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Tang JP, Lafeuille P, Socolov A, Diamond SS, Aptekar J, Moore TB, Nie EH, Hanudel MR, Nowicki TS. Hypophosphatemia Correction Reduces ICANS Incidence and Duration in CAR T-cell Therapy: A Pooled Clinical Trial Analysis. CANCER RESEARCH COMMUNICATIONS 2024; 4:2589-2597. [PMID: 39269033 PMCID: PMC11448391 DOI: 10.1158/2767-9764.crc-24-0250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/31/2024] [Accepted: 09/09/2024] [Indexed: 09/15/2024]
Abstract
A common complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS), which presents with encephalopathy, aphasia, inattention, somnolence, seizures, weakness, or cerebral edema. Despite its significant morbidity, there are currently no effective targeted treatments. Given the clinical similarities between ICANS and the neurological manifestations of acute hypophosphatemia, we retrospectively reviewed 499 patients treated with CD19-targeted CAR T-cell therapy across multiple clinical trials between 2015 and 2020. In addition to clinical toxicities experienced by the patients, we also interrogated the impact of serum electrolyte data and repletion of corresponding electrolyte deficiencies with ICANS incidence, severity, and duration. Hypophosphatemia was a common occurrence in CAR T-cell recipients and the only electrolyte derangement associated with a significantly higher cumulative incidence of ICANS. Moreover, phosphorus repletion in patients with hypophosphatemia was associated with significantly decreased ICANS incidence and duration. Hypophosphatemia was uniquely associated with encephalopathy neurological adverse events, which also showed the strongest positive correlation with both ICANS and cytokine release syndrome severity. These findings suggest that serum phosphorus could be a reliable biomarker for ICANS, and expeditious, goal-directed phosphorus repletion in response to serum hypophosphatemia could be a safe, inexpensive, and widely available intervention for such patients. SIGNIFICANCE Herein we show that phosphorus repletion in patients with hypophosphatemia receiving anti-CD19 chimeric antigen receptor T-cell therapeutics was associated with significantly decreased immune effector cell-associated neurotoxicity syndrome (ICANS) incidence and symptom duration. Given the significant morbidity associated with ICANS and lack of targeted interventions, hypophosphatemia may serve as both a useful biomarker and an inexpensive intervention for ICANS.
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Affiliation(s)
- Jack Pengfei Tang
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
| | | | | | | | - Jacob Aptekar
- Medidata, a Dassault Systèmes Company, New York, New York.
| | - Theodore B. Moore
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
| | - Esther H. Nie
- Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, California.
| | - Mark R. Hanudel
- Division of Pediatric Nephrology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
| | - Theodore S. Nowicki
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
- Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California.
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.
- Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California.
- Molecular Biology Institute, University of California Los Angeles, Los Angeles, California.
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Utrilla Fornals A, Costas-Batlle C, Medlin S, Menjón-Lajusticia E, Cisneros-González J, Saura-Carmona P, Montoro-Huguet MA. Metabolic and Nutritional Issues after Lower Digestive Tract Surgery: The Important Role of the Dietitian in a Multidisciplinary Setting. Nutrients 2024; 16:246. [PMID: 38257141 PMCID: PMC10820062 DOI: 10.3390/nu16020246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 12/31/2023] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Many patients undergo small bowel and colon surgery for reasons related to malignancy, inflammatory bowel disease (IBD), mesenteric ischemia, and other benign conditions, including post-operative adhesions, hernias, trauma, volvulus, or diverticula. Some patients arrive in the operating theatre severely malnourished due to an underlying disease, while others develop complications (e.g., anastomotic leaks, abscesses, or strictures) that induce a systemic inflammatory response that can increase their energy and protein requirements. Finally, anatomical and functional changes resulting from surgery can affect either nutritional status due to malabsorption or nutritional support (NS) pathways. The dietitian providing NS to these patients needs to understand the pathophysiology underlying these sequelae and collaborate with other professionals, including surgeons, internists, nurses, and pharmacists. The aim of this review is to provide an overview of the nutritional and metabolic consequences of different types of lower gastrointestinal surgery and the role of the dietitian in providing comprehensive patient care. This article reviews the effects of small bowel resection on macronutrient and micronutrient absorption, the effects of colectomies (e.g., ileocolectomy, low anterior resection, abdominoperineal resection, and proctocolectomy) that require special dietary considerations, nutritional considerations specific to ostomized patients, and clinical practice guidelines for caregivers of patients who have undergone a surgery for local and systemic complications of IBD. Finally, we highlight the valuable contribution of the dietitian in the challenging management of short bowel syndrome and intestinal failure.
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Affiliation(s)
| | - Cristian Costas-Batlle
- Department of Nutrition and Dietetics, Bradford Teaching Hospitals NHS Foundation Trust, Bradford BD9 6RJ, UK;
| | | | - Elisa Menjón-Lajusticia
- Gastroenterology, Hepatology and Nutrition Unit, University Hospital San Jorge, 22004 Huesca, Spain;
| | - Julia Cisneros-González
- Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain; (J.C.-G.); (P.S.-C.)
| | - Patricia Saura-Carmona
- Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain; (J.C.-G.); (P.S.-C.)
| | - Miguel A. Montoro-Huguet
- Gastroenterology, Hepatology and Nutrition Unit, University Hospital San Jorge, 22004 Huesca, Spain;
- Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain; (J.C.-G.); (P.S.-C.)
- Department of Medicine, Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain
- Aragon Health Research Institute (IIS Aragon), University of Zaragoza, 22002 Huesca, Spain
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van Kempen TATG, Hulshof TG, Gerrits WJJ, Zijlstra RT. Review: The amazing gain-to-feed ratio of newly weaned piglets: sign of efficiency or deficiency? Animal 2023; 17:100987. [PMID: 37820408 DOI: 10.1016/j.animal.2023.100987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 08/31/2023] [Accepted: 09/07/2023] [Indexed: 10/13/2023] Open
Abstract
Shortly after weaning, piglets generally eat dry feed poorly; but nevertheless, a phenomenal gain-to-feed ratio is achieved as they gain about as much weight as they eat (150-200 g/d). The high gain-to-feed ratio, though, cannot be explained by their nutrient intake or nutrient repartitioning. Analyses based on tissue composition and bio-electrical impedance data showed that newly weaned piglets lose fat, maintain protein, and gain large amounts of water because of edema. This edema, which may well contribute up to one kg of BW, seems to be triggered by refeeding syndrome. Refeeding syndrome in adult humans occurs when subjects fast for an extended period of time (weeks) that results in downshifts in metabolic activity and concomitant shedding of phosphate (PO4), magnesium (Mg), and potassium (K) in urine. If food is abruptly reintroduced, thus, resulting in strong insulin spikes, metabolism is triggered but hampered by a lack of PO4, Mg, K, and thiamine, causing hypophosphatemia, metabolic stress, and edema. In piglets, the same process appears to happen immediately after weaning but in hours rather than weeks, possibly linked to their high metabolic rate. Refeeding syndrome can be lethal in humans but does not appear to be directly lethal in piglets. Our attempts to prevent it through altered diet composition and/or controlled feeding programs have not resulted in better performance at the end of the nursery phase. A practical ramification of weaning-induced edema is that growth and gain-to-feed ratio data immediately after weaning should be interpreted with caution. In addition, diets arguably should be formulated to not strongly trigger insulin release, while high lysine levels are not needed as the gain is not based on protein accretion.
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Affiliation(s)
- Theo A T G van Kempen
- Department of Animal Science, North Carolina State University, Raleigh, NC 27695-7621, USA.
| | | | - Walter J J Gerrits
- Animal Nutrition Group, Department of Animal Science, Wageningen University & Research, Wageningen 6700AH, the Netherlands
| | - Ruurd T Zijlstra
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Alberta, Canada
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Dock-Nascimento DB, Ribeiro AC, Silva Junior JM, de Aguilar-Nascimento JE. Impact of Nutritional Management on Survival of Critically Ill Malnourished Patients with Refeeding Hypophosphatemia. Arch Med Res 2023; 54:231-238. [PMID: 36805190 DOI: 10.1016/j.arcmed.2023.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 01/31/2023] [Accepted: 02/07/2023] [Indexed: 02/19/2023]
Abstract
BACKGROUND Early nutritional therapy may aggravate hypophosphatemia in critically ill patients. AIM To investigate the influence of the type nutritional therapy on the survival of critically-ill malnourished patients at refeeding hypophosphatemia risk. METHODS Retrospective cohort study including malnourished, critically-ill adults, admitted from June 2014-December 2017 in an intensive care unit (ICU) at a tertiary hospital. Refeeding hypophosphatemia risk was defined as low serum phosphorus levels (<2.5 mg/dL) seen at two timepoints: before the initiation and at day 4 of the nutritional therapy. Patients receiving enteral nutrition (EN) were compared with those receiving supplemental parenteral nutrition (SPN-EN plus parenteral nutrition). Primary outcome was 60 d survival. Secondary endpoint was the incidence of refeeding hypophosphatemia risk. RESULTS We included 468-321 patients (68.6%) received EN and 147 (31.4%) received SPN. The mortality rate was 36.3% (n = 170). Refeeding hypophosphatemia risk was found in 116 (24.8%) patients before and in 177 (37.8%) at day 4 of nutritional therapy. The 60 d mean survival probability was greater for patients receiving SPN both before (42.4 vs. 22.4%, p = 0.005) and at day 4 (37.4 vs. 25.8%, p = 0.014) vs. patients receiving EN at the same timepoints. Cox regression showed a hazard ratio of 3.3 and 2.4 for patients at refeeding hypophosphatemia risk before and at day 4 of EN, respectively, compared to the SPN group at the same timepoints. CONCLUSION Refeeding hypophosphatemia risk was frequent in malnourished ICU patients and the survival for patients receiving SPN seemed associated with better survival than EN only.
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Affiliation(s)
| | - Amanda Coelho Ribeiro
- Postgraduate Program in Health Sciences, Federal University of Mato Grosso Cuiabá, Brazil
| | - João Manoel Silva Junior
- Postgraduate Program in Anesthesiology of University of São Paulo, Brazil; Anesthesiology Department of Hospital do Servidor Publico Estadual, São Paulo, Brazil
| | - José Eduardo de Aguilar-Nascimento
- Postgraduate Program in Health Sciences, Federal University of Mato Grosso Cuiabá, Brazil; University Center of Várzea Grande Medical School, Cuiabá, Brazil.
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Tang JP, Peters CW, Quiros C, Wang X, Klomhaus AM, Yamada RE, Timmerman JM, Moore TB, Nowicki TS. Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy. Cancer Immunol Res 2022; 10:1433-1440. [PMID: 36259217 PMCID: PMC9722515 DOI: 10.1158/2326-6066.cir-22-0418] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/27/2022] [Accepted: 09/15/2022] [Indexed: 01/10/2023]
Abstract
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.
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Affiliation(s)
- Jack Pengfei Tang
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Cole W. Peters
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Crystal Quiros
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Xiaoyan Wang
- Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, California
| | - Alexandra M. Klomhaus
- Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, California
| | - Reiko E. Yamada
- Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, California
| | - John M. Timmerman
- Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, California
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California
| | - Theodore B. Moore
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Theodore S. Nowicki
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California
- Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California
- Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California
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Zafar M, Saddler F, Parvin J, Hennebry E, Pereira R, Austin M. Complexities of Long-Term Care With Gastro-Jejunal (GJ) Feeding Tubes and Enteral Migration During COVID-19 Pandemic Times: A Case Report. Cureus 2022; 14:e27870. [PMID: 35968246 PMCID: PMC9366242 DOI: 10.7759/cureus.27870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2022] [Indexed: 11/05/2022] Open
Abstract
Gastro-jejunostomy tubes, or percutaneous endoscopic gastrostomy tubes with jejunal extension (PEG-J), hold a significant role in the long-term nutritional management of patients with poor oral intake. This can be for a variety of reasons; ranging from metabolic conditions, including diabetes mellitus, inherited or congenital conditions like Ehler Danlos syndrome, or patients with neurological disorders, such as stroke, advanced Parkinson's disease or multiple sclerosis. Although they are very helpful for the overall nutritional needs of such patients, they are associated with complications, including the dislodging of jejunal tubes. The need to promptly recognise, investigate and manage this, in a timely manner, is vital, particularly during the COVID-19 pandemic times, as such patients may be associated with multiple comorbidities.
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Ramrattan A, Mohammed S, Rahman M. Refeeding Syndrome With Hyperemesis Gravidarum: A Case Report. Cureus 2022; 14:e27178. [PMID: 35910703 PMCID: PMC9312512 DOI: 10.7759/cureus.27178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2022] [Indexed: 11/30/2022] Open
Abstract
Refeeding syndrome refers to a clinical condition whereby biochemical abnormalities such as hypokalemia, hypomagnesemia, and mainly hypophosphatemia occur upon recommencement of feeding, typically in malnourished catabolic patients. A 36-year-old female presented at 30 weeks gestation with hyperemesis gravidarum. During this admission, the patient developed transaminitis with low platelets prompting suspicion of hemolysis, elevated liver enzymes low platelets (HELLP) syndrome, but the concurrent findings of severe hypophosphatemia and rhabdomyolysis were not in favor of HELLP syndrome but that of refeeding syndrome. These clinical entities proved to be a diagnostic dilemma but, ultimately, the patient was managed under refeeding syndrome. The multidisciplinary approach amongst gastroenterology, internal medicine, obstetrics, hematology, and dietetics departments led to the slowing up of the titration of caloric feeds, which ultimately led to full recovery.
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Florea DA, Grumezescu V, Bîrcă AC, Vasile BȘ, Mușat M, Chircov C, Stan MS, Grumezescu AM, Andronescu E, Chifiriuc MC. Design, Characterization, and Antibacterial Performance of MAPLE-Deposited Coatings of Magnesium Phosphate-Containing Silver Nanoparticles in Biocompatible Concentrations. Int J Mol Sci 2022; 23:ijms23147910. [PMID: 35887261 PMCID: PMC9321465 DOI: 10.3390/ijms23147910] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/15/2022] [Accepted: 07/16/2022] [Indexed: 01/21/2023] Open
Abstract
Bone disorders and traumas represent a common type of healthcare emergency affecting men and women worldwide. Since most of these diseases imply surgery, frequently complicated by exogenous or endogenous infections, there is an acute need for improving their therapeutic approaches, particularly in clinical conditions requiring orthopedic implants. Various biomaterials have been investigated in the last decades for their potential to increase bone regeneration and prevent orthopedic infections. The present study aimed to develop a series of MAPLE-deposited coatings composed of magnesium phosphate (Mg3(PO4)2) and silver nanoparticles (AgNPs) designed to ensure osteoblast proliferation and anti-infective properties simultaneously. Mg3(PO4)2 and AgNPs were obtained through the cooling bath reaction and chemical reduction, respectively, and then characterized through X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Selected Area Electron Diffraction (SAED). Subsequently, the obtained coatings were evaluated by Infrared Microscopy (IRM), Fourier-Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (SEM). Their biological properties show that the proposed composite coatings exhibit well-balanced biocompatibility and antibacterial activity, promoting osteoblasts viability and proliferation and inhibiting the adherence and growth of Staphylococcus aureus and Pseudomonas aeruginosa, two of the most important agents of orthopedic implant-associated infections.
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Affiliation(s)
- Denisa Alexandra Florea
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
| | - Valentina Grumezescu
- National Institute for Lasers, Plasma and Radiation Physics, 409 Atomistilor Street, 077125 Magurele, Romania;
| | - Alexandra Cătălina Bîrcă
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
| | - Bogdan Ștefan Vasile
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
| | - Mihaela Mușat
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
| | - Cristina Chircov
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
| | - Miruna S. Stan
- Research Institute of the University of Bucharest (ICUB), University of Bucharest, 050657 Bucharest, Romania;
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
| | - Alexandru Mihai Grumezescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
- Research Institute of the University of Bucharest (ICUB), University of Bucharest, 050657 Bucharest, Romania;
- Academy of Romanian Scientists, Ilfov No. 3, 050044 Bucharest, Romania;
| | - Ecaterina Andronescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, 011061 Bucharest, Romania; (D.A.F.); (A.C.B.); (B.Ș.V.); (M.M.); (C.C.); (A.M.G.)
- Academy of Romanian Scientists, Ilfov No. 3, 050044 Bucharest, Romania;
- Correspondence:
| | - Mariana Carmen Chifiriuc
- Academy of Romanian Scientists, Ilfov No. 3, 050044 Bucharest, Romania;
- Department of Microbiology, Faculty of Biology, University of Bucharest, Aleea Portocalelor Str. 1-3, District 5, 060101 Bucharest, Romania
- The Romanian Academy, Calea Victoriei 25, District 1, 010071 Bucharest, Romania
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Farooq A, Hernandez L, Swain SM, Shahid RA, Romac JMJ, Vigna SR, Liddle RA. Initiation and severity of experimental pancreatitis are modified by phosphate. Am J Physiol Gastrointest Liver Physiol 2022; 322:G561-G570. [PMID: 35293263 PMCID: PMC9054345 DOI: 10.1152/ajpgi.00022.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/28/2022] [Accepted: 03/09/2022] [Indexed: 01/31/2023]
Abstract
Proper mitochondrial function and adequate cellular ATP are necessary for normal pancreatic protein synthesis and sorting, maintenance of intracellular organelles and enzyme secretion. Inorganic phosphate is required for generating ATP and its limited availability may lead to reduced ATP production causing impaired Ca2+ handling, defective autophagy, zymogen activation, and necrosis, which are all features of acute pancreatitis. We hypothesized that reduced dietary phosphate leads to hypophosphatemia and exacerbates pancreatitis severity of multiple causes. We observed that mice fed a low-phosphate diet before the induction of pancreatitis by either repeated caerulein administration or pancreatic duct injection as a model of pressure-induced pancreatitis developed hypophosphatemia and exhibited more severe pancreatitis than normophosphatemic mice. Pancreatitis severity was significantly reduced in mice treated with phosphate. In vitro modeling of secretagogue- and pressure-induced pancreatic injury was evaluated in isolated pancreatic acini using cholecystokinin and the mechanoreceptor Piezo1 agonist, Yoda1, under low and normal phosphate conditions. Isolated pancreatic acini were more sensitive to cholecystokinin- and Yoda1-induced acinar cell damage and mitochondrial dysfunction under low-phosphate conditions and improved following phosphate supplementation. Importantly, even mice on a normal phosphate diet exhibited less severe pancreatitis when treated with supplemental phosphate. Thus, hypophosphatemia sensitizes animals to pancreatitis and phosphate supplementation reduces pancreatitis severity. These appear to be direct effects of phosphate on acinar cells through restoration of mitochondrial function. We propose that phosphate administration may be useful in the treatment of acute pancreatitis.NEW & NOTEWORTHY Impaired ATP synthesis disrupts acinar cell homeostasis and is an early step in pancreatitis. We report that reduced phosphate availability impairs mitochondrial function and worsens pancreatic injury. Phosphate supplementation improves mitochondrial function and protects against experimental pancreatitis, raising the possibility that phosphate supplementation may be useful in treating pancreatitis.
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Affiliation(s)
- Ahmad Farooq
- Department of Medicine, Duke University, Durham, North Carolina
| | | | - Sandip M Swain
- Department of Medicine, Duke University, Durham, North Carolina
| | - Rafiq A Shahid
- Department of Medicine, Duke University, Durham, North Carolina
| | | | - Steven R Vigna
- Department of Medicine, Duke University, Durham, North Carolina
| | - Rodger A Liddle
- Department of Medicine, Duke University, Durham, North Carolina
- Veterans Affairs Health Care System, Durham, North Carolina
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Hypophosphatemia Is More Common and Is Prognostic of Poorer Outcomes in Severe Alcoholic Pancreatitis. Pancreas 2021; 50:1440-1444. [PMID: 35041345 DOI: 10.1097/mpa.0000000000001952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The aim of this study was to determine if hypophosphatemia is more common in patients with severe alcohol-induced acute pancreatitis (AAP). METHODS This is a retrospective, single institution, cohort study that analyzed 147 patients admitted to the hospital for AAP. Multivariate logistic regression was used to determine if hypophosphatemia would be related to clinical outcomes of disease severity. RESULTS Hypophosphatemia was more common in patients with severe AAP at admission; in addition, all patients with severe AAP (100%) eventually developed hypophosphatemia during admission, relative to those with mild (43%) and moderately severe (54%) AAP. The magnitude of the lowest phosphate measurement obtained during admission was lower in patients with severe AAP (mean, 1.5 mg/dL, standard deviation [SD], 0.5 mg/dL) relative to those with mild (mean, 2.6 mg/dL; SD, 0.9 mg/dL) and moderately severe (mean, 2.3 mg/dL; SD, 0.9 mg/dL) AAP (P < 0.001). Finally, patients who developed hypophosphatemia during admission were more likely to require intensive care unit admission (P < 0.001), vasopressors (P = 0.01), or intubation (P = 0.003). CONCLUSIONS Hypophosphatemia is more common and of greater magnitude in patients admitted to the hospital with severe AAP. In addition, patients with severe AAP who develop hypophosphatemia during admission are more likely to have poorer clinical outcomes.
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11
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Sobhy E, Kader RA, Aboulfotouh A, Eshra M, Sayed M. Associations of measured resting energy expenditure with predictive equations, NUTRIC score, and patient outcomes. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2021; 33:35. [PMID: 34690491 PMCID: PMC8520770 DOI: 10.1186/s43162-021-00060-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 06/26/2021] [Indexed: 11/12/2022] Open
Abstract
Background Indirect calorimetry is the reference method for measuring resting energy expenditure (REE), but the necessary equipment and technical expertise are not always available. Meanwhile, the NUTrition Risk in the Critically ill (NUTRIC) scale is designed to identify patients who would benefit from nutrition therapy, but no data are available regarding the association of NUTRIC scores with REE. Several predictive formulas are available as alternatives to indirect calorimetry for calculation of energy requirements, but they have not been compared in a homogeneous group of critically ill patients. The purpose of the study is to examine the correlations between energy expenditure and NUTRIC scores or patient outcomes, and to compare measured REE with estimations of energy expenditure. Methods In this observational, prospective study, indirect calorimetry was performed on 50 mechanically ventilated patients. Energy expenditure was also estimated with the bodyweight-based, Faisy–Fagon, and Penn-State PSUm equations. Results REE was higher in patients who survived treatment than in those who died, and was positively correlated with length of stay and duration of ventilation. NUTRIC scores did not correlate with REE. The Faisy–Fagon equation overestimated expenditure, whereas PSUm was unbiased and accurate. Calculations based on 25 kcal/kg bodyweight/day overestimated expenditure, whereas 23 kcal/kg/day produced unbiased estimates with greater accuracy than PSUm. Conclusion REE was positively associated with patient outcomes. Energy expenditure was accurately predicted by calculations of 23 kcal/kg bodyweight/day.
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Affiliation(s)
- Elham Sobhy
- Internal Medicine Department, KasrAlainy Cairo University, Cairo, Egypt
| | - Radwa Abdel Kader
- Internal Medicine Department, KasrAlainy Cairo University, Cairo, Egypt
| | | | - Mohammed Eshra
- Physiology Department, KasrAlainy Cairo University, Cairo, Egypt
| | - Mohamed Sayed
- Internal Medicine Department, KasrAlainy Cairo University, Cairo, Egypt.,Giza, Egypt
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12
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Farooq A, Richman CM, Swain SM, Shahid RA, Vigna SR, Liddle RA. The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis. Gastroenterology 2021; 161:982-995.e2. [PMID: 34051238 PMCID: PMC8380702 DOI: 10.1053/j.gastro.2021.05.048] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 05/05/2021] [Accepted: 05/20/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Heavy alcohol consumption is a common cause of acute pancreatitis; however, alcohol abuse does not always result in clinical pancreatitis. As a consequence, the factors responsible for alcohol-induced pancreatitis are not well understood. In experimental animals, it has been difficult to produce pancreatitis with alcohol. Clinically, alcohol use predisposes to hypophosphatemia, and hypophosphatemia has been observed in some patients with acute pancreatitis. Because of abundant protein synthesis, the pancreas has high metabolic demands, and reduced mitochondrial function leads to organelle dysfunction and pancreatitis. We proposed, therefore, that phosphate deficiency might limit adenosine triphosphate synthesis and thereby contribute to alcohol-induced pancreatitis. METHODS Mice were fed a low-phosphate diet (LPD) before orogastric administration of ethanol. Direct effects of phosphate and ethanol were evaluated in vitro in isolated mouse pancreatic acini. RESULTS LPD reduced serum phosphate levels. Intragastric administration of ethanol to animals maintained on an LPD caused severe pancreatitis that was ameliorated by phosphate repletion. In pancreatic acinar cells, low-phosphate conditions increased susceptibility to ethanol-induced cellular dysfunction through decreased bioenergetic stores, specifically affecting total cellular adenosine triphosphate and mitochondrial function. Phosphate supplementation prevented ethanol-associated cellular injury. CONCLUSIONS Phosphate status plays a critical role in predisposition to and protection from alcohol-induced acinar cell dysfunction and the development of acute alcohol-induced pancreatitis. This finding may explain why pancreatitis develops in only some individuals with heavy alcohol use and suggests a potential novel therapeutic approach to pancreatitis. Finally, an LPD plus ethanol provides a new model for studying alcohol-associated pancreatic injury.
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Affiliation(s)
- Ahmad Farooq
- Department of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Courtney M Richman
- School of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Sandip M Swain
- Department of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Rafiq A Shahid
- Department of Pathology, Brown University, Providence, Rhode Island
| | - Steven R Vigna
- Department of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Rodger A Liddle
- Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Veterans Affairs Health Care System, Durham, North Carolina.
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13
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Improda N, Mazzeo F, Rossi A, Rossi C, Improda FP, Izzo A. Severe hypercalcemia associated with hypophosphatemia in very premature infants: a case report. Ital J Pediatr 2021; 47:155. [PMID: 34233724 PMCID: PMC8264973 DOI: 10.1186/s13052-021-01104-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 06/06/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Severe hypercalcemia is rare in newborns; even though often asymptomatic, it may have important sequelae. Hypophosphatemia can occur in infants experiencing intrauterine malnutrition, sepsis and early high-energy parenteral nutrition (PN) and can cause severe hypercalcemia through an unknown mechanism. Monitoring and supplementation of phosphate (PO4) and calcium (Ca) in the first week of life in preterm infants are still debated. CASE PRESENTATION We report on a female baby born at 29 weeks' gestation with intrauterine growth retardation (IUGR) experiencing sustained severe hypercalcemia (up to 24 mg/dl corrected Ca) due to hypophosphatemia while on phosphorus-free PN. Hypercalcemia did not improve after hyperhydration and furosemide but responded to infusion of PO4. Eventually, the infant experienced symptomatic hypocalcaemia (ionized Ca 3.4 mg/dl), likely exacerbated by contemporary infusion of albumin. Subsequently, a normalization of both parathyroid hormone (PTH) and alkaline phosphatase (ALP) was observed. CONCLUSIONS Although severe hypercalcemia is extremely rare in neonates, clinicians should be aware of the possible occurrence of this life-threatening condition in infants with or at risk to develop hypophosphatemia. Hypophosphatemic hypercalcemia can only be managed with infusion of PO4, with strict monitoring of Ca and PO4 concentrations.
