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    Epidemiology and Outcomes of Cardiac Arrest in Pediatric Cardiac ICUs.
    Pediatr Crit Care Med 2017 Jul 21. Epub 2017 Jul 21.
    1Department of Pediatric Cardiology, Section of Cardiac Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL. 2Departments of Pediatric Critical Care Medicine and Pediatric Cardiology, Children's National Health System, Washington, D.C. 3Department of Pediatric Cardiology, Medical City Children's Hospital, Dallas, TX. 4Department of Pediatric Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 5Department of Pediatrics and Communicable Diseases, Division of Cardiology, C. S. Mott Children's Hospital and University of Michigan Medical School, Ann Arbor, MI.
    Objectives: In-hospital cardiac arrest occurs in 2.6-6% of children with cardiac disease and is associated with significant morbidity and mortality. Much remains unknown about cardiac arrest in pediatric cardiac ICUs; therefore, we aimed to describe cardiac arrest epidemiology in a contemporary multicenter cardiac ICU cohort. Read More

    Arginine and citrulline for the treatment of MELAS syndrome.
    J Inborn Errors Metab Screen 2017 Jan 24;5. Epub 2017 Mar 24.
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
    MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. Read More

    Low sensitivity of anion gap to detect clinically significant lactic acidosis in the emergency department.
    Clin Biochem 2017 Jul 20. Epub 2017 Jul 20.
    Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, AB, Canada. Electronic address:
    Introduction: Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactate. Read More

    [Disorders of water and electrolyte metabolism and changes in acid-base balance in patients with ascitic liver cirrhosis].
    Cas Lek Cesk 2017 ;156(3):150-152
    In patients with advanced cirrhosis with ascites disorders of water and electrolyte metabolism are often present and they are associated with changes in acid-base balance. These changes can be very complicated, their diagnosis and treatment difficult. Dilutional hyponatremia is the most common disorder. Read More

    Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex.
    Mol Cell 2017 Jul 11. Epub 2017 Jul 11.
    Department of Biochemistry and Molecular Biology and The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia. Electronic address:
    Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that catalyzes the phosphorylation of monoacylglycerol and diacylglycerol to lysophosphatidic acid and phosphatidic acid, respectively. Mutations in AGK cause Sengers syndrome, which is characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Here we identified AGK as a subunit of the mitochondrial TIM22 protein import complex. Read More

    Seasonal and maternal effects on acid-base, l-lactate, electrolyte, and hematological status of 205 dairy calves born to eutocic dams.
    J Dairy Sci 2017 Jul 12. Epub 2017 Jul 12.
    Institute of Animal Husbandry, Faculty of Agricultural and Environmental Science, Szent István University, Páter Károly utca 1, H-2100 Gödöllő, Hungary; Department and Clinic for Production Animals, University of Veterinary Medicine, H-2225 Üllő-Dóra Major, Hungary.
    In this study, we used linear mixed models to determine the effects of season, time of sampling relative to birth (factors), duration of the delivery process, duration of maternal grooming, calf body weight (BW) at birth, and time of day (covariates) on values of venous blood gas, acid-base and electrolyte parameters, and l-lactate concentrations in dairy calves born to eutocic dams in summer (SUM, n = 101) and winter (WIN, n = 104). Neonatal vitality was assessed at 0, 1, and 24 h after delivery in a linear scoring system using muscle tone, erection of the head, muscle reflexes, heart rate, and sucking drive as criteria. Simultaneously with vitality scoring, venous blood samples were collected by jugular venipuncture. Read More

    Is it safe to acutely discontinue insulin therapy in patients with chronic hyperglycaemia starting GLP-1R agonists?
    BMJ Case Rep 2017 Jul 14;2017. Epub 2017 Jul 14.
    Department of Endocrinology, Sligo General Hospital, Sligo, Ireland.
    We report two patients with chronic hyperglycaemia secondary to type 2 diabetes who developed severe vomiting on d. The first patient was diagnosed with a mixed picture of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) and the second, with DKA. They were on insulin therapy which was discontinued on commencing d because of inefficacy and weight gain. Read More

