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Cureus May 2022D-lactic acidosis (D-LA) is closely associated with short bowel syndrome (SBS). Decreased intestinal absorption results in the delivery of carbohydrates to the colon,...
D-lactic acidosis (D-LA) is closely associated with short bowel syndrome (SBS). Decreased intestinal absorption results in the delivery of carbohydrates to the colon, where the fermentation by colonic flora leads to D-LA. Systemic absorption of D-lactic acid results in anion-gap metabolic acidosis (AGMA), LA, and neurologic symptoms. In this report, we describe the case of a 43-year-old man with Crohn's disease (CD) and bowel resection who presented with abdominal pain and slurred speech. He was found to have AGMA and persistent LA despite receiving intravenous fluids, which improved after carbohydrate restriction. A high index of suspicion for D-LA should be maintained when encountering patients who have undergone bowel resection and with unexplained AGMA.
PubMed: 35783896
DOI: 10.7759/cureus.25471 -
Neurology Jun 2022Stroke management in the context of primary mitochondrial disease is clinically challenging, and the best treatment options for patients with stroke-like episodes remain...
BACKGROUND AND OBJECTIVES
Stroke management in the context of primary mitochondrial disease is clinically challenging, and the best treatment options for patients with stroke-like episodes remain uncertain. We sought to perform a systematic review of the safety and efficacy of l-arginine use in the acute and prophylactic management of stroke-like episodes in patients with mitochondrial disease.
METHODS
The systematic review was registered in PROSPERO (CRD42020181230). We searched 6 databases from inception to January 15, 2021: MEDLINE, Embase, Scopus, Web of Science, CINAHL, and ClinicalTrials.gov. Original articles and registered trials available, in English, reporting l-arginine use in the acute or prophylactic management of stroke-like episodes in patients with genetically confirmed mitochondrial disease were eligible for inclusion. Data on safety and treatment response were extracted and summarized by multiple observers. Risk of bias was assessed by the methodologic quality of case reports, case series, and a risk-of-bias checklist for nonrandomized studies. Quality of evidence was synthesized with the Oxford Centre for Evidence-Based Medicine Levels of Evidence and Grade of Recommendations. The predetermined main outcome measures were clinical response to l-arginine treatment, adverse events, withdrawals, and deaths (on treatment and/or during follow-up), as defined by the author.
RESULTS
Thirty-seven articles met inclusion criteria (0 randomized controlled trials; 3 open-label; 1 retrospective cohort; 33 case reports/case series) (N = 91 patients; 86% m.3243A>G). In the case reports, 54% of patients reported a positive clinical response to acute l-arginine, of which 40% were concomitantly treated with antiepileptic drugs. Improved headache at 24 hours was the greatest reported benefit in response to IV l-arginine in the open-label trials (31 of 39, 79%). In 15 of 48 patients (31%) who positively responded to prophylactic l-arginine, antiepileptic drugs were either used (7 of 15) or unreported (8 of 15). Moderate adverse events were reported in the follow-up of both IV and oral l-arginine treatment, and 11 patients (12%) died during follow-up or while on prophylactic treatment.
DISCUSSION
The available evidence is of poor methodologic quality and classified as Level 5. IV and oral l-arginine confers no demonstrable clinical benefit in either the acute or prophylactic treatment of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, with more robust controlled trials required to assess its efficacy and safety profile.
Topics: Acidosis, Lactic; Anticonvulsants; Arginine; Humans; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Retrospective Studies; Stroke
PubMed: 35428733
DOI: 10.1212/WNL.0000000000200299 -
Nefrologia 2019
Topics: Acidosis, Lactic; Acute Kidney Injury; Aged; Contraindications, Drug; Diuretics; Female; Humans; Hypoglycemic Agents; Male; Metformin; Renal Dialysis
PubMed: 31208831
DOI: 10.1016/j.nefro.2019.03.005 -
Journal of Education & Teaching in... Jul 2021Glycogenic hepatopathy is a rare condition that may be seen in patients with poorly controlled diabetes mellitus. This is a case presentation of a 15-year-old female...
UNLABELLED
Glycogenic hepatopathy is a rare condition that may be seen in patients with poorly controlled diabetes mellitus. This is a case presentation of a 15-year-old female with type 1 diabetes mellitus who was not fully adherent to her insulin regimen and presented in acute diabetic ketoacidosis. She had the associated symptom of two months of abdominal pain. The patient's ketoacidosis resolved during her hospitalization with insulin and intravenous fluid management; however, her lactic acid and liver transaminases remained persistently elevated. Abdominal ultrasound was consistent with parenchymal liver disease and a clinical diagnosis of glycogenic hepatopathy was made. Management consisted of tight glucose control. After discharge, the patient was followed closely by pediatric endocrinology and pediatric gastroenterology, and once her glucose was optimized, her transaminitis and lactic acidosis resolved. Although an uncommon condition, it is important to consider glycogenic hepatopathy in diabetic patients with poor glucose control, abdominal pain, transaminitis and lactic acidosis.