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Affiliation(s)
- Nicola Improda
- Department of Translational Medical Sciences, Section of Pediatrics, Federico II University of Naples, Naples, Italy. .,Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples "Federico II", Via S. Pansini, 5, 80131, Naples, Italy.
| | - Francesca Mazzeo
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, Italy
| | - Alessandro Rossi
- Department of Translational Medical Sciences, Section of Pediatrics, Federico II University of Naples, Naples, Italy
| | - Claudia Rossi
- Department of Ophthalmology, Umberto I Hospital, Nocera Inferiore, Italy
| | | | - Angelo Izzo
- Neonatal Intensive Care Unit, Malzoni Medical Center, Avellino, Italy
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14
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Olsen SU, Hesseberg K, Aas AM, Pripp AH, Ranhoff AH, Bye A. A comparison of two different refeeding protocols and its effect on hand grip strength and refeeding syndrome: a randomized controlled clinical trial. Eur Geriatr Med 2021; 12:1201-1212. [PMID: 34086194 DOI: 10.1007/s41999-021-00520-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/19/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE Optimal refeeding protocols in older malnourished hospital patients remain unclear. We aimed to compare the effect of two different refeeding protocols; an assertive and a cautious protocol, on HGS, mortality and refeeding syndrome (RFS), in patients ≥ 65 years METHODS: Patients admitted under medical or surgical category and at risk of RFS, were randomized to either an enteral nutrition (EN) refeeding protocol of 20 kcal/kg/day, reaching energy goals within 3 days (intervention group), or a protocol of 10 kcal/kg/day, reaching goals within 7 days (control group). Primary outcome was the difference in hand grip strength (HGS) at 3 months follow-up, in an intention to treat analysis. RFS (phosphate < 0.65 mmol/L) during the hospital stay and mortality rates at 3 months were secondary outcomes. RESULTS A total of 85 patients were enrolled, with mean (SD) age of 79.8(7.4) and 54.1% female, 41 in the intervention group and 44 in the control group. HGS was similar at 3 months with mean change of 0.42 kg (95% CI - 2.52 to 3.36, p = 0.78). Serum phosphate < 0.65 mmol/L was seen in 17.1% in the intervention group and 9.3% in the control group, p = 0.29. There was no difference in mortality rates (39% vs 34.1%, p = 0.64). An indication of more respiratory distress was found in the intervention group, 53.6% vs 30.2%, p = 0.029. CONCLUSION A more assertive refeeding protocol providing 20 kcal/kg/day did not result in improved HGS measured 3 months after discharge compared with a cautious refeeding (10 kcal/kg/day) protocol. No difference in incidence of mortality or RFS was found. TRIAL REGISTRATION ClinicalTrials.gov Protocol Record 2017/FO148295, Registered: 21st of February, 2017.
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Affiliation(s)
- Sissel Urke Olsen
- Department of Clinical Dietetics, Diakonhjemmet Hospital, Oslo, Norway.
| | - Karin Hesseberg
- Department of Physiotherapy, Diakonhjemmet Hospital, Oslo, Norway
| | - Anne-Marie Aas
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Are Hugo Pripp
- Faculty of Health Sciences, Oslo Metropolitan University (OsloMet), Oslo, Norway
| | - Anette Hylen Ranhoff
- Department of Clinical Science, University of Bergen, 7804, Bergen, Norway.,Medical Department, Diakonhjemmet Hospital, Bergen, Oslo, Norway
| | - Asta Bye
- Department of Nursing and Health Promotion, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.,Regional Advisory Unit for Palliative Care, Department of Oncology, Oslo University Hospital, Oslo, Norway
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15
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Refeeding syndrome occurs among older adults regardless of refeeding rates: A systematic review. Nutr Res 2021; 91:1-12. [PMID: 34130206 DOI: 10.1016/j.nutres.2021.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 05/01/2021] [Accepted: 05/11/2021] [Indexed: 11/22/2022]
Abstract
Refeeding syndrome is a life-threatening clinical disorder that can occur when treating malnutrition. The aim was to examine the current knowledge of refeeding syndrome in patients ≥ 65 + years with special focus on the incidence of hypophosphatemia (HP) in relation to refeeding rate (kcal/kg/day), number of days until the lowest level of phosphate occurs (day of nadir), refeeding rates and adverse events, and death. Specifically, we hypothesized that higher energy provision would cause a higher incidence of HP. A search was conducted in the available databases. Two cohort studies, 1 case control, and a total of 12 case series/case reports, which accounted for 19 individual patient cases, were eligible. The incidence of HP (<0.5 mmol/L) was 15% and 25% in the 2 cohort studies and 4% in the case control study. The mean day of nadir was between days 2 and 3 in the cohort studies, day 11 in the case control study, and day 3 in the cases series/case reports. Importantly, a rapid drop in phosphate occurred receiving both 30 kcal/kg/day and 8 to 10 kcal/kg/day. The cohort studies reported high death rates-26% and 23%-using both 10 and 20 kcal/kg/day, respectively. Adverse events were noted in most all case series/case reports. Clinicians should be aware that HP may occur in up to 25% of older hospitalized adults, and importantly, it occurs even when refeeding cautiously. Hence, electrolytes should be closely monitored, especially between days 2 and 4, which is when the day of nadir occurs most frequently.
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16
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Koumakis E, Cormier C, Roux C, Briot K. The Causes of Hypo- and Hyperphosphatemia in Humans. Calcif Tissue Int 2021; 108:41-73. [PMID: 32285168 DOI: 10.1007/s00223-020-00664-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 01/20/2020] [Indexed: 12/11/2022]
Abstract
Phosphate homeostasis involves several major organs that are the skeleton, the intestine, the kidney, and parathyroid glands. Major regulators of phosphate homeostasis are parathormone, fibroblast growth factor 23, 1,25-dihydroxyvitamin D, which respond to variations of serum phosphate levels and act to increase or decrease intestinal absorption and renal tubular reabsorption, through the modulation of expression of transcellular transporters at the intestinal and/or renal tubular level. Any acquired or genetic dysfunction in these major organs or regulators may induce hypo- or hyperphosphatemia. The causes of hypo- and hyperphosphatemia are numerous. This review develops the main causes of acquired and genetic hypo- and hyperphosphatemia.
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Affiliation(s)
- Eugénie Koumakis
- Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Reference Center for Rare Genetic Bone Disorders, OSCAR Filière, Rheumatology Department, Cochin Hospital, AP-HP Centre-Paris University, 27 Rue du Faubourg Saint-Jacques, 75014, Paris, France.
| | - Catherine Cormier
- Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Reference Center for Rare Genetic Bone Disorders, OSCAR Filière, Rheumatology Department, Cochin Hospital, AP-HP Centre-Paris University, 27 Rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Christian Roux
- Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Reference Center for Rare Genetic Bone Disorders, OSCAR Filière, Rheumatology Department, Cochin Hospital, AP-HP Centre-Paris University, 27 Rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Karine Briot
- Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Reference Center for Rare Genetic Bone Disorders, OSCAR Filière, Rheumatology Department, Cochin Hospital, AP-HP Centre-Paris University, 27 Rue du Faubourg Saint-Jacques, 75014, Paris, France
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17
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Whitelaw M, Nagata JM. Nutritional Considerations for Boys and Men with Eating Disorders. EATING DISORDERS IN BOYS AND MEN 2021:137-147. [DOI: 10.1007/978-3-030-67127-3_11] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Ribeiro AC, Dock-Nascimento DB, Silva JM, Caporossi C, Aguilar-Nascimento JED. Hypophosphatemia and risk of refeeding syndrome in critically ill patients before and after nutritional therapy. ACTA ACUST UNITED AC 2020; 66:1241-1246. [PMID: 33027452 DOI: 10.1590/1806-9282.66.9.1241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 02/26/2020] [Indexed: 01/28/2023]
Abstract
OBJECTIVE To investigate the prevalence of hypophosphatemia as a marker of refeeding syndrome (RFS) before and after the start of nutritional therapy (NT) in critically ill patients. METHODS Retrospective cohort study including 917 adult patients admitted at the intensive care unit (ICU) of a tertiary hospital in Cuiabá-MT/Brasil. We assessed the frequency of hypophosphatemia (phosphorus <2.5mg/dl) as a risk marker for RFS. Serum phosphorus levels were measured and compared at admission (P1) and after the start of NT (P2). RESULTS We observed a significant increase (36.3%) of hypophosphatemia and, consequently, a greater risk of RFS from P1 to P2 (25.6 vs 34.9%; p<0.001). After the start of NT, malnourished patients had a greater fall of serum phosphorus. Patients receiving NT had an approximately 1.5 times greater risk of developing RFS (OR= 1.44 95%CI 1.10-1,89; p= 0.01) when compared to those who received an oral diet. Parenteral nutrition was more associated with hypophosphatemia than either enteral nutrition (p=0,001) or parenteral nutrition supplemented with enteral nutrition (p=0,002). CONCLUSION The frequency of critically ill patients with hypophosphatemia and at risk for RFS on admission is high and this risk increases after the start of NT, especially in malnourished patients and those receiving parenteral nutrition.
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Affiliation(s)
- Amanda Coelho Ribeiro
- Nutricionista, Mestre em Ciências da Saúde pelo Programa de Pós-Graduação em Ciências da Saúde da Universidade Federal de Mato Grosso, Cuiabá, MT, Brasil
| | - Diana Borges Dock-Nascimento
- Nutricionista, Professor Doutor Associado II, Faculdade de Nutrição da UFMT, Departamento de Alimentos e Nutrição em Cuiabá-MT. Professor orientador do Programa de Pós-Graduação em Ciências da Saúde da Universidade Federal de Mato Grosso, Cuiabá, MT, Brasil
| | - João Manoel Silva
- Médico, Professor orientador do Programa de Pós-Graduação em Anestesiologia da Universidade de São Paulo, São Paulo, SP, Brasil.,Componente do corpo clínico do Hospital Israelita Albert Einstein, São Paulo, SP, Brasil
| | - Cervantes Caporossi
- Médico, Professor Doutor do Programa de Pós-Graduação em Ciências da Saúde da Universidade Federal de Mato Grosso, Cuiabá, MT, Brasil
| | - José Eduardo de Aguilar-Nascimento
- Médico, Professor Doutor do Programa de Pós-Graduação em Ciências da Saúde da Universidade Federal de Mato Grosso, Cuiabá, MT, Brasil.,Diretor do Curso de Medicina do Centro Universitário de Várzea Grande (Univag), Várzea Grande, MT, Brasil
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19
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Jordaan A, de Freitas D, Hurst H, Alderdice J, Curwell J, Brenchley P, Hutchison A, Summers A. Malnutrition and Refeeding Syndrome Associated with Encapsulating Peritoneal Sclerosis. Perit Dial Int 2020. [DOI: 10.1177/089686080702700125] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- A. Jordaan
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - D.G. de Freitas
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - H. Hurst
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - J. Alderdice
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - J. Curwell
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - P.E.C. Brenchley
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - A.J. Hutchison
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
| | - A.M. Summers
- Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester, United Kingdom
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20
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Otero-Asman JR, Quesada JM, Jim KK, Ocampo-Sosa A, Civantos C, Bitter W, Llamas MA. The extracytoplasmic function sigma factor σ VreI is active during infection and contributes to phosphate starvation-induced virulence of Pseudomonas aeruginosa. Sci Rep 2020; 10:3139. [PMID: 32081993 PMCID: PMC7035377 DOI: 10.1038/s41598-020-60197-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 02/07/2020] [Indexed: 12/27/2022] Open
Abstract
The extracytoplasmic function sigma factor σVreI of the human pathogen Pseudomonas aeruginosa promotes transcription of potential virulence determinants, including secretion systems and secreted proteins. Its activity is modulated by the VreR anti-σ factor that inhibits the binding of σVreI to the RNA polymerase in the absence of a (still unknown) inducing signal. The vreI-vreR genes are expressed under inorganic phosphate (Pi) starvation, a physiological condition often encountered in the host that increases P. aeruginosa pathogenicity. However, whether or not σVreI is active in vivo during infection and contributes to the Pi starvation-induced virulence of this pathogen has not been analyzed yet. Using zebrafish embryos and a human alveolar basal epithelial cell line as P. aeruginosa hosts, we demonstrate in this work that σVreI is active during infection and that lack of σVreI considerably reduces the Pi starvation-induced virulence of this pathogen. Surprisingly, lack of the σVreI inhibitor, the VreR anti-σ factor, also diminishes the virulence of P. aeruginosa. By transcriptomic analyses we show that VreR modulates gene expression not only in a σVreI-dependent but also in a σVreI-independent manner. This includes potential virulence determinants and transcriptional regulators that could be responsible for the reduced virulence of the ΔvreR mutant.
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Affiliation(s)
- Joaquín R Otero-Asman
- Department of Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, Granada, Spain
| | - José M Quesada
- Department of Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, Granada, Spain
| | - Kin K Jim
- Department of Medical Microbiology and Infection Control, Amsterdam University medical centers, location VU University, Amsterdam, The Netherlands
| | - Alain Ocampo-Sosa
- Service of Microbiology, Hospital Universitario Marqués de Valdecilla-Instituto de Investigación Sanitaria Valdecilla, Santander, Spain
| | - Cristina Civantos
- Department of Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, Granada, Spain
| | - Wilbert Bitter
- Department of Medical Microbiology and Infection Control, Amsterdam University medical centers, location VU University, Amsterdam, The Netherlands
| | - María A Llamas
- Department of Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, Granada, Spain.
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Abstract
Clinical nutrition is emerging as a major area in gastroenterology practice. Most gastrointestinal disorders interfere with digestive physiology and compromise nutritional status. Refeeding syndrome (RS) may increase morbidity and mortality in gastroenterology patients. Literature search using the keywords "Refeeding Syndrome", "Hypophosphatemia", "Hypomagnesemia" and "Hypokalemia". Data regarding definition, pathophysiology, clinical manifestations, risk factors, management and prevention of RS were collected. Most evidence comes from case reports, narrative reviews and scarse observational trials. RS results from the potentially fatal shifts in fluid and electrolytes that may occur in malnourished patients receiving nutritional therapy. No standard definition is established and epidemiologic data is lacking. RS is characterized by hypophosphatemia, hypomagnesemia, hypokalemia, vitamin deficiency and abnormal glucose metabolism. Oral, enteral and parenteral nutrition may precipitate RS. Awareness and risk stratification using NICE criteria is essential to prevent and manage malnourished patients. Nutritional support should be started using low energy replacement and thiamine supplementation. Correction of electrolytes and fluid imbalances must be started before feeding. Malnourished patients with inflammatory bowel disease, liver cirrhosis, chronic intestinal failure and patients referred for endoscopic gastrostomy due to prolonged dysphagia present high risk of RS, in the gastroenterology practice. RS should be considered before starting nutritional support. Preventive measures are crucial, including fluid and electrolyte replacement therapy, vitamin supplementation and use of hypocaloric regimens. Gastroenterology patients must be viewed as high risk patients but the impact of RS in the outcome is not clearly defined in current literature.
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22
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Tatsumi S, Katai K, Kaneko I, Segawa H, Miyamoto KI. NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating inorganic phosphate. Pflugers Arch 2018; 471:109-122. [PMID: 30218374 DOI: 10.1007/s00424-018-2204-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 08/29/2018] [Accepted: 09/06/2018] [Indexed: 12/18/2022]
Abstract
The solute carrier 34 (SLC34) family of membrane transporters is a major contributor to Pi homeostasis. Many factors are involved in regulating the SLC34 family. The roles of the bone mineral metabolism factors parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) in Pi homeostasis are well studied. Intracellular Pi is thought to be involved in energy metabolism, such as ATP production. Under certain conditions of altered energy metabolism, plasma Pi concentrations are affected by the regulation of a Pi shift into cells or release from the tissues. We recently investigated the mechanism of hepatectomy-related hypophosphatemia, which is thought to involve an unknown phosphaturic factor. Hepatectomy-related hypophosphatemia is due to impaired nicotinamide adenine dinucleotide (NAD) metabolism through its effects on the SLC34 family in the liver-kidney axis. The oxidized form of NAD, NAD+, is an essential cofactor in various cellular biochemical reactions. Levels of NAD+ and its reduced form NADH vary with the availability of dietary energy and nutrients. Nicotinamide phosphoribosyltransferase (Nampt) generates a key NAD+ intermediate, nicotinamide mononucleotide, from nicotinamide and 5-phosphoribosyl 1-pyrophosphate. The liver, an important organ of NAD metabolism, is thought to release metabolic products such as nicotinamide and may control NAD metabolism in other organs. Moreover, NAD is an important regulator of the circadian rhythm. Liver-specific Nampt-deficient mice and heterozygous Nampt mice have abnormal daily plasma Pi concentration oscillations. These data indicate that NAD metabolism in the intestine, liver, and kidney is closely related to Pi metabolism through the SLC34 family. Here, we review the relationship between the SLC34 family and NAD metabolism based on our recent studies.
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Affiliation(s)
- Sawako Tatsumi
- Department of Molecular Nutrition, Institution of Biomedical Science, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.,Department of Food Science and Nutrition, School of Human Cultures, The University of Shiga Prefecture, Hikone, Japan
| | - Kanako Katai
- Faculty of Human Life and Science, Department of Food Science and Nutrition, Doshisha Women's College of Liberal Arts, Kyoto, Japan
| | - Ichiro Kaneko
- Department of Molecular Nutrition, Institution of Biomedical Science, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
| | - Hiroko Segawa
- Department of Molecular Nutrition, Institution of Biomedical Science, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
| | - Ken-Ichi Miyamoto
- Department of Molecular Nutrition, Institution of Biomedical Science, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
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23
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Araujo Castro M, Vázquez Martínez C. The refeeding syndrome. Importance of phosphorus. Med Clin (Barc) 2018; 150:472-478. [PMID: 29448987 DOI: 10.1016/j.medcli.2017.12.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 11/25/2017] [Accepted: 12/02/2017] [Indexed: 11/29/2022]
Abstract
Refeeding syndrome (RS) is a complex disease that occurs when nutritional support is initiated after a period of starvation. The hallmark feature is the hypophosphataemia, however other biochemical abnormalities like hypokalaemia, hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are common. The incidence of RS is unknown as no universally accepted definition exists, but it is frequently underdiagnosed. RS is a potentially fatal, but preventable, disorder. The identification of patients at risk is crucial to improve their management. If RS is diagnosed, there is one guideline (NICE 2006) in place to help its treatment (but it is based on low quality of evidence). The aims of this review are: highlight the importance of this problem in malnourished patients, discuss the pathophysiology and clinical characteristics, with a final series of recommendations to reduce the risk of the syndrome and facilitate the treatment.
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Affiliation(s)
- Marta Araujo Castro
- Servicio de Endocrinología y Nutrición, Hospital Universitario Rey Juan Carlos, Madrid, España.
| | - Clotilde Vázquez Martínez
- Servicio de Endocrinología y Nutrición, Hospital Universitario Fundación Jiménez Díaz, Madrid, España
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A Dialysis Patient With Hyperphosphatemia, Hyperkalemia, and Azotemia Without an Excessive Intake. Kidney Int Rep 2017; 2:770-773. [PMID: 29142992 PMCID: PMC5678649 DOI: 10.1016/j.ekir.2017.02.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Coulden AE, Rickard LJ, Crooks N, Arora N. Phosphate replacement in the critically ill: potential implications for military patients. J ROY ARMY MED CORPS 2017; 164:112-115. [PMID: 29025961 DOI: 10.1136/jramc-2017-000843] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 09/20/2017] [Accepted: 09/22/2017] [Indexed: 11/03/2022]
Abstract
BACKGROUND Severe hypophosphataemia in the intensive care unit (ICU) setting has been widely associated with adverse clinical outcomes across multiple organ systems, as well as increased mortality. However, the clinical significance of mild or moderate hypophosphataemia remains uncertain. This can lead to heterogeneous phosphate replacement protocols across different institutions. The aim of this study was to assess the significance of mild and moderate hypophosphataemia on clinical outcomes across several organ systems. METHOD All patients over a 3-week period in our ICU were retrospectively analysed with admission serum phosphate compared with subsequent clinical outcomes after admission. Low serum phosphate (0.3-1.0 mmol/L), according to local protocol, was compared with normal serum phosphate (>1.0 mmol/L). RESULTS Of the 72 patients admitted to intensive therapy unit during this period, 14/72 (19%) had phosphate levels deemed low (<1.0 mmol/L) and received phosphate supplementation. No significant difference was found between groups in terms of cardiac arrhythmias (p=0.55), capillary blood glucose (p=0.08) and serum lactate (p=0.32). Low phosphate (0.3-1.0 mmol/L) was not associated with increased likelihood of requiring ventilation. Platelet count was significantly lower in the low phosphate group (p=0.008). CONCLUSION In our study, mild and moderate hypophosphataemia was not associated with adverse clinical outcome across most organ systems analysed. Given the current evidence and results of this study, we would suggest that there is a trend towards over-replacement of phosphate, representing a potential clinical safety issue as well as clear financial implications.
