Unveiling of Type B Lactic Acidosis From Systemic Lupus Erythematosus-Associated B-cell Lymphoma: A Fatal Oncology Emergency.

Type B lactic acidosis is a rare oncological emergency usually associated with leukemia and lymphoma but also with solid malignancies. It can often go unrecognized as a possible source of lactic acidosis, leading to a delay in treatment. We review a 56-year-old woman with systemic lupus erythematosus and generalized lymphadenopathy being evaluated for underlying malignancy who presented with dyspnea, fatigue, and hematemesis. The patient was hemodynamically unstable and had severe lactic acidosis, leukocytosis, electrolyte derangements, multiple organ damage, and worsening diffuse lymphadenopathy. She was initially treated for septic shock due to acalculous cholecystitis on imaging with antibiotics and a cholecystostomy. The latter was complicated by a liver laceration requiring explorative laparotomy and open cholecystectomy, during which an excisional biopsy of the omental lymph node was done and confirmed B-cell lymphoma with marked plasmacytic differentiation. Her lactic acidosis never fully cleared despite surgery, and the refractory nature of it despite appropriate treatment of septic shock confirmed the diagnosis of type B lactic acidosis from underlying B-cell lymphoma. Chemotherapy was deferred due to the acuity of the condition. She continued to deteriorate despite aggressive management and was transitioned to comfort measures only per family request, following which she passed away. Type B lactic acidosis should be suspected in oncology patients without clinical evidence of ischemia who are not responding to fluid resuscitation and appropriate treatment of septic shock. Prompt recognition and early initiation of antineoplastic agents should be considered, when possible, to prevent adverse outcomes.

Stress Hyperglycemia Secondary to Abdominal Emergency Mimicking Diabetic Ketoacidosis in a Pediatric Patient.

Abdominal pain in a pediatric patient with diabetic ketoacidosis (DKA) can be mistaken for surgical or septic causes of acute abdomen. Both DKA and surgical abdominal emergencies can cause lactic acidosis (LA), which makes it challenging to differentiate between them. Fluid therapy resulting in quick alleviation of metabolic acidosis could be a valuable sign in differentiating surgical abdomen from DKA. In this report, we present a case of the surgical abdomen with stress hyperglycemia that mimicked DKA.

Acute Onset Lactic Acidosis Secondary to Linezolid.

Linezolid has been the mainstay of treatment for multidrug-resistant Gram-positive bacteria. Common adverse effects with linezolid include diarrhea, nausea, headache, and bone marrow suppression. A less common and understudied side effect is lactic acidosis. This study describes a 19-year-old man with linezolid-induced lactic acidosis (LILA). The patient was admitted for the management of acute decompensated systolic heart failure, which improved on guideline-directed medication therapy (GDMT). During hospitalization, he developed an erythematous weeping cellulitis infection of his right lower extremity and was started on linezolid 600 mg every 12 hours with wound and blood cultures collected. After one day of treatment with linezolid, lactic acid levels acutely increased from 1.8 mmol/L to 5 mmol/L without any other interventions. Suspecting possible LILA, linezolid was transitioned to cephalexin with a reduction of lactic acid to 2.4 mmol/L, one day following linezolid cessation. After two days of linezolid cessation, lactic acid levels decreased to 1.9 mmol/L. Lactic acidosis can have profound hemodynamic consequences for patients, including death. A meta-analysis study of 35 articles with 47 patients (28 males, 18 females, and one non-binary) was done, which found a 25.5% mortality rate associated with LILA. Due to this high mortality, having a greater understanding of the associated risk factors with LILA is very important. This case study aims to inform clinicians of the potential harmful side effects associated with linezolid, as well as the understudied risk factors involved in LILA that are needed to prevent its occurrence.

Transcutaneous delivery of sodium bicarbonate increases intramuscular pH.

