management of lactic acidosis

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) have acquired a foothold in managing type 2 diabetes mellitus, but few concerns have arisen regarding their overall safety profile. The aim of this study is to assess the potential risk of DPP-4 inhibitors by analyzing data from the FDA Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: This is a retrospective study which explored the FAERS database till March 2023 for the collection of safety reports...

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established...

BACKGROUND: Current labelling advises discontinuation of metformin when estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 due to increased risk of lactic acidosis. However, in real-world practice, the risk-benefit ratios remain uncertain. We examined the risk associations of discontinued-metformin use with cardiorenal and clinical outcomes in patients with type 2 diabetes (T2D) and advanced chronic kidney disease. METHODS: In this territory-wide, retrospective cohort and target trial emulation study, we included Chinese patients attending the Hong Kong Hospital Authority (HA) and enrolled in the Risk-Assessment-and-Management-Programme-for-Diabetes-Mellitus (RAMP-DM) from 2002 to 2019...

An 11-month-old girl with severe acidosis, lethargy and vomiting, was diagnosed with holocarboxylase synthetase deficiency. She received biotin and was stable until age 8 years when vomiting, severe acidosis, hypoglycemia, and hyperammonemia developed. Management with intravenous glucose aiming to stimulate anabolism led to hyperglycemic ketoacidosis. Insulin therapy rapidly corrected biochemical parameters, and clinical status improved. We propose that secondary Krebs cycle disturbances affecting pancreatic beta cells impaired glucose-stimulated insulin secretion, resulting in insulinopenia...

Ethylene glycol (EG) is an organic compound used in antifreeze. In 2020 alone, there were 5,277 EG exposures, with only 617 reported as intentional ingestions. Therefore, encountering EG toxicity is rare; however, it is essential to identify it promptly based on a focused history, exam, and rapid identification of commonly associated EG-induced metabolic derangements. If the diagnosis is not made within 12 hours of ingestion or exposure, severe morbidity and mortality can occur. Previous reports of EG poisoning have occurred in the setting of a lactate gap (LG) and osmolar gap (OG); however, they also had commonly associated findings of EG toxicity such as high anion gap acidosis (HAGMA), acute kidney injury (AKI), hypocalcemia, calcium oxalate stones, and suggestive histories of EG ingestion...

Combining a Sodium-Glucose-Cotransporter-2-inhibitor (SGLT2i) with metformin is recommended for managing hyperglycemia in patients with type 2 diabetes (T2D) who have cardio-renal complications. Our study aimed to investigate the metabolic effects of SGLT2i and metformin, both individually and synergistically. We treated leptin receptor-deficient (db/db) mice with these drugs for two weeks and conducted metabolite profiling, identifying 861 metabolites across kidney, liver, muscle, fat, and plasma. Using linear regression and mixed-effects models, we identified two SGLT2i-specific metabolites, X-12465 and 3-hydroxybutyric acid (3HBA), a ketone body, across all examined tissues...

Elevated cancer metabolism releases lactic acid and CO2 into the under-perfused tumor microenvironment, resulting in extracellular acidosis. The surviving cancer cells must adapt to this selection pressure; thus, targeting tumor acidosis is a rational therapeutic strategy to manage tumor growth. However, none of the major approved treatments are based explicitly on disrupting acid handling, signaling, or adaptations, possibly because the distinction between acid-sensitive and acid-resistant phenotypes is not clear...

Clostridia perfringens infection outside the gastrointestinal system is rare. Here, we report on a 75-year-old man with history of end-stage renal disease presenting after a syncopal event with lactic acidosis, leukocytosis, and mild hyper-bilirubinemia. Chest imaging revealed a loculated, left-sided pleural effusion; diagnostic thoracentesis identified Clostridia perfringens , consistent with an empyema. Video-assisted thoracic left lung decortication was performed; tissue culture also speciated Clostridia perfringens ...

INTRODUCTION: Traumatic pneumothorax (PTX) is a common occurrence in thoracic trauma patients, with a majority requiring tube thoracostomy (TT) for management. Recently, the "35-mm" rule has advocated for observation of patients with PTX less than 35 mm on chest computed tomography (CT) scan. This rule has not been examined in chest x-ray (CXR). We hypothesize that a similar size cutoff can be determined in CXR predictive of need for tube thoracostomy. METHODS: We performed a single-institution retrospective review of patients with traumatic PTX from 2018 - 2022, excluding those who underwent TT prior to CXR...