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Affiliation(s)
- A E Coulden
- Intensive Care, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - L J Rickard
- Intensive Care, Heart of England NHS Foundation Trust, Birmingham, UK
| | - N Crooks
- Intensive Care, Heart of England NHS Foundation Trust, Birmingham, UK
| | - N Arora
- Intensive Care, Heart of England NHS Foundation Trust, Birmingham, UK
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Bernard AC, Magnuson B, Tsuei BJ, Swintosky M, Barnes S, Kearney PA. Defining and Assessing Tolerance in Enteral Nutrition. Nutr Clin Pract 2017; 19:481-6. [PMID: 16215143 DOI: 10.1177/0115426504019005481] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Nutrition support has become widely recognized as an essential component of optimal care for acutely ill patients. Enteral nutrition is preferred over parenteral routes when possible. However, prescribed enteral nutritional regimens are sometimes met with side effects and even complications. These adverse events have been collectively termed "intolerance," and forms of intolerance occur in a spectrum from bothersome at least to life threatening when most severe. Here we discuss nutritional access and its maintenance, introduce and define intolerance, and then review the current literature with regard to principal forms of enteral nutrition intolerance.
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Affiliation(s)
- Andrew C Bernard
- Section on Trauma and Surgical Critical Care, Department of Surgery, C224 Division of General Surgery, University of Kentucky College of Medicine, 800 Rose Street, Lexington, Kentucky 40536-0298, USA.
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Abstract
Hypophosphatemia is a potentially life-threatening complication of reinstating nutrition in a malnourished patient. Refeeding syndrome is a term that refers to various metabolic abnormalities that may complicate carbohydrate administration in subnourished patient populations. Hypophosphatemia is the most well-known, and perhaps most significant, element of the refeeding syndrome and may result in sudden death, rhabdomyolysis, red cell dysfunction, and respiratory insufficiency. This review briefly examines refeeding-induced hypophosphatemia in the hospitalized patient in hopes of making clinicians more aware of this common, but often overlooked, potentially dangerous problem.
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Mena Nannig P, Cubillos Celis MP, Toro Jara C, Zuñiga Vergara C. Perfil bioquímico en sangre de cordón en prematuros extremos y crecimiento fetal. ACTA ACUST UNITED AC 2016; 87:250-4. [DOI: 10.1016/j.rchipe.2015.11.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 11/03/2015] [Accepted: 11/05/2015] [Indexed: 11/28/2022]
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Leitner M, Burstein B, Agostino H. Prophylactic Phosphate Supplementation for the Inpatient Treatment of Restrictive Eating Disorders. J Adolesc Health 2016; 58:616-20. [PMID: 26774639 DOI: 10.1016/j.jadohealth.2015.12.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Revised: 11/01/2015] [Accepted: 12/03/2015] [Indexed: 10/22/2022]
Abstract
PURPOSE The medical stabilization of adolescent patients with restrictive eating disorders can be associated with refeeding syndrome, a potentially fatal complication preceded by refeeding hypophosphatemia (RH). Whether RH can be prevented by routine prophylactic phosphate supplementation has not been previously examined. This study sought to determine the safety and efficacy of a refeeding strategy that incorporates prophylactic phosphate supplementation to prevent RH. METHODS Retrospective chart data were collected for patients aged younger than 18 years with restrictive eating disorders admitted to a tertiary pediatric inpatient ward between January 2011 and December 2014. All patients were refed with a standardized protocol that included prophylactic oral phosphate supplementation (1.0 ± .2 mmol/kg/day). RESULTS During the 4-year study period, 75 admissions (70 patients) were included for analysis. The mean age and percent median body mass index of included patients were 15.3 years and 83.5%, respectively. Seven out of 75 (9%) had percent median body mass index of <70% and 26 out of 75 (35%) had percent body weight loss >20%. All patients were normophosphatemic at the time of admission (mean serum phosphate 1.24 ± .2 mmol/L). Serial laboratory evaluation revealed that all supplemented patients maintained serum phosphate levels >1.0 mmol/L during the initial 7 days of refeeding. Eleven patients became mildly hyperphosphatemic (range 1.81-2.17 mmol/L) with no associated clinical consequences. Additional analysis of 11 patients presenting with hypophosphatemia before refeeding revealed that with supplementation, phosphate values normalized by Day 1, and this group experienced no further RH episodes during initial refeeding. CONCLUSIONS Prophylactic oral phosphate supplementation appears safe, and no episodes of RH occurred in patients with restrictive eating disorders undergoing inpatient refeeding.
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Affiliation(s)
- Maya Leitner
- Division of Adolescent Medicine, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada
| | - Brett Burstein
- Division of Pediatric Emergency Medicine, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada
| | - Holly Agostino
- Division of Adolescent Medicine, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
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Norris ML. Phosphate Supplementation During Refeeding of Hospitalized Adolescents With Anorexia Nervosa-Watch and Wait or Empirically Treat. J Adolesc Health 2016; 58:593-4. [PMID: 27210006 DOI: 10.1016/j.jadohealth.2016.03.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Accepted: 03/29/2016] [Indexed: 11/25/2022]
Affiliation(s)
- Mark L Norris
- Division of Adolescent Medicine, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
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Wu HC, Lee LC, Wang WJ. Associations among time-average mineral values, mortality and cardiovascular events in hemodialysis patients. Ren Fail 2015; 37:343-53. [PMID: 26375759 DOI: 10.3109/0886022x.2015.1087862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
UNLABELLED Mineral and bone disease (CKD-MBD), disorders of mineral metabolism, is associated with mortality and cardiovascular disease in dialysis patients. However, the associations among time average mineral values (P, Ca and PTH) and clinical outcomes are not well investigated. OBJECTIVES This study examines the associations among mineral values and clinical outcomes from a single medical center. METHODS Adult patients who initiate hemodialysis in Taoyuan General Hospital from 2008 to 2013 were enrolled. We examined these associations using baseline and time-average model. The clinical outcomes included mortality, major adverse cardiovascular events (MACE) and cardiovascular events. We also examined the association between achieve K/DOQI guidelines' targets and clinical outcomes. RESULTS From a total of 284 hemodialysis patients, none of the baseline mineral values is associated with mortality and cardiovascular event, except hyperphosphatemia. Compared to patients achieved K/DOQI guidelines' targets, time average hyperphosphatemia is associated with MACE and first cardiovascular event [the adjusted hazard ratios (AHRs) are 6.343 and 3.278); whereas time average hypercalcemia is associated with MACE marginally (the AHR is 5.964). None of above clinical outcomes is related to hyperparathyroidism. The AHRs for mortality in those who only met PTH targets and none of the mineral value targets are 1.73 and 1.74, whereas the AHRs for cardiovascular events in those who met only Ca, only PTH, and none of the targets are 1.73, 1.81 and 2.54 (all ps < 0.05). CONCLUSION Time-average phosphate is associated with cardiovascular events after initiation of dialysis. Among mineral values, serum phosphate is still the strongest predictor for mortality and cardiovascular events.
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Affiliation(s)
- Hung-Chieh Wu
- a Division of Nephrology, Department of Internal Medicine , Taoyuan General Hospital, Ministry of Health and Welfare , Taoyuan , Taiwan .,b College of Nursing, Chang Gung University of Science and Technology , Taoyuan , Taiwan
| | - Lin-Chien Lee
- c Department of Physical Medicine and Rehabilitation , Cheng Hsin General Hospital , Taipei , Taiwan , and
| | - Wei-Jie Wang
- a Division of Nephrology, Department of Internal Medicine , Taoyuan General Hospital, Ministry of Health and Welfare , Taoyuan , Taiwan .,b College of Nursing, Chang Gung University of Science and Technology , Taoyuan , Taiwan .,d Department of Biomedical Engineering , Chung Yuan Christian University , Taoyuan , Taiwan
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Chen LJ, Chen HL, Bair MJ, Wu CH, Lin IT, Lee YK, Chu CH. Refeeding syndrome in Southeastern Taiwan: Our experience with 11 cases. World J Gastroenterol 2014; 20:10525-10530. [PMID: 25132771 PMCID: PMC4130862 DOI: 10.3748/wjg.v20.i30.10525] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Revised: 03/13/2014] [Accepted: 05/05/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To present our experience with refeeding syndrome in southeastern Taiwan.
METHODS: We conducted a retrospective study during a 2-year period at the Mackay Memorial Hospital, Taitung Branch. We enrolled patients with very little or no nutrition intake for more than 10 d, a high risk group of refeeding syndrome, including those suffering from alcohol abuse, cancerous cachexia, chronic malnutrition, and prolonged starvation.