    [The treatment of AKI in nephrology hospitalization: the SLE-HDF 15 litres in 10 hours].
    G Ital Nefrol 2017 Jun;34(3):85-95
    Nephrology and Dialysis Unity, S. Caterina N, Hospital, Galatina, Lecce, Italy.
    The AKI in intensive care has been widely treated by international and national guidelines. The treatment of AKI in patients not requiring admission in Intensive Care Unit, but often hospitalized in Nephrology Unit, it is showed of less relevance. For over 5 years we have used for the treatment of AKI of patients admitted in Nephrology Unit an intermittent slow technique, implemented in approximately 600 patients with AKI for a total of about 3000 treatments. Read More

    Mitochondrial dysfunction and cerebral metabolic abnormalities in patients with mitochondrial encephalomyopathy subtypes: Evidence from proton MR spectroscopy and muscle biopsy.
    CNS Neurosci Ther 2017 Aug 11;23(8):686-697. Epub 2017 Jul 11.
    Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
    Aims: Accumulated evidence indicates that cerebral metabolic features, evaluated by proton magnetic resonance spectroscopy ((1) H-MRS), are sensitive to early mitochondrion dysfunction associated with mitochondrial encephalomyopathy (ME). The metabolite ratios of lactate (lac)/Cr, N-acetyl aspartate (NAA)/creatine (Cr), total choline (tCho)/Cr, and myoinositol (mI)/Cr are measured in the infarct-like lesions by (1) H-MRS and may reveal metabolic changes associated with ME. However, the application of this molecular imaging technique in the investigation of the pathology of ME subtypes is unknown. Read More

    LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR tomographic, and biochemical study.
    Mitochondrion 2017 Jul 8. Epub 2017 Jul 8.
    Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    LYRM7 is involved in the last steps of mitochondrial complex III assembly where it acts as a chaperone for the Rieske iron‑sulfur (Fe-S) protein in the mitochondrial matrix. Using exome sequencing, we identified homozygosity for a splice site destroying 4 base pair deletion in LYRM7 in a child with recurrent lactic acidotic crises and distinct early-onset leukencephalopathy. Sanger sequencing showed variant segregation in similarly affected family members. Read More

    Serum lactate level and mortality in metformin-associated lactic acidosis requiring renal replacement therapy: a systematic review of case reports and case series.
    BMC Nephrol 2017 Jul 10;18(1):229. Epub 2017 Jul 10.
    Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, 2, Yude Rd., North Dist, Taichung City, 404, Taiwan.
    Background: The current practice concerning timing, mode, and dose of renal replacement therapy (RRT) in patients with metformin-associated lactic acidosis (MALA) with renal failure remains unknown. To investigate whether serum lactate level and prescription pattern of RRT are associated with mortality in patients with MALA requiring RRT.

    Methods: We searched PubMed/Medline and EMBASE from inception to Sep 2014 and applied predetermined exclusion criteria. Read More

    Hemoglobin-Based Oxygen Carrier (HBOC) Development in Trauma: Previous Regulatory Challenges, Lessons Learned, and a Path Forward.
    Adv Exp Med Biol 2017 ;977:343-350
    Keipert Corp. Life Sciences Consulting, San Diego, CA, USA, 92130.
    Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. Read More

    Acid-base disorders in liver disease.
    J Hepatol 2017 Jul 3. Epub 2017 Jul 3.
    Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria. Electronic address:
    Next to the kidneys and lungs, the liver has been recognized as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. Although the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model allows a more in-depth pathophysiological understanding and clinical judgement of acid-base disorders in patients with liver diseases. Read More