A 59-year-old male with a history of alcohol abuse presented with altered mental status. Upon examination, he was hypertensive and lethargic, and laboratory results revealed severe transaminitis, coagulopathy, and lactic acidosis, despite having normal serum alcohol levels. Additionally, his urine drug screen tested positive for methamphetamine. Following the exclusion of infectious, autoimmune, and other common causes of acute hepatitis, a diagnosis of methamphetamine-induced acute hepatitis was established...

BACKGROUND/PURPOSE: MEGDHEL syndrome is a rare autosomal recessive metabolic disorder, which is characterized by 3-methylglutaconic aciduria with deafness-dystonia, hepatopathy, encephalopathy and Leigh-like syndrome. It is caused by biallelic pathogenic variants in the SERAC1 gene. Due to the unspecific symptoms and the diverse manifestations of the clinical phenotype, the diagnosis is challenging. Infantile MEGDHEL syndrome often has a severe disease course with acute liver failure...

BACKGROUND: Metformin is a biguanide hyperglycemic agent used to manage non-insulin-dependent diabetes mellitus. Adverse reactions include mainly mild gastrointestinal adverse effects, but severe complications, such as metformin-associated lactic acidosis (MALA) can occur. Metformin is excreted renally and, therefore, not recommended in patients with renal impairment. The reported incidence of MALA is 3 cases per 100,000 patient-years. CASE REPORT: A 79-year-old woman with a complex medical history, including end-stage renal disease on dialysis and type 2 diabetes, presented to the emergency department (ED) for altered mental status...

UNLABELLED: MELAS - an acronym for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes - is a multiorgan disease caused by a mutation in mitochondrial DNA (mtDNA). Its clinical manifestations are highly variable; mainly stroke-like episodes, seizures, recurrent headaches, or muscle weakness. However, gastrointestinal complications such as chronic intestinal pseudo-obstruction (IPO), pancreatitis, gastroparesis and hepatopathy are also common. In this report we describe a young patient with gastrointestinal complication of MELAS which led to superior mesenteric artery syndrome (SMAS)...

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...

BACKGROUND: Deoxyguanosine kinase (DGUOK) deficiency is a rare mitochondrial disorder characterized by early onset liver failure and varying degrees of neurologic dysfunction. Patients typically present during infancy with progressive hepatic dysfunction leading to liver failure, which can precede neurologic deterioration. Outcomes posttransplantation are historically worse than average and the role of liver transplantation remains controversial. These factors, in combination with the increasing number of patients being diagnosed via molecular genetic testing, may impede waitlist access...

BACKGROUND: Glycogen storage disease (GSD) is a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. GSD type Ia is a congenital deficiency of the enzyme responsible for the final step in glucose production by glycolysis, resulting in impaired carbohydrate metabolism. CASE PRESENTATION: A 14-year-old boy with GSD type Ia was scheduled for a maxillary cystectomy under general anesthesia. He was taking oral sugars such as uncooked cornstarch regularly to prevent hypoglycemia...

Metformin-associated lactic acidosis (MALA) is a severe side effect of metformin treatment. We encountered an exceedingly rare case of MALA in a patient taking metformin at recommended doses who had no risk factors except for advanced age. A 77-year-old male with a diagnosis of lactic acidosis was referred to our facility. He was taking 250 mg/day of metformin for diabetes. Although he had no pre-existing chronic kidney disease, he developed acute kidney injury upon admission, leading to the diagnosis of MALA based on the test results and history of metformin use...

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may be a life-saving rescue therapy for patients with severe cardiac disease of any origin and circulatory failure. Data in the literature have demonstrated that the use of advanced mechanical circulation has resulted in improvements in both survival and quality of life; despite this, cardiogenic shock and refractory cardiac arrest remain conditions with high mortality. Opportune identification of patients who can benefit from it may improve outcomes...

Timely diagnosis of persistent neonatal hypoglycemia is critical to prevent neurological sequelae, but diagnosis is complicated by the heterogenicity of the causes. We discuss two cases at separate institutions in which clinical management was fundamentally altered by the results of molecular genetic testing. In both patients, critical samples demonstrated hypoketotic hypoglycemia and a partial glycemic response to glucagon stimulation, thereby suggesting hyperinsulinism (HI). However, due to rapid genetic testing, both patients were found to have deoxyguanosine kinase (DGUOK)-related mitochondrial DNA depletion syndrome, an unexpected diagnosis...

BACKGROUND: Metformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential...