Contributing factors to hypophosphatemia development in critically Ill ventilated patients: a retrospective cohort study.

Hypophosphatemia (serum phosphate < 2.5 mg/dL) is a major concern when initiating nutritional support. We evaluated which factors contribute to hypophosphatemia development in critically ill patients, as well as the association between hypophosphatemia and mortality. A retrospective cohort study of patients who were ventilated for at least 2 days in a 16-bed mixed ICU. Data collected includes demographics, Acute Physiology & Chronic Health Evaluation 2 (APACHE2) admission score, Sequential Organ Failure Assessment score at 24 h (SOFA24), hourly energy delivery, plasma phosphate levels during the first 2 weeks of admission, ICU length of stay (LOS), length of ventilation (LOV), and mortality (ICU and 90 days). For the hypophosphatemia development model, we considered mortality as a competing risk. For mortality analysis, we used the Cox proportional hazards model considering hypophosphatemia development as a time-varying covariate. 462 patients were used in the analysis. 59.52% of the patients developed hypophosphatemia. Several factors were associated with a decreased risk of hypophosphatemia: age, BMI, pre-admission diabetes diagnosis, APACHE2, SOFA24, first kidney SOFA score, hospital admission time before ICU admission, and admission after liver transplantation. Admission due to trauma was associated with an increased risk of hypophosphatemia. Survival analysis with hypophosphatemia as a time-varying covariate showed a protective effect of hypophosphatemia from mortality (HR 0.447, 95% CI 0.281, 0.712). Age, APACHE2, and SOFA24 score were found to be significantly associated with ICU mortality. Fasting duration in the ICU before nutritional support initiation was not found to be significantly associated with hypophosphatemia. We examined several fasting intervals (12 h, 24 h, 36 h, 48 h, 60 h, 72 h). In each fast interval, we compared the prevalence of hypophosphatemia among patients who fasted the specified length of time, with those who did not fast for the same length of time. In each fasting interval, hypophosphatemia prevalence was lower in the fasting group compared to the non-fasting group. However, this difference was insignificant. BMI, APACHE2, and hospital LOS before ICU admission were inversely associated with hypophosphatemia development. Fasting for up to 72 h in the ICU before starting nutritional support did not affect hypophosphatemia occurrence. Hypophosphatemia was associated with lower mortality.

Risk factors for the development of refeeding syndrome in adults: A systematic review.

Identifying patients with a particularly high risk of refeeding syndrome (RFS) is essential for taking preventive measures. To guide the development of clinical decision-making and risk prediction models or other screening tools for RFS, increased knowledge of risk factors is needed. Therefore, we conducted a systematic review to identify risk factors for the development of RFS. PubMed, EMBASE, Cochrane Library, and Web of Science were searched from January 1990 until March 2023. Studies investigating demographic, clinical, drug use, laboratory, and/or nutrition factors for RFS were considered. The Newcastle-Ottawa Scale was used to appraise the methodological quality of included studies. Of 1589 identified records, 30 studies were included. Thirty-three factors associated with increased risk of RFS after multivariable adjustments were identified. The following factors were reported by two or more studies, with 0-1 study reporting null findings: a previous history of alcohol misuse, cancer, comorbid hypertension, high Acute Physiology and Chronic Health Evaluation II score, high Sequential Organ Failure Assessment score, low Glasgow coma scale score, the use of diuretics before refeeding, low baseline serum prealbumin level, high baseline level of creatinine, and enteral nutrition. The majority of the studies (20, 66.7%) were of high methodological quality. In conclusion, this systematic review informs on several risk factors for RFS in patients. To improve risk stratification and guide development of risk prediction models or other screening tools, further confirmation is needed because there were a small number of studies and a low number of high-quality studies on each factor.

Incidence and Risk Factors of Refeeding Syndrome in Preterm Infants.

This study aimed to evaluate the incidence and risk factors associated with refeeding syndrome (RFS) in preterm infants (≤32 weeks gestational age) during their first week of life. Infants (gestational age ≤ 32 weeks; birth weight < 1500 g) who were admitted to the neonatal intensive care unit (NICU), level III, and received parenteral nutrition between January 2015 and April 2024 were retrospectively evaluated. Modified log-Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the relative risk of risk factors. Of the 760 infants identified, 289 (38%) developed RFS. In the multivariable regression analysis, male, intraventricular hemorrhage (IVH), and sodium phosphate significantly affected RFS. Male infants had significantly increased RFS risk (aRR1.31; 95% CI 1.08-1.59). The RFS risk was significantly higher in infants with IVH (aRR 1.71; 95% CI 1.27-2.13). However, infants who received higher sodium phosphate in their first week of life had significantly lower RFS risk (aRR 0.67; 95% 0.47-0.98). This study revealed a notable incidence of RFS among preterm infants aged ≤32 gestational weeks, with sex, IVH, and low sodium phosphate as significant risk factors. Refined RFS diagnostic criteria and targeted interventions are needed for optimal management.

A Case of Prolonged Wernicke's Encephalopathy After Treatment With IV Thiamine Due to the Subsequent Development of Refeeding Syndrome.

Wernicke's encephalopathy (WE) is a rare, life-threatening condition in which thiamine deficiency causes dysfunction of the Kreb's cycle, accumulation of lactic acid in the brain tissues, and irreversible cognitive impairment. Prompt treatment with IV thiamine can reverse the process. The classic Wernicke's triad of ataxia, memory issues, and ocular abnormalities is not often present. Caine's criteria, which requires two of the following: dietary deficiencies, ocular abnormalities, altered cognition or mental status, and cerebellar dysfunction, is highly sensitive and specific for Wernicke's diagnosis, especially in patients with alcohol use disorder. Refeeding syndrome (RS) has similar risk factors to WE, including disease states that lead to malnutrition. Patients with RS develop WE due to thiamine depletion that occurs when oral nutrition is reinitiated after a period of poor oral intake. We present a patient with initially undetected WE who developed RS after the initiation of treatment with IV thiamine. RS prolonged the neurologic symptoms of WE and led to an extended hospital stay and significant physical debility. In our patient, WE preceded RS instead of occurring as a consequence of it. The case highlights that if one of these disorders is present, the other may not be far behind. When WE precedes RS, prolonged treatment with IV thiamine may be warranted until the symptoms of both disorders resolve.

Sex-Specific changes in stress circuitry of the nucleus tractus solitarius following food deprivation in two rat strains.

Food deprivation is used in many experimental models and is becoming increasingly prevalent in human diets. The impact of food deprivation on specific brain regions, including the nucleus of the tractus solitarius (NTS), a region that is involved in hunger and satiety sensing, remains to be determined. The NTS is a heterogeneous nucleus that includes corticotropin releasing factor receptor 1 (CRF1) neurons. CRF1 is implicated in both stress and appetite regulation, but the effects of food deprivation on CRF1 NTS neurons are unclear. We used immunofluorescence to examine the effects of 24-hour food deprivation on NTS activity in male and female Sprague-Dawley (SD) rats and CRF1-cre rats using cFos, an immediate early gene and neuronal marker of activation. NTS activity was increased in food deprived male but not female SD rats. In food deprived CRF1-cre rats, males had an increased proportion of active CRF1 + neurons with no change in females. In CRF1-cre rats, increased global NTS activity was observed in food deprived and refed males. Activation of CRF1 + neurons was also increased after deprivation but was reduced by refeeding. In females, food deprivation decreased global NTS activity that was then increased by refeeding, while CRF1 activity was unchanged. Collectively, these data suggest the NTS is differentially activated after food deprivation in a sex-specific manner, whereby males are more sensitive than females. These results provide insight into the role of brainstem stress circuitry in changes associated with conditions including intermittent fasting and eating disorders like anorexia.

Secondary carnitine deficiency during refeeding in severely malnourished patients with eating disorders: a retrospective cohort study.

BACKGROUND: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes. METHOD: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC). RESULTS: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21-35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8-14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214-0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217-0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170-40.833, p = 0.032). CONCLUSIONS: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.

Carnitine is an amino acid derivative that plays an important role in the promotion and regulation of fatty acid metabolism, and carnitine deficiency is assumed in patients with anorexia nervosa associated with chronic starvation, but there are few reports on this issue. This study represents the inaugural documentation of hypocarnitinemia in severely malnourished patients with eating disorders, including anorexia nervosa. Hypocarnitinemia, particularly in cases of severe undernutrition (BMI < 13 kg/m²) was observed during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment was considered a potential indicator of hypocarnitinemia. Although no apparent association with adverse events other than anemia during refeeding was identified, clinical manifestations of hypocarnitinemia may occur when a sudden increase in energy demand is added to a change in the physical condition of the patient group. Further investigation is required to determine the clinical significance of hypocarnitinemia.

Refeeding hypophosphatemia is a common cause of delirium in critically ill patients: A retrospective study.

BACKGROUND: The purpose was to explore the correlation between refeeding hypophosphatemia and delirium and analyze the related factors in critically ill patients. METHODS: We conducted a retrospective review of critically ill patients admitted to Nanjing Drum Tower Hospital between September 2019 and March 2021. The patients were divided into delirium and nondelirium groups. Demographic data, underlying diseases, laboratory findings, comorbidities, nutritional intake and overall prognosis were collected and analyzed. RESULTS: In total, 162 patients were included and divided into delirium (n=54) and nondelirium (n=108) groups. Serum phosphorus levels in the two groups decreased significantly in the first three days (P1, P2, P3) after nutrient intake compared with baseline before nutrient intake (Ppre). P1 and P2 were significantly lower in the delirium group compared to the nondelirium group. The maximum blood phosphorus reduction (Pmax) in the first three days after nutrient intake was significantly higher in the delirium group than in the nondelirium group. The time of Pmax in the delirium group was on the first day after nutrient intake. Multivariable logistic regression analysis identified starting route of nutrition and P1< 0.845 mmol/L as the independent predictors of delirium development in critically ill patients. CONCLUSION: The incidence of delirium in critically ill patients is high and associated with refeeding hypophosphatemia. Delirium may occur with serum phosphorus levels less than 0.845 mmol/L on the first day.

Nutritional management of hyperlipaemia in a jenny: a brief report.

An adult jenny (5-years-old, non-pregnant) was presented to the Veterinary Teaching Hospital (VTH) of the University of Sassari, with a recent history of appetite loss, extreme underweight condition and reluctance to move. On physical inspection, emaciation [body condition score, BCS: 3/9], muscular waste [muscular condition score, MCS: 1/5], loose/running faeces [faecal score, FS: 2/8], and a general state of mild dehydration were found. Blood analyses outlined a general undernourishment condition [circulating albumins, ALB: 17.6 g/L (21.6-31.6 g/L)] with underlying systemic inflammatory profile and moderate increase in circulating enzymes to explore liver function [aspartate amino-transferase, AST: 657 u/L (279-430 u/L); alanine amino-transferase ALT: 60 u/L (5-14 u/L); gamma-glutamyl-transferase, γ-GT: 87 IU/L (14-69 IU/L); total bilirubin close to the upper limit, TB: 0.20 mg/dL(0.07-0.21 mg/dL)]and hyperlipaemia [TG: 8.70 mmol/L (0.60-2.87 mmol/L)], following fat depots mobilisation, with total cholesterol closed to the lower limit of the physiological range. Hyper-phosphataemia was linked to haemolytic anaemia [P:1.81 mmol/L (0.77-1.39 mmol/L) and red blood cells, RBC: 4.14 1012/L (4.40-7.10 1012)] aligned with the TB to the upper limit. On ultrasound abdominal imaging, enlarged and hyper-echogenic liver was observed. Based on the clinical evaluation, a condition of hepatic lipidosis was diagnosed, requiring dedicated nutritional treatment to solve the extreme emaciation along with the metabolic disorder in support of medical therapy. A two-step feeding protocol was planned to support treatments aiming at immediate re-hydration (Ringer lactate solution 2 ml/kg/8 h). The nutritional objectives were meant at first to restart the voluntary feed intake. Gradual increasing energy provision through a palatable hay-based diet was planned to cover one fourth of daily metabolizable energy requirement calculated on the expected metabolic weight, adjusted according to the daily intake of feed and clinical condition. At the conclusion of this first 7-day phase, circulating blood parameters were closer to the reference values and the BCS moved from 3 to 4 out of 9. Bowel motility was restored, and faecal score improved (4/8). In the second phase, allowance to pasture and a combination diet with compound mixed feed were designed. Within four weeks of starting the nutritional plan, blood parameters were re-established to reference values. The gradual feed provision calculated in this two-phase approach proved successful in support of the overall clinical improvement observed after four weeks of treatment, in a severely undernourished jenny with compromised liver functions.