    Metformin Safety Warnings and Diabetes Drug Prescribing Patterns for Older Nursing Home Residents.
    J Am Med Dir Assoc 2017 Jul 1. Epub 2017 Jul 1.
    Department of Health Services, Policy, and Practice, School of Public Health, Brown University, Providence, RI; Department of Medicine, Alpert Medical School, Brown University, Providence, RI.
    Objective: Diabetes mellitus is common in US nursing homes (NHs), and the mainstay treatment, metformin, has US Food and Drug Administration (FDA) boxed warnings indicating safety concerns in those with advanced age, heart failure, or renal disease. Little is known about treatment selection in this setting, especially for metformin. We quantified the determinants of initiating sulfonylureas over metformin with the aim of understanding the impact of FDA-labeled boxed warnings in older NH residents. Read More

    Sodium-glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes: a review of US FDA data and possible conclusions.
    Int J Nephrol Renovasc Dis 2017 15;10:153-158. Epub 2017 Jun 15.
    Kidney and Hypertension Section, Joslin Diabetes Center, Harvard Medical School.
    Objective: To evaluate whether adverse event reports to the US Food and Drug Administration on incidents of ketoacidosis from use of sodium glucose cotransport inhibitors (SGLT2 inhibitors) provide insight into ways this new class of drugs is being prescribed with other antihyperglycemic agents; to examine possible mechanisms to explain ketoacidosis.

    Design And Methods: Reports of adverse events concerned to SGLT2 inhibitors, namely, empagliflozin, dapagliflozin, and canagliflozin were obtained under the Freedom of Information Act for 5 years ending in August 31, 2015. The data were evaluated for incidents of ketoacidosis by looking for keywords such as diabetic ketoacidosis, ketoacidosis, lactic acidosis, acidosis, and metabolic acidosis. Read More

    Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy.
    Blood Purif 2017 Jul 1;44(3):198-205. Epub 2017 Jul 1.
    Department of General and Specialist Medicine, Nephrology, Dialysis and Transplantation U, CTO Hospital, Torino, Italy.
    Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT).

    Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Read More

    Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus.
    Iran J Basic Med Sci 2017 May;20(5):511-515
    Department of Pathology Liaquat University of Medical and Health Sciences Jamshoro, Sindh, Pakistan.
    Objectives: Causality of occurrence of metformin-associated lactic acidosis (MALA) is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR) against MALA in induced diabetic rat model. Read More

    Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial.
    Lancet Oncol 2017 Jun 23. Epub 2017 Jun 23.
    UZ Leuven, Campus Gasthuisberg, Leuven, Belgium.
    Background: Evofosfamide is a hypoxia-activated prodrug of bromo-isophosphoramide mustard. We aimed to assess the benefit of adding evofosfamide to doxorubicin as first-line therapy for advanced soft-tissue sarcomas.

    Methods: We did this international, open-label, randomised, phase 3, multicentre trial (TH CR-406/SARC021) at 81 academic or community investigational sites in 13 countries. Read More

    Fatal lactic acidosis in hepatitis B virus-associated decompensated cirrhosis treated with tenofovir: A case report.
    Medicine (Baltimore) 2017 Jun;96(25):e7133
    Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.
    Rationale: Recently tenofovir disoproxil fumarate (TDF) has been widely used as a first-line therapy for chronic hepatitis B (CHB) infection. Although TDF demonstrates successful viral suppression, the possibility of renal failure and lactic acidosis has been proposed with TDF administration, especially in human immunodeficiency virus co-infected patients. However, TDF induced lactic acidosis has never been reported in CHB mono-infected patients. Read More

    The clinical and genetic characteristics in children with mitochondrial disease in China.
    Sci China Life Sci 2017 Jul 16;60(7):746-757. Epub 2017 Jun 16.
    Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
    Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing (NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. Read More

