Thiamine-responsive megaloblastic anaemia in a young adult with acute pancytopenia.

Thiamine-responsive megaloblastic anaemia (TRMA) is a rare autosomal recessive disorder characterised by the clinical triad of megaloblastic anaemia, sensorineural hearing loss and diabetes mellitus (DM) in young patients. We present a case of a young man with type 1 DM who presented with pancytopenia of unclear aetiology, initially attributed to a COVID-19 infection. After obtaining a bone marrow biopsy and pursuing genetic testing, two pathogenic variants of the SLC19A2 gene consistent with TRMA were discovered in this patient. Treatment with 100 mg of thiamine oral supplementation daily led to the complete resolution of his pancytopenia. It is important to consider a genetic cause of pancytopenia in a young person. Early recognition and diagnosis of TRMA can be life-altering given early treatment can reduce insulin requirements and resolve anaemia.

Clinical profile and thiamine transporter gene (SLC19A2 and SLC19A3) variations in infants with thiamine-responsive pulmonary hypertension and acute respiratory infection.

Maternal thiamine deficiency is prevalent in low- and middle-income countries. Thiamine-responsive pulmonary hypertension (TRPHTN) in exclusively breastfed infants is reported in India. Thiamine transporter gene (ThTR) variations have not been studied. This study compared the presentation of exclusively breastfed infants with respiratory distress diagnosed as TRPHTN or acute respiratory infection (ARI). We investigated pathogenic variations in the SLC19A2 and SLC19A3 ThTr genes in a representative sample. Observational study. Tertiary care pediatric unit of a teaching hospital in southern India. Data collection was prospective. We included exclusively breastfed infants between 1 and 6 months of age with respiratory distress. Infants with PHTN in echocardiography and lactic acidosis (LA) received thiamine. TRPHTN was diagnosed based on response within 72 h. Infants with fever, chest findings, and positive microbiology were managed as ARI. The ThTr genes were sequenced and analyzed. Chi-square and stratified analysis were done to determine TRPHTN risk. Forty infants with TRPHTN and 42 with ARI were included. The median pulmonary arterial pressure in the TRPHTN group was 51.5 mmHg. Mild PHTN was seen in 65%, moderate in 22.5%, and severe in 12.5%. Cardiac failure (P < .001), stridor and aphonia (P < .001), encephalopathy (P = .024), LA (P < .001), and PHTN (P <.001) facilitated the diagnosis. The adjusted risk was 17.3 (95% confidence interval 7.8-38.3; P <.001). The ThTR sequencing showed wild-type genotypes. TRPHTN has a distinct, identifiable presentation. Lactate and pulmonary pressure estimations are useful investigations in thiamine deficiency endemic areas. We could not demonstrate a genetic variation that determines susceptibility.

Cross-Sectional Study of Thiamine Deficiency and Its Associated Risks in Emergency Care.

Background: Growing data indicates that thiamine deficiency occurs during acute illness in the absence of alcohol use disorder. Our primary objective was to measure clinical factors associated with thiamine deficiency in patients with sepsis, diabetic ketoacidosis, and oncologic emergencies. Methods: This was an analysis of pooled data from cross-sectional studies that enrolled adult emergency department (ED) patients at a single academic center with suspected sepsis, diabetic ketoacidosis, and oncologic emergencies. We excluded patients who had known alcohol use disorder or who had received ED thiamine treatment prior to enrollment. Investigators collected whole blood thiamine levels in addition to demographics, clinical characteristics, and available biomarkers. We defined thiamine deficiency as a whole blood thiamine level below the normal reference range and modeled the adjusted association between this outcome and age. Results: There were 269 patients, of whom the average age was 57 years; 46% were female, and 80% were Black. Fifty-five (20.5%) patients had thiamine deficiency. In univariate analysis, age >60 years (odds ratio [OR] 2.5, 95% confidence interval [CI], 1.3-4.5), female gender (OR 1.9, 95% CI 1.0-3.4), leukopenia (OR 4.9, 95% CI 2.3-10.3), moderate anemia (OR 2.8, 95% CI 1.5-5.3), and hypoalbuminemia (OR 2.2, 95% CI 1.2-4.1) were associated with thiamine deficiency. In adjusted analysis, thiamine deficiency was significantly higher in females (OR 2.1, 95% CI 1.1-4.1), patients >60 years (OR 2.0, 95% CI 1.0-3.8), and patients with leukopenia (OR 5.1, 95% CI 2.3-11.3). Conclusion: In this analysis, thiamine deficiency was common and was associated with advanced age, female gender, and leukopenia.