Prevalence, predictive factors, and outcomes of refeeding syndrome among medically critically ill patients: A retrospective cohort study.

BACKGROUND: Refeeding syndrome (RFS) is a life-threatening metabolic derangement occurring when nutrition is reintroduced after prolonged starvation. Limited data exist regarding RFS prevalence, risk factors, and outcome, particularly in critically ill patients. METHODS: A retrospective cohort study was conducted in a medical intensive care unit from June 2018 to August 2020. RFS diagnostic criteria from the National Institute for Health and Care Excellence (NICE) and the American Society for Parenteral and Enteral Nutrition (ASPEN) were used. The primary outcome was 30-day mortality. RESULTS: Among 216 patients, RFS was diagnosed in 22.7% and 27.3% of patients per the NICE and ASPEN criteria, respectively. There was no significant difference in 30-day mortality between patients with and without RFS (22/59 [37.3%] vs 53/157 [33.8%]; P = 0.627). Independent predictors of RFS were malignancy (odds ratio [OR] = 2.09; 95% CI = 1.06-4.15; P = 0.035), septic shock (OR = 2.26; 95% CI = 1.17-4.39; P = 0.016), and high NICE RFS risk classification (OR = 2.52; 95% CI = 1.20-5.31; P = 0.015). Factors associated with reduced RFS risk were Sequential Organ Failure Assessment (SOFA) scores >12 (OR = 0.45; 95% CI = 0.23-0.88; P = 0.020) and high-dose vasopressor treatment (OR = 0.34; 95% CI = 0.14-0.79; P = 0.012). CONCLUSION: RFS affected one-fourth of the critically ill patients but did not significantly impact 30-day mortality. Malignancy, septic shock, and high NICE RFS risk classification were positively associated with RFS, whereas high SOFA scores and extensive vasopressor use were linked to decreased risk.

Refeeding syndrome risk at ICU admission is an independent predictor of ICU readmission but it was not associated with mortality or length of stay in critically ill patients.

OBJECTIVES: This study evaluated the association between refeeding syndrome (RFS) risk and intensive care unit (ICU)/in-hospital mortality and length of stay (LOS) and ICU readmission in critically ill patients. METHODS: This secondary analysis of a cohort study included patients aged ≥ 18 years admitted at ICU 24 h before data collection. We evaluated RFS risk based on the National Institute for Health and Clinical Excellence (NICE), stratifying it into four categories (no, low, high, and very-high risk). SETTING: Five adult ICUs in Brazil. MAIN OUTCOME MEASURES: ICU/in-hospital mortality and LOS and ICU readmission data were obtained from electronic medical records analysis, following patients until discharge (alive or not). RESULTS: The study involved 447 patients, categorized into no (19.2 %), low (28.6 %), high (48.8 %), and very-high (3.4 %) RFS risk groups. No significant differences emerged between the two groups (at RFS risk and no RFS risk) regarding the ICU death ratio (34.3 % versus 23.4 %) and LOS (5 versus 4 days), respectively. In contrast, patients at RFS risk experienced higher in-hospital mortality rates (34.3 % versus 23.4 %) prolonged hospital LOS (21 days versus 17 days), and increased ICU readmission rates (15 % versus 8.4 %) than patients without RFS risk. After adjusting for age and Sequential Organ Failure Assessment (SOFA) Score, we found no association between RFS risk and increased mortality in the ICU or hospital. Also, there was no significant association between RFS risk and prolonged LOS in the ICU or hospital setting. However, patients identified as at risk of RFS showed nearly double the odds of ICU readmission (Odds ratio, 1.90; 95 % CI 1.02-3.43). CONCLUSIONS: This study found no significant association between RFS risk and increased mortality in both the ICU and hospital settings, nor was there a significant association with prolonged LOS in the ICU or hospital among critically ill patients. However, patients at risk of RFS exhibited nearly double the odds of ICU readmission. IMPLICATIONS FOR CLINICAL PRACTICE: Our findings may contribute to understanding risks associated with ICU readmissions, highlighting the complexity of discharge decision-making through comprehensive assessments.

