Prolonged Fasting Research Articles

Hepatic ketogenesis is not required for starvation adaptation in mice

ObjectiveIn response to bacterial inflammation, anorexia of acute illness is protective and is associated with the induction of fasting metabolic programs such as ketogenesis. Forced feeding during the anorectic period induced by bacterial inflammation is associated with suppressed ketogenesis and increased mortality. As ketogenesis is considered essential in fasting adaptation, we sought to determine the role of ketogenesis in illness-induced anorexia. MethodsA mouse model of inducible hepatic specific deletion of the rate limiting enzyme for ketogenesis (HMG-CoA synthase 2, Hmgcs2) was used to investigate the role of ketogenesis in endotoxemia, a model of bacterial inflammation, and in prolonged starvation. ResultsMice deficient of hepatic Hmgcs2 failed to develop ketosis during endotoxemia and during prolonged fasting. Surprisingly, hepatic HMGCS2 deficiency and the lack of ketosis did not affect survival, glycemia, or body temperature in response to endotoxemia. Mice with hepatic ketogenic deficiency also did not exhibit any defects in starvation adaptation and were able to maintain blood glucose, body temperature, and lean mass compared to littermate wild-type controls. Mice with hepatic HMGCS2 deficiency exhibited higher levels of plasma acetate levels in response to fasting. ConclusionsCirculating hepatic-derived ketones do not provide protection against endotoxemia, suggesting that alternative mechanisms drive the increased mortality from forced feeding during illness-induced anorexia. Hepatic ketones are also dispensable for surviving prolonged starvation in the absence of inflammation. Our study challenges the notion that hepatic ketogenesis is required to maintain blood glucose and preserve lean mass during starvation, raising the possibility of extrahepatic ketogenesis and use of alternative fuels as potential means of metabolic compensation.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC. Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

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.

Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals

Background/objectivesProlonged fasting triggers a stress response within the human body. Our objective was to investigate the impact of prolonged fasting, in conjunction with stress, on kynurenine pathway metabolites.Subjects/methodsHealthy males were divided into fasting group (zero-calorie-restriction) for 6 days (FAST, n = 14), and control group (CON, n = 10). Blood and saliva samples were collected at baseline, Day 2, Day 4, Day 6 during fasting period, and 1 week after resuming regular diet. Plasma levels of kynurenine pathway metabolites were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Plasma and salivary samples were analyzed for stress markers.ResultsA pronounced activation of the kynurenine pathway in individuals on FAST trial was revealed. Concentrations of picolinic acid (PIC), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were significantly increased, with peak levels observed on Day 6 (P < 0.0001). Conversely, concentrations of tryptophan (TRP) and quinolinic acid (QUIN) decreased (P < 0.0001), while kynurenine (KYN) and nicotinamide (NAM) levels remained stable. Cortisol and noradrenaline concentrations remained unchanged. However, adrenaline levels significantly increased on Day 4 within FAST compared to CON (P = 0.005). Notably, all deviations in kynurenine pathway metabolite levels returned to baseline values upon resuming regular diet following the 6-day fasting regimen, even when weight and BMI parameters were not restored.ConclusionsExtended fasting over 6 days induces the kynurenine pathway and has minimal effects on stress markers. Restoration of metabolite concentrations upon regular feeding implies rapid adaptation of the kynurenine pathway synthetic enzymes to maintain homeostasis when faced with perturbations.

Exogenous Ketone Esters as a Potential Therapeutic for Treatment of Sarcopenic Obesity.

Identifying effective treatment(s) for sarcopenia and sarcopenic obesity are of paramount importance as the global population advances in age and obesity continues to be a worldwide concern. Evidence has shown that a ketogenic diet can be beneficial for preservation of muscle quality and function in older adults, but long-term adherence is low due in part to the high-fat (> 80%), very low carbohydrate (< 5%) composition of the diet. When provided in adequate amounts, exogenous ketone esters can increase circulating ketones to concentrations that exceed those observed during prolonged fasting or starvation without significant alterations in the diet. Ketone esters first emerged in the mid-1990s and their use in pre-clinical and clinical research has escalated within the past 10-15 years. We present findings from a narrative review of the existing literature for a proposed hypothesis on the effects of exogenous ketones as a therapeutic for preservation of skeletal muscle and function within the context of sarcopenic obesity and future directions for exploration. Much of the reviewed literature herein examines the mechanisms of the ketone diester (R, S-1,3-butanediol diacetoacetate) on skeletal muscle mass, muscle protein synthesis, and epigenetic regulation in murine models. Additional studies are needed to further examine the key regulatory factors producing these effects in skeletal muscle, examine convergent and divergent effects among different ketone ester formulations, and establish optimal frequency and dosing regimens to translate these findings into humans.