TOPICS
Diabetic ketoacidosis, hepatopathy, lactic acidosis, transaminitis, glycogen, diabetes mellitus. Brown D, et al. A Case Report of Glycogenic Hepatopathy. JETem 2021. 6(3):V1-3.
PubMed: 37465067
DOI: 10.21980/J8SQ0Z -
Annals of Medicine and Surgery (2012) Jun 2023Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS) is a rare neurodegenerative inherited disorder that is characterized by stroke-like...
UNLABELLED
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS) is a rare neurodegenerative inherited disorder that is characterized by stroke-like episodes, seizures, endocrine, and multiple system involvement. It is important to consider it as a differential diagnosis in a young patient with stroke-like episodes as it is progressive and has multiple complications.
CASE PRESENTATION
A 28-year-old male presented with slurring of speech and drowsiness for 7 h. He was a diagnosed case of type 2 diabetes mellitus, Wolf-Parkinson-White syndrome, and bilateral hearing loss.
CLINICAL FINDINGS AND INVESTIGATIONS
The patient had expressive aphasia with impaired fluency, repetition, and naming. After being discharged, he represented with loss of consciousness and involuntary movements of the whole body. MRI and MRS showed extension of hyperintense lesions to parieto-occipital regions from temporal regions not limited by vascular territories. MELAS was considered, which was confirmed by molecular genetic analysis. Coenzyme Q10 was used for MELAS. Insulin, Linagliptin, and levetiracetam were used for diabetes and seizures. Regular follow-up was advised to the patient.MELAS is an important syndrome to consider in any young patient presenting with unexplained stroke disorders. A high index of suspicion is needed in an appropriate clinical setting to avoid misdiagnosis.
PubMed: 37363571
DOI: 10.1097/MS9.0000000000000712 -
Cureus Apr 2022Metformin is widely prescribed as the first-line medication for type II diabetes mellitus. While the gastrointestinal side effects of metformin such as nausea, vomiting,...
Metformin is widely prescribed as the first-line medication for type II diabetes mellitus. While the gastrointestinal side effects of metformin such as nausea, vomiting, diarrhea, and heartburn are quite common, one dangerous side effect of metformin, lactic acidosis, is extensively discussed yet rarely reported. Here, we discuss a 53-year-old female with type II diabetes mellitus who presented to an emergency department (ED) with chief complaints of dizziness and lightheadedness. The patient had chronic kidney disease (CKD) with a baseline estimated glomerular filtration rate (eGFR) of 45 mL/minute/1.73 m. Initial laboratory results showed acute kidney injury (AKI) with hyperkalemia and lactic acidosis of 20 mmol/L. The patient was admitted to the ICU requiring emergent dialysis. Later, she was diagnosed with metformin-associated lactic acidosis (MALA). Her AKI and lactic acidosis subsequently improved. Metformin-associated lactic acidosis (MALA) is a rare but serious side effect of metformin. It is primarily reported in patients with chronic renal failure; therefore, it should be used with caution in these patients. Renal replacement therapy (RRT) is the critical management option for patients with MALA. Because of this, physicians prescribing metformin should carefully monitor all patients and assess the risk of developing severe side effects.
PubMed: 35602825
DOI: 10.7759/cureus.24220 -
Journal of the American Heart... May 2022Background Lactic acidosis is associated with mortality in patients with cardiogenic shock (CS). Elevated lactate levels and systemic acidemia (low blood pH) have both...
Background Lactic acidosis is associated with mortality in patients with cardiogenic shock (CS). Elevated lactate levels and systemic acidemia (low blood pH) have both been proposed as drivers of death. We, therefore, analyzed the association of both high lactate concentrations and low blood pH with 30-day mortality in patients with CS. Methods and Results This was a 2-center historical cohort study of unselected patients with CS with available data for admission lactate level or blood pH. CS severity was graded using the Society for Cardiovascular Angiography and Intervention (SCAI) shock classification. All-cause survival at 30 days was analyzed using Kaplan-Meier curves and Cox proportional-hazards analysis. There were 1814 patients with CS (mean age, 67.3 years; 68.5% men); 51.8% had myocardial infarction and 53.0% had cardiac arrest. The distribution of SCAI shock stages was B, 10.8%; C, 30.7%; D, 38.1%; and E, 18.7%. In both cohorts, higher lactate or lower pH predicted a higher risk of adjusted 30-day mortality. Patients with a lactate ≥5 mmol/L or pH <7.2 were at increased risk of adjusted 30-day mortality; patients with both lactate ≥5 mmol/L and pH <7.2 had the highest risk of adjusted 30-day mortality. Patients in SCAI shock stages C, D, and E had higher 30-day mortality in each SCAI shock stage if they had lactate ≥5 mmol/L or pH <7.2, particularly if they met both criteria. Conclusions Higher lactate and lower pH predict mortality in patients with cardiogenic shock beyond standard measures of shock severity. Severe lactic acidosis may serve as a risk modifier for the SCAI shock classification. Definitions of refractory or hemometabolic shock should include high lactate levels and low blood pH.
Topics: Acidosis; Acidosis, Lactic; Aged; Cohort Studies; Female; Humans; Lactic Acid; Male; Shock; Shock, Cardiogenic
PubMed: 35491996
DOI: 10.1161/JAHA.121.024932 -
Epilepsy Associated With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes.Frontiers in Neurology 2021The present study explored the clinical characteristics and prognostic factors of epilepsy in patients with mitochondrial encephalomyopathy, lactic acidosis, and...
The present study explored the clinical characteristics and prognostic factors of epilepsy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Thirty-four MELAS patients were included in the present study. They were diagnosed by clinical characteristics, genetic testing, muscle biopsy, and retrospective analysis of other clinical data. The patients were divided into three groups according to the effects of treatment after at least 2 years of follow-up. Epilepsy was more common in male MELAS patients than in females (20/14). The age of onset ranged from 0.5 to 57 years, with an average of 22.6 years. Patients with epilepsy and MELAS had various forms of seizures. Focal seizures were the most common type affecting 58.82% of patients, and some patients had multiple types of seizures. The abnormal EEG waves were mainly concentrated in the occipital (69.57%), frontal (65.22%) and temporal lobes (47.83%). Overall, the prognosis of patients with epilepsy and MELAS was poor. Poor prognosis was associated with brain atrophy ( = 0.026), status epilepticus ( < 0.001), and use of anti-seizure medications with high mitochondrial toxicity ( = 0.015). Avoiding the application of anti-seizure medications with high mitochondrial toxicity, controlling seizures more actively and effectively, and delaying the occurrence and progression of brain atrophy as much as possible are particularly important to improve the prognosis of patients with MELAS and epilepsy.
PubMed: 34177782
DOI: 10.3389/fneur.2021.675816 -
Journal of Thoracic Disease Feb 2020Thiamine (vitamin B1) is a water-soluble vitamin essential for human health. Thiamine deficiency is causal and/or contributory in a number of debilitating diseases... (Review)
Review
Thiamine (vitamin B1) is a water-soluble vitamin essential for human health. Thiamine deficiency is causal and/or contributory in a number of debilitating diseases including beri-beri, the Wernicke-Korsakoff syndrome, optic neuropathy, and others. While thiamine deficiency is relatively rare in developed nations as a result of dietary supplementation, thiamine deficiency is more common in nutritionally compromised populations. Thiamine pyrophosphate, a thiamine derivative, is essential to the citric acid cycle and thiamine deficiency can result in impaired aerobic respiration and cellular energy production. Thiamine also plays an important role in the pentose phosphate pathway and other key metabolic processes. Although thiamine deficiency is a known cause of lactic acidosis, it has been recently evaluated as a potential contributor to refractory lactic acidosis and organ injury in septic shock and other shock states. In this article, we review the epidemiology of thiamine deficiency in septic shock and the existing evidence base supporting thiamine supplementation. We conclude that specific sepsis phenotypes may stand to benefit the most from thiamine supplementation, and efforts might be made to identify and supplement these patients early in their hospital course.
PubMed: 32148929
DOI: 10.21037/jtd.2019.12.82 -
World Journal of Diabetes Aug 2022Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data...
BACKGROUND
Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.
AIM
To analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.
METHODS
We performed a systematic search from PubMed, Science Direct, (https://www.referencecitationanalysis.com/) and Google Scholar databases using the terms "metformin" AND "toxicity" OR "overdose" OR "lactic acidosis" OR "hyperlactatemia". The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported toxicity or overdose of metformin in adults, published in the English language. Data regarding baseline demographics, clinical presentation, therapeutic interventions, intensive care unit course and overall outcome were collected.
RESULTS
Two hundred forty-two individual cases were analysed, from 158 case reports and 26 case series, with a cumulative mortality of 19.8%. 214 (88.4%) patients were diabetics on metformin. 57 (23.6%) had acute ingestion, but a great majority (76.4%) were on metformin in therapeutic doses when they developed toxicity. Metformin associated lactic acidosis (MALA) was the most commonly reported adverse effect present in 224 (92.6%) patients. Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia. The organ support used was renal replacement therapy (RRT) (68.6%), vaso-pressors (58.7%) and invasive mechanical ventilation (52.9%). A majority of patients (68.6%) received RRT for toxin removal, renal dysfunction and correction of MALA. Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.
CONCLUSION
Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions. These patients may develop severe lactic acidosis, leading to significant morbidity and need for organ support. Despite severe MALA and the need for multiple organ support, they may have good outcomes, especially when RRT is used. The dose of metformin, serum pH, lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.
PubMed: 36159225
DOI: 10.4239/wjd.v13.i8.654