Thiamine: An indispensable regulator of paediatric neuro-cardiovascular health and diseases.

The sustainable developmental goals emphasize good health, reduction in preventable neonatal and under-five mortalities, and attaining zero hunger. However, South Asian countries report a higher incidence of neonatal and under-five mortalities when compared to the Western world, many of which are attributed to maternal and perinatal micronutrient deficiencies. Isolated nutrient deficiency in the absence of calorie deficit poses a diagnostic challenge since such deficiencies present with acute multisystemic and enigmatic manifestations. Thiamine (vitamin B1) is a micronutrient of prime importance which exerts indispensable roles in energy metabolism. Deficiency of thiamine can lead to catastrophic consequences. This review provides insight into the biochemical actions of thiamine in energy metabolism, the compromised aerobic metabolism resulting from thiamine deficiency, and the crucial role of thiamine in the proper functioning of the nervous, cardiovascular, and immune systems. The review also explores the acute life-threatening consequences of thiamine deficiencies in neonates and infants and the speculative role of thiamine in other pathologies like encephalopathy, sepsis, and autism spectrum disorders. However, routine assessment of thiamine in pregnant women and neonates is yet to be implemented, due to the lack of affordable and automated diagnostic techniques, and the cost-intensive nature of mass spectrometry-based quantification. CONCLUSION: Physicians are recommended to have a low threshold for suspecting thiamine deficiency especially in vulnerable populations. Laboratory diagnosis of thiamine deficiency needs to be implemented as a standard of care, especially in endemic regions. Further, public health policies on food fortification, mandatory supplementation, and surveillance are imperative to eliminate thiamine deficiency-induced health hazards. WHAT IS KNOWN: • South Asian countries report a higher incidence of neonatal and under-five mortalities, many of which are attributed to maternal and perinatal micronutrient deficiencies. • Preventable causes of neonatal/ infantile deaths include birth factors (low birth weight, birth asphyxia), infectious diseases (pneumonia, diarrhoea, tetanus, tuberculosis, measles, diphtheria, malaria, acute infections), deficiency diseases and genetic diseases (vitamin & mineral deficiencies, IEMs, congenital heart disease, unexplained PPHN, SIDS etc). WHAT IS NEW: • Acute thiamine deficiency presenting as multisystemic syndromes, has unfortunately been a long standing unresolved public health concern. However, accessible surveillance and diagnostic strategies remain elusive in most clinical settings. • Despite decades of reports and emerging guidelines, diagnosis of thiamine deficiency is often missed and policy mandates at national level are yet to be implemented even in endemic countries. • This review provides a comprehensive summary of the biochemical role of thiamine, its key functions and effects on major organ systems, the diagnostic gap, the enigmatic presentation of acute thiamine deficiency, the plausible role of thiamine in other pathologies and the preventive measures at individual and community level.

Atypical presentation of Wernicke encephalopathy due to thiamine deficiency in a patient post sleeve gastrectomy.

We present a case of a woman in her 20s who presented to the emergency department with a 1-month history of blurry vision, lower extremity weakness in both legs and progressive numbness involving the feet and anterior chest. On admission, the patient was unable to ambulate. She was 3 months status post laparoscopic vertical sleeve gastrectomy for weight loss and using transdermal vitamin patches for nutritional supplementation. Laboratory values revealed low levels of vitamin B1, vitamin A, vitamin D, folic acid and copper levels. The patient was diagnosed with Wernicke encephalopathy and possible peripheral neuropathy secondary to thiamine deficiency. She was started on intravenous thiamine 500 mg three times a day and folate 1 mg one time a day for 3 days and then transitioned to oral thiamine 500 mg along with a multivitamin tablet. Improvement in ophthalmoplegia, weakness, sensation and cognition was noticed after initiating treatment.