Preoperative Education is Associated with Adherence to Downstream Components and Outcomes in a Colorectal Surgery Enhanced Recovery Program.

This study evaluated the association between preoperative education and adherence to downstream components of enhanced recovery programs (ERPs) and surgical outcomes among patients undergoing elective colorectal surgery. ERPs improve outcomes for surgical patients. While preoperative education is an essential component of ERPs, its relationship with other components is unclear. This was a retrospective cohort study of all ERP patients undergoing elective colorectal surgery from 2019 to 2022. Our institutional ERP database was linked with American College of Surgeons National Surgical Quality Improvement Program data and stratified by adherence to preoperative education. Primary outcomes included adherence to individual ERP components and secondary outcomes included high-level ERP adherence (>70% of components), length of stay (LOS), readmissions, and 30-day complications. A total of 997 patients were included. The mean (SD) age was 56.5 (15.8) years, 686 (57.3%) were female, and 717 (71.9%) were white. On adjusted analysis, patients who received preoperative education (n = 877, 88%) had higher adherence rates for the following ERP components: no prolonged fasting (estimate = +19.6%; P < 0.001), preoperative blocks (+8.0%; P = 0.02), preoperative multimodal analgesia (+18.0%; P < 0.001), early regular diet (+15.9%; P < 0.001), and postoperative multimodal analgesia (+6.4%; P < 0.001). High-level ERP adherence was 13.4% higher (P < 0.01) and LOS was 2.0 days shorter (P < 0.001) for those who received preoperative education. Classification and regression tree analysis identified preoperative education as the first-level predictor for adherence to early regular diet, the second-level predictor for LOS, and the third-level predictor for ERP high-level adherence. Preoperative education is associated with adherence to ERP components and improved surgical outcomes.

Liberal Preoperative Fasting in Adults Undergoing Elective Surgery: A Scoping Review Protocol.

Prolonged fasting before surgery has negative effects on the physiology and psychology of patients. Preoperative liberal fasting proposes that patients can drink clear liquids before entering the operating theater, challenging the guideline strategy of a two-hour preoperative liquid fast for adults. In recent years, there have been an increasing number of studies on liberal preoperative fasting in adults. However, currently there is no consensus on the safe amount of fluid consumed, adverse effects, or benefits of this new policy. This scoping review protocol will map the existing evidence of liberal preoperative fasting in adults undergoing elective surgery for clinical practice, to summarize more scientific evidence to healthcare professionals when providing perioperative care. Methods and Analysis. The methodology will follow the six steps of the Arksey and O'Malley methodological framework and be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review. A comprehensive search of six databases will be performed from their inception to 31 May 2023 to identify suitable English studies. Two trained investigators will independently screen and extract the data, and any disagreements will be judged by a third investigator. The results of the study will be presented as graphs or tables. Ethics and Dissemination. This scoping review only examines literature in the database, without reference to human or animal studies, and therefore does not require ethical approval. The findings of this scoping review will be published in peer-reviewed journals or presented at conferences. The Registration Number. This scoping review has been registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/PMW7C).

Abstract PO1-20-10: Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity

Abstract Wernicke encephalopathy (WE) is an acute medical syndrome that manifests as a clinical triad of encephalopathy, gait ataxia, and oculomotor dysfunction, requiring urgent treatment. Early recognition and treatment can prevent severe neurological morbidity and the chronic neurological consequence of WE, known as Korsakoff syndrome. Thiamine (vitamin B1) deficiency is the root cause of WE, which can occur due to several underlying conditions, including chronic alcoholism, hyperemesis of pregnancy, malnutrition, prolonged fasting, and malignancy. In cases of malignancy, WE is often undiagnosed or misdiagnosed because the presenting symptoms can be confused with several other complications of malignancy. We present the case of a 47-year-old woman with no significant medical history who was diagnosed with triple negative metastatic breast cancer and admitted to the hospital with confusion, memory loss, and progressive lower extremity weakness. During her breast cancer treatments, she experienced significant nausea and vomiting, leading to a prolonged state of nutritional imbalance. Patient underwent extensive infectious and neurological workup for encephalopathy including lumbar puncture which was negative for leptomeningeal disease or infection. MRI brain did not show any new metastatic lesions however revealed enhancement of mammillary bodies bilaterally. Mammillary body enhancement can be seen in WE but not always present on imaging. She was treated for WE with high dose of thiamine infusion for five days, resulting in an improvement of her neurological symptoms. Diagnosing WE in cancer patients is challenging, as there are various factors to consider, such as cerebral metastasis, infection, chemotherapy treatment, and electrolyte imbalances, that can cause neurological symptoms. Cancer patients are at high risk for development of WE due to chemotherapy or whole brain radiation induced nausea and vomiting that can lead to chronic malnutrition. The typical triad of symptoms is not present in many cases and presenting symptoms can be nonspecific which makes the diagnosis challenging. As a result, WE is often underdiagnosed in such patients, making it essential to educate the physician community about this acute neurological manifestation that can be easily treated. A high index of suspicion is necessary for early recognition, and prompt treatment can prevent Korsakoff syndrome, thereby enhancing the overall quality of life of patients with malignancy. Citation Format: Archit Patel, Arya Mariam Roy, Ronald Alberico, Shipra Gandhi. Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-10.

Fasting Metabolic Profiles are Cell-Autonomous in Elephant Seal Primary Muscle Cells

Northern elephant seals ( Mirounga angustirostris) undergo prolonged terrestrial fasts during energetically intensive life stages including breeding, molting, and postnatal development. Fasting-tolerant vertebrates generally extend the second phase of fasting, during which body mass declines but homeostasis is preserved through reliance on lipid fuel sources and sparing of body protein stores. In elephant seals, the postnatal fast coincides with development of the extensive body oxygen stores required to support extended breath-hold diving, as well as an increased capacity for apnea-related metabolic suppression. Studies in grizzly bears, another large-bodied fasting-tolerant mammal, have identified both serum-derived and intrinsic cellular regulation of the adipocyte metabolic phenotype. However, it is unknown whether these mechanisms extend across species, tissue, or fasting type (active vs inactive). Thus, we derived proliferative primary skeletal muscle cells (myoblasts) from weaned elephant seal pups; biopsies that yielded cells were collected at both early (~1 week) and late (~8 weeks) points in the postnatal fast. We found that total ATP production rate was greater in myoblasts collected from animals late in the fast (27% increase over early, p=0.08). Throughout the fast, myoblasts relied predominantly on glycolytic rather than oxidative ATP production (p&lt;0.001), and this reliance increased as the fast progressed (p&lt;0.014). Together, these data suggest that metabolic reliance is at least partially cell-autonomous in elephant seal myoblasts. KNA is supported by an NSF Graduate Research Fellowship (DGE 1752814 &amp; 2146752) and a UC Berkeley Fellowship. JPV-M is supported by a NIH/NIGMS grant (R35GM146951). Research was funded by UC Berkeley startup funds and the Winkler Family Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Prolonged Fasting on Cloacal Microbiota of Crotalus durissus with Different Corporal Scores

Aims: This study provides a detailed analysis of the composition and diversity of the bacterial community within the cloacal cavity of Crotalus durissus (Cascavel) under the influence of diet and the corporal score of breeding snakes through metagenomics analysis. For this aim, the study also provides a body condition score protocol for the classification of snakes as thin, normal, and obese. Study Design: The experimental groups were established from snake body conditions such as visibility of ribs, the aspect of the side view, the upper and ventral view, and the aspect of the final portion, of the neck and square bone. Place and Duration of Study: The research was conducted at S-Inova Laboratory at Don Bosco Catholic University, between December 2017 and February 2019 (Mato Grosso do Sul, Brazil). Methodology: There are 3 groups of score corporations: thin (n=3), normal (n=3), and obese (n=3). The first sample of each animal was obtained 7 days after feeding and the second sample after 50 days of fasting. The metagenomic DNA was extracted from all 18 swab samples through DNeasy® PowerSoil® Kit (Qiagen). Thereafter the samples were submitted to sequencing, performed using the 2 x 250bp paired-end sequencing on a single run of an Illumina HiSeq, followed by the application of bioinformatics tools. Results: The most representative phyllo for all the samples was Proteobacteria (69,4%), followed by Bacteroidetes (19,2%) and Synergists (11,2%). In the group of obese snakes, the phylum Proteobacteria still being the group with the higher relative abundance in the two moments, with a decrease of 9,6%, as well as the phylum Bacteroidetes which decreased by 5,5% in the second moment (after fasting). Differently, the groups of the normal and thin have a decrease of 37,2% and 29,4% respectively of the phylum Proteobacteria and an increase of the relative abundance of 35% and 27,9% of the phylum Bacteroidetes. Before prolonged fasting the groups obtained 213 shared OTUs which reduced to 206 after the prolonged fasting, suggesting that, in general, the treatment influences microbial communities of the groups, which was possible to observe when analyzed and compared individually. The index of Shannon diversity showed that before the fasting, the groups of obese snakes and normal presented a bigger richness of species, differently from the thin group that showed more diversity after 50 days of fasting. The variance analysis showed that the obese snakes presented a bigger proximity to the samples collected before the prolonged fasting. The samples showed greater proximity in PCA analyses and ANOVA when considering the prolonged fasting time than when compared by body score. Conclusion: With this study, it was possible to conclude that prolonged fasting can influence the cloacal microbiota of the snake Crotalus durissus, except in the individuals considered obese.

Differentiating non-epileptic seizures from epileptic seizures in Glut1 deficiency syndrome.

To investigate the clinical characteristics of non-epileptic seizures due to transient brain dysfunction caused by energy deficiency after prolonged fasting or exercise in individuals with glucose transporter type 1 deficiency syndrome (Glut1DS), and then elucidate further the seizure features to distinguish non-epileptic seizures from epileptic seizures. This retrospective case-control study included 57 non-epileptic seizures and 23 epileptic seizures (control group) in 14 individuals (11 males, three females; aged 5-44 years, median = 20 years) with Glut1DS, all with a heterozygous pathogenic SLC2A1 mutation. Non-epileptic seizures were classified as paroxysmal altered consciousness (n = 8), movement disorders (n = 35) (eye-head movements, ataxia, spasticity, weakness, involuntary movement), dysaesthesia (n = 8), and vomiting (n = 6) at the peak ages at onset of 5 to 10 years. Ketogenic diet therapy was effective in 33 of 43 (77%) non-epileptic seizures. Providing supplementary food before high-impact exercise or during attacks prevented or mitigated non-epileptic seizures in some individuals. Glut1DS-associated non-epileptic seizures are fundamentally situation-related seizures with specific provoking and ameliorating factors. Non-epileptic seizures can be distinguished from epileptic seizures by the absence of complete consciousness loss and rapid postictal recovery despite prolonged seizures. Non-epileptic seizures are not well recognized but require different therapeutic approaches compared to epileptic seizures. Awareness of the differentiation of non-epileptic seizures from epileptic seizures is essential when performing preventive or therapeutic decision-making for acute exacerbation seizures. Non-epileptic seizures are invariably situation-related seizures. Non-epileptic seizures were classified as altered consciousness, movement disorders, dysaesthesia, and vomiting. Non-epileptic seizures were characterized by the absence of complete consciousness loss and were accompanied by rapid recovery. Non-epileptic seizures can occur simultaneously or consecutively with another. Supplementary food can be effective in preventing the development of sustained exercise-induced movement disorders.

Exploring the Preoperative Fasting and Perioperative Hemodynamic variability in Elective Surgery Under General Anesthesia

Background: It is usual practice all over the world to abstain from eating or drinking before surgery. Currently, the preferred protocol, according to the American Society of Anesthesiologists guidelines, is the 6-4-2 hour No Per Os protocol for solid, milk, and clear fluids respectively, although it is not universally applicable. Extended fasting may intensify negative outcomes including hemodynamic fluctuations. Hemodynamic stability stands as cornerstone in perioperative care as fluctuation can have serious consequences. This study aim was to explore current prevalence of preoperative fasting and hemodynamic fluctuations in elective surgery under general anesthesia. Methods: A six-month Cross-sectional comparative study was conducted on 200 patients at Mardan Medical Complex (MMC) approved by the Ethical Committee, Bacha Khan Medical College (BKMC) Mardan. The data was collected through patient interview in preoperative, medical records, and monitoring perioperatively. SPSS software statistical analysis was conducted using repeated measures ANOVA to assess perioperative changes in these parameters. Test statistics, including p-value were computed to determine the significance of hemodynamic variability. Results: All patients underwent prolonged fasting, with a mean fluid fasting time of 10.33 hours (SD=1.07) and an average solid fasting time of 10.34 hours (SD=1.11). There was a gradual minor drop-in heart rate (HR) from induction to the recovery phase, with statistical significance of 0.02, while no statistically significant variability in mean systolic and diastolic blood pressure was recorded. Conclusion: The study found that patients were undergoing midnight fasting, with a mean duration of 10.33 hrs. Perioperative hemodynamics showed minor decreases in heart rate from the induction to the recovery phase, with statistical significance of 0.02. Our study contributes to the ongoing discourse on preoperative fasting practices and perioperative hemodynamics.

Blood-brain barrier disruption and edema formation due to prolonged starvation in wild-type mice.

Different types of diseases have been treated by restricted caloric intake or fasting. Although during this long time, fasting protective measures, for example, supplements, are given to the patients to protect vital organs such as the liver and kidney, little attention is given to the brain. The current research aims to investigate hypoglycemia due to prolonged fasting disrupts blood-brain barrier (BBB) in mice. Immunohistochemistry (IHC) and in situ hybridization (ISH) techniques were used to examine the expression of different genes. Evans blue extravasation and wet-dry technique were performed to evaluate the integrity of BBB and the formation of brain edema, respectively. We confirmed that hypoglycemia affected mice fasting brain by examining the increased expression of glucose transporter protein 1 and hyperphosphorylation of tau protein. We subsequently found downregulated expression of some genes, which are involved in maintaining BBB such as vascular endothelial growth factor (VEGF) in astrocytes and claudin-5 (a vital component of BBB) and VEGF receptor (VEGFR1) in endothelial cells by ISH. We also found that prolonged fasting caused the brain endothelial cells to express lipocalin-2, an inflammatory marker of brain endothelial cells. We performed Evans blue extravasation to show more dye was retained in the brain of fasted mice than in control mice as a result of BBB disruption. Finally, wet-dry method showed that the brain of prolonged fasted mice contained significantly higher amount of water confirming the formation of brain edema. Therefore, special attention should be given to the brain during treatment with prolonged fasting for various diseases. Our results demonstrated that hypoglycemia due to prolonged fasting disrupts BBB and produces brain edema in wild-type mice, highlighting the importance of brain health during treatment with prolonged fasting.

Effect of Fluid Therapy in Early Morning on the Incidence of Post-Induction Hypotension During Non-Cardiac Surgery After Noon: A Single-Center Retrospective Study.

