Refeeding Syndrome Research Articles

Advancements in Inpatient Medical Management of Malnutrition in Children and Adolescents with Restrictive Eating Disorders

There is an urgent need to identify best practices for hospital treatment of youth with malnutrition secondary to restrictive eating disorders, including anorexia nervosa (AN) and avoidant/restrictive food intake disorder (ARFID). Certain physical health complications of malnutrition, such as bradycardia, hypotension, and hypothermia, often lead to hospitalization. These acute medical complications improve with refeeding, or short-term nutritional rehabilitation, and will resolve with ongoing recovery. Historically, refeeding was approached with extreme caution, with lower calorie protocols that advanced slowly and required weeks to restore medical stability.( 1 Shamim T. Golden N.H. Arden M. Filiberto L. Shenker I.R. Resolution of vital sign instability: an objective measure of medical stability in anorexia nervosa. J Adolesc Health. 2003; 32: 73-77 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar , 2 Garber A.K. Mauldin K. Michihata N. Buckelew S.M. Shafer M.A. Moscicki A.B. Higher calorie diets increase rate of weight gain and shorten hospital stay in hospitalized adolescents with anorexia nervosa. J Adolesc Health. 2013; 53: 579-584 Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar , 3 Golden N.H. Keane-Miller C. Sainani K.L. Kapphahn C.J. Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome. J Adolesc Health. 2013; 53: 573-578 Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar ) Prolonged hospitalizations place eating disorders among the top 6 most “common and costly” pediatric mental health diagnoses.( 4 Bardach N.S. Coker T.R. Zima B.T. Murphy J.M. Knapp P. Richardson L.P. Edwall G. Mangione-Smith R. Common and costly hospitalizations for pediatric mental health disorders. Pediatrics. 2014; 133: 602-609 Crossref PubMed Scopus (150) Google Scholar ) This paper reviews current evidence on refeeding approaches for hospitalized youth with eating disorders. Recent findings suggest that high calorie refeeding is a clinically safe method of inpatient management and, more importantly, improves clinical outcomes.

63 Influence of diet and body condition on blood chemistry and body composition during the refeeding process

Starved horses with low body condition scores (BCS, < 3 out of 9) continues to be a prominent welfare concern, yet limited nutritional studies on the reconditioning process exist. The aim of this study was to determine how alternative diets affected blood chemistry panels and body composition in mature, starved (initial BCS 1 or 2) light breed horses during the refeeding process (final BCS 4, UTK IACUC 2811–1220). Horses (n = 10, 18.8 ± 2.5 y (mean ± SD), BCS 1.4 ± 0.5, 3 geldings and 6 mares, light breeds) were placed on a control diet (C; 100% digestible energy, DE, from grass hay and Purina Free Balance) or a concentrate diet (S; 50 % DE from grass hay and 50% DE from Purina Equine Senior). Diets were formulated to increase caloric intake in accordance with previously established refeeding recommendations and the NRC (2007), where horses were increased from 50% DE to 100% DE over 10 d to prevent refeeding syndrome, and then were increased up to 145% DE as needed based on weekly body weight (BW) until a BCS of 4 was reached. Weekly BW and BCS were assessed by 3 independent reviewers and plasma samples collected at each BCS increase based on reviewer average and an increase in of 16–20 kg in BW. Diet and BCS effects on blood chemistry and body composition were analyzed using generalized linear mixed models in SAS, with breed and individual animals as random effects, and mean separation using Tukey's adjustment.Significance was detected at P < 0.05 (SAS 9.4, Cary, NC). Non-normally distributed data were rank transformed as determined by Shapiro-Wilk. Of the 10 horses in the study, 3 were euthanized within 10d of enrollment due to infectious disease or colic unassociated with dietary treatment, 1 was disenrolled due to pneumonia, and the remaining 6 horses were fully reconditioned (C: n = 3, S: n = 3). Horses were recovered similarly between diet groups (change in BW: C = 46.15 ± 9.9 kg, S = 41.8 ± 14.9 kg, mean ± SD, P > 0.05). Plasma creatine kinase differed by BCS (P = 0.0007), whereas creatinine differed by both diet (P = 0.006) and BCS (P < 0.0001); however, all values were within normal limits. Lactose was lower in BCS 4 horses compared with all other scores, yet all values were also within normal ranges (P = 0.0007). Rib fat thickness was greater in BCS 4 horses (C = 0.35(0.08)mm, S = 0.38(0.20)mm, median(IQR)) than all other BCS (P = 0.001). Rump fat thickness was highest in BCS 4 horses (S = 0.36 (0.13), C = 0.30 (0.05)). Based on our findings, grass hay and complete feed concentrates can be used to successfully recover emaciated horses. Further studies would be helpful in determining optimal refeeding protocols.