Low expression of thiamine pyrophosphokinase-1 contributes to brain susceptibility to thiamine deficiency.

Thiamine deficiency is a well-known risk factor for the development of severe encephalopathy, such as Wernicke encephalopathy and Korsakoff syndrome, but the underlying mechanism is still mysterious. This study aims to investigate the expression levels of thiamine metabolism genes in different tissues and their impact on brain susceptibility to thiamine deficiency. The mRNA and protein levels of four genes known to be associated with thiamine metabolism: thiamine pyrophosphokinase-1 ( Tpk ), Solute carrier family 19 member 2 ( Slc19a2 ), Slc19a3 , and Slc25a19 , in the brain, kidney, and liver of mice were examined. Thiamine diphosphate (TDP) levels were measured in these tissues. Mice were subjected to dietary thiamine deprivation plus pyrithiamine (PTD), a specific TPK inhibitor, or pyrithiamine alone to observe the reduction in TDP and associated pathological changes. TPK mRNA and protein expression levels were lowest in the brain compared to the kidney and liver. Correspondingly, TDP levels were also lowest in the brain. Mice treated with PTD or pyrithiamine alone showed an initial reduction in brain TDP levels, followed by reductions in the liver and kidney. PTD treatment caused significant neuron loss, neuroinflammation, and blood-brain barrier disruption, whereas dietary thiamine deprivation alone did not. TPK expression level is the best indicator of thiamine metabolism status. Low TPK expression in the brain appears likely to contribute to brain susceptibility to thiamine deficiency, underscoring a critical role of TPK in maintaining cerebral thiamine metabolism and preventing thiamine deficiency-related brain lesions.

Predicting Recurrent Deficiency and Suboptimal Monitoring of Thiamin Deficiency in Patients with Metabolic and Bariatric Surgery.

INTRODUCTION: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. METHODS: We analyzed a large sample of data from patients with MBS (n = 878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. RESULTS: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. CONCLUSIONS: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

[Bibliometric visualization analysis of thiamine-responsive megaloblastic anemia syndrome].

Visual analysis of the current status, research hotspots, evolving trends, and future prospects in the field of thiamine-responsive megaloblastic anemia syndrome (TRMA), providing new insights and directions for subsequent research on the pathogenic mechanisms and prevention strategies of TRMA. Taking the core database of Web of Science as the literature source, selecting TRMA-related literature records published from 1997 to 2023 as the research object, and using R software and Citexs database to conduct visual analysis and discussion of the research content. The results showed that a total of 89 publications related to the topic were published from 1997 to 2023, with an average annual publication volume of 3 papers. Classified by country, it was found that the United States, and Israel among other countries and institutions, published a significant number of papers. Through keyword frequency analysis, high frequencies of keywords such as diabetes, deafness, thiamine-responsive megaloblastic anemia, and mutations in the solute carrier family 19 member 2 (SLC19A2) gene were observed, indicating that to date, these keywords have been the main research directions, highlighting a gradually reached consensus on the mechanism exploration of TRMA. In conclusion, TRMA research focuses on the mechanisms of hot topics such as diabetes, deafness, and thiamine-responsive megaloblastic anemia, and the core gene SLC19A2 research may currently become a new breakthrough point for future molecular studies.

Race explains substantial variance in whole blood thiamine diphosphate concentrations.

