An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.
Humans ; Infant, Newborn ; Female ; Aged ; Mutation ; Hyperlactatemia ; ATPases Associated with Diverse Cellular Activities/chemistry* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*

Combined oxidative phosphorylation deficiency-17 (COXPD-17) is very rare and is caused by homozygous or compound heterozygous mutations in the ELAC2 gene on chromosome 17p12. The ELAC2 gene functions as a mitochondrial tRNA processing gene, and only 4 different pathogenic mutations have been reported in ELAC2-associated mitochondrial dysfunction involving oxidative phosphorylation. Affected patients show various clinical symptoms and prognosis, depending on the genotype. We report a novel mutation in the ELAC2 gene (c.95C>G [p.Pro32Arg], het), in an infant with COXPD-17 who presented with encephalopathy including central apnea and intractable epilepsy, and growth and developmental retardation. During hospitalization, consistently elevated serum lactic acid levels were noted, indicative of mitochondrial dysfunction. The patient suddenly died of shock of unknown cause at 5 months of age. This is the first case report of COXPD-17 in Korea and was diagnosed based on clinical characteristics and genetic analysis.
Brain Diseases ; Drug Resistant Epilepsy ; Genotype ; Growth and Development ; Hospitalization ; Humans ; Hyperlactatemia ; Infant ; Korea ; Lactic Acid ; Oxidative Phosphorylation* ; Prognosis ; RNA, Transfer ; Shock ; Sleep Apnea, Central

Quercetin and resveratrol are known to have beneficial effects on the diabetes and diabetic complication, however, the effects of combined treatment of these compounds on diabetes are not fully revealed. Therefore, the present study was designed to investigate the combined antidiabetic action of quercetin (QE) and resveratrol (RS) in streptozotocin (STZ)-induced diabetic rats. To test the effects of co-treated with these compounds on diabetes, serum glucose, insulin, lipid profiles, oxidative stress biomarkers, and ions were determined. Additionally, the activities of hepatic glucose metabolic enzymes and histological analyses of pancreatic tissues were evaluated. 50 male Sprague-Dawley rats were divided into five groups; normal control, 50 mg/kg STZ-induced diabetic, and three (30 mg/kg QE, 10 mg/kg RS, and combined) compound-treated diabetic groups. The elevated serum blood glucose levels, insulin levels, and dyslipidemia in diabetic rats were significantly improved by QE, RS, and combined treatments. Oxidative stress and tissue injury biomarkers were dramatically inhibited by these compounds. They also shown to improve the hematological parameters which were shown to the hyperlactatemia and ketoacidosis as main causes of diabetic complications. The compounds treatment maintained the activities of hepatic glucose metabolic enzymes and structure of pancreatic β-cells from the diabetes, and it is noteworthy that cotreatment with QE and RS showed the most preventive effect on the diabetic rats. Therefore, our study suggests that cotreatment with QE and RS has beneficial effects against diabetes. We further suggest that cotreatment with QE and RS has the potential for use as an alternative therapeutic strategy for diabetes.
Animals ; Biomarkers ; Blood Glucose ; Diabetes Complications ; Dyslipidemias ; Glucose ; Humans ; Hyperlactatemia ; Insulin ; Ions ; Ketosis ; Male ; Oxidative Stress ; Quercetin* ; Rats* ; Rats, Sprague-Dawley ; Streptozocin

OBJECTIVE: To evaluate the clinical characteristics, therapeutic interventions, and outcomes of patients with septic shock admitted to the emergency department (ED). METHODS: This study was a preliminary, descriptive analysis of a prospective, multi-center, observational registry of the EDs of 10 hospitals participating in the Korean Shock Society. Patients aged 19 years or older who had a suspected or confirmed infection and evidence of refractory hypotension or hypoperfusion were included. RESULTS: A total of 468 patients were enrolled (median age, 71.3 years; male, 55.1%; refractory hypotension, 82.9%; hyperlactatemia without hypotension, 17.1%). Respiratory infection was the most common source of infection (31.0%). The median Sepsis-related Organ Failure Assessment score was 7.5. The sepsis bundle compliance was 91.2% for lactate measurement, 70.3% for blood culture, 68.4% for antibiotic administration, 80.3% for fluid resuscitation, 97.8% for vasopressor application, 68.0% for central venous pressure measurement, 22.0% for central venous oxygen saturation measurement, and 59.2% for repeated lactate measurement. Among patients who underwent interventions for source control (n=117, 25.1%), 43 (36.8%) received interventions within 12 hours of ED arrival. The in-hospital, 28-day, and 90-day mortality rates were 22.9%, 21.8%, and 27.1%, respectively. The median ED and hospital lengths of stay were 6.8 hours and 12 days, respectively. CONCLUSION: This preliminary report revealed a mortality of over 20% in patients with septic shock, which suggests that there are areas for improvement in terms of the quality of initial resuscitation and outcomes of septic shock patients in the ED.
Central Venous Pressure ; Compliance ; Emergency Service, Hospital ; Humans ; Hyperlactatemia ; Hypotension ; Lactic Acid ; Male ; Mortality ; Oxygen ; Patient Care Bundles ; Prospective Studies ; Resuscitation ; Sepsis ; Shock* ; Shock, Septic*