Introduction: Oral bicarbonate loading improves the buffering of metabolic acidosis and may improve exercise performance but can also result in gastric distress. Momentous' PR Lotion contains a novel composition intended to provide a transdermal delivery vehicle for sodium bicarbonate which could allow the same ergogenic effect without the gastric distress. The present study explored the effect of transdermal delivery of sodium bicarbonate in a resting condition. Methods: We measured the pH from intramuscular dialysate, via microdialysis, of the vastus lateralis during a 2 h application of PR Lotion (40 g of lotion per leg) in 9 subjects (3 women, 6 men). Venous blood samples were obtained for serum pH before and after application. A placebo time control was also performed in 4 subjects (2 women, 2 men). We hypothesized that PR Lotion application would increase pH of intramuscular dialysate. Results: PR Lotion resulted in a rise in pH of 0.13 ± 0.04 units (p < 0.05), which translates to a 28% reduction in [H+]. Increases in serum pH were smaller (∼9%) yet consistent (p < 0.05). In contrast, placebo time control pH tended to decrease (p = 0.08). The effect of PR Lotion on pH tended to correlate with the dose per kg body weight of each individual (r = 0.70, p = 0.08). Conclusion: These observations support the idea of transdermal bicarbonate delivery impacting pH buffering both systemically and intramuscularly. Further work investigating these potential benefits in an exercising model would be critical to establishing PR Lotion's utility as an ergogenic aid.

Prenatal diagnosis of pyruvate dehydrogenase E1-α deficiency: a case report / 中华围产医学杂志

This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

A Rare Case of Type B Neonatal Pyruvate Carboxylase Enzyme Deficiency Presenting With Refractory Lactic Acidosis in the Early Neonatal Period.

Pyruvate carboxylase (PC) enzyme deficiency is a rare genetic disorder inherited in an autosomal recessive (AR) manner. PC, a mitochondrial enzyme, converts pyruvate to oxaloacetate (OAA), which enters the tricarboxylic acid (TCA) cycle. Based on the tissue type, intermediate metabolites of the TCA cycle play a vital role in gluconeogenesis, lipogenesis, synthesis of nicotinamide adenine dinucleotide phosphate (NADPH), and neurotransmitter glutamate in the astrocytes. The severity of clinical presentation depends on the type of PC deficiency and on the residual enzyme activity. We present a term female infant admitted with refractory lactic acidosis that developed soon after birth. On biochemical evaluation, serum ammonia was 125 µmol/L; plasma amino acid analysis showed elevated citrulline, lysine, proline, decreased glutamine, and aspartic acid; urine organic acid analysis showed markedly increased lactic acid, and moderately elevated 3-hydroxy-butyric and acetoacetic acid. MRI brain demonstrated abnormal diffuse white matter edema, loculated and septate large cysts along the caudothalamic notch as well as lateral aspect of the frontal horn bilaterally. Magnetic resonance (MR) spectroscopy showed large amounts of lactate peak. Molecular genetic analysis showed two pathogenic variants in the PC gene confirming the diagnosis of PC enzyme deficiency. The infant was discharged home on palliative and hospice care, and she died on the 22nd day after birth.

Identification of two novel variants of BCS1L gene in a patient with classical GRACILE syndrome.

BCS1L pathogenic variants cause widely different clinical phenotypes. Disease phenotypes can be as mild as Björnstad syndrome, characterized by pili torti (abnormal flat twisted hair shafts) and sensorineural hearing loss, or as severe as GRACILE syndrome, characterized by growth restriction, aminoaciduria, cholestasis, iron overload, lactic acidosis and early death. BCS1L pathogenic variants are also linked to an undefined complex III deficiency, a heterogeneous condition generally involving renal and hepatic pathologies, hypotonia, and developmental delays. So far, all patients with GRACILE syndrome carry a homozygous p.Ser78Gly variant in BCS1L gene by reviewing articles. A 24-day-old boy presented with typical clinical phenotype of GRACILE syndrome. The Whole Exome Sequencing confirmed that the patient had a missense variant (c.245C > T, p.Ser82Leu) and a small deletion (c.231_232delCA, p. Ser78Cysfs*9) in BCS1L gene inherited from his father and mother separately, he died at 5 months of age. We reported a patient with GRACILE syndrome and identified two novel variants in BCS1L gene. Our study expands the mutational spectrum of BCS1L gene associated with GRACILE syndrome and will be beneficial for genetic diagnosis.

A case of combined oxidative phosphorylation deficiency type 10 with tachypnea as first manifestation / 中华围产医学杂志

A term infant born small for gestational age presented with tachypnea as the first symptom one week after birth and had recurrent lactic acidosis. Whole-exome sequencing revealed compound heterozygous variants of c.1640C>T(p.A547V) and c.1274delG(p.G425Efs*23) in MTO1 gene, based on which the patient was diagnosed as combined oxidative phosphorylation deficiency type 10. The patient developed Klebsiella pneumoniae sepsis and died at 41 days of age. Combined oxidative phosphorylation deficiency type 10 is a type of mitochondrial disease inherited in an autosomal recessive manner. Patients with the onset of symptoms in the neonatal period are likely to have a poor prognosis and there is no effective treatment at present. The heterozygous variants of c.1640C>T and c.1274delG detected in this case are de novo variants, which expand the spectrum of variants in MTO1 gene.

Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation / 中华内科杂志

Objective:To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily.Methods:The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test.Results:A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively ( P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively ( P<0.001, P=0.001). Conclusion:The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

Metformin-induced Lactic Acidosis Reported in the Youngest Pediatric Patient with Impaired Renal Function.

Metformin is a widely used biguanide for the treatment of type 2 diabetes mellitus. Metformin-induced lactic acidosis (MALA) is a rare but potentially fatal entity in the pediatric age group, seen mainly in suicide attempts in adolescents. MALA has not yet been reported in younger patients or pediatric patients taking regular therapeutic doses. Here, we report a three-year-old female receiving therapeutic metformin who developed MALA. MALA should be suspected in patients with unexplained lactic acidosis and on regular metformin, especially in the setting of renal impairment or hypoxic events.

Síndrome MELAS en pediatría. Reporte de caso / MELAS Syndrome in pediatrics. Case report

Resumen Introducción. El síndrome de encefalopatía mitocondrial, acidosis láctica y episodios similares a un accidente cerebrovascular (MELAS, por su sigla en inglés) es una de las enfermedades mitocondriales más frecuentes. Estas patologías se caracterizan por ser hereditarias, multisistémicas y progresivas, y por causar un compromiso predominantemente neurológico que provoca discapacidad y mortalidad, por lo que el diagnóstico temprano y la consejería genética son de gran importancia para mejorar el pronóstico de estos pacientes. Presentación del caso. Paciente femenina de cinco años quien fue llevada a consulta al servicio de pediatría por convulsión y ataxia, y en quien se evidenció retraso psicomotor. Aunque los estudios de neuroimagen fueron normales, se observó hiperlactatemia. Se encontró una relación lactato/piruvato >20, por lo que se sospechó enfermedad mitocondrial. Seis meses después, la paciente presentó deterioro neurológico progresivo caracterizado por alteración de la consciencia, mioclonías y hemiparesia. Se realizó tomografía axial computarizada de cráneo y resonancia magnética por espectroscopia que permitieron identificar una lesión isquémica occipital y aumento del lactato cerebral, respectivamente. Para confirmar el diagnóstico de síndrome MELAS, se solicitó estudio de ADN mitocondrial, en el que se observó la mutación m.3243A>G en el gen MT-TL1. La paciente tuvo un rápido deterioro, presentando una involución de las capacidades adquiridas, falleciendo a los cuatro años del inicio de los signos clínicos. Conclusión. Las enfermedades mitocondriales deben ser consideradas en pacientes con antecedentes de epilepsia y otras alteraciones neurológicas como ataxia e involución del neurodesarrollo.

Abstract Introduction: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) syndrome is the most common mitochondrial disease. These diseases are hereditary, multi-systemic and progressive, and lead to a predominant neurological involvement that causes disability and death, so early diagnosis and genetic counseling are of great importance for improving the prognosis of these patients. Case presentation: Five-year-old female patient who was taken to the pediatrics service of the hospital due to epileptic seizure, psychomotor retardation and ataxia. Although in the first medical consultation her neuroimaging studies were normal, hyperlactatemia was identified. In addition, a lactate to pyruvate ratio >20 was observed, so a mitochondrial disease was suspected. Six months later, the patient showed progressive deterioration of her health condition. A cranial CT scan and a magnetic resonance spectroscopy allowed the identification of an ischemic lesion in the occipital lobe and increased cerebral lactate levels, respectively. In order to confirm the MELAS syndrome diagnosis, a mitochondrial DNA study was requested, in which the m.3243A>G mutation was found. Unfortunately, the patient had a rapid deterioration of her health condition, showing a regression of her acquired functions, and died four years after the onset of the clinical signs. Conclusion: Mitochondrial diseases diagnosis should always be considered in patients with a history of epilepsy and other neurological disorders such as ataxia and neurodevelopmental regression.

Distúrbios ácido-base nas doenças hepáticas / Acid-base disorders in liver diseases

O objetivo deste artigo foi abordar as controvérsias científicas acerca dos distúrbios ácido-base nas doenças hepáticas. Nos estágios avançados da doença hepática, os distúrbios ácido-base atuam de forma complexa, comprometendo a qualidade de vida do paciente e desafiando o manejo clínico. A literatura apresenta a alcalose respiratória como uma das principais alterações, porém há uma longa discussão sobre o mecanismo fisiopatológico; em especial, citam-se a hipóxia, a hipocapnia e o nível de progesterona. Nas desordens metabólicas, com destaque para a acidose, os estudos apontam principalmente o lactato, os unmeasured ions ou íons não medidos e as alterações hidroeletrolíticas, mas cada componente desse sobressai-se dependendo da fase da doença estudada, compensada ou descompensada. As controvérsias dos distúrbios ácido-base nas doenças hepáticas devem-se ora à complexidade da fisiopatologia da própria doença, ora à necessidade de mais estudos esclarecedores.

The aim of this study is to address the scientific controversy about acid-base disorders in liver diseases. In the end stage of liver diseases, the acid-base disorder has a complex performance, impairing the patient's quality of life and challenging the clinic management. Although the literature shows respiratory alkalosis as one of the main alterations, there is a long discussion about the pathophysiological mechanism, specially regarding hypoxia, hypocapnia, and progesterone level. In metabolic disorders, especially acidosis, the studies mainly indicate the lactate, unmeasured ions, and hydroelectrolytic alterations, but, depending on the disease phase, either compensated or decompensated, each element has a particular action. The controversy about acid-base disorders in liver diseases is associated with the complexity of this condition, as well as with the necessity of more specialized research.

[The 475th case: renal tubular acidosis, renal failure, anemia, and lactic acidosis].

A 47-year-old female patient presented nausea and vomiting for half a year and elevated serum creatinine for 3 days. Proximal renal tubular acidosis (RTA) complicated with anemiawas confirmed after admission. Secondary factors, such as autoimmune disease, drugs, poison, monoclonal gammopathy, were excluded. Renal biopsy revealed acute interstitial nephritis. The patient was administrated with daily prednisone 50 mg, sodium bicarbonate 4 g, 3 times per day, erythropoietin 3 000 U, 2 times per week, combined with potassium, calcium, and calcitriol tablets. Serum creatinine reduced to 90 µmol/L. However nausea and vomiting deteriorated with lactic acidosis. Bone marrow biopsy indicated the diagnosis of non-Hodgkin lymphoma, therefore the patient was treated with chemotherapy. Although metabolic acidosis improved gradually after chemotherapy, severe pneumocystis carinii pneumonia developed two weeks later. The patient refused further treatment and was discharged.

The 475th case: renal tubular acidosis, renal failure, anemia, and lactic acidosis / 中华内科杂志

A 47-year-old female patient presented nausea and vomiting for half a year and elevated serum creatinine for 3 days. Proximal renal tubular acidosis (RTA) complicated with anemiawas confirmed after admission. Secondary factors, such as autoimmune disease, drugs, poison, monoclonal gammopathy, were excluded. Renal biopsy revealed acute interstitial nephritis. The patient was administrated with daily prednisone 50 mg, sodium bicarbonate 4 g, 3 times per day, erythropoietin 3 000 U, 2 times per week, combined with potassium, calcium, and calcitriol tablets. Serum creatinine reduced to 90 μmol/L. However nausea and vomiting deteriorated with lactic acidosis. Bone marrow biopsy indicated the diagnosis of non-Hodgkin lymphoma, therefore the patient was treated with chemotherapy. Although metabolic acidosis improved gradually after chemotherapy, severe pneumocystis carinii pneumonia developed two weeks later. The patient refused further treatment and was discharged.