Deficiency for thiamine (vitamin B1), traditionally assessed via the activity of the thiamine-dependent enzyme erythrocyte transketolase, has been reported in individuals with alcohol use disorder (AUD) and in people with HIV; concentrations of the metabolically active diphosphate form, however, have yet to be reported in HIV cohorts and results in AUD are equivocal. In this cross-sectional study, samples from 170 AUD, 130 HIV, and 100 healthy control individuals were analyzed to test the hypothesis that AUD and HIV groups relative to healthy controls would show low whole blood thiamine diphosphate (TDP) concentrations related to peripheral neuropathy. TDP concentrations were not different in the 3 study groups (P = .6141) but were lower in Black (n = 172) relative to White (n = 155) individuals (P < .0001) regardless of group. In a multiple regression, race relative to diagnoses explained more than 10 times the variance in whole blood TDP concentrations (F4,395 = 3.5, P = .0086; r2 = 15.1]. Performance on a measure of peripheral neuropathy (2-point discrimination) was worse in the HIV and AUD cohorts relative to the healthy control group (P < .0001) but was not associated with TDP concentrations. These findings suggest that Black individuals carry a heightened vulnerability for low whole blood TDP concentrations, but the clinical significance and mechanisms underlying these results remain to be determined.

Neurologic complications of thiamine (B1) deficiency following bariatric surgery in adolescents.

BACKGROUND: The prevalence of obesity among children and adolescents is rising and poses a major health concern. Bariatric surgery is well established in adults and has become an option for adolescents. Thiamine (B1) deficiency is common following bariatric surgery in adults. It may present as Beri-Beri, Wernicke encephalopathy, or Korsakoff psychosis. OBJECTIVE: Our aim was to describe the clinical features, diagnosis, and treatment of adolescents who presented with B1 deficiency after bariatric surgery at one center, and to summarize the data from the literature. PATIENTS: Three adolescents with morbid obesity (two boys and one girl, aged 15.5 to- 17-years-old), presented at Schneider Children's Medical Center of Israel with progressive lower limb pain and weakness 2-3 month following a bariatric procedure (sleeve gastrectomy or narrowing of a bariatric band). The girl also had upper limb involvement and cerebellar signs. All three were non-compliant with micronutrient supplementation. After admission, they received intravenous B1 and oral multivitamin supplementation, and their symptoms improved considerably. CONCLUSIONS: Micronutrient supplementation following bariatric surgery is crucial to prevent deficiencies. In adolescents, compliance with micronutrient supplementation should be assessed before and after such surgery. Thiamine deficiency may cause polyneuropathy, among other symptoms. Treatment reduces the severity of neurological complications.

Vitamin B1 Deficiency Identified from Incidental Detection of Hyperlactatemia: A Case Report.

Introduction: Vitamin B1 deficiency poses a significant risk of impaired consciousness, with manifestations ranging from anorexia and fatigue to severe neurological and cardiovascular disturbances. Wernicke's encephalopathy, a neurological disorder stemming from vitamin B1 deficiency, presents as the triad of ophthalmoplegia, altered mental state, and cerebellar ataxia. However, these symptoms are not consistently present, complicating the diagnosis. In addition, subclinical vitamin B1 deficiency can progress unnoticed until severe complications arise. Studies indicate a high rate of undiagnosed cases, emphasizing the need for early detection and intervention. Case presentation: We present the case of a 65-year-old man in whom hyperlactatemia was incidentally detected, leading to the diagnosis of vitamin B1 deficiency. The patient, presenting with vertigo and vomiting, had been eating boxed lunches bought from convenience stores following the death of his wife 3 years earlier. Vertigo gradually improved with rest, but the persistence of hyperlactatemia prompted further investigation, revealing low vitamin B1 levels and high pyruvate levels. Treatment with dietary adjustments and supplements significantly improved his symptoms. Discussion: In this case, hyperlactatemia was found in a vertigo patient, revealing asymptomatic vitamin B1 deficiency. Elevated lactate is often linked with conditions like sepsis but can also stem from overlooked factors such as low vitamin B1 levels due to poor diet habits like consuming fried foods. Conclusion: This case highlights the importance of considering vitamin B1 deficiency in patients with unexplained hyperlactatemia, even in high-income countries. Early detection can prevent progression to the severe complications associated with Wernicke's encephalopathy. Proactive measurement of lactate levels in at-risk populations may facilitate early diagnosis and intervention, ultimately improving patient outcomes.

Stem Cell Therapy and Thiamine Deficiency-Induced Brain Damage.