RESULTS: A total of 11 patients (7 males, 4 females) with nasogastric feeding were included as having refeeding syndrome. Most of them had the symptoms of diarrhea, lethargy, and leg edema. The initial nutritional supplement was found to be relatively high in calories (1355.1 ± 296.2 kcal/d), high in protein (47.3 ± 10.4 gm/d), low in vitamin B1 (2.0 ± 0.5 mg/d), low in potassium (1260.4 ± 297.7 mg/d), and low in phosphorus (660.1 ± 151.8 mg/d). Furthermore, hypophosphatemia (2.4 ± 0.9 mg/dL) was noted during follow-up. Based on the suggestions of a dietician and a gastroenterologist, the clinical disorders of diarrhea, malaise and leg edema were significantly improved. The level of phosphate was also increased (3.3 ± 0.6 mg/dL).
CONCLUSION: Refeeding syndrome is an overlooked and risky disorder that has some potentially fatal complications. Nasogastric feeding in nursing homes is an important risk factor for patients and deserves greater attention based on the initial results of this study.
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Blumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: techniques, problems and solutions. World J Gastroenterol 2014; 20:8505-8524. [PMID: 25024606 PMCID: PMC4093701 DOI: 10.3748/wjg.v20.i26.8505] [Citation(s) in RCA: 264] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2013] [Revised: 02/23/2014] [Accepted: 04/15/2014] [Indexed: 02/06/2023] Open
Abstract
Gastroenteric tube feeding plays a major role in the management of patients with poor voluntary intake, chronic neurological or mechanical dysphagia or gut dysfunction, and patients who are critically ill. However, despite the benefits and widespread use of enteral tube feeding, some patients experience complications. This review aims to discuss and compare current knowledge regarding the clinical application of enteral tube feeding, together with associated complications and special aspects. We conducted an extensive literature search on PubMed, Embase and Medline using index terms relating to enteral access, enteral feeding/nutrition, tube feeding, percutaneous endoscopic gastrostomy/jejunostomy, endoscopic nasoenteric tube, nasogastric tube, and refeeding syndrome. The literature showed common routes of enteral access to include nasoenteral tube, gastrostomy and jejunostomy, while complications fall into four major categories: mechanical, e.g., tube blockage or removal; gastrointestinal, e.g., diarrhea; infectious e.g., aspiration pneumonia, tube site infection; and metabolic, e.g., refeeding syndrome, hyperglycemia. Although the type and frequency of complications arising from tube feeding vary considerably according to the chosen access route, gastrointestinal complications are without doubt the most common. Complications associated with enteral tube feeding can be reduced by careful observance of guidelines, including those related to food composition, administration rate, portion size, food temperature and patient supervision.
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Abstract
Body water, electrolytes, and acid-base balance are important considerations in the evaluation and treatment of small ruminants and camelids with any disease process, with restoration of these a priority as adjunctive therapy. The goals of fluid therapy should be to maintain cardiac output and tissue perfusion, and to correct acid-base and electrolyte abnormalities. Hypoglycemia, hyperkalemia, and acidosis are the most life-threatening abnormalities, and require most immediate correction.
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Maiorana A, Vergine G, Coletti V, Luciani M, Rizzo C, Emma F, Dionisi-Vici C. Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis. Nutrition 2014; 30:948-52. [PMID: 24985016 DOI: 10.1016/j.nut.2014.02.019] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Revised: 02/18/2014] [Accepted: 02/19/2014] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses. METHODS We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction. RESULTS A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses. CONCLUSIONS Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly responds to thiamine administration.
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Affiliation(s)
- Arianna Maiorana
- Division of Metabolism and Research Unit of Metabolic Biochemistry, Department of Pediatric Medicine, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
| | - Gianluca Vergine
- Division of Nephrology and Dialysis, Department of Nephrology & Urology, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Valentina Coletti
- Division of Hematology, Department of Hematology and Oncology, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Matteo Luciani
- Division of Hematology, Department of Hematology and Oncology, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Cristiano Rizzo
- Division of Metabolism and Research Unit of Metabolic Biochemistry, Department of Pediatric Medicine, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Francesco Emma
- Division of Nephrology and Dialysis, Department of Nephrology & Urology, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Carlo Dionisi-Vici
- Division of Metabolism and Research Unit of Metabolic Biochemistry, Department of Pediatric Medicine, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
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Goyale A, Ashley SL, Taylor DR, Elnenaei MO, Alaghband-Zadeh J, Sherwood RA, le Roux CW, Vincent RP. Predicting refeeding hypophosphataemia: insulin growth factor 1 (IGF-1) as a diagnostic biochemical marker for clinical practice. Ann Clin Biochem 2014; 52:82-7. [DOI: 10.1177/0004563214523739] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH). Methods A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a ≥30% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration. Results High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver–operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting ≥30% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75–98%]) and specificity (65% [95% CI 41–85%]) was 63.7 µg/L, with a likelihood ratio of 2.59. Conclusion Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice.
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Affiliation(s)
- Atul Goyale
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Sarah L Ashley
- Department of Nutrition and Dietetics, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - David R Taylor
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Manal O Elnenaei
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Jamshid Alaghband-Zadeh
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Roy A Sherwood
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Carel W le Roux
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
- Experimental Pathology, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Ireland
| | - Royce P Vincent
- Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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Agostino H, Erdstein J, Di Meglio G. Shifting paradigms: continuous nasogastric feeding with high caloric intakes in anorexia nervosa. J Adolesc Health 2013; 53:590-4. [PMID: 23871800 DOI: 10.1016/j.jadohealth.2013.06.005] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2013] [Revised: 06/04/2013] [Accepted: 06/05/2013] [Indexed: 11/19/2022]
Abstract
PURPOSE The initial goal of admission for a patient with anorexia nervosa is physiologic stabilization through nutritional rehabilitation balanced against the risk of refeeding syndrome. Recent alternative approaches emphasize meal composition, limiting carbohydrates, to reduce risk. The Montreal Children's Hospital has instituted a standardized high-calorie continuous nasogastric (NG) refeeding protocol for the initial management of inpatient adolescents with restrictive eating disorders. This study aims to confirm that this protocol results in a shorter admission duration and faster rate of weight gain without increased incidence of complications. METHODS Retrospective chart review of patients with restrictive eating disorders admitted to the Montreal Children's Hospital during December 2003 to December 2011. Those treated with higher calorie NG refeeding protocol (N = 31) were compared with those managed with a standard bolus meal treatment (N = 134). RESULTS Length of stay was significantly reduced in the NG-fed cohort (NG cohort 33.8 days; bolus-fed cohort 50.9 days; p = .0002). Mean rate of weight gain in the NG group was significantly improved for both the first and second week when compared with the bolus-fed cohort (1.22 kg/week (1), p = .01; 1.06 kg/week (.9), p = .04). No significant difference was found in the rate of complications or electrolyte abnormalities with 90% of the NG-fed cohort receiving prophylactic phosphate supplementation from admission. CONCLUSIONS This study provides further evidence to support the treatment of undernourished inpatients with restrictive type eating disorders with a higher initial caloric intake to achieve rapid and safe nutritional rehabilitation.
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Affiliation(s)
- Holly Agostino
- Division of Adolescent Medicine and Pediatric Gynecology, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
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Mizumoto H, Mikami M, Oda H, Hata D. Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral nutrition. Pediatr Int 2012; 54:715-7. [PMID: 23005906 DOI: 10.1111/j.1442-200x.2012.03590.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
This report describes a small-for-date extremely low birth weight infant who manifested bradycardic events, respiratory failure, and hemolytic jaundice during her first week of life. These complications were attributed to severe hypophosphatemia and hypokalemia. Inadequate supply and refeeding syndrome triggered by early aggressive parenteral nutrition were responsible for electrolyte abnormalities.
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Affiliation(s)
- Hiroshi Mizumoto
- Department of Pediatrics, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
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Short bowel syndrome presenting with re-feeding syndrome in a Han Chinese patient: a case report. J Med Case Rep 2012; 6:137. [PMID: 22647322 PMCID: PMC3375196 DOI: 10.1186/1752-1947-6-137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2010] [Accepted: 05/30/2012] [Indexed: 11/10/2022] Open
Abstract
Introduction Re-feeding syndrome is common in patients with long-term starvation. To the best of our knowledge this case is the first to report a patient with short bowel syndrome developing re-feeding syndrome 12 years after the bowel resection. Case presentation A 33-year-old Chinese Han man underwent small bowel resection leaving only 40 cm of bowel, without an ileocecal valve, 12 years previously. At that time he was weaned from total parenteral nutrition and had a normal diet. He later developed features of severe malnutrition, and when parenteral nutrition was given, he developed re-feeding syndrome. Conclusion Although re-feeding syndrome is a common complication in patients with any kind of nutritional support, and known to us for many years, high risk patients still need more attention and monitoring. Re-feeding syndrome in this case was not only a macronutrients deficiency but also a micronutrient deficient, and prompt supplement therapy and organ function support proved to be successful.
