hospitalization severity of disease parameters was worse in group A compared to group B, including acute physiology and chronic health evaluation (APACHE) score, admission lactate level, ventilation days, inotropic support, renal replacement therapy, tracheostomy, and ICU hospitalization. Group A had fewer delirium events without difference of maximal delirium score. No difference in mortality rate was observed.
CONCLUSIONS: Thiamine administration was associated with lower delirium prevalence despite longer ICU admission times and higher disease severity parameters at admission and during ICU stay.

The relationship between thiamine blood level (TBL) and cognition remains uncertain, including among alcohol-dependent persons (ADP).
To evaluate this relationship during protocol-driven inpatient alcohol detoxification treatment including thiamine supplementation (AD + Th).
Prospective 3-week study with 100 consecutively admitted detoxification-seeking ADP (47.7 ± 11 years old, 21% females) without superseding comorbidities requiring treatment. TBL and Montreal Cognitive Assessment (MoCA) were measured at admission (t1, pre-AD + Th) and discharge (t3, post-AD + Th). Frontal Assessment Battery (FAB) was performed at t1. AD + Th included abstinence, pharmacological alcohol withdrawal syndrome treatment, and oral thiamine supplementation (200 mg/day for 14 days). Regression and mediation analyses assessed TBL-cognition relationships.
We found no cases of Wernicke Encephalopathy (WE) and only one case of thiamine deficiency. Both MoCA and TBL significantly improved across AD + Th (with medium-to-large effect sizes). At t1, TBL significantly predicted MoCA and FAB sum scores (medium effect sizes; extreme and very strong evidence, respectively). The clear TBL-MoCA association disappeared at t3. In multivariate regression and mediation analyses exploring key influential factors of cognition (identified by LASSO regression), the TBL-MoCA interactions did not relevantly change at t1 and t3. Age, serum transaminases, vitamin D levels, drinking-years, and depression score weakly modified the relationship.
TBL was a robust predictor of pre-detoxification cognitive impairment, and both TBL and cognition improved significantly during AD + Th (including abstinence) in our ADP population, supporting routine thiamine supplementation for ADP, even those at low WE-risk. The TBL-cognition relationship was minimally confounded by age, alcohol-toxicity proxies, mood, and vitamin D levels.

To determine the prevalence and time course of thiamine deficiency (TD) in PICU patients.
Multicenter, prospective, cohort study between May 2019 and November 2019.
Three university-based tertiary care, mixed medical-surgical PICUs in Ankara, Turkey.
PICU patients 1 month to 18 years old.
None.
We studied 476 patients and grouped them by TD status on days 1 and 3 of the PICU admission. There might be a risk of unintended bias since we excluded 386 patients because of the absence of consent, inadequate blood samples, loss of identifier information, and recent vitamin supplementation. On day 1, TD was present in 53 of 476 patients (11.1%) and median (minimum-maximum) thiamine levels were 65.5 ng/mL (5-431 ng/mL). On day 3, TD was present in 27 of 199 patients (13.6%) with repeated measurement. The median (minimum-maximum) thiamine levels were 63 ng/mL (13-357 ng/mL). The time course of TD from day 1 to day 3 in these 199 patients was as follows. In 21 of 199 patients (10.6%) with TD on day 1, 11 of 21 (52%) continued to have TD on day 3 and the other 10 of 21 patients (48%) improved to no longer having TD. In 178 of 199 patients (89.4%) without TD on day 1, 16 of 178 (9%) went on to develop TD by day 3, and the other 162 of 178 (91%) continued to have normal thiamine status.
In the PICU population in three centers in Turkey, the prevalence of TD in the sample of patients was 11.1%. In those TD patients who had serial studies, we also identified that by day 3 some continued to be TD, and some patients improved to normal thiamine status. Of concern, however, is the population who develop TD over the course of PICU stay.

The 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.
Two 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.
No 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.
The 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.

UNASSIGNED: Confabulations refer to the emergence of memories of experiences and events that are incorrect in place and time, or never took place. In alcoholic Korsakoff\'s syndrome, confabulations have been frequently reported, but seldomly been investigated. Traditional reports on confabulations state that confabulations in KS mainly occur in the post-acute phase of the illness. The aim of the study was to investigate whether confabulations extinguish in KS.
UNASSIGNED: An observational rating of confabulation behaviour (the NVCL-R) was completed for 172 KS patients with alcoholic KS. Post-acute and chronic KS patients were compared cross-sectionally in two centres.
UNASSIGNED: Provoked and spontaneous confabulations were present in post-acute and chronic patients. Patients residing in a long-term care facility more often presented themselves with spontaneous confabulations than patients in a diagnostic centre.
UNASSIGNED: In contrast to the traditional view, confabulations may be present throughout the course of KS, and are possibly more frequently present in patients receiving care in specialised long-term care facilities than in patients who receive less intensive support.Key pointsConfabulations are a central characteristic of Korsakoff\'s syndromeIn contrast to popular belief, confabulations may be present in acute and chronic Korsakoff\'s syndromeThe severity of confabulations is related to an unfavourable disease outcome in KSA longitudinal approach would help the confirmation of finding no decline in confabulations over time.