Post-induction hypotension (PIH) is a common clinical phenomenon linked to increased morbidity and mortality in various non-cardiac surgeries. Patients with surgery in the afternoon may have preoperative hypovolemia caused by prolonged fasting and dehydration, which increases the risk of hypotension during the induction period. However, studies on the fluid therapy in early morning combating PIH remain inadequate. Therefore, we aimed to investigate the influence of prophylactic high-volume fluid in the early morning of the operation day on the incidence of PIH during non-cardiac surgery after noon. We reviewed the medical records of patients who underwent non-cardiac surgery after noon between October 2021 and October 2022. The patients were divided into two groups based on whether they received a substantial volume of intravenous fluid (high-volume group) or not (low-volume group) in the early morning of the surgery day. We investigated the incidence of PIH and intraoperative hypotension (IOH) as well as the accumulated duration of PIH in the first 15 minutes. In total, 550 patients were included in the analysis. After propensity score matching, the incidence of PIH was 39.7% in the high-volume group and 54.1% in the low-volume group. Multivariate logistic regression analysis showed that patients in the high-volume group had lower incidence of hypotension after induction compared with the low-volume group (odds ratio, 0.55; 95% CI, 0.34-0.89; p = 0.016). The high-volume fluid infusion in the preoperative morning was significantly correlated with the decreased duration of PIH (p = 0.013), but no statistical difference was observed for the occurrence of IOH between the two groups (p = 0.075). The fluid therapy of more than or equal to 1000 mL in the early morning of the surgery day was associated with a decreased incidence of PIH compared with the low-volume group in patients undergoing non-cardiac surgery after noon.

549 A Nationwide Pilot Study Testing a Remotely-Delivered Prolonged Nightly Fasting Intervention in Stressed Midlife Adults Living with Obesity and Memory Decline

OBJECTIVES/GOALS: Cognitive decline is associated with obesity, stress, poor sleep, and circadian rhythm misalignment, which are themselves functionally intertwined. Irregular food intake timing exacerbates these all. Prolonged nightly fasting (PNF) aligns food intake with innate circadian rhythms. METHODS/STUDY POPULATION: A nationwide, remotely-delivered, 2-arm randomized controlled trial was conducted to assess feasibility and 8-week outcomes of cognition, stress, sleep, eating behaviors, and general eating habits, after a PNF intervention (14-hr nightly fast, 6 nights/week, no calories after 8pm) compared to a health education control (HEC) condition. Eligible participants were living with obesity, stress (Perceived stress scale-4 (PSS-4) total score ≥5), and memory “not as good as it used to be.” Data were collected via Zoom meetings with participants and trained staff and entered into REDCap. All participants had weekly staff check-in calls to report fasting times (PNF group only) and feedback. RESULTS/ANTICIPATED RESULTS: Eligible participants were enrolled from 37 of 50 US states; N=58, 86% women, 71% white, 93% non-Latinx, mean (SD) 50.1 (5.1) years of age, BMI 35.6 (3.6) kg/m^2. No group differences existed at baseline. Linear mixed-effects models were used to compare group differences across all outcome changes. Compared to the HEC condition, the PNF intervention was associated with improved sleep quality (Pittsburgh Sleep Quality Index; B = -2.52; SE = 0.90; 95% CI-4.30 to -0.74; p=0.006). Stress, everyday cognition, and emotional eating behavior significantly changed over time (p&lt;0.02), but there were no group differences. Analysis of feasibility outcomes are on-going. DISCUSSION/SIGNIFICANCE: Changing food intake timing 6 days per week, to exclude nighttime eating without mandating food quality/quantity change, may benefit many individuals living with obesity, stress and memory decline to improve their sleep. Improved sleep quality may lead to more health benefits over time.

Glucagon-Like Peptide-1 Receptor Agonists Increase Solid Gastric Residue Rates on Upper Endoscopy Especially in Patients With Complicated Diabetes: A Case-Control Study.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) prescribed for weight loss and type 2 diabetes mellitus (T2DM) can delay gastric emptying, but risk factors and impact on procedure outcomes remain unclear. We compared frequency of gastric residue on upper endoscopy in patients on a GLP-1RA and propensity score-matched controls in this retrospective case-control study of consecutive patients undergoing endoscopic procedures over a 3.5-year period. GLP-1RAs were not held before endoscopy. The gastric residue presence was assessed by reviewing endoscopy reports and images. Predictors and consequences of gastric residue with GLP-1RA were determined. In 306 GLP-1RA users compared with matched controls, rates of gastric residue were significantly higher with GLP-1RA use (14% vs 4%, P < 0.01), especially in patients with T2DM (14% vs 4%, P < 0.01), with insulin dependence (17% vs 5%, P < 0.01) and T2DM complications (15% vs 2%, P < 0.01). Lower gastric residue rates were noted after prolonged fasting and clear liquids for concurrent colonoscopy (2% vs 11%, P < 0.01) and in patients with afternoon procedures (4% vs 11%, P < 0.01). While 22% with gastric residue required intubation and 25% had early procedure termination, no procedural complications or aspiration were recorded. GLP-1RA use is associated with increased gastric residue on upper endoscopy, particularly in patients with T2DM, surpassing the impact of opiates alone. Risk is highest in the presence of T2DM complications while prolonged fasting and a clear-liquid diet are protective. This increased risk of gastric residue does not appear to translate to an increased risk of procedural complications.

Intermittent Fasting-Improved Glucose Homeostasis Is Not Entirely Dependent on Caloric Restriction in db/db Male Mice.

Intermittent fasting (IF), which involves prolonged fasting intervals accompanied by caloric restriction, is an effective dietary treatment for obesity and diabetes. Although IF offers many benefits, it is difficult to determine whether these benefits are the consequences of caloric restriction. Every-other-day feeding (EODF) is a commonly used IF research model. This study was designed to identify other effectors of EODF, in addition to caloric restriction, and the possible underlying mechanisms. Diabetic db/db mice were divided into three groups: ad libitum (AL), meal-feeding (MF) and EODF. The MF model was employed to attain a level of caloric restriction comparable to EODF, with food distribution evenly divided between 10 AM and 6 PM, thereby minimizing the fasting interval. EODF yielded greater improvements in glucose homeostasis than MF in db/db mice by reducing fasting glucose levels and enhancing glucose tolerance. However, these effects on glucose metabolism were less pronounced in lean mice. Furthermore, ubiquitination of the liverspecific glucocorticoid receptor (GR) facilitated its degradation, and downregulating Kruppel-like factor 9 (KLF9), which ultimately suppressed liver gluconeogenesis in diabetic EODF mice. Although GR and KLF9 might mediate the metabolic benefits of EODF, the potential benefits of EODF might be limited by elevated serum glucocorticoid (GC) levels in diabetic EODF mice. Overall, this study suggests that the metabolic benefits of EODF in improving glucose homeostasis are independent of caloric restriction, possibly due to the downstream effects of liver-specific GR degradation.

Design and Rationale of Prolonged Nightly Fasting for Multiple Myeloma Prevention (PROFAST): Protocol for a Randomized Controlled Pilot Trial.

Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-fasting timing with sleep-wake cycles favorably affects metabolic pathways implicated in MM. We describe the design and rationale of a randomized controlled pilot trial evaluating the efficacy of a regular, prolonged nighttime fasting schedule among individuals with overweight or obesity at high risk for developing MM or a related lymphoid malignancy. We aim to investigate the effects of 4-month prolonged nightly fasting on body composition and tumor biomarkers among individuals with overweight or obesity with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or smoldering Waldenström macroglobulinemia (SWM). Individuals with MGUS, SMM, or SWM aged ≥18 years and a BMI of ≥25 kg/m2 are randomized to either a 14-hour nighttime fasting intervention or a healthy lifestyle education control group. Participants' baseline diet and lifestyle patterns are characterized through two 24-hour dietary recalls: questionnaires querying demographic, comorbidity, lifestyle, and quality-of-life information; and wrist actigraphy measurements for 7 days. Fasting intervention participants are supported through one-on-one telephone counseling by a health coach and automated SMS text messaging to support fasting goals. Primary end points of body composition, including visceral and subcutaneous fat (by dual-energy x-ray absorptiometry); bone marrow adiposity (by bone marrow histology); and tumor biomarkers, specifically M-proteins and serum free light-chain concentrations (by gel-based and serum free light-chain assays), are assessed at baseline and after the 4-month study period; changes therein from baseline are evaluated using a repeated measures mixed-effects model that accounts for the correlation between baseline and follow-up measures and is generally robust to missing data. Feasibilityis assessed as participant retention (percent dropout in each arm) and percentage of days participants achieved a ≥14-hour fast. The PROlonged nightly FASTing (PROFAST) study was funded in June 2022. Participant recruitment commenced in April 2023. As of July 2023, six participants consented to the study. The study is expected to be completed by April 2024, and data analysis and results are expected to be published in the first quarter of 2025. PROFAST serves as an important first step in exploring the premise that prolonged nightly fasting is a strategy to control obesity and obesity-related mechanisms of myelomagenesis. In evaluating the feasibility and impact of prolonged nightly fasting on body composition, bone marrow adipose tissue, and biomarkers of tumor burden, this pilot study may generate hypotheses regarding metabolic mechanisms underlying MM development and ultimately inform clinical and public health strategies for MM prevention. ClinicalTrials.gov NCT05565638; http://clinicaltrials.gov/ct2/show/NCT05565638. DERR1-10.2196/51368.

Spontaneous Pneumomediastinum in Children: Underdiagnosis and Overtreatment

Background: Spontaneous pneumomediastinum (SPM) is a rare and benign self-limiting condition characterized by the presence of air in the mediastinum without an apparent cause. Boerhaave syndrome, on the other hand, is a rare condition caused by spontaneous esophageal perforation due to severe vomiting. The mediastinum is a complex anatomical region housing vital organs, making clinical comprehension challenging. Objectives: There is no established approach to diagnosing and treating children with SPM. Despite similarities in the presence of air in the mediastinum, SPM and Boerhaave syndrome are distinct entities. However, the primary challenge for patients is ruling out esophageal perforation. We aimed to highlight this rare issue by presenting the results of our patient series to guide further examination in pediatric patients with mediastinal air. Methods: We included twenty-four pediatric patients diagnosed with SPM between 2014 and 2022. Demographic and clinical characteristics, diagnostic procedures, treatments, and follow-up details were retrospectively recorded. Results: The mean age of the twenty male and four female patients was 14 years. Common triggers included coughing (45%), increased physical exertion (33%), and retching/vomiting (8%). All patients experienced chest pain, with additional symptoms such as dyspnea (50%), neck pain (30%), and dysphagia (12%). Symptoms resolved within two days of hospitalization. Patients were often misdiagnosed and received inappropriate treatment at other centers before being transferred to our hospital. A fluoroscopic esophagogram conducted within an average of 22 hours from admission revealed no abnormalities. Oral feeding was withheld for an average of 28 hours. The mean duration of symptom-free hospitalization without treatment was 32 hours. Conclusions: It appears that emergency department physicians may lack familiarity with pneumomediastinum. Surgeons' concerns about missing Boerhaave's syndrome may lead to unnecessary tests, prolonged fasting, and hospital stays for patients with SPM.

Enucleation of a solitary pancreatic tail insulinoma: a case report and review of the literature

Introduction: Insulinomas are the most common pancreatic neuroendocrine tumors. They secrete insulin and result in endogenous hyperinsulinaemic hypoglycemia. The diagnosis of insulinoma was classically based on the fulfillment of Whipple’s triad; hypoglycaemia (plasma glucose &lt;50mg/dL), neuroglycopaenic symptoms, and the prompt relief of such symptoms with the administration of glucose. Preoperative localization of the insulinoma will help to plan the type of surgery necessary, either enucleation or pancreatic resection, and also decide on the approach, either open or laparoscopic. Case description: A 53-year-old farmer presented with neuroglycopenia symptoms with biochemical evidence of endogenous hyperinsulinaemic hypoglycemia during the mixed meal test. Imaging evidence in the form of CT and MRI showed a benign, approximately 1cm, solitary pancreatic tail insulinoma. Intraoperative ultrasonography confirmed the findings and the patient underwent enucleation of the tumor. Histology revealed a grade 2 pancreatic neuroendocrine tumor with confirmation of an insulinoma on immunohistochemistry. Conclusion: Pancreatic insulinomas, a rare pancreatic tumor, the commonest of the pNET present with neuroglycopenia. Diagnosis entails biochemical confirmation of endogenous hyperinsulinaemic hypoglycemia on a 72-hour prolonged fasting test. Noninvasive imaging in the form of CT as the first line, followed by MRI is used for localization and assessment of resectability. EUS and ASVS are additional invasive imaging in diagnostic difficulty. Enucleation and intraoperative ultrasonography is the treatment of choice for small, benign, pancreatic insulinomas.