Wernicke's encephalopathy (WE) is a major central nervous system disorder resulting from thiamine deficiency (TD) in which a number of brain regions can develop serious damage including the thalamus and inferior colliculus. Despite decades of research into the pathophysiology of TD and potential therapeutic interventions, little progress has been made regarding effective treatment following the development of brain lesions and its associated cognitive issues. Recent developments in our understanding of stem cells suggest they are capable of repairing damage and improving function in different maladys. This article puts forward the case for the potential use of stem cell treatment as a therapeutic strategy in WE by first examining the effects of TD on brain functional integrity and its consequences. The second half of the paper will address the future benefits of treating TD with these cells by focusing on their nature and their potential to effectively treat neurodegenerative diseases that share some overlapping pathophysiological features with TD. At the same time, some of the obstacles these cells will have to overcome in order to become a viable therapeutic strategy for treating this potentially life-threatening illness in humans will be highlighted.

Vitamin C and Thiamin Deficiencies in Patients Undergoing Laparoscopic and Robotic Gastric Band Removal.

Outcomes after adjustable gastric banding (AGB) were unsatisfactory and many devices need to be removed for dysphagia. Vitamin C and thiamin deficiency are rare conditions in industrialized countries. Patients undergoing AGB removal (90% for dysphagia) from 2021 to 2023 (laparoscopic 15 and robotic 5) were tested for vitamin C and thiamin levels. Twenty patients (8 m/12 f median aged 56 (range 33.6-79.4) were included. BMI at AGB removal was 39.7 (range 24.4-50.1) kg/m2. Only 20% of patients had normal thiamin levels, 30% had low levels, 20% were deficient, and 30% were critically low. Only 25% of patients had normal vitamin C levels, 40% had low levels, 25% were deficient, and 10% were critically low. One third of patients had HbA1c levels between 5.8 and 6.4 and 22% had levels >6.5; 60% of patients had hyperlipidemia. Adjustable gastric banding patients develop concerning rates of vitamin C and thiamin deficiency, and routine testing for levels is recommended.

Wernicke Encephalopathy After Roux-en-Y Gastric Bypass Presenting with Altered Mental Status-A Video Case Report.

Wernicke encephalopathy (WE) is a seldom encountered yet significant neuropsychiatric ailment resulting from a deficiency in thiamine (vitamin B1). While commonly linked with chronic alcoholism or insufficient dietary intake, instances of WE following bariatric and metabolic surgeries, notably laparoscopic Roux-en-Y gastric bypass (RYGB), have been sporadically documented. This case study elucidates the condition of a male patient who, 3 months after undergoing RYGB to address severe obesity, displayed abrupt alterations in mental status, swiftly ameliorated by immediate administration of intravenous high-dose thiamine.

Altered Mental Status and Cardiac Failure Due to Thiamine Deficiency in an Overweight Teen.

We describe an overweight but otherwise previously healthy 17-year-old female who presented with altered mental status and rapidly progressive weakness. She was ultimately diagnosed with Wernicke encephalopathy and wet beriberi resulting from severe thiamine deficiency. She required admission to the pediatric ICU because of hypoventilation with progressive weakness and worsening encephalopathy and was found to have impaired cardiac function as assessed by echocardiography. Her heart function and encephalopathy improved on initiation of thiamine repletion. She remained in inpatient rehabilitation for 10 months but still remained weak at discharge. Thiamine deficiency is not commonly considered in the United States as a diagnosis other than in patients with severe alcohol use disorder. However, thiamine may be depleted in as little as 2 weeks if nutrition is inadequate. In such a setting, thiamine deficiency is an important etiology to consider early in the pediatric patient with altered mentation especially because it can be readily and safely treated.

Use of Thiamine Supplementation in Pregnant Women Diagnosed With Hyperemesis Gravidarum and Wernicke Encephalopathy.

Hyperemesis gravidarum is the most common condition requiring hospital care for women during the first 20 weeks of pregnancy and may lead to malnutrition, dehydration, and vitamin deficiencies. Depletion of vitamins such as thiamine may result in the development of Wernicke encephalopathy, a severe neurological disorder that can increase the risk for mortality and morbidity for the mother and fetus. A lack of awareness regarding the relationship of hyperemesis gravidarum and Wernicke encephalopathy may result in delayed treatment and disease management. Glucose administration in the presence of thiamine deficiency may induce Wernicke encephalopathy; protocols are needed to ensure dextrose is used for women with hyperemesis gravidarum in times of prolonged vomiting and poor oral intake only after first administering thiamine. This article includes a discussion of best practices for thiamine supplementation with hyperemesis gravidarum and Wernicke encephalopathy.

Whole blood thiamine, intravenous thiamine supplementation and delirium occurrence in the intensive care unit: retrospective cohort analyses.

BACKGROUND: Thiamine di-phosphate is an essential cofactor in glucose metabolism, glutamate transformation and acetylcholinesterase activity, pathways associated with delirium occurrence. We hypothesised that a deficiency in whole blood thiamine and intravenous thiamine supplementation could impact delirium occurrence. AIM: To establish whether a deficiency in whole blood thiamine and/or intravenous thiamine supplementation within 72 h of intensive care admission is associated with delirium occurrence. METHOD: The first dataset was secondary analysis of a previous study in an intensive care unit in the Netherlands, reported in 2017. The second dataset contained consecutive intensive care admissions 2 years before (period 1: October 2014 to October 2016) and after (period 2: April 2017 to April 2019) routine thiamine supplementation was introduced within 72 h of admission. Delirium was defined as a positive Confusion Assessment Method-Intensive Care Unit score(s) in 24 h. RESULTS: Analysis of the first dataset (n = 57) using logistic regression showed no relationship between delirium and sepsis or whole blood thiamine, but a significant association with age (p = 0.014). In the second dataset (n = 3074), 15.1% received IV thiamine in period 1 and 62.6% during period 2. Hierarchical regression analysis reported reduction in delirium occurrence in the second period; this did not reach statistical significance, OR = 0.81 (95% CI 0.652-1.002); p = 0.052. CONCLUSION: No relationship was detected between whole blood thiamine and delirium occurrence on admission, at 24 and 48 h. It remains unclear whether routine intravenous thiamine supplementation during intensive care admission impacts delirium occurrence. Further prospective randomised clinical trials are needed.

Subclinical thiamine deficiency results in failed reproduction in Arctic foxes.

Thiamine deficiency can result in life-threatening physiological and neurological complications. While a thiamine-deficient diet may result in the onset of such symptoms, the presence of thiaminase - an enzyme that breaks down thiamine - is very often the cause. In such instances, thiaminase counteracts the bioavailability and uptake of thiamine, even when food-thiamine levels are adequate. Here, we report on a case of failed reproduction in seven Arctic fox (Vulpes lagopus) breeding pairs kept at a captive breeding facility, including the presentation of severe thiamine deficiency symptoms in two male foxes. Symptoms included ataxia, obtundation, truncal sway, star-gazing and visual impairment. Blood tests were inconclusive, yet symptoms resolved following treatment with a series of thiamine hydrochloride injections, thereby verifying the diagnosis. A fish-dominated feed, which for the first time had been frozen for a prolonged period, was identified as the likely source of thiaminase and subsequent deterioration in the animals' health. Symptoms in the two males arose during the annual mating period. All seven breeding pairs at the captive breeding station failed to reproduce - a phenomenon never recorded during the captive breeding facility's preceding 17-year operation. Relating our findings to peer-reviewed literature, the second part of this case report assesses how thiamine deficiency (due to thiaminase activity) likely resulted in subclinical effects that impaired the production of reproduction hormones, and thereby led to a complete breeding failure. While previous work has highlighted the potentially lethal effects of thiamine deficiency in farmed foxes, this is, to our knowledge the first study showing how subclinical effects in both males and females may inhibit reproduction in foxes in general, but specifically Arctic foxes. The findings from our case report are not only relevant for captive breeding facilities, but for the welfare and management of captive carnivorous animals in general.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

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. STUDY DESIGN: 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. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.