Metformin is a first line treatment for type II diabetes. Cases of metformin-associated lactic acidosis are regularly reported. A direct causal link between metformin overdose and lactic acidosis is not clearly established. The aim of this study is to describe cases of metformin-associated lactic acidosis, to assess their vital et renal prognosis, and to analyze the correlations between metforminemia, lactacidemia, pH and death.

Cases of metformin-associated lactic acidosis from a single hospital center in Saint-Denis, France, between 2010 and 2022 were analyzed. Inclusion criteria were patients aged 18 or older, treated with metformin, metabolic acidosis with a pH inferior to 7.35 and lactacidemia superior to 5mmol/l.

Twenty-eight patients were included. Median age was 65 years old. Voluntary intoxication was present in 17% of cases. Metformin was contraindicated in 39% of cases. All patients presented with acute kidney injury at admission. Mortality rate was 7%. No factor was associated with death in the univariate analysis. Correlation between pH, lactacidemia, creatininemia and glycated hemoglobin was found. There was no correlation between metforminemia and lactacidemia.

Metformin-associated lactic acidosis is a rare complication. Its prognosis is inconstant, varying with the presence or absence of a severe disease causing the overdose. No association was found between clinical data, biological data and death.

We aimed to explore the application value of unsupervised machine learning in identifying acute gastrointestinal injury (AGI) after extracorporeal circulation for acute type A aortic dissection (ATAAD).

Patients who underwent extracorporeal circulation for ATAAD at the First Hospital of Lanzhou University from January 2016 to January 2021 were included. Unsupervised machine learning algorithm was used to stratify patients into different phenogroups according to the similarity of their clinical features and laboratory test results. The differences in the incidence of perioperative AGI and other adverse events among different phenogroups were compared. Logistic regression was used to analyze the high-risk factors for AGI in each phenogroups and random forest (RF) algorithms were used to construct diagnostic models for AGI in different phenogroups.

A total of 188 patients were included, with 166 males and 22 females. Unsupervised Machine Learning stratified patients into three phenogroups (phenogroup A, B, and C). Compared with other phenogroups, phenogroup B patients were older (P < 0.01), had higher preoperative lactate and D-dimer levels, and had the highest incidence of AGI (52.5%, P < 0.001) and in-hospital mortality (18.6%, P = 0.002). The random forest model showed that the top four risk factors for AGI in phenogroup B were cardiopulmonary bypass time, operation time, aortic clamping time, and ventilator time, which were significantly different from other phenogroups. The areas under the curve (AUCs) for diagnosing postoperative AGI of phenogroup A, B, and C were 0.943 (0.854-0.992), 0.990 (0.966-1.000), and 0.964 (0.899-0.997) using the RF model, respectively.

Phenogroup stratification based on unsupervised learning can accurately identify high-risk populations for postoperative AGI in ATAAD, providing a new approach for implementing individualized preventive and therapeutic measures in clinical practice.

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

Metformin has been used for ages to treat diabetes mellitus due to its safety profile and low cost. However, metformin has variable pharmacokinetics in patients, and due to its poor oral absorption, the therapeutic doses are relatively high, causing unpleasant gastrointestinal adverse effects. Therefore, novel derivatives of metformin have been synthesized during the past decades. Particularly, after the mid-2000 s, when organic cation transporters were identified as the main metformin carriers, metformin derivatives have been under intensive investigation. Nevertheless, due to the biguanide structure, derivatives of metformin have been challenging to synthesize. Moreover, the mechanisms of metformin's action are not fully understood to date, and since it has multifunctional properties, the interests have switched to re-purposing for other diseases. Indeed, metformin derivatives have been demonstrated in many cases to be more effective than metformin itself and have the potential to be used in different diseases, including several types of cancers and neurodegenerative diseases. On the other hand, the pleiotropic nature of metformin and its derivatives can also create challenges. Not all properties are fit for all diseases. In this review, the history of the development of metformin-like compounds is summarized, and insights into their potential for future drug discovery are discussed.

This study aimed to determine the relationship between the postoperative lactate dynamic levels, the postoperative acute gastrointestinal injury (AGI), and the prognosis among the patients who underwent surgical treatment for an acute Stanford type-A aortic dissection (aTAAD).

A total of 271 aTAAD patients were recruited and monitored. Of the 271 aTAAD patients, 29.2% developed an AGI and were designated as the AGI group (n = 79); the other patients (n = 192) were designated as the non-AGI group. According to the 2-year follow up, the aTAAD patients were also divided into the alive and death subgroups for further analysis.

Binary logistic regression analysis revealed that the postoperative 4-h lactate (P4L) level, time-to-return to the normal blood lactate level (TRNL), postoperative 16-h lactate (P16L) level, and neutrophil granulocyte (NEU) count had a good predictive value for an AGI after aTAAD. The 8-week and 2-year mortality rates were higher in the AGI group than the non-AGI group (P < 0.05). Basic data and clinical characteristics were significantly different between the alive and death groups (P < 0.05). A higher AGI rate and mortality occurred in the P4L level ≥10.15 mmol/L subgroup, TRNL ≥21-h subgroup, P16L level ≥2.95 mmol/L subgroup, NEU count ≥10.9 × 10⁹/L subgroup, PaO₂ < 77.7 mmHg subgroup, WBC count ≥9.58 × 10⁹/L subgroup, and the operative time ≥427 min subgroup than the corresponding comparison subgroups (P < 0.05). The postoperative 0-h lactate (P0L) level, TRNL, postoperative 24-h lactate (P24L) level, D-dimer level, fibrinogen degradation products (FDP) level, duration of mechanical ventilation, and length of hospitalization were independent factors influencing the 30-day mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). Cox regression multivariate analysis after univariate analysis of all-cause mortality showed the TRNL, postoperative 12-h lactate (P12L) level, P16L level, P24L level, D-dimer level, FDP level, and length of hospitalization were independently associated with the 2-year mortality rate in patients who underwent surgery for an aTAAD (P < 0.05).

The postoperative lactate changes and TRNL effectively predicted postoperative AGI and the mortality rate in patients with who underwent surgery for an aTAAD. The TRNL and P24L level were independent risk factors for the 30-day and 2-year mortality rates in patients who underwent surgery for an aTAAD.