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Dror Y, Almashanu S, Lubart E, Sela BA, Shimoni L, Segal R. The Impact of Refeeding on Blood Fatty Acids and Amino Acid Profiles in Elderly Patients. JPEN J Parenter Enteral Nutr 2012; 37:109-16. [DOI: 10.1177/0148607112443260] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Yosef Dror
- School of Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Tel-Hashomer, Israel
| | - Shlomo Almashanu
- Department of Community Genetics, Israeli Ministry of Health, Tel-Hashomer, Israel
| | - Emilia Lubart
- Geriatric Medical Center, Shmuel Harofeh, Beer Yaakov, Israel
- The Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Ben-Ami Sela
- The Sackler Faculty of Medicine, Tel Aviv University, Israel
- Institute of Chemical Pathology, Sheba Medical Center, Tel-Hashomer, Israel
| | - Liron Shimoni
- School of Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Tel-Hashomer, Israel
| | - Refael Segal
- Geriatric Medical Center, Shmuel Harofeh, Beer Yaakov, Israel
- The Sackler Faculty of Medicine, Tel Aviv University, Israel
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Nutritional treatment a various clinical setting--practical considerations. POLISH JOURNAL OF SURGERY 2012; 83:681-7. [PMID: 22343207 DOI: 10.2478/v10035-011-0110-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Zhang F, Xu X, Zhou B, He Z, Zhai Q. Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding. PLoS One 2011; 6:e27553. [PMID: 22096593 PMCID: PMC3212576 DOI: 10.1371/journal.pone.0027553] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2011] [Accepted: 10/19/2011] [Indexed: 12/31/2022] Open
Abstract
Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes.
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Affiliation(s)
- Fang Zhang
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Xiang Xu
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Ben Zhou
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Zhishui He
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Qiwei Zhai
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
- * E-mail:
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Brenner K, KuKanich KS, Smee NM. Refeeding syndrome in a cat with hepatic lipidosis. J Feline Med Surg 2011; 13:614-7. [PMID: 21719333 PMCID: PMC10822410 DOI: 10.1016/j.jfms.2011.05.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2011] [Indexed: 11/17/2022]
Abstract
Refeeding syndrome is characterized by severe hypophosphatemia occurring in patients given enteral or parenteral nutrition after severe weight loss. There are few veterinary reports that describe this syndrome but it is well documented in human medicine. This report describes a case of a domestic shorthair cat diagnosed with hepatic lipidosis following a 4-week history of decreased appetite and weight loss and in whom refeeding syndrome was documented after initiation of enteral nutrition. Clinical findings, blood work abnormalities and disease progression in this patient are described from the time of diagnosis through to recovery. A review of the current literature pertinent to this clinical syndrome is included.
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Affiliation(s)
- Karen Brenner
- Department of Clinical Sciences, Kansas State University, College of Veterinary Medicine, Manhattan, KS 66506, USA
| | - Kate S. KuKanich
- Department of Clinical Sciences, Kansas State University, College of Veterinary Medicine, Manhattan, KS 66506, USA
| | - Nicole M. Smee
- Department of Clinical Sciences, Kansas State University, College of Veterinary Medicine, Manhattan, KS 66506, USA
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46
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Does aggressive refeeding in hospitalized adolescents with anorexia nervosa result in increased hypophosphatemia? J Adolesc Health 2010; 46:577-82. [PMID: 20472215 DOI: 10.1016/j.jadohealth.2009.11.207] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2009] [Revised: 11/13/2009] [Accepted: 11/18/2009] [Indexed: 11/23/2022]
Abstract
PURPOSE Concerns about refeeding syndrome have led to relatively conservative nutritional rehabilitation in malnourished inpatients with anorexia nervosa (AN), which delays weight gain. Compared to other programs, we aggressively refed hospitalized adolescents. We sought to determine the incidence of hypophosphatemia (HP) in 12-18-year-old inpatients in order to inform nutritional guidelines in this group. METHODS A 1-year retrospective chart review was undertaken of 46 admissions (29 adolescents) with AN admitted to the adolescent ward of a tertiary children's hospital. Data collected over the initial 2 weeks included number of past admissions, nutritional intake, weight, height, body mass index, and weight change at 2 weeks. Serum phosphorus levels and oral phosphate supplementation was recorded. RESULTS The mean (SD) age was 15.7 years (1.4). The mean (SD) ideal body weight was 72.9% (9.1). Sixty-one percent of admissions were commenced on 1,900 kcal (8,000 kJ), and 28% on 2,200 kcal (9,300 kJ). Four patients were deemed at high risk of refeeding syndrome; of these patients, three were commenced on rehydration therapy and one on 1,400 kcal (6,000 kJ). All patients were graded up to 2,700 kcal (11,400 kJ) with further increments of 300 kcal (1,260 kJ) as required. Thirty-seven percent developed mild HP; no patient developed moderate or severe HP. Percent ideal body weight at admission was significantly associated with the subsequent development of HP (p = .007). CONCLUSIONS These data support more aggressive approaches to nutritional rehabilitation for hospitalized adolescents with AN compared to current recommendations and practice.
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Naves-Díaz M, Passlick-Deetjen J, Guinsburg A, Marelli C, Fernández-Martín JL, Rodríguez-Puyol D, Cannata-Andía JB. Calcium, phosphorus, PTH and death rates in a large sample of dialysis patients from Latin America. The CORES Study. Nephrol Dial Transplant 2010; 26:1938-47. [PMID: 20513773 DOI: 10.1093/ndt/gfq304] [Citation(s) in RCA: 112] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Mineral metabolism parameters may play a role in the survival of patients with chronic kidney disease (CKD). METHODS In the CORES Study, we analysed the association between calcium, phosphorus and PTH and mortality (all-cause and cardiovascular) in 16 173 haemodialysis (HD) patients over 18 years from six Latin American countries, who underwent haemodialysis up to 54 months. Unadjusted, case-mix-adjusted and time-dependent multivariable-adjusted hazard ratio (HR) of death were calculated for categories of serum albumin-corrected calcium (Ca(Alb)), phosphorus and PTH using as 'reference values' the range in which the lowest death rate was observed. Age, gender, vitamin D treatment, diabetes, vintage, vascular access, weight, blood pressure and laboratory variables (serum albumin, haemoglobin, creatinine, ferritin and Kt/V) were used as confounding variables. RESULTS Low (<9.5 mg/dL) and high (>10.5 mg/dL) Ca(Alb) increased the HR for all-cause mortality. Low (<9.0 mg/dL) Ca(Alb) increased the HR for cardiovascular mortality. High phosphorus (>5.5 mg/dL) increased the HR for both all-cause and cardiovascular mortality. Low phosphorus (<4.0 and <3.0 mg/dL) increased the HR for both all-cause and cardiovascular mortality. Furthermore, low (<150 pg/mL) and high (>500 and >300 pg/mL) PTH increased the HR for both all-cause and cardiovascular mortality. In addition, only phosphorus >6.0 mg/dL increased the HR for cardiovascular hospitalizations. No effect was observed with Ca(Alb) or PTH. CONCLUSIONS In summary, in 16,173 HD patients, elevated and reduced serum levels of albumin-corrected calcium, phosphorus and PTH levels were associated with increments in all-cause mortality. Similar results were obtained when only cardiovascular mortality was analysed.
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Affiliation(s)
- Manuel Naves-Díaz
- Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Universidad de Oviedo, Julián Claveria s/n, 33006 Oviedo, Spain
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Todd SR, Sucher JF, Moore LJ, Turner KL, Hall JB, Moore FA. A multidisciplinary protocol improves electrolyte replacement and its effectiveness. Am J Surg 2010; 198:911-5. [PMID: 19969151 DOI: 10.1016/j.amjsurg.2009.04.032] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2009] [Revised: 04/04/2009] [Accepted: 04/08/2009] [Indexed: 11/25/2022]
Abstract
BACKGROUND We implemented a multidisciplinary electrolyte replacement protocol in a tertiary referral center surgical intensive care unit. The purpose of this study was to evaluate its efficacy. METHODS This was a retrospective study. The electrolyte replacement protocol was designed for the replacement of potassium, magnesium, and phosphorous and was nurse driven. Data evaluated included patient demographics and details specific to electrolyte replacement. Univariate analyses were performed by using the Student t test and the Fisher exact test. A P value of <.05 was considered significant. RESULTS After implementation of the protocol, overall electrolyte replacement improved from 70% to 79% (P = .03), and its overall effectiveness increased from 50% to 65% (P = .01). Individual electrolyte replacement, effectiveness, and dosing varied. CONCLUSIONS The implementation of a multidisciplinary electrolyte replacement protocol in a tertiary referral center surgical intensive care unit significantly improved both overall electrolyte replacement and its effectiveness.
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Affiliation(s)
- S Rob Todd
- Department of Surgery, The Methodist Hospital, Weill Cornell Medical College, 6550 Fannin Street, Smith Tower 1661, Houston, TX 77030, USA.
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Kerac M, Bunn J, Seal A, Thindwa M, Tomkins A, Sadler K, Bahwere P, Collins S. Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi. Lancet 2009; 374:136-44. [PMID: 19595348 DOI: 10.1016/s0140-6736(09)60884-9] [Citation(s) in RCA: 130] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING Department for International Development (DfID).
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Abstract
Refeeding syndrome is defined as severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished, refeeding patients. Hypophosphatemia is its predominant concern, though its occurrence is unusual in uremic patients due to the concomitant hyperphosphatemia. This case study reports a 56-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) therapy who was admitted for peritonitis. Ileus and diarrhea developed during admission; enteral feeding was given initially and then shifted to total parenteral nutrition (TPN) because of poor digestion. A lower concentration of phosphate was administered in the TPN formula initially due to high initial serum phosphate level. However, severe hypophosphatemia (0.3 mg/dL) developed on the second day after TPN supplementation. Continuous intravenous phosphate (total 6 mmol of phosphate) was supplied immediately. Unfortunately, the sudden onset of conscious loss and cardiac arrest happened on the third day of TPN. It should be emphasized that severe refeeding hypophosphatemia can also develop early in uremic patients with hyperphosphatemia.
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Affiliation(s)
- Kang-Kuei Lin
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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