    Evaluation of the concurrent use of dolutegravir and metformin in human immunodeficiency virus-infected patients.
    Int J STD AIDS 2017 Jan 1:956462417695995. Epub 2017 Jan 1.
    5 Department of Pharmacy, Virginia Commonwealth University Health System, Richmond, VA, USA.
    An analysis of the interaction between dolutegravir and metformin was conducted in the HIV ambulatory clinic setting. This was a multicenter, retrospective case series evaluating adult, HIV-infected patients concurrently prescribed dolutegravir and metformin. Historical electronic medical records were utilized to collect case-specific data. Read More

    Glycyrrhetic acid, but not glycyrrhizic acid, strengthened entecavir activity by promoting its subcellular distribution in the liver via efflux inhibition.
    Eur J Pharm Sci 2017 Aug 13;106:313-327. Epub 2017 Jun 13.
    Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address:
    Entecavir (ETV) is a superior nucleoside analogue used to treat hepatitis B virus (HBV) infection. Although its advantages over other agents include low viral resistance and the elicitation of a sharp decrease in HBV DNA, adverse effects such as hepatic steatosis, hepatic damage and lactic acidosis have also been reported. Glycyrrhizin has long been used as hepato-protective medicine. Read More

    Refractory Lactic Acidosis in Small Cell Carcinoma of the Lung.
    Case Rep Crit Care 2017 23;2017:6148350. Epub 2017 May 23.
    Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
    Background: Elevated lactate levels in critically ill patients are most often thought to be indicative of relative tissue hypoxia or type A lactic acidosis. Shock, severe anemia, and thromboembolic events can all cause elevated lactate due to tissue hypoperfusion, as well as the mitochondrial dysfunction thought to occur in sepsis and other critically ill states. Malignancy can also lead to elevation in lactate, a phenomenon described as type B lactic acidosis, which is much less commonly encountered in the critically ill. Read More

    Mitochondrial Cardiomyopathy Presenting as Dilated Phase of Hypertrophic Cardiomyopathy Diagnosed with Histological and Genetic Analyses.
    Case Rep Cardiol 2017 23;2017:9473917. Epub 2017 May 23.
    Department of Cardiology, Japanese Red Cross Ashikaga Hospital, Ashikaga, Japan.
    We report a case with 46-year-old man diagnosed with mitochondrial cardiomyopathy in the dilated phase of hypertrophic cardiomyopathy. Since cardiac magnetic resonance imaging, beta-methyl-p-(123)I-iodophenyl-pentadecanoic myocardial scintigraphy, and positron emission tomography/computed tomography revealed no remarkable findings, we performed electron microscopic examination, which aided in diagnosing mitochondrial cardiomyopathy. Muscle biopsy was also compatible with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and DNA analysis also concluded it. Read More

    Pseudo-thrombotic thrombocytopenic purpura presenting as multi-organ dysfunction syndrome: A rare complication of pernicious anemia.
    SAGE Open Med Case Rep 2017 6;5:2050313X17713149. Epub 2017 Jun 6.
    Interfaith Medical Center, Brooklyn, NY, USA.
    Objective: We present a rare case of pernicious anemia presented as multi-organ dysfunction syndrome, later found to have pseudo-thrombotic thrombocytopenic purpura.

    Methods: An 86-year-old female presented with respiratory distress, altered mental status, acute renal failure and was intubated in emergency room. She was found to have severe anemia, thrombocytopenia, high lactate, high lactate dehydrogenase and low haptoglobin. Read More

    Changes in metformin use in chronic kidney disease.
    Clin Kidney J 2017 Jun 28;10(3):301-304. Epub 2017 Mar 28.
    Division of Nephrology, Kaiser Permanente, Southern California Permanente Medical Group, Fontana, CA, USA.
    Metformin is one of the oldest and most widely prescribed antidiabetic medicines worldwide. It is the only such medicine that has shown a reduction of cardiovascular mortality in diabetes mellitus type 2. Since many diabetic patients have chronic kidney disease, its use is often curtailed by practitioners due to fear of lactic acidosis and the US Food and Drug Administration (FDA) warnings that, until recently, had been in place for decades. Read More