[A case of hyperlacticemia caused by linezolid in severely burned patient].

On October 3rd, 2017, one male patient, aged 27 years, was admitted to our hospital 6 hours after hydrothermal scald of torso, buttocks, and limbs. The total area of burn was about 60% total body surface area, and the depth was from deep partial-thickness burn to full-thickness burn. Immediately after admission, the patient was given symptomatic support treatments, such as anti-shock, fluid replacement, and anti-infection, etc. After being treated by debridement and xenogenic (porcine) skin grafting for 2 times, the wounds were healed well. On the 12th day of admission, linezolid was used to prevent infection according to the results of microbial culture and drug sensitivity test, since when the level of his blood lactate continued to increase. After 8 days, linezolid was discontinued and vitamin B1 was given orally for 1 week, and the level of lactic acid gradually decreased to normal in result. This case was used mainly to analyze whether linezolid could directly cause hyperlacticemia and its important mechanism, aiming at reminding clinicians of being alert to the risk of hyperlacticemia when using linezolid. If hyperlacticemia occurs, linezolid should be discontinued immediately and vitamin B1 should be taken orally to correct the high lactic acid value, and the treatment plan should be adjusted if necessary.

Does reduced oxygen delivery cause lactic acidosis in falciparum malaria? An observational study.

BACKGROUND: Lactic acidosis with an elevated lactate-pyruvate ratio suggesting anoxia is a common feature of severe falciparum malaria. High lactate levels are associated with parasitized erythrocyte sequestration in the microcirculation. To assess if there is an additional contribution to hyperlactataemia from relatively inadequate total oxygen delivery, oxygen consumption and delivery were investigated in patients with malaria. METHODS: Adult Bangladeshi and Indian patients with uncomplicated (N = 50) or severe (N = 46) falciparum malaria or suspected bacterial sepsis (N = 27) and healthy participants as controls (N = 26) were recruited at Chittagong Medical College Hospital, Chittagong, Bangladesh and Ispat General Hospital, Rourkela, India. Oxygen delivery (DO2I) was estimated from pulse oximetry, echocardiographic estimates of cardiac index and haematocrit. Oxygen consumption (VO2I) was estimated by expired gas collection. RESULTS: VO2I was elevated in uncomplicated median (IQR) 185.1 ml/min/m2 (135-215.9) and severe malaria 192 ml/min/m2 (140.7-227.9) relative to healthy persons 107.9 ml/min/m2 (69.9-138.1) (both p < 0.001). Median DO2I was similar in uncomplicated 515 ml/min/m2 (432-612) and severe 487 ml/min/m2 (382-601) malaria and healthy persons 503 ml/min/m2 (447-517) (p = 0.27 and 0.89, respectively). The VO2/DO2 ratio was, therefore, increased by similar amounts in both uncomplicated 0.35 (0.28-0.44) and severe malaria 0.38 (0.29-0.48) relative to healthy participants 0.23 (0.17-0.28) (both p < 0.001). VO2I, DO2I and VO2/DO2 did not correlate with plasma lactate concentrations in severe malaria. CONCLUSIONS: Reduced total oxygen delivery is not a major contributor to lactic acidosis in severe falciparum malaria.

A case of hyperlacticemia caused by linezolid in severely burned patient / 中华烧伤杂志

On October 3rd, 2017, one male patient, aged 27 years, was admitted to our hospital 6 hours after hydrothermal scald of torso, buttocks, and limbs. The total area of burn was about 60% total body surface area, and the depth was from deep partial-thickness burn to full-thickness burn. Immediately after admission, the patient was given symptomatic support treatments, such as anti-shock, fluid replacement, and anti-infection, etc. After being treated by debridement and xenogenic (porcine) skin grafting for 2 times, the wounds were healed well. On the 12th day of admission, linezolid was used to prevent infection according to the results of microbial culture and drug sensitivity test, since when the level of his blood lactate continued to increase. After 8 days, linezolid was discontinued and vitamin B1 was given orally for 1 week, and the level of lactic acid gradually decreased to normal in result. This case was used mainly to analyze whether linezolid could directly cause hyperlacticemia and its important mechanism, aiming at reminding clinicians of being alert to the risk of hyperlacticemia when using linezolid. If hyperlacticemia occurs, linezolid should be discontinued immediately and vitamin B1 should be taken orally to correct the high lactic acid value, and the treatment plan should be adjusted if necessary.

