Elevated Lactic Acid Levels Research Articles

Evaluation of the clinical efficacy of Pediococcus acidilactici CCFM6432 in alleviating depression

Aim: Accumulating evidence highlights the crucial role of the “gut-brain axis” and emphasizes the potential of dietary interventions to improve brain health through this pathway. This study assesses the effects of the probiotic Pediococcus acidilactici CCFM6432 on mood, sleep, and gastrointestinal function in patients with depressive disorder. Methods: This clinical trial is a randomized, placebo-controlled study (Registration: ChiCTR2300071025). It enrolled 39 adult patients diagnosed with depressive disorder, who were randomly assigned to either the placebo control group (n = 19) or the CCFM6432 intervention group (n = 20). The intervention period spanned four weeks. Assessments were conducted at both the beginning and end of the trial, including comprehensive questionnaire evaluations and the collection of serum and fecal samples. Results: In comparison to the placebo, treatment with CCFM6432 significantly decreased depression and anxiety scores, as well as ameliorated gastrointestinal dysfunction and poor sleep quality commonly associated with mood disorders. Microbiota analysis revealed an increase in species richness without notable changes in overall diversity, yet Pediococcus species was found to be more abundant post-treatment. Functional analysis indicated reduced activity in the NOD-like receptor signaling pathway, suggesting anti-inflammatory effects induced by the probiotic. Metabolomic profiling identified elevated levels of fecal lactic acid, which correlated with lower Hospital Anxiety and Depression Scale (HADS) scores, thereby linking probiotic metabolism to mood enhancement. Conclusion: These findings imply that CCFM6432 may improve brain function by modulating gut microbiota and their mediated immune homeostasis, underscoring its potential as an adjunctive treatment for mental disorders.

Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway

High levels of urinary lactate are an increased risk of progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how lactate drive DKD. Epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial cells polarity and cell-cell adhesion, and the acquisition of mesenchymal-like phenotypes, is widely recognized a critical contributor to DKD. Here, we found a switch from oxidative phosphorylation (OXPHOS) toward glycolysis in AGEs-induced renal tubular epithelial cells, thus leading to elevated levels of renal lactic acid. We demonstrated that reducing the lactate levels markedly delayed EMT progression and improved renal tubular fibrosis in DKD. Mechanically, we observed lactate increased the levels of histone H3 lysine 14 lactylation (H3K14la) in DKD. ChIP-seq & RNA-seq results showed histone lactylation contributed to EMT process by facilitating KLF5 expression. Moreover, KLF5 recognized the promotor of cdh1 and inhibited its transcription, which accelerated EMT of DKD. Additionally, nephro-specific knockdown and pharmacological inhibition of KLF5 diminished EMT development and attenuated DKD fibrosis. Thus, our study provides better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD by disruption of the lactate-drived H3K14la/KLF5 pathway.

Effects of soil bulk density on respiratory metabolism and medicinal quality of Rehmannia Glutinosa root

As one of the famous "four huai medicines", Rehmannia glutinosa has a longstanding usage history. This study aimed to determine how variations in soil bulk density impact the respiration metabolism of R. glutinosa root tubers and, consequently, the quality of its medicinal components. We evaluated the enzymatic activities and key metabolic compounds of R. glutinosa across a range of soil bulk densities, which included: pyruvate kinase (PK), pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), lactate dehydrogenase (LDH), isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and the content of pyruvate, ethanol, lactic acid, succinic acid, malic acid, and quality indicators. High soil bulk density increased the activities of PK, PDC, ADH, and LDH, while decreasing SDH, MDH, and IDH in the roots. This shift in enzymatic activities corresponded to elevated levels of ethanol and lactic acid, and lowered levels of succinic and malic acids. In the additionally, the growth and development of aboveground parts of R. glutinosa were seriously hindered under high bulk weight treatment, and the number of root tubers decreased, root coarser and root length shortened, and the contents of catalpa alcohol and mullein were significantly reduced. Our findings suggest an optimal soil bulk density for R. glutinosa growth to be between 1.2 g/cm3 and 1.4 g/cm3. Based on changes in respiratory metabolism and medicinal quality indicators of R. glutinosa under different soil bulk densities, our findings suggest the optimal soil bulk density for R. glutinosa growth is 1.2 g/cm3 to 1.4 g/cm3. Excessively high soil bulk density will affect the growth and quality formation of R. glutinosa by influencing its metabolism. Recognizing this optimal range is crucial for maximizing the medicinal quality of R. glutinosa, offering valuable insights for cultivation practices.