BACKGROUND: We evaluated the clinical usefulness of the quick Sepsis-Related Organ Failure Assessment (qSOFA) score (based on the 2016 definition of sepsis) at intensive care unit admission in Korean patients with bacteremia. METHODS: We retrospectively analyzed clinical data from 236 patients between March 2011 and February 2016. In addition to the qSOFA, the Modified Early Warning score (MEWS) and systemic inflammatory response syndrome (SIRS) criteria were calculated. RESULTS: The patients' median age was 69 years, and 61.0% were male. Of the patients, 127 (53.8%) had a qSOFA score ≥2 points. They had significantly higher rates of septic shock, thrombocytopenia, and hyperlactatemia, and increased requirements for ventilator care, neuromuscular blocking agents, vasopressors, and hemodialysis within 72 hours after intensive care unit admission. They also had a significantly higher 28-day mortality rate. When analyzed using common thresholds (MEWS ≥5 and ≥2 SIRS criteria), patients with a MEWS ≥5 had the same results as those with a qSOFA score ≥2 (P < 0.05). However, patients with ≥2 SIRS criteria showed no significant differences. CONCLUSIONS: Our results show that a qSOFA score ≥2 at admission is a useful screening tool for predicting disease severity and medical resource usage within 72 hours after admission, and for predicting 28-day mortality rates in patients with bacteremia. In addition, qSOFA scores may be more useful than SIRS criteria in terms of prognostic utility.
Bacteremia* ; Critical Care* ; Humans ; Hyperlactatemia ; Intensive Care Units* ; Korea* ; Male ; Mass Screening ; Mortality ; Neuromuscular Blocking Agents ; Prognosis ; Renal Dialysis ; Retrospective Studies ; Sepsis ; Shock, Septic ; Systemic Inflammatory Response Syndrome ; Thrombocytopenia ; Ventilators, Mechanical

PURPOSE: This study was performed to compare clinical significance between lactate and carboxyhemoglobin (COHb) in a patient with carbon monoxide (CO) poisoning. METHODS: We conducted a 13-year retrospective study on CO poisoning patients who visited the emergency departments of the Medical Center between October 2004 and January 2016. The patients were divided into two groups according to initial lactate levels. Patients with serum lactate levels of ≤2 mmol/L were classified as the normolactatemia group (n=14), and patients with serum lactate levels of >2 mmol/L were classified as the hyperlactatemia group (n=34). General characteristics, clinical features, and laboratory findings of the two groups were compared. In addition, we compared initial lactate levels with COHb levels according to complications, neurological disorder, myocardial enzyme elevation, and abnormal Glasgow Coma Scale (GCS) score in patients with CO poisoning. We also analyzed the correlation between laboratory parameters and lactate levels. RESULTS: Forty-eight patients were enrolled in this study. The hyperlactatemia group had significantly more neurological disorders and consciousness disorders than the normolactatemia group (p<0.001), and COHb, creatine phosphokinase MB, and troponin I levels were also significantly higher in the hyperlactatemia group (p<0.001, p=0.017, and p=0.007). Lactate levels were significantly elevated in patients with elevated cardiac enzymes (p=0.001), neurological disorders (p<0.001), complications (p=0.001), and abnormal GCS score (p<0.001), whereas COHb levels were not significantly increased in all subjects. The correlation between COHb and lactate levels was weak (r=0.313, p=0.030), and a positive correlation was found between lactate and bicarbonate (HCO3), white blood cell, and troponin I (p<0.001). The diagnostic value of lactate for severe CO poisoning was analyzed using a receiver operating characteristic curve. The optimal cut-off value of lactate was 2.2 mmol/L with 83.3% sensitivity and 91.7% specificity (p<0.001). CONCLUSION: Lactate has significant diagnostic efficacy in patients with CO poisoning. It is recommended that lactate level be measured for appropriate treatment and prognostic evaluation of CO poisoning.
Carbon Monoxide Poisoning* ; Carbon Monoxide* ; Carbon* ; Carboxyhemoglobin* ; Consciousness Disorders ; Creatine Kinase ; Emergency Service, Hospital ; Glasgow Coma Scale ; Humans ; Hyperlactatemia ; Lactates ; Lactic Acid* ; Leukocytes ; Nervous System Diseases ; Poisoning ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Troponin I

Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica. The model reproduces numerous symptoms characteristic of human sepsis including hyperlactatemia, hyperglycemia, leukopenia, hypothermia and the hyperproduction of several pro-inflammatory cytokines. Hence, it was chosen to investigate the proposed ability of Pep19-2.5—an anti-endotoxic peptide with high affinity to lipopolysaccharide and lipoprotein—to attenuate sepsis-associated pathologies in combination with an antibiotic (ceftriaxone). We demonstrate that a combination of Pep19-2.5 and ceftriaxone administered intravenously to the rabbits (1) kills bacteria and eliminates bacteremia 30 min post challenge; (2) inhibits Toll-like receptor 4 agonists in serum 90 min post challenge; (3) reduces serum levels of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α); and (4) reverts to hypothermia and gives rise to temperature values indistinguishable from basal levels 330 min post challenge. The two components of the combination displayed synergism in some of these activities, and Pep19-2.5 notably counteracted the endotoxin-inducing potential of ceftriaxone. Thus, the combination therapy of Pep19-2.5 and ceftriaxone holds promise as a candidate for human sepsis therapy.
Animals ; Bacteremia ; Bacteria ; Bacterial Infections ; Cause of Death ; Ceftriaxone ; Cytokines ; Homicide* ; Humans ; Hyperglycemia ; Hyperlactatemia ; Hypothermia ; Leukopenia ; Mice ; Models, Animal ; Pathology ; Rabbits* ; Salmonella enterica ; Sepsis* ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha

PURPOSE: Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes. MATERIALS AND METHODS: This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007–2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m2. Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35. RESULTS: Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Most patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327–15.965)]. CONCLUSION: Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.
Acidosis, Lactic* ; Anoxia ; Cross-Sectional Studies ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Glomerular Filtration Rate ; Humans ; Hydrogen-Ion Concentration ; Hyperlactatemia ; Lactic Acid* ; Metformin* ; Mortality ; Perfusion ; Plasma ; Prevalence ; Risk Factors

PURPOSE: Patients suffering from acute poisoning by different substances often visit the emergency department (ED) and receive various prognoses according to the toxic material and patients' condition. Hyperlactatemia, which is an increased blood lactate level that generally indicates tissue hypoperfusion, is commonly utilized as a prognostic marker in critically ill patients such as those with sepsis. This study was conducted to investigate the relationships between blood lactate and clinical prognosis in acute poisoned patients. METHODS: This retrospective study was conducted from January 2013 to June 2014 at a single and regional-tertiary ED. We enrolled study patients who were examined for blood test with lactate among acute intoxicated patients. The toxic materials, patient demographics, laboratory data, and mortalities were also reviewed. Additionally, we analyzed variables including blood lactate to verify the correlation with patient mortality. RESULTS: A total of 531 patients were enrolled, including 24 (4.5%) non-survivors. Patient age, Glasgow coma scale (GCS), serum creatinine (Cr), aspartate transaminase (AST), and serum lactate differed significantly between survivors and non-survivors in the binary logistic regression analysis. Among these variables, GCS, AST, and lactate differed significantly. The median serum lactate levels were 2.0 mmol/L among survivors and 6.9 mmol/L among non-survivors. The AUC with the ROC curve and odds ratio of the initial serum lactate were 0.881 and 3.06 (0.89-8.64), respectively. CONCLUSION: Serum lactate was correlated with fatalities of acute poisoning patients in the ED; therefore, it may be used as a clinical predictor to anticipate their prognoses.
Area Under Curve ; Aspartate Aminotransferases ; Creatinine ; Critical Illness ; Demography ; Emergencies* ; Emergency Service, Hospital* ; Glasgow Coma Scale ; Hematologic Tests ; Humans ; Hyperlactatemia ; Lactic Acid* ; Logistic Models ; Mortality* ; Odds Ratio ; Poisoning ; Prognosis ; Retrospective Studies ; ROC Curve ; Sepsis ; Survivors

BACKGROUNDAfter cardiac surgery, central venous oxygen saturation (ScvO 2 ) and serum lactate concentration are often used to guide resuscitation; however, neither are completely reliable indicators of global tissue hypoxia. This observational study aimed to establish whether the ratio between the veno-arterial carbon dioxide and the arterial-venous oxygen differences (P(v-a)CO 2 /C(a-v)O 2 ) could predict whether patients would respond to resuscitation by increasing oxygen delivery (DO 2 ).

METHODSWe selected 72 patients from a cohort of 290 who had undergone cardiac surgery in our institution between January 2012 and August 2014. The selected patients were managed postoperatively on the Intensive Care Unit, had a normal ScvO 2 , elevated serum lactate concentration, and responded to resuscitation by increasing DO 2 by >10%. As a consequence, 48 patients responded with an increase in oxygen consumption (VO 2 ) while VO 2 was static or fell in 24.

RESULTSAt baseline and before resuscitative intervention in postoperative cardiac surgery patients, a P(v-a)CO 2 /C(a-v)O 2 ratio ≥1.6 mmHg/ml predicted a positive VO 2 response to an increase in DO 2 of >10% with a sensitivity of 68.8% and a specificity of 87.5%.

CONCLUSIONSP(v-a)CO 2 /C(a-v)O 2 ratio appears to be a reliable marker of global anaerobic metabolism and predicts response to DO 2 challenge. Thus, patients likely to benefit from resuscitation can be identified promptly, the P(v-a)CO 2 /C(a-v)O 2 ratio may, therefore, be a useful resuscitation target.

Adult ; Aged ; Blood Gas Analysis ; Carbon Dioxide ; blood ; Cardiac Surgical Procedures ; Female ; Humans ; Hyperlactatemia ; blood ; therapy ; Intensive Care Units ; statistics & numerical data ; Lactic Acid ; blood ; Male ; Middle Aged ; Oxygen Consumption ; physiology ; Prospective Studies ; Resuscitation