UNASSIGNED: The objective of this study was to investigate the correlation between metformin exposure and the incidence of lactic acidosis in critically ill patients.
UNASSIGNED: The patients with type 2 diabetes mellitus (T2DM) were included from Medical Information Mart for Intensive Care IV database (MIMIC-IV). The primary outcome was the incidence of lactic acidosis. The secondary outcomes were lactate level and in-hospital mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. The multivariate logistic regression was used to explore the correlation between metformin exposure and the incidence of lactic acidosis. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion.
UNASSIGNED: We included 4939 patients. There were 2070 patients in the metformin group, and 2869 patients in the nonmetformin group. The frequency of lactic acidosis was 5.7% (118/2070) in the metformin group and it was 4.3% (122/2869) in the nonmetformin group. There was a statistically significant difference between the two groups (P < 0.05). The lactate level in the metformin group was higher than in the nonmetformin group (2.78 ± 2.23 vs. 2.45 ± 2.24, P < 0.001). After PSM, the frequency of lactic acidosis (6.3% vs. 3.7%, P < 0.001) and lactate level (2.85 ± 2.38 vs. 2.40 ± 2.14, P < 0.001) were significantly higher in the metformin group compared with the nonmetformin group. In multivariate logistic models, the frequency of lactic acidosis was obviously increased in metformin group, and the adjusted odds ratio (OR) of metformin exposure was 1.852 (95% confidence interval (CI) = 1.298-2.643, P < 0.001). The results were consistent with subgroup analysis except for respiratory failure subgroup. Metformin exposure increased lactate level but did not affect the frequency of lactic acidosis in patients of respiratory failure with hypercapnia. However, the in-hospital mortality between metformin and nonmetformin group had no obvious difference (P = 0.215). In sensitivity analysis, metformin exposure showed similar effect as the original cohort.
UNASSIGNED: In critically ill patients with T2DM, metformin exposure elevated the incidence of lactic acidosis except for patients of respiratory failure with hypercapnia, but did not affect the in-hospital mortality.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms.
METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L.
RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007).
CONCLUSIONS: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

OBJECTIVE: This study examined how frontline nurse managers (FLNMs) perceive and experience formal and informal social support and how personal factors and social support relate to their transformational leadership (TL) behaviors.
BACKGROUND: Ineffective leadership by FLNMs is associated with costly outcomes. Evidence suggests that leadership development is a function of personal and social factors; however, a better understanding of this process is needed.
METHODS: A convergent mixed-methods design was used. The quantitative strand included a cross-sectional survey in a sample of FLNMs. The qualitative strand used a semistructured interview and a descriptive qualitative approach with a subset of this sample.
RESULTS: Formal and informal social support is positively related to the TL behaviors of FLNMs as evidenced by the convergent data. The influence of family members in the work-related decisions of FLNMs has been underreported in the literature and is an area for consideration in supporting retention and desired leadership behaviors.
CONCLUSIONS: The findings of this study imply a need for organizations to establish systems that endorse the growth of FLNMS, create opportunities for career advancement, and integrate members of the FLNMs\' personal support systems into recognition initiatives.