    Targeting oxygen sensing prolyl hydroxylase (PHD) for metformin-associated lactic acidosis treatment.
    Mol Cell Biol 2017 Jun 12. Epub 2017 Jun 12.
    Department of Biochemistry, Department of Anesthesiology, and Translational Research Center, Keio University School of Medicine, Tokyo, Japan.
    Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anti-cancer and anti-aging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate transcription factor HIF (hypoxia-inducible factor) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels. Read More

    Arterial versus venous lactate: a measure of sepsis in children.
    Eur J Pediatr 2017 Aug 10;176(8):1055-1060. Epub 2017 Jun 10.
    Institute for Medical and Biomedical Education, St. George's University of London, London, SW17 0QT, UK.
    This study assessed the agreement between arterial and venous blood lactate and pH levels in children with sepsis. This retrospective, three-year study involved 60 PICU patients, with data collected from electronic or paper patient records. The inclusion criteria comprised of children (≤17 years old) with sepsis and those who had a venous blood gas taken first with an arterial blood gas taken after within one hour. Read More

    Fructose-1,6-bisphosphatase deficiency caused by a novel homozygous Alu element insertion in the FBP1 gene and delayed diagnosis.
    J Pediatr Endocrinol Metab 2017 May 23. Epub 2017 May 23.
    .
    Fructose-1,6-bisphosphatase (FBPase) enzyme deficiency is one of the treatable autosomal recessive inherited metabolic disorders. If diagnosed early, FBPase deficiency has a favorable prognosis. We report the clinical and biochemical findings of a 9. Read More

    Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction.
    PLoS One 2017 8;12(6):e0178125. Epub 2017 Jun 8.
    Genetic Metabolic Disorders Research Unit, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
    Glycyl-tRNA synthetase (GARS; OMIM 600287) is one of thirty-seven tRNA-synthetase genes that catalyses the synthesis of glycyl-tRNA, which is required to insert glycine into proteins within the cytosol and mitochondria. To date, eighteen mutations in GARS have been reported in patients with autosomal-dominant Charcot-Marie-Tooth disease type 2D (CMT2D; OMIM 601472), and/or distal spinal muscular atrophy type V (dSMA-V; OMIM 600794). In this study, we report a patient with clinical and biochemical features suggestive of a mitochondrial respiratory chain (MRC) disorder including mild left ventricular posterior wall hypertrophy, exercise intolerance, and lactic acidosis. Read More

    Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review.
    J Transl Med 2017 Jun 7;15(1):129. Epub 2017 Jun 7.
    Psychology Department, College of Health and Biomedicine, Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia.
    Background: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of D-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of D-lactic acidosis (D-la). Read More

    Intramyocellular lipid excess in the mitochondrial disorder MELAS: MRS determination at 7T.
    Neurol Genet 2017 Jun 25;3(3):e160. Epub 2017 May 25.
    Rare Brain Disorders Program (S.G., J.M.P.), Department of Neurology and Neurotherapeutics, Department of Pediatrics (S.G., J.M.P.), Advanced Imaging Research Center (J.R., C.R.M.), Department of Radiology (J.R., C.R.M.), Department of Internal Medicine (C.R.M.), Department of Physiology (J.M.P.), and Eugene McDermott Center for Human Growth & Development/Center for Human Genetics (J.M.P.), The University of Texas Southwestern Medical Center, Dallas.
    Objective: There is a paucity of objective, quantifiable indicators of mitochondrial disease available for clinical and scientific investigation.