Optimizing Recovery in Elderly Patients: Anabolic Benefits of Glucose Supplementation during the Rehydration Period.

BACKGROUND: Since many acutely admitted older adults display signs of dehydration, treatment using balanced crystalloids is an important part of medical care. Additionally, many of these patients suffer from chronic malnutrition. We speculated that the early addition of glucose might ameliorate the hospital-related drop of caloric intake and modify their catabolic status. METHODS: We included patients 78 years and older, admitted acutely for non-traumatic illnesses. The patients were randomized into either receiving balanced crystalloid (PlasmaLyte; group P) or balanced crystalloid enriched with 100 g of glucose per liter (group G). The information about fluid balance and levels of minerals were collected longitudinally. RESULTS: In the G group, a significantly higher proportion of patients developed signs of refeeding syndrome, i.e., drops in phosphates, potassium and/or magnesium when compared to group P (83.3 vs. 16.7%, p < 0.01). The drop in phosphate levels was the most pronounced. The urinalysis showed no differences in the levels of these minerals in the urine, suggesting their uptake into the cells. There were no differences in the in-hospital mortality or in the 1-year mortality. CONCLUSION: The short-term administration of balanced crystalloids with glucose induced an anabolic shift of electrolytes in acutely admitted older adults.

Nutritional Strategies for Preterm Neonates and Preterm Neonates Undergoing Surgery: New Insights for Practice and Wrong Beliefs to Uproot.

The nutrition of preterm infants remains contaminated by wrong beliefs that reflect inexactitudes and perpetuate old practices. In this narrative review, we report current evidence in preterm neonates and in preterm neonates undergoing surgery. Convictions that necrotizing enterocolitis is reduced by the delay in introducing enteral feeding, a slow advancement in enteral feeds, and the systematic control of residual gastric volumes, should be abandoned. On the contrary, these practices prolong the time to reach full enteral feeding. The length of parenteral nutrition should be as short as possible to reduce the infectious risk. Intrauterine growth restriction, hemodynamic and respiratory instability, and patent ductus arteriosus should be considered in advancing enteral feeds, but they must not translate into prolonged fasting, which can be equally dangerous. Clinicians should also keep in mind the risk of refeeding syndrome in case of high amino acid intake and inadequate electrolyte supply, closely monitoring them. Conversely, when preterm infants undergo surgery, nutritional strategies are still based on retrospective studies and opinions rather than on randomized controlled trials. Finally, this review also highlights how the use of adequately fortified human milk is strongly recommended, as it offers unique benefits for immune and gastrointestinal health and neurodevelopmental outcomes.

Characterization of adaptive expression regulation of yellowtail kingfish (Seriola lalandi) leptin, receptor, and receptor overlapping transcript genes in response to fasting and re-feeding strategies.