Nutritional Status, Refeeding Syndrome and Some Associated Factors of Patients at COVID-19 Hospital in Vietnam.

Multisystem inflammatory syndrome is associated with COVID-19 and can result in reduced food intake, increased muscle catabolism, and electrolyte imbalance. Therefore COVID-19 patients are at high risk of being malnourished and of refeeding syndrome. The present study aimed to determine the prevalence and correlates of malnutrition and refeeding syndrome (RS) among COVID-19 patients in Hanoi, Vietnam. This prospective cohort study analyzed data from 1207 patients who were treated at the COVID-19 hospital of Hanoi Medical University (HMUH COVID-19) between September 2021 and March 2022. Nutritional status was evaluated by the Global Leadership Initiative on Malnutrition (GLIM) and laboratory markers. GLIM-defined malnutrition was found in 614 (50.9%) patients. Among those with malnutrition, 380 (31.5%) and 234 (19.4%) had moderate and severe malnutrition, respectively. The prevalence of risk of RS was 346 (28.7%). Those with severe and critical COVID symptoms are more likely to be at risk of RS compared to those with mild or moderate COVID, and having severe and critical COVID-19 infection increased the incidence of RS by 2.47 times, compared to mild and moderate disease. There was an association between levels of COVID-19, older ages, comorbidities, the inability of eating independently, hypoalbuminemia and hyponatremia with malnutrition. The proportion of COVID-19 patients who suffered from malnutrition was high. These results underscore the importance of early nutritional screening and assessment in COVID-19 patients, especially those with severe and critical infection.

Micronutrient use in critical care: Survey of clinical practice

Micronutrients, principally vitamins and minerals, play an important role both in health and in disease. Parenteral micronutrient products are commonly prescribed for critically ill patients both in line with the terms of the product's license, and for other indications where there is an underpinning physiological rationale, or precedent, for their use but little evidence. This survey sought to understand United Kingdom (UK) prescribing practice in this area. A 12-question survey was circulated to healthcare professionals working in UK critical care units. The survey was designed to explore several aspects of micronutrient prescribing or recommendation practice by the critical care multidisciplinary team, including indications and underpinning clinical rationale for using these products, dosing, and considerations with respect to micronutrients delivered as part of nutrition. Results were analysed, exploring indications, considerations relating to diagnoses, therapies including renal replacement therapies, and method of nutrition. 217 responses were included in the analysis, with 58% from physicians and the remaining 42% from nurses, pharmacists, dietitians and other healthcare disciplines. Vitamins were most commonly prescribed or recommended for Wernicke's encephalopathy (prescribed or recommended by 76% of respondents), treatment of refeeding syndrome (64.5%), and for patients with unknown or uncertain alcohol intake history (63.6%). These clinically suspected or confirmed indications were cited more frequently as a reason to prescribe than laboratory identified deficiency states. 20% of respondents indicated that they would prescribe or recommend parenteral vitamins for patients requiring renal replacement therapy. The practice of vitamin C prescribing was heterogeneous, including dose and indication. Trace elements were prescribed or recommended less often than vitamins, with the most frequently reported indications being for patients requiring parenteral nutrition (42.9%), biochemically confirmed deficiency states (35.9%), and for treatment of refeeding syndrome (26.3%). Micronutrient prescribing in ICUs in the UK is heterogeneous, with clinical scenarios where there is an evidence base or an established precedent for their use often guiding decisions to use micronutrient products. Further work to examine the potential benefits and harms on patient-oriented outcomes of micronutrient product administration should be undertaken, to facilitate their judicious and cost-effective use, with a focus on areas where they have a theoretical benefit.

Refeeding Syndrome Awareness among Physicians of King Abdullah Medical City in Makkah, Saudi Arabia.