    Methods: To this end, we explore intramyocellular lipid (IMCL) accumulation noninvasively by 7T magnetic resonance spectroscopy (MRS) as a reporter of metabolic dysfunction in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). We reasoned that mitochondrial dysfunction may impair muscle fat metabolism, resulting in lipid deposition (as is sometimes observed in biopsies), and that MRS is well suited to quantify these lipids. Read More

    Hyperlactetemia And Its Trends In Critically Ill Children Admitted In Pediatric Intensive Care Unit Of A Developing Country.
    J Ayub Med Coll Abbottabad 2016 Oct-Dec;28(4):660-663
    Department Of Paediatrics and Child Health, Aga Khan University Karachi, Pakistan.
    Background: There is increasing evidence that in setting of critical ailments clinical signs lag biomarkers like Lactate and hyperlactetemia can be the only marker for this disorder. This study was conducted to describe the incidence of hyperlactatemia in critically ill children and its association with outcome.

    Methods: Retrospective review of medical records of all children who had their lactic acid (LA) levels measured during their admission in PICU from January 2014 to December 2015 was done. Read More

    Clinical manifestations in two patients with pyruvate dehydrogenase deficiency and long-term survival.
    Hum Genome Var 2017 1;4:17020. Epub 2017 Jun 1.
    Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    Pyruvate dehydrogenase E1-alpha deficiency (PDHAD) results in lactic acidosis and hyperpyruvatemia. Two patients with PDHAD, a man with a p.R263Q mutation, and a girl with a p. Read More

    Human dihydrolipoamide dehydrogenase (E3) deficiency: Novel insights into the structural basis and molecular pathomechanism.
    Neurochem Int 2017 Jun 2. Epub 2017 Jun 2.
    Department of Medical Biochemistry, MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, Budapest, Hungary. Electronic address:
    This review summarizes our present view on the molecular pathogenesis of human (h) E3-deficiency caused by a variety of genetic alterations with a special emphasis on the moonlighting biochemical phenomena related to the affected (dihydro)lipoamide dehydrogenase (LADH, E3, gene: dld), in particular the generation of reactive oxygen species (ROS). E3-deficiency is a rare autosomal recessive genetic disorder frequently presenting with a neonatal onset and premature death; the highest carrier rate of a single pathogenic dld mutation (1:94-1:110) was found among Ashkenazi Jews. Patients usually die during acute episodes that generally involve severe metabolic decompensation and lactic acidosis leading to neurological, cardiological, and/or hepatological manifestations. Read More

    Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.
    Pediatr Diabetes 2017 Aug 1;18(5):327-331. Epub 2017 Jun 1.
    Glycogen Storage Disease Program, Connecticut Children's Medical Center, Hartford, Connecticut.
    Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes. Read More

    Renal function markers and metformin eligibility.
    Minerva Endocrinol 2017 May 31. Epub 2017 May 31.
    Serviço de Endocrinologia do Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal.
    Background: Metformin is the cornerstone of the pharmacological therapy for type 2 Diabetes (T2D). It belongs to the biguanide class of drugs and it improves hepatic insulin resistance and enhances GLP-1 and peptide YY secretion. Although being considered safe regarding hypoglycemic risk, renal dysfunction remains the main obstacle to its use due to the underlying risk of lactic acidosis. Read More

    Metformin is not associated with lactic acidosis in patients with diabetes undergoing coronary artery bypass graft surgery: a case control study.
    BMC Pharmacol Toxicol 2017 May 30;18(1):38. Epub 2017 May 30.
    Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
    Background: Metformin associated lactic acidosis (MALA) is a rare but lethal complication. There is no consensus regarding when to stop and resume metformin in patients who undergo coronary artery bypass grafting (CABG). This study aimed to determine if uninterrupted metformin administration in patients with diabetes undergoing CABG increases the risk of lactic acidosis. Read More

    Combination Clearance Therapy and Barbiturate Coma for Severe Carbamazepine Overdose.
    Pediatrics 2017 May;139(5)
    Divisions of Medicine Critical Care,
    A 15-year-old female subject presented comatose, in respiratory failure and shock, after the intentional ingestion of ∼280 extended-release 200-mg carbamazepine tablets with a peak serum concentration of 138 µg/mL (583.74 µmol/L). The patient developed clinical seizures and an EEG pattern of stimulus-induced rhythmic, periodic, or ictal discharges, suggestive of significant cortical dysfunction. Read More

    Consideration of alternative causes of lactic acidosis: Thiamine deficiency in malignancy.
    Am J Emerg Med 2017 May 15. Epub 2017 May 15.
    Department of Medicine, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, United States.
    Lactic acidosis is a common metabolic acidosis characterized by increased serum lactate and is usually associated with a decreased blood pH. Lactic acidosis has many different causes but has been differentiated into type A, hypoxic causes, and type B, non-hypoxic causes. Tissue hypoxia, type A, is the most common cause, usually secondary to processes such as sepsis and multi-organ failure. Read More

    Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.
    Expert Opin Drug Saf 2017 Jul 1;16(7):833-843. Epub 2017 Jun 1.
    a Dipartimento di Anestesia, Rianimazione ed Emergenza-Urgenza , Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico , Milan , Italy.
    Introduction: Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Read More

    Diabetes Update: New Pharmacotherapy for Type 2 Diabetes.
    FP Essent 2017 May;456:27-35
    University of Tennessee Health Science Center Department of Medical Education, 920 Madison Building 7th floor, Memphis, TN 3816-30000.
    Multiple new drugs for managing type 2 diabetes have entered the market in the past 5 years. Guidelines from the American Diabetes Association recommend metformin for initial therapy, followed by a second drug if A1c goals are not met or initially for patients with A1c levels greater than 9%. Conversely, the American Association of Clinical Endocrinologists recommends initial management with two drugs if the A1c level is greater than 7. Read More

    Risk of acute kidney injury and survival in patients treated with Metformin: an observational cohort study.
    BMC Nephrol 2017 May 19;18(1):163. Epub 2017 May 19.
    Division of Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK.
    Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure.

    Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. Read More

    Case report: a novel frameshift mutation in the mitochondrial cytochrome c oxidase II gene causing mitochondrial disorder.
    BMC Neurol 2017 May 18;17(1):96. Epub 2017 May 18.
    Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.
    Background: Mitochondrial cytochrome c oxidase 2, MT-CO2, encodes one of the three subunits, which form the catalytic core of cytochrome c oxidase (COX), complex IV. Mutations in MT-CO2 are rare and the associated phenotypes are variable including nonsyndromic and syndromic forms of mitochondrial diseases.

    Case Presentation: We describe a 30-year-old man with cognitive decline, epilepsy, psychosis, exercise intolerance, sensorineural hearing impairment, retinitis pigmentosa, cataract and lactic acidosis. Read More

    [Importance of stopping some medications in case of gastrointestinal disturbances leading to dehydration].
    Rev Med Liege 2017 May;72(5):266-271
    Service de Diabétologie, Nutrition et Maladies métaboliques et Unité de Pharmacologie clinique, CHU de Liège, Site Sart Tilman, Liège, Belgique.
    This clinical case draws attention to the importance of stopping some medications in case of gastrointestinal disturbances that could induce dehydration. The latter can provoke an acute renal failure, which may lead to a toxic accumulation of these pharmacological agents and/or increase their nephrotoxicity. This may induce a vicious circle that is potentially dangerous and even fatal. Read More

    Renal manifestations of primary mitochondrial disorders.
    Biomed Rep 2017 05 12;6(5):487-494. Epub 2017 Apr 12.
    Paulista de Medicina School, Federal University of São Paulo, Primeiro Andar CEP, São Paulo 04039-032, SP, Brazil.
    The aim of the present review was to summarize and discuss previous findings concerning renal manifestations of primary mitochondrial disorders (MIDs). A literature review was performed using frequently used databases. The study identified that primary MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or in the later course of the MID. Read More

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