Leptins and other related genes have been proven to play vital roles in food intake, weight control, and other life activities. While the function of leptins in yellowtail kingfish (Seriola lalandi) has not yet been explored, in the present study, we investigated the structure and preliminary function of four leptin-related genes in S. lalandi. In detail, the sequence of two leptin genes (lepa and lepb), one leptin receptor gene (lepr), and one leptin receptor overlapping transcript (leprot) gene were obtained by homology cloning and RACE methods, in which lepa and lepb have similar structure. Moreover, homologous sequence alignment and evolutionary analysis of all four genes were clustered with Seriola dumerili. The tissue distribution of these four genes in thirteen tissues of yellowtail kingfish was detected by RT-qPCR. Both lepa and leprot were highly expressed in the brain and ovary, while lepb was highly expressed in the pituitary, gill, muscle, and ovary; lepr was highly expressed in the gill, kidney, and ovary. Additionally, these four genes also played roles in embryo development and early growth and development of larvae and juveniles of yellowtail kingfish. Finally, the function of leptin and leptin-related genes was investigated during fasting and re-feeding adaption of yellowtail kingfish. The results showed that these four genes have different regulation functions in five tissues; for example, the mRNA levels of lepa, lepr, and leprot in the brain decreased during fasting and immediately increased after re-feeding, while the mRNA level of lepb did not show significant fluctuation during starvation but significantly lowered after re-feeding. However, lepa and lepb mRNA levels were significantly elevated during fasting and returned to control levels after re-feeding, and there were no significant changes in the expression of lepr and leprot in the liver during fasting and after re-feeding. Moreover, the body mass of fish in the experimental group was measured, and compensatory growth was found after the resumption of feeding. These results suggested that leptin and receptor genes play different functions in different tissues to regulate the physiological state of fish in food deficiency and gain processes.

The incidence and mortality of refeeding syndrome in older hospitalized patients, based on three different diagnostic criteria: A longitudinal study.

BACKGROUND & AIMS: Refeeding syndrome (RFS) lacks both a global definition and diagnostic criteria. Different diagnostic criteria are used; serum phosphate (traditional criterion (TC)), the Friedli consensus recommendations, and the ASPEN. We investigated the incidence of RFS in older hospitalized patients and the mortality rates in patients with or without RFS using these three different diagnostic criteria. METHODS: This is a longitudinal study with data originating from a randomized controlled trial conducted between March 2017 and August 2019. A total of 85 malnourished hospitalized patients at risk of RFS according to the National Institute for Health and Clinical Excellence tool for detecting patients at risk of RFS, were included. All patients were provided with enteral tube feeding, and electrolytes were measured daily during the intervention period. Friedli and ASPEN included phosphate, magnesium, and potassium in their definitions, but used different cut-off values. Incidences were recorded, and Kaplan-Meier estimates were used to determine whether mortality was more prevalent in patients with RFS. Regression analysis was used to test for confounders regarding the association between RFS and death, and Kappa was used to test for agreement between the three diagnostic criteria. RESULTS: The mean (SD) age of the patients was 79.8 (7.4) years, and the mean (SD) BMI was 18.5 (3.4) kg/m2. The mean (SD) kcal/kg/day was 19 (11) on day one and 26 (15) on day seven. The incidences of RFS differed with the criteria used; 12.9% (TC), 31.8% (Friedli), and 65.9% (ASPEN). Mortality was high, with 36.5% (n = 31) and 56.5% (n = 48) of patients dead at three-month and one-year follow-up, respectively. In the TC, 8/11 (72.7%) with RFS vs. 40/74 (54.1%) without RFS died within one-year, in Friedli 15/27 (55.5%) with RFS vs. 33/58 (56.9%) without RFS died, and in ASPEN 32/56 (65.9%) with RFS, vs. 16/29 (55.2%) without RFS died within one-year. There was no statistically significant difference in mortality between patients with or without RFS regardless of which criteria were used. Age was the only variable associated with death at one-year. The Kappa analysis showed very low agreement between the categories. CONCLUSION: Our results show that using different diagnostic criteria significantly impacts incidence rates. However, regardless of criteria used, the mortality was not significantly higher in the group of patients with RFS compared to the patients without RFS. Furthermore, none of the criteria showed a significant association with death at one-year. This supports the need for a global unified diagnostic criterion for RFS. This study was registered in ClinicalTrials.gov (identifier NCT03141489).

Persistent Hypomagnesemia in the Context of Refeeding and Supplementation: A Case Report.

Refeeding syndrome is characterized by electrolyte imbalances that occur during nutritional replenishment in malnourished patients. Hypomagnesemia is a potential complication.  We present a unique case of a female, young adult patient with anorexia nervosa who experienced persistent hypomagnesemia during inpatient refeeding that did not resolve with magnesium supplementation. Extended diagnostic evaluation included genetic testing that revealed heterozygous variants of uncertain significance in the PKD1 and SCNN1G genes as well as a pathogenic variant in the SMARCAL1 gene. These variants are not currently associated with a known renal disorder.  While the extensive work-up for persistent hypomagnesemia in the context of appropriate supplementation did not yield a definitive diagnosis, this case emphasizes the need to pursue alternative etiologies and treatments of unexpectedly refractory electrolyte abnormalities during the course of refeeding.