Refeeding syndrome (RFS) is a lethal condition of metabolic disturbances that arise from the sudden switch of metabolism from a state of starvation to one of nourishment. Quick recognition would reduce health complications. Physicians who are unaware of the syndrome will not identify and treat it. As nutritional risk is associated with the risk of RFS, physicians should be aware of it. To determine whether the physicians of King Abdullah Medical City (KAMC) in Makkah know of RFS and, if so, have skills in diagnosis and managing the syndrome. One hundred and fifty-nine physicians of KAMC were recruited in a cross-sectional study. They were asked to complete a questionnaire by face-to-face interview. The questionnaire was designed to capture physicians' knowledge and ability to manage RFS based on the awarding of certain scoring points. The level of knowledge among physicians had a significant association between knowledge and age (p = 0.021) and medical specialty (p = 0.010). Additionally, the most knowledgeable physicians were those who work in critical care (21.4%). Around 18% of physicians were not able to manage RFS. Lacking knowledge of RFS and how to manage it leads to critical life-threatening complications. Physicians need nutritional education to help them diagnose RFS and consult dietitians to avoid its complications.

Mirtazapine-induced psychosis on a young patient with severe malnutrition

IntroductionMirtazapine is an antidepressant commonly prescribed to patients with depression and problems with weight and sleep. Case reports on Mirtazapine-induced psychosis either on initiation or increase in dosage in elderly patients and those with renal and liver impairment are found in the literature.ObjectivesTo present a case of Mirtazapine-induced psychosis in a patient with severe malnutrition, and with no history of psychosis and despite on sedating antipsychotic.MethodsThis is a case report.ResultsMs. NC, a 40-year-old female with major depressive disorder, anorexia nervosa, stimulant use disorder, and sedative, anxiolytic, hypnotic use disorder with no history of psychosis even when intoxicated or during withdrawal, was admitted for involuntary inpatient psychiatric care for detoxification and management of severe malnutrition. Ms. NC has always been conscious with her weight growing up but it was only during the COVID-19 pandemic that excessive preoccupation with weight and symptoms of clinical depression were noted. Ms. NC restricted her diet and engaged in excessive exercise resulting to BMI of 16.1. She started use cocaine and diazepam daily to address the weight and mood, and sleep and anxiety, respectively. Due to a suicidal attempt, consult was done with a psychiatrist, and patient was eventually maintained on Mirtazapine 30mg and Gabapentin 100mg which addressed the mood and sleep. Despite improvement in mood and decrease in use of cocaine and diazepam, patient started to use methamphetamine around once a week. Despite with euthymic mood, preoccupation with weight resurfaced. After a few months, she restricted her food intake to only four times a week with no binge-eating or purging resulting to BMI to 13.8. Upon admission, Mirtazapine 30mg was continued and Gabapentin was increased to 300mg. Special care in her food intake was done to prevent refeeding syndrome. Benzodiazepine withdrawals symptoms were minimal. She has normal values for electrolytes, liver function tests and creatinine. On the first days of admission, she was noted to be irritable and was mostly asleep. On the fifth hospital day, she started to have difficulty sleeping and was placed on Olanzapine up to 10mg and Gabapentin 600mg but no improvement in sleep. On the tenth hospital day, Mirtazapine was increased to 45mg and later in the night, had visual and auditory hallucinations and paranoia. Upon discontinuation of Mirtazapine and initiation with Clozapine up to 75mg, the psychosis resolved after five days.ConclusionsMirtazapine-induced psychosis may be seen in patients with severe malnutrition. Despite its advantages in terms of weight gain and sleep, psychiatrists should be wary of this possible side effect when initiating or increasing Mirtazapine for patients with severe malnutrition.Disclosure of InterestNone Declared

Refeeding Syndrome—Diagnostic Challenges and the Potential of Clinical Decision Support Systems.

Refeeding syndrome (RFS) can occur in malnourished patients when normal, enteral, or parenteral feeding is resumed. The syndrome often goes unrecognized and may, in the most severe cases, result in death. The diagnosis of RFS can be crucially facilitated by the use of clinical decision support systems (CDSS). The literature in PubMed was searched for current treatment recommendations, randomized intervention studies, and publications on RFS and CDSS. We also took account of insights gained from the development and implementation of our own CDSS for the diagnosis of RFS. The identification of high-risk patients and the recognition of manifest RFS is clinically challenging due to the syndrome's unspecific symptoms and physicians' lack of awareness of the risk of this condition. The literature shows that compared to patients without RFS, malnourished patients with RFS have significantly greater 6-month mortality (odds ratio 1.54, 95% confidence interval: [1.04; 2.28]) and an elevated risk of admission to intensive care (odds ratio 2.71 [1.01; 7.27]). In a prospective testing program, use of our own CDSS led to correct diagnosis in two thirds of cases. RFS is difficult to detect and represents a high risk to the patients affected. Appropriate CDSS can identify such patients and ensure proper professional care.

Development and validation of risk prediction model for refeeding syndrome in neurocritical patients.

The incidence of refeeding syndrome (RFS) in critically ill patients is high, which is detrimental to their prognoses. However, the current status and risk factors for the occurrence of RFS in neurocritical patients remain unclear. Elucidating these aspects may provide a theoretical basis for screening populations at high risk of RFS. A total of 357 patients from January 2021 to May 2022 in a neurosurgery ICU of a tertiary hospital in China were included using convenience sampling. Patients were divided into RFS and non-RFS groups, based on the occurrence of refeeding-associated hypophosphatemia. Risk factors for RFS were determined using univariate and logistic regression analyses, and a risk prediction model for RFS in neurocritical patients was developed. The Hosmer-Lemeshow test was used to determine the goodness of fit of the model, and the receiver operator characteristic curve was used to examine its discriminant validity. The incidence of RFS in neurocritical patients receiving enteral nutrition was 28.57%. Logistic regression analyses showed that history of alcoholism, fasting hours, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores, low serum albumin, and low baseline serum potassium were risk factors of RFS in neurocritical patients (p < 0.05). The Hosmer-Lemeshow test showed p = 0.616, and the area under the ROC curve was 0.791 (95% confidence interval: 0.745-0.832). The optimal critical value was 0.299, the sensitivity was 74.4%, the specificity was 77.7%, and the Youden index was 0.492. The incidence of RFS in neurocritical patients was high, and the risk factors were diverse. The risk prediction model in this study had good predictive effects and clinical utility, which may provide a reference for assessing and screening for RFS risk in neurocritical patients.

Interaction between inorganic phosphate concentration and glucose metabolism in mild refeeding syndrome model.

Refeeding syndrome is a major clinical problem that leads to fatal complications in patients suffering from malnutrition. Hypophosphatemia inevitably is observed at the onset of refeeding syndrome and therefore is monitored during refeeding; however, the causes of metabolic changes in phosphate concentration during refeeding remain poorly understood. In a previous study, we established a refeeding syndrome model employing total parenteral nutrition with insulin-induced hypophosphatemia, but the symptoms were severe and the metabolic mechanisms in this model may not have been representative of clinical conditions. Therefore, we established a new animal model of mild refeeding syndrome by using a shorter fasting period followed by a single refeeding. These mild refeeding syndrome-model rats exhibited hypophosphatemia without increases in urinary phosphate excretion. Interestingly, administration of the combination of phosphate and insulin during refeeding promoted insulin secretion during refeeding. This model implies that Pi may directly promote insulin secretion in pancreatic cells. These results clarify the interaction between phosphate and glucose metabolism pancreatic cells during refeeding syndrome in a mild refeeding syndrome model.

Re-feeding syndrome in children treated for severe acute malnutrition

Objective: To determine the prevalence of re-feeding syndrome in children treated for severe acute malnutrition (SAM). Methodology: This cross-sectional study was performed at Department of Pediatrics, King Abdullah Teaching Hospital, Mansehra, Pakistan from October 2020 to April 2021. A total of 186 children of either gender aged 1-5 years and admitted with SAM were included. Children with SAM were given F75-proxy every two hours for 2 days and then were fed with a locally made formula aimed to replace F-100 (F100-proxy), 6 times a day for a further duration of 2 days. After completing three days at the hospital, blood was drawn for measurements of blood and serum levels of phosphate, potassium, calcium and magnesium. Results: In a total of 186 children with SAM, the mean age was 3±1.21 years while 100 (53.8%) children were aged between 1-3 years. There were 146 (78.5%) boys and 40 (21.5%) girls representing a male to female ratio of 3.5:1. Re-feeding syndrome was noted among 25 (13.4%) children. Conclusion: Children with SAM were found to have high prevalence of re-feeding syndrome. Early recognition with appropriate treatment can be the key to a successful outcome in these children.

Assessment and Treatment of Eating Disorders.