Idebenone ameliorates statin-induced myotoxicity in atherosclerotic ApoE−/− mice by reducing oxidative stress and improving mitochondrial function

Statins are the first line of choice for the treatment for atherosclerosis, but their use can cause myotoxicity, a common side effect that may require dosage reduction or discontinuation. The exact mechanism of statin-induced myotoxicity is unknown. Previous research has demonstrated that the combination of idebenone and statin yielded superior anti-atherosclerotic outcomes. Here, we investigated the mechanism of statin-induced myotoxicity in atherosclerotic ApoE−/− mice and whether idebenone could counteract it. After administering simvastatin to ApoE−/− mice, we observed a reduction in plaque formation as well as a decrease in their exercise capacity. We observed elevated levels of lactic acid and creatine kinase, along with a reduction in the cross-sectional area of muscle fibers, an increased presence of ragged red fibers, heightened mitochondrial crista lysis, impaired mitochondrial complex activity, and decreased levels of CoQ9 and CoQ10. Two-photon fluorescence imaging revealed elevated H2O2 levels in the quadriceps, indicating increased oxidative stress. Proteomic analysis indicated that simvastatin inhibited the tricarboxylic acid cycle. Idebenone treatment not only further reduced plaque formation but also ameliorated the impaired exercise capacity caused by simvastatin. Our study represents the inaugural comprehensive investigation into the mechanisms underlying statin-induced myotoxicity. We have demonstrated that statins inhibit CoQ synthesis, impair mitochondrial complex functionality, and elevate oxidative stress, ultimately resulting in myotoxic effects. Furthermore, our research marks the pioneering identification of idebenone's capability to mitigate statin-induced myotoxicity by attenuating oxidative stress, thereby safeguarding mitochondrial complex functionality. The synergistic use of idebenone and statin not only enhances the effectiveness against atherosclerosis but also mitigates statin-induced myotoxicity.

Pneumatosis Intestinalis and Pneumoperitoneum After Lung Transplantation: Single-Center Experience and Systematic Review.

Background: Pneumatosis intestinalis (PI) and pneumoperitoneum are some of the complications after lung transplantation (LT). But only limited reports are published. The purpose of this study is to review our experience and perform a systematic review to discuss the possible causes, risk factors, and management. Methods: We reviewed the characteristics, management, and outcome of the patients who developed PI or pneumoperitoneum after LT in our institution from 2013 to 2022. We also performed a systematic review to discuss the management and outcome. Results: PI and pneumoperitoneum were found in 15 out of 729 patients (2.06%) in our institution. We also found 50 patients in the systematic review. Tracheostomy was performed in 40% and gastrointestinal procedures were performed in 55.6%. Laparotomy was performed in 23.4%. A total of 44.6% of patients had benign physical exams or no symptoms. Rejection was seen in 42.9%. A total of 28.6% of patients died during follow-up periods. Conclusions: This report has the largest number of patients so far with PI and pneumoperitoneum after LT. These conditions have a high rejection and high mortality rate. Mechanical ventilation, tracheostomy, gastrointestinal procedure, CMV infection, Clostridium difficile (C. difficile) infection, and immunosuppression can be the risk factors, and the management includes laparotomy or conservative management. It is generally recommended to proceed with laparotomy if patients have portal venous gas, elevated white blood cell count, elevated lactic acid level, decreased bicarbonate level, elevated amylase level, metabolic acidosis, abdominal tenderness, or abdominal distension. Otherwise, most of the patients recover with conservative management with nil per os (NPO), metronidazole, ganciclovir, antibiotics, high-flow oxygen, and holding mycophenolate mofetil (MMF).

THU384 Too Sweet To Digest; A Case Of Persistent Lactic Acidosis Secondary To Glycogenic Hepatopathy

Abstract Disclosure: T. Ayub: None. L.A. Robles: None. F. Sami: None. S. Saleem: None. S. Guntupalli: None. Glycogenic hepatopathy (GH) is an under-recognized cause of persistent lactic acidosis and hepatomegaly in patients with uncontrolled DM and diabetic ketoacidosis (DKA). A 19-year-old female with history of type 1 DM with recurrent DKA presented with complaints of nausea, vomiting and abdominal pain for 1 week. Physical exam showed normal vitals and lower abdominal tenderness. Her initial labs showed glucose 250 mg/dl, high anion gap metabolic acidosis with beta hydroxy butyrate of 11.3 mmol/l, lactic acid 3.2mm/l, and mild transaminitis. She was diagnosed with DKA and started on insulin drip. Anion gap responded to IV insulin and fluid therapy and was transitioned to SQ insulin. However, she had increase in her lactic acid (8.2mm/l), without hemodynamic compromise, despite fluid resuscitation. Secondary work up including blood, urine, sputum cultures were non diagnostic for an infectious etiology. Abdominal imaging showed a liver span of 26 cm. There were no signs of end organ hypoperfusion, medication or toxin mediated insult as evident by normal transthoracic echo, iron studies, urine drug screen, alcohol level and negative hepatitis panel. Review of prior hospitalizations showed recurrent episodes of DKA with similar uptrend in lactic acid levels with negative secondary work up. Prior imaging revealed hepatomegaly during DKA episodes with resolution after strict glycemic control. Given uncontrolled DM type 1 with reversible and recurrent hepatomegaly, transaminitis, hyperlipidemia and elevated lactic acid, a clinical diagnosis of glycogenic hepatopathy was made. Patient declined liver biopsy due to concerns for complications. She was discharged on home insulin regimen with outpatient follow up. GH or hepatic glycogenosis is a reversible cause of lactic acidosis and hepatomegaly seen in uncontrolled DM type 1. Pathogenesis involves presence of fluctuating levels of hyperglycemia and insulin, concomitantly, that leads to glycogen storage. Insulin inhibits gluconeogenesis resulting in decreased conversion of pyruvate to glucose and high lactic acid levels, in the absence of any infectious, metabolic and hypoxic etiology. Lactic acidosis can be worsened when treated with high dose Insulin. Definite diagnosis of GH requires liver biopsy or gradient dual-echo MRI but can be made clinically in the setting of uncontrolled DM1, hepatomegaly, transaminitis and elevated lactic acid levels. Prompt recognition of GH can prevent unnecessary diagnostic testing and can decrease the duration of hospital stay. Treatment is strict glycemic control with resolution of condition and no long-term complications. Presentation: Thursday, June 15, 2023

Discrepancy between two invasive blood pressure measurements in patients receiving intra-aortic balloon pump therapy

BackgroundHemodynamic monitoring is imperative for patients with cardiogenic shock undergoing Intra-aortic Balloon Pump (IABP) therapy. Blood pressure monitoring encompasses non-invasive, invasive peripheral arterial pressure (IPAP), and invasive central aortic pressure (ICAP) methods. However, marked disparities exist between IPAP and ICAP. This study examined the discrepancies between IPAP and ICAP and their clinical significance.MethodsA retrospective analysis was conducted on cardiogenic shock patients who underwent IABP therapy and were admitted to the Coronary Care Unit (CCU) of a tertiary hospital in China from March 2017 to November 2022. The Bland–Altman plot illustrated the discrepancy between IPAP and ICAP. A clinically significant difference between ICAP and IPAP measurements was defined as ≥ 10 mmHg, which could necessitate alterations in blood pressure management according to current guidelines that recommend maintaining a mean arterial pressure (MAP) ≥ 70 mmHg.ResultsIn total, 162 patients were included in the final analysis. In patients without vasopressors, the difference between ICAP and IPAP was 5.73 mmHg (95% limits of agreement [LOA], -16.98 to 28.44), whereas, in patients with vasopressors, it was 4.36 mmHg (95% LOA, -17.31 to 26.03). ICAP measurements exceeded IPAP in patients undergoing IABP therapy. However, the difference was not statistically significant between the two groups. Multivariate logistic regression revealed that higher serum lactate levels (Odds ratio [OR], 1.14; 95% confidence interval [CI], 1.03–1.27; p = 0.013) and age ≥ 60 years (OR, 13.20; 95% CI, 1.50–115.51; p = 0.020) were associated with an increased likelihood of a clinically significant MAP discrepancy. Conversely, a history of coronary heart disease was associated with a decreased likelihood (OR, 0.34; 95% CI, 0.13–0.90; p = 0.031).ConclusionsNotable discrepancies between ICAP and IPAP measurements exist in cardiogenic shock patients undergoing IABP therapy. ICAP exceeds IPAP, and factors such as age ≥ 60 years, elevated lactic acid levels, and absence of coronary heart disease contribute to this discrepancy. Enhanced vigilance is warranted for these patients, and the consideration of peripheral invasive monitoring in conjunction with IABP therapy is advised.

Revitalizing performance: Exploring the influence of sports massage and PNF stretching on lactic acid recovery in females futsal athletes

Elevated levels of lactic acid in the blood and muscles following intense training or competition can have detrimental effects on physical performance and increase the likelihood of injury. Therefore, it is crucial to identify effective recovery techniques to mitigate fatigue promptly. The objective of this study was to assess the impact of sports massage and the Proprioceptive Neuromuscular Facilitation (PNF) method on the recovery of lactic acid in athletes. This study employed a true-experimental design using a pretest-posttest without a control group. A sample of 20 female futsal athletes was divided into two groups: the sports massage group (SM) consisting of 10 participants, and the PNF method group also comprising 10 participants. Lactic acid levels were assessed before exercise, immediately after completing the anaerobic exercise, and immediately after the recovery intervention based on the respective group allocation. The results showed an increase in lactic acid after anaerobic exercise in both groups. The SM group experienced a significant decrease compared to the PNF group which did not experience a significant decrease. A significant disparity was observed in the mean lactic acid levels between the two groups in the post-test data. In conclusion, the application of sports massage following anaerobic exercise proves to be effective in reducing lactic acid concentrations in futsal athletes compared to the PNF method. The findings of this study are anticipated to yield advantages for coaches, sports medical teams, and athletes by lowering lactic acid levels, enhancing sports performance, and mitigating injury risks. Practically, the findings underscore the potential benefits of incorporating a 15-minute sports massage into the recovery routine of female futsal players.

Uncertain significance mutation in the POLR3B gene in a Syrian boy with leukodystrophy: a case report.

A 4-year-old boy presented in the neurologic clinic with delayed psychomotor development and progressive neurologic symptoms that started from the age of 20 months. Physical examination revealed ataxic features and a global development delay. The MRI was significant for hypomyelination. The most common causes of leukodystrophy were rolled out. He was referred to an inherited metabolic disease specialist under suspect of inborn metabolic errors because of laboratory analysis, which showed elevated levels of lactic acid, pyruvate, 4-Hydroxy-Phenylactic acid, 3-Hydroxy propionic acid, and decreased levels of PCO2, HCO3, total CO2, 25-Hydroxyvitamin D. These results were unspecific and mitochondrial disease was highly suspected. However, the genetic study was requested to get a defined diagnosis and treatment; the whole exon sequencing result showed a homozygous variant of uncertain significance mutation; related to an amino acid change from Ile to Thr at position 1002 in the POLR3B gene, which helped us to reveal the final diagnosis, and the genetic counseling were recommended for the next pregnancies. POLR3-related Leukodystrophy is a very rare disease. The early diagnosis should be raised depending on clinical history and MRI findings after other conditions were rolled out, and the confirmed diagnosis depends on the genetic study.

Pulmonary thromboembolism following organophosphate