Severe hypoglycemia with reduced liver volume as an indicator of end-stage malnutrition in patients with anorexia nervosa: a retrospective observational study.

BACKGROUND: Hypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume. METHODS: Forty-eight patients with anorexia nervosa with a body mass index (BMI) of < 13 kg/m2 were included (median BMI: 10.51 kg/m2 on admission). Liver volume was measured in 36 patients who underwent abdominal computed tomography (CT), and the "estimated liver weight/ideal body weight" was used as the liver volume index. Seventeen blood test items were analyzed during the first 60 days. RESULTS: Liver volume significantly decreased when abdominal CTs were conducted shortly before or after hypoglycemia compared to when the scans were performed during periods without hypoglycemia. Five patients with severe hypoglycemia on days 13-18 after admission had a very low nutritional intake; of them, four showed a marked decrease in liver volume. Severe hypoglycemia was accompanied by low serum triglycerides and liver dysfunction. Patients experiencing hypoglycemia of blood glucose levels < 55 mg/dL (< 3.05 mmol/L) (32 patients; median lowest BMI: 9.45 kg/m2) exhibited significantly poorer blood findings for most of the 17 items, except serum phosphorus and potassium, than did those not experiencing hypoglycemia (16 patients; median lowest BMI: 11.2 kg/m2). All patients with a poor prognosis belonged to the hypoglycemia group. Empirically, initiating re-nutrition at 500 kcal/day (20-25 kcal/kg/day), increasing to 700-800 kcal/day after a week, and then gradually escalating can reduce serious complications following severe hypoglycemia. CONCLUSIONS: Liver volume reduction accompanied by hypoglycemia, low serum triglyceride levels, and liver dysfunction occurs when the body's stored energy sources are depleted and external nutritional intake is inadequate, suggesting that the liver was consumed as a last resort to obtain energy essential for daily survival. This pathophysiology, distinct from refeeding syndrome, indicates the terminal stage of malnutrition and is a risk factor for complications and poor prognosis. In treatment, extremely low nutrient levels should be avoided.

This study aimed to clarify the pathophysiology of severe malnutrition in patients with anorexia nervosa by focusing on liver volume. The small size of the liver was almost always accompanied by hypoglycemia within a week. In several cases, extremely low nutritional intake, continued for approximately 2 weeks after admission, resulted in severe hypoglycemia and a marked decrease in liver volume. The 32 patients with hypoglycemia presented worse blood test items related to liver function, nutrition, and blood cell count compared to the 16 patients without such a condition. All cases with poor prognosis were in the hypoglycemia group. These findings suggest that severe hypoglycemia with decreased liver volume indicates the end stage of malnutrition. Liver volume reduction is considered a reflection of the liver's consumption of itself as a last resort for energy procurement for daily survival when the body's stored energy sources are depleted, and external nutritional intake is insufficient. When managing such patients, extremely low nutritional administration should be avoided.

Starvation hepatitis and refeeding-induced hepatitis: mechanism, diagnosis, and treatment.

Anorexia nervosa (AN) is one of the most common psychiatric disorders among young adults and is associated with a substantial risk of death from suicide and medical complications. Transaminase elevations are common in patients with AN at the time of hospital admission and have been associated with longer lengths of hospital stay. Multiple types of hepatitis may occur in these patients, including two types that occur only in patients with AN: starvation hepatitis and refeeding-induced hepatitis. Starvation hepatitis is characterized by severe transaminase elevation in patients in the advanced phase of protein-energy deprivation and is associated with complications of severe starvation, such as hypoglycaemia, hypothermia, and hypotension. Refeeding-induced hepatitis is characterized by a milder increase in transaminases that occurs in the early refeeding phase and is associated with hypophosphatemia, hypokalemia, and hypomagnesaemia. Among the most common forms of hepatitis, drug-induced liver injury is particularly relevant in this patient cohort, given the frequent use and abuse of methamphetamines, laxatives, antidepressants, and antipsychotics. In this review, we provided an overview of the different forms of anorexic-associated hepatitis, a diagnostic approach that can help the clinician to correctly frame the problem, and indications on their management and treatment.