Sepsis-associated hyperlactatemia (SAHL), Lactic acidosis, is a common problem in critically ill patients. The prevalence of Lactic acidosis is estimated to be approximately 1% of all hospitalized nonsurgical patients. The purpose of our study was to reveal possible associations between the level of Lactate with sepsis biomarkers: PCT, IL 6, and PO2 in the presence of ACE 2 inhibitors in Covid-19 infected and non-infected patients with Septic Shock. We conducted a cohort study, comparing outcomes of 212 critically ill patients with Septic shock, who were treated in the intensive care unit of First University Clinic of Tbilisi State Medical University during the 2020-2021 years. Inclusion criteria for the study were: Age>40ys; COVID-19 and other respiratory diseases associated with Septic shock, with respiration dysfunctions with prior exposure to ACE2 inhibitors o no history of treatment with the ACE2 inhibitors. Patients enrolled in the study were individuals who were diagnosed with COVID-19 infection and septic shock, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors; patients with septic shock who were not infected with COVID-19, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors. According to lactate level, the studied patients were divided into subgroups: lactate <3 mMol/l, and lactate > 3 mmol/l. In patients with septic shock who were not infected with COVID-19 the main Causative microorganisms were gram-negative bacteria. In patients\' blood the Interleukin-6 (IL-6), lactate, procalcitonin (PCT), pO2, and pulmonary pressure were investigated. Results of the study show that the rise in lactate levels in COVID-19-infected and non-infected patients was accompanied by an increase in PCT content and a decrease in pO2 level in blood. Therefore, serum lactate levels can be used as a prognostic marker of the severity of septic shock in COVID-19-infected and noninfected patients. In COVID-19-infected patients together with the increased lactate level, increases the level of IL-6, which indicates the important link between the quality of immunological disorders, inflammation, and COVID-19 infection in patients with ARDS and sepsis. These alterations were not prevented by the prior use of the ACE2 inhibitors. In COVID-19-infected and noninfected patients who didn\'t use ACE2 inhibitors, high lactate levels were accompanied by decreased pulmonary pressure which was normalized in patients who prior used ACE2 inhibitors.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels.
In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality.
142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes.
In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function.
The study was registered at Clinicaltrials.gov (NCT04766008).

Lactic acidosis is a clinical status related to clinical worsening. Actually, higher levels of lactate is a well-established trigger of emergency situations. The aim of this work is to build-up a prehospital early warning score to predict 2-day mortality and intensive care unit (ICU) admission, constructed with other components of the lactic acidosis besides the lactate.
Prospective, multicenter, observational, derivation-validation cohort study of adults evacuated by ambulance and admitted to emergency department with acute diseases, between January 1st, 2020 and December 31st, 2021. Including six advanced life support, thirty-eight basic life support units, referring to four hospitals (Spain). The primary and secondary outcome of the study were 2-day all-cause mortality and ICU-admission. The prehospital lactic acidosis (PLA) score was derived from the analysis of prehospital blood parameters associated with the outcome using a logistic regression. The calibration, clinical utility, and discrimination of PLA were determined and compared to the performance of each component of the score alone.
A total of 3334 patients were enrolled. The final PLA score included: lactate, pCO2, and pH. For 2-day mortality, the PLA showed an AUC of 0.941 (95%CI: 0.914-0.967), a better performance in calibration, and a higher net benefit as compared to the other score components alone. For the ICU admission, the PLA only showed a better performance for AUC: 0.75 (95%CI: 0.706-0.794).
Our results showed that PLA predicts 2-day mortality better than other lactic acidosis components alone. Including PLA score in prehospital setting could improve emergency services decision-making.

The clinical significance of hypophosphatemia in cardiac surgery has not been investigated extensively. The aim of this study was to evaluate the association of postoperative hypophosphatemia and lactic acidosis in cardiac surgery patients at the time of intensive care unit (ICU) admission.
A retrospective cohort study.
At a single academic center.
Patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020.
None.
Serum phosphate and lactate levels were measured upon ICU admission in patients undergoing nontransplant cardiac surgery with cardiopulmonary bypass. There were 681 patients in the low-phosphate (<2.5 mg/dL) group and 2,579 patients in the normal phosphate group (2.5-4.5 mg/dL). A higher proportion of patients in the low phosphate group (26%; 179 of 681; 95% CI: 23-30) had severe lactic acidosis compared to patients in the normal phosphate group (16%; 417 of 2,579; 95% CI: 15-18). In an unadjusted logistic regression model, patients in the low phosphate group had 1.9-times the odds of having severe lactic acidosis (serum lactate ≥4.0 mmol/L) when compared to patients in the normal phosphate group (95% CI: 1.5-2.3), and still 1.4-times the odds (95% CI: 1.1-1.7) after adjusting for several possible confounders.
Hypophosphatemia is associated with lactic acidosis in the immediate postoperative period in cardiac surgery patients. Future studies will need to investigate it as a potential treatment target for lactic acidosis.