Eating disorders are serious psychiatric conditions in terms of chronicity and have the highest mortality rate among psychiatric disorders. The assessment and treatment of eating disorders are also challenging, due to patients' denial of their illness and reluctance for change. Despite a large number of previous assessment and treatment studies, new strategies to overcome these difficulties are still needed. This study casts light on four aspects; involvement of the brain's reward system, stages of change in relationship with motivation, refeeding syndrome during renourishment, and gut microbiota changes relating to chronicity. Further studies relating to these aspects are encouraged.

Preterm infant nutrition: considerations for infants at risk of refeeding syndrome.

Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management.

A Clinician's View of Wernicke-Korsakoff Syndrome.

The purpose of this article is to improve recognition and treatment of Wernicke-Korsakoff syndrome. It is well known that Korsakoff syndrome is a chronic amnesia resulting from unrecognized or undertreated Wernicke encephalopathy and is caused by thiamine (vitamin B1) deficiency. The clinical presentation of thiamine deficiency includes loss of appetite, dizziness, tachycardia, and urinary bladder retention. These symptoms can be attributed to anticholinergic autonomic dysfunction, as well as confusion or delirium, which is part of the classic triad of Wernicke encephalopathy. Severe concomitant infections including sepsis of unknown origin are common during the Wernicke phase. These infections can be prodromal signs of severe thiamine deficiency, as has been shown in select case descriptions which present infections and lactic acidosis. The clinical symptoms of Wernicke delirium commonly arise within a few days before or during hospitalization and may occur as part of a refeeding syndrome. Wernicke encephalopathy is mostly related to alcohol addiction, but can also occur in other conditions, such as bariatric surgery, hyperemesis gravidarum, and anorexia nervosa. Alcohol related Wernicke encephalopathy may be identified by the presence of a delirium in malnourished alcoholic patients who have trouble walking. The onset of non-alcohol-related Wernicke encephalopathy is often characterized by vomiting, weight loss, and symptoms such as visual complaints due to optic neuropathy in thiamine deficiency. Regarding thiamine therapy, patients with hypomagnesemia may fail to respond to thiamine. This may especially be the case in the context of alcohol withdrawal or in adverse side effects of proton pump inhibitors combined with diuretics. Clinician awareness of the clinical significance of Wernicke delirium, urinary bladder retention, comorbid infections, refeeding syndrome, and hypomagnesemia may contribute to the recognition and treatment of the Wernicke-Korsakoff syndrome.

Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years

BackgroundWhether higher parenteral amino acid intake improves outcomes in infants with extremely low birth weight is unclear.MethodsIn this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned infants with birth weights of less than 1000 g at 8 neonatal intensive care units to receive amino acids at a dose of 1 g per day (intervention group) or placebo in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability as assessed with the Bayley Scales of Infant and Toddler Development and neurologic examination at 2 years, corrected for gestational age at birth. Secondary outcomes were the components of the primary outcome as well as the presence or absence of neonatal disorders, the rate of growth, and nutritional intake.ResultsWe enrolled 434 infants (217 per group) in this trial. Survival free from neurodisability was observed in 97 of 203 children (47.8%) in the intervention group and in 102 of 205 (49.8%) in the placebo group (adjusted relative risk, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.56). Death before the age of 2 years occurred in 39 of 217 children (18.0%) in the intervention group and 42 of 217 (19.4%) in the placebo group (adjusted relative risk, 0.93; 95% CI, 0.63 to 1.36); neurodisability occurred in 67 of 164 children (40.9%) in the intervention group and 61 of 163 (37.4%) in the placebo group (adjusted relative risk, 1.16; 95% CI, 0.90 to 1.50). Neurodisability was moderate to severe in 27 children (16.5%) in the intervention group and 14 (8.6%) in the placebo group (adjusted relative risk, 1.95; 95% CI, 1.09 to 3.48). More children in the intervention group than in the placebo group had patent ductus arteriosus (adjusted relative risk, 1.65; 95% CI, 1.11 to 2.46). In a post hoc analysis, refeeding syndrome occurred in 42 of 172 children in the intervention group and 26 of 166 in the placebo group (adjusted relative risk, 1.64; 95% CI, 1.09 to 2.47). Eight serious adverse events occurred.ConclusionsIn infants with extremely low birth weight, extra parenteral amino acids at a dose of 1 g per day for 5 days after birth did not increase the number who survived free from neurodisability at 2 years. (Funded by the New Zealand Health Research Council and others; ProVIDe Australian New Zealand Clinical Trials Registry number, ACTRN12612001084875.)

Hyperphosphatemia during nutrition recovery in patients with severe anorexia nervosa

IntroductionAnorexia nervosa (AN) is a disorder associated with many medical complications. Regarding phosphorus metabolism, the only recognized alteration is hypophosphatemia associated with refeeding syndrome. However, in our clinical practice, we have observed a high frequency of hyperphosphatemia in late phases of nutrition therapy in severely undernourished AN patients, which has barely been described. Materials and methodsWe carried out a retrospective study of patients with AN hospitalized for severe decompensation of the disease. ResultsEleven patients were included, all women, with a median age of 23 years [20−46] and a body mass index at admission of 12.2 kg/m2 [11.7−13.1]. Hyperphosphatemia was noted in 9 of the 11 cases (81.8%) with a median time to onset of 53 days [30−75]. The median peak serum phosphorus (P) level was 5.1 mg/dl [4.9−5.4]. An inverse relationship was found between the increase in P levels and phosphorus supplementation at the onset of admission. The magnitude of the P increase was associated with the body weight gain achieved during nutrition therapy. ConclusionLate hyperphosphatemia during nutrition therapy in severely undernourished AN patients affects more than 80% of cases. Body weight gain throughout nutrition therapy is a predictor of increased P levels.

Clinical Considerations in Specialized Nutrition in Critically III Patients

Specialized nutrition support (SNS) is required when oral intake is either limited or not possible for a prolonged period of time. Common indications for SNS include patients in critical care, those with dysphagia, unconscious patients who cannot be fed, severely malnourished patients, and those with intestinal malabsorption. The two forms of SNS are enteral nutrition and parenteral nutrition. Enteral feeding is always preferred whenever possible, but parenteral feeding may be instituted if the patient has a nonfunctional GI tract (e.g., gastroschisis, short bowel syndromes), and/or if enteral feeding is contraindicated. Patients who are on SNS may develop several complications related to feeding tubes or intravenous catheters, as well as additional metabolic complications such as electrolyte imbalances, hyperglycemia, refeeding syndrome, gallstone disease, and nonalcoholic fatty liver disease.

Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy.

A major complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS), which presents as aphasia, confusion, weakness, somnolence, seizures, and coma. This is similar to the neurologic manifestations of hypophosphatemia, which can result from sudden increases in metabolic demand for phosphorylated intermediates (e.g., refeeding syndrome and sepsis). Given these similarities, we investigated whether CAR T-cell effector metabolic activity is associated with increased extracellular phosphate consumption and a possible association between hypophosphatemia and ICANS. In vitro 4-1BB and CD28 CD19-targeted CAR T-cell effector activity was found to be associated with increased consumption of media phosphorus, which was temporally associated with increased single-cell effector secretomic activity and increased phosphorus-dependent metabolic demand of the CAR T cells. A clinical cohort of 77 patients treated with CD19-targeted CAR T-cell therapy demonstrated a significant anticorrelation between serum phosphorus and ICANS incidence and severity, with earlier onset of hypophosphatemia after CAR T-cell infusion more likely to result in neurotoxicity. These results imply phosphorous level monitoring could alert to the development of ICANS in clinical scenarios. See related Spotlight by Tobin et al., p. 1422.

S2279 Bisphosphonate-Induced Esophageal Stricture: A Situation of Unusual Severity

Introduction: Pill-induced esophageal stricture is a rare but well-documented condition associated with various causative agents. Potassium chloride and quinine are the most common causes and are more likely to produce stricture than other agents (such as Bisphosphonates and Tetracyclines). Predisposing factors include older age, male gender, sustained release medication formulation and prior esophageal structural abnormality. Case Description/Methods: An 80-year-old female with history of osteoporosis taking Alendronate presented with 3 weeks history of progressive solid and liquid dysphagia and endorsed 20 lbs weight loss. The patient reported inability to keep any food down for 3 days prior to presentation and had begun requiring the use of oral suction at bedside due to inability to swallow her own saliva. She appeared clinically stable on exam. He laboratory study showed profound electrolytes abnormality. Esophagogastroduodenoscopy (EGD) showed circumferential mid esophageal ulceration that progressed to a narrow stricture that could not be traversed even with a stricture scope (5.9 mm diameter). Alendronate was discontinued and the patient was treated with liquid formulation omeprazole twice daily. Her diet was slowly advanced from clear liquid to mince. Her hospitalization was prolonged because she developed refeeding syndrome after reinitiating her diet. She was discharged after her electrolytes normalized. Two months after her initial presentation, her dysphagia had completely resolved. A repeat EGD revealed a tapered benign-appearing stricture in the distal esophagus, which was traversed without resistance with a standard gastroscope. Balloon dilation was performed to a diameter of 13 mm without creation of a mucosal rent (Figure). Discussion: This case highlights the severity and potential rapid progression of pill-induced esophageal damage caused by Bisphosphonate therapy. Esophagitis or esophageal mucosa ulceration are common. The mucosal damage is caused by direct contact of the drug with the esophageal mucosa. Reports of stricture formation from Alendronate use are rare. Stricture formation may be caused by chronic inflammation from long-term use. Clinicians should have a low index suspicion in a high-risk patient presenting with classic symptoms of dysphagia. In addition, patients should receive counseling on proper pill ingestion technique to prevent potential damage.Figure 1.: See attachment.

The Performances of SNAQ, GLIM, mNICE, and ASPEN for Identification of Neurocritically Ill Patients at High Risk of Developing Refeeding Syndrome.

We previously found that neurocritically ill patients are prone to refeeding syndrome (RFS), a potentially life-threatening complication. However, there is no unified or validated consensus on the screening tool for RFS so far. We aimed to validate and compare the performance of four screening tools for RFS in neurocritically ill patients. We conducted a single-center, observational, retrospective cohort study among neurocritically ill adult patients who were admitted to the neurocritical care unit (NCU), and who received enteral nutrition for 72 h or longer. They were scored on the Short Nutritional Assessment Questionnaire (SNAQ), the Global Leadership Initiative on Malnutrition (GLIM), the modified criteria of the Britain’s National Institute for Health and Care Excellence (mNICE), and ASPEN Consensus Recommendations for Refeeding Syndrome (ASPEN) scales to predict RFS risk via admission data. The performance of each scale in predicting RFS was evaluated. Logistic regression analysis was used to identify the independent risk factors for RFS, and they were added to the above scales to strengthen the identification of RFS. Of the 478 patients included, 84 (17.57%) developed RFS. The sensitivity of the SNAQ and GLIM was only 20.2% (12.6–30.7%), although they had excellent specificities of 84.8% (80.8–88.1%) and 86.0% (82.1–89.2%), respectively; mNICE predicted RFS with a sensitivity of 48.8% (37.8–59.9%) and a specificity of 65.0% (60.0–69.9%); ASPEN had the highest Youden index, with a sensitivity and specificity of 53.6% (42.4–64.4%) and 64.7% (59.8–69.4%), respectively. The Area Under the receiver operating characteristic Curves (AUC) of SNAQ, GLIM, mNICE, and ASPEN to predict RFS were 0.516 (0.470–0.561), 0.533 (0.487–0.579), 0.568 (0.522–0.613), and 0.597 (0.551–0.641), respectively. We identified age, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Glasgow Coma Scale (GCS) score as independent risk factors of RFS, and the combination of GCS and age can improve the AUC of ASPEN to 0.664 (0.620–0.706) for predicting RFS. SNAQ, GLIM, mNICE, and ASPEN do not perform well in identifying neurocritically ill patients at high risk of RFS, although ASPEN appears to have relatively a good validity among them. Combining GCS and age with ASPEN slightly improves RFS recognition, but it still leaves a lot of room for improvement.

Thiamine: A Case Report on Wernicke Syndrome and Anorexia Nervosa

Anorexia nervosa (AN) is a severe eating disorder. Although Wernicke’s encephalopathy (WE) is frequently associated with alcohol abuse, non-alcoholic WE has been described in AN associated with malnutrition and refeeding syndrome. This work aims to present a case report of non-alcoholic WE associated with AN. A 27-year-old woman diagnosed with AN was admitted to the hospital for a low weight of 33 kg and body mass index of 12.9 kg/m2. The patient started a nutritional plan, and two weeks after, she presented a sudden onset of psychomotor slowing, disorganized behaviour, nocturnal enuresis and the need for feeding support. On evaluation, she also had a defect in attention and memory with confabulation. Due to the diagnostic hypothesis of metabolic encephalopathy, the patient started thiamine with progressive clinical improvement.AN carries a lethal risk associated with severe nutritional deficits and medical complications, so careful surveillance, assessment and early intervention are required.