Acidosis láctica por metformina. Reporte de dos casos / Metformin lactic acidosis. Report of two cases

RESUMEN La metformina es uno de los medicamentos más utilizados como primera línea para control de la diabetes mellitus tipo 2; tiene un papel benéfico en la mortalidad cardiovascular y bajo riesgo de producir hipoglucemia; sin embargo, no está exenta de efectos adversos, de los cuales, el más temido es la acidosis láctica, cuya incidencia es de 7,4 casos por 100.000 usuarios del medicamento por año. Los principales factores de riesgo para desarrollar dicha complicación son la insuficiencia renal aguda o crónica, la falla cardíaca, la enfermedad hepática y el uso concomitante de medicamentos que bloquean la cadena respiratoria de la mitocondria. El tratamiento incluye la reanimación hídrica, el soporte y, en algunos casos, el bicarbonato. La terapia de reemplazo renal ha sido exitosa en estos pacientes, pero las indicaciones para hacerla aún no son claras porque la metformina es una molécula parcialmente dializable y se requiere hemodiálisis prolongada para reducir suficientemente sus niveles. A pesar del tratamiento intensivo, la mortalidad asociada a esta complicación continúa siendo muy alta. El diagnóstico temprano y el tratamiento oportuno son fundamentales para mejorar el pronóstico.

SUMMARY Metformin lactic acidosis. Report of two cases Metformin is recommended as a first-line treatment for patients with diabetes mellitus type 2; it has a cardiovascular protective effect, and low risk of hypoglycemia. However, a severe but infrequent complication of its use is lactic acidosis, which has high morbidity and mortality rates. The estimated incidence of metformin lactic acidosis is 7,4 cases per 100.000 patients per year. Main risk factors are acute or chronic renal disease, congestive heart failure, hepatic failure, and concomitant use of drugs that affect metformin clearance or energy metabolism. Treatment includes hydration with crystalloids, support measures, and intravenous bicarbonate. Renal replacement therapy has been successful for treating metformin-associated lactic acidosis, but there are still no clear indications for it, because metformin is a partially dialyzable molecule and prolonged hemodialysis is required to reduce its levels sufficiently. Despite current treatment, mortality remains high. Early diagnosis and prompt multidisciplinary support are essential to improve outcome in these patients.

Acidosis láctica asociada a metformina: caso clínico / Metformin-associated lactic acidosis: report of one case

Metformin-associated lactic acidosis is a severe and infrequent adverse event. Early diagnosis is essential to start an early treatment, which often has favorable results. We report a 56 years old non-insulin-requiring type 2 diabetic female who developed a severe metabolic acidosis associated with metformin in relation to an acute renal failure secondary to infectious diarrhea. Early treatment with bicarbonate and continuous hemofiltration allowed a quick improvement of the patient. Metformin-associated lactic acidosis has an elevated mortality (50-80%) and has a specific and effective treatment. Therefore, the condition must be born in mind.

Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review.

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). METHODS: D-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high D-lactate levels. Fifty-nine D-la episodes were included in the qualitative synthesis comparing D-la symptoms with ME/CFS diagnostic criteria. A narrative review of D-la mechanisms and relevance for ME/CFS was provided. RESULTS: The majority of neurological disturbances reported in D-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported D-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS. LIMITATIONS: Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for D-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined. CONCLUSIONS: Shared symptomatology and underlying microbiota-gut-brain interactions raise the possibility of a continuum of acute (D-la) versus chronic (ME/CFS) presentations related to D-lactate absorption. Measurement of D-lactate in ME/CFS is needed to effectively evaluate whether subclinical D-lactate levels affect neurological symptoms in this clinical population.