BACKGROUND: MetforminHydrochloride is an antidiabetic used for many years, currently; it considered the first choice in treatment of type 2 diabetes (T2D). It decreases insulin resistance, does not induce hypoglycaemia, increases glucose utilization in the liver and skeletal muscle, and decreases hepatic glucose production. Its adverse effects (AE) are gastrointestinal, decrease in vitamin B12 absorption, abnormalities of hemogram and rarely skin reactions. The objective of this study was to report the type and frequency of AEs of Metformin Hydrochloride used in the therapeutic management of T2D patients admitted to the medical center and the diabetes home of Sidi Bel-Abbès in Algeria.
METHODS: A cross-sectional descriptive study was carried out over a period of four months, from January 1st, 2017 to April 30th, 2017, involving 130 patients treated with Metformin Hydrochloride consulting at Mimoun City Diabetes Home and Gambetta Diabetes Center in the town of Sidi Bel-Abbès. The primary outcome measure was the determination of the type and frequency of AEs related to normal dosages or overdose use of Metformin Hydrochloride in T2D. Data were collected from patient records, using a questionnaire, and analyzed using Statistical Package for the Social Sciences, version 20 software.
RESULTS: 130 patients were included, including 82 women, with a mean age of 51.08±8.85 years (30-66). One hundred and ninety-eight (198) AEs were reported, an average of 1.52 AEs per patient. Among them, 95 (47.98%) AEs are digestive disorders (30.77% of patients suffered from diarrhea, 10.77% had nausea and vomiting, 8.46% suffered from abdominal pain and bloating, 3.85% lost their taste, 7.69% complained of epigastric cramps and 11.54% of anorexia), 29 (14.65%) AEs are hypoglycaemia, 73 (36.87%) AEs are other symptoms and 1 (0.50%) EI is vitamin B12 deficiency and no cases of lactic acidosis or allergic reaction were reported. Five (3.85%) patients had a total and lasting intolerance to Metformin Hydrochloride leading to its discontinuation following persistent diarrhoea.
CONCLUSIONS: AEs of Metformin Hydrochloride used in the management of T2D patients consulting at the medical center and the Diabetes home of Sidi Bel-Abbès are frequent. Digestive disorders were the most frequent, diarrhea was very frequent and led to discontinuation of treatment in 3.85% of T2D patients, followed by nausea and vomiting, then abdominal pain, bloating and epigastric cramps, and rarely taste metallic. Hypoglycaemia was frequent following its association with insulin, the onset of headaches and fatigue were frequent, but no case of lactic acidosis or allergic reaction was reported. Due to a lack of means, the dosage of homocysteine and methylmalonic acid had not been carried out to confirm the vitamin B12 deficiency in the patient whose level was less than 200ng/mL. A precise assessment of the imputability of reported AEs is necessary.

BACKGROUND: The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the mitochondrial DNA. Although the initial diagnostic criteria correlate with a range of clinical phenotypes, including clinical onset after the age of 40, there is still lack of a unified single diagnostic standard for MELAS.
METHODS: A 71-year-old female patient with recurrent stroke was reported. Magnetic resonance imaging showed a cerebral gyrus-like diffusion weighted imaging high signal lesion in the parietal-occipital lobe and the area of this lesion expanded with disease progression. The MRS result showed significantly inverted Lac/Lip peaks. The nucleic acid sequencing result displayed a MT-TWm.5541C>T mutation, and a 12.86% mutation rate in the blood sample. The patient had a 6-year history of type 2 diabetes.
CONCLUSIONS: Patients with the MELAS syndrome may present with a variety of clinical manifestations. Our data demonstrated that, for patients with atypical cerebral infarction and suspected MELAS syndrome, gene sequencing and muscle biopsy should be performed in time. This case provides a reference for the diagnostic criteria of MELAS syndrome.