Evaluation of a Novel Enteral Phosphorus Therapy with Enteral Nutrition during a National Intravenous Sodium Phosphate Shortage.

The purpose of this study was to evaluate the efficacy and safety of intragastric administration of small volumes of sodium enema solution containing phosphorus as phosphorus replacement therapy in critically ill patients with traumatic injuries who required continuous enteral nutrition. Adult patients (>17 years of age) who had a serum phosphorus concentration <3 mg/dL (0.97 mmol/L) were evaluated. Patients with a serum creatinine concentration >1.4 mg/dL (124 µmol/L) were excluded. Patients were given 20 mL of saline enema solution intragastrically, containing 34 mmol of phosphorus and mixed in 240 mL water. A total of 55% and 73% of patients who received one (n = 22) or two doses (n = 11) had an improvement in the serum phosphorus concentration, respectively. The serum phosphorus concentration increased from 2.5 [2.1, 2.8] mg/dL (0.81 [0.69, 0.90] mmol/L) to 2.9 [2.2, 3.0] mg/dL (0.94 [0.71, 0.97 mmol/L) for those who received two doses (p = 0.222). Excluding two patients with a marked decline in serum phosphorus by 1.3 mg/dL (0.32 mmol/L) resulted in an increase in the serum phosphorus concentration from 2.3 [2.0, 2.8] mg/dL (0.74 [0.65, 0.90] mmol/L) to 2.9 [2.5, 3.2] mg/dL (0.94 [0.81, 1.03] mmol/L; n = 9; p = 0.012). No significant adverse effects were noted. Our data indicated that intragastric phosphate administration using a small volume of saline enema solution improved the serum phosphorus concentrations in most patients.

LLL 44-4 : Micronutrients in acute disease and critical illness.

Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed.

Sex differences in electrolyte abnormalities indicating refeeding syndrome risk among hospitalized adolescents and young adults with eating disorders.

BACKGROUND: Refeeding syndrome is the gravest possible medical complication in malnourished patients undergoing refeeding in the hospital. We previously reported that males with malnutrition secondary to eating disorders required more calories and had longer hospital stays than females; however, sex differences in electrolyte abnormalities indicating refeeding syndrome risk remain unknown. The objective of this study was to assess differences in electrolyte abnormalities indicating refeeding syndrome risk among male and female adolescents and young adults with eating disorders hospitalized for medical instability. METHODS: We retrospectively reviewed the electronic medical records of 558 patients aged 9-25 years admitted to the University of California, San Francisco Eating Disorders Program for medical instability between May 2012 and August 2020. Serum was drawn per standard of care between 5 and 7 am each morning and electrolyte abnormalities indicating refeeding syndrome risk were defined as: hypophosphatemia (< 3.0 mg/dL), hypokalemia (< 3.5 mEq/L), and hypomagnesemia (< 1.8 mg/dL). Logistic regression was used to assess factors associated with electrolyte abnormalities indicating refeeding syndrome risk. RESULTS: Participants included 86 (15.4%) males and 472 (84.6%) females, mean (SD) age 15.5 (2.8) years. Rates of refeeding hypophosphatemia (3.5%), hypokalemia (8.1%), and hypomagnesemia (11.6%) in males hospitalized with eating disorders were low, with no statistically significant differences from females. Older age was associated with higher odds of refeeding hypophosphatemia and hypomagnesemia. Lower percent median body mass index and greater weight suppression at admission were associated with higher odds of refeeding hypophosphatemia. CONCLUSIONS: Rates of electrolyte abnormalities indicating refeeding syndrome risk were low in males hospitalized for eating disorders and rates did not significantly differ from females. Together with our finding that males have higher caloric requirements and longer hospital length of stay, the finding that electrolyte abnormalities indicating refeeding syndrome risk were not greater in males than females supports future research to evaluate the safety and efficacy of higher calorie and/or faster advancing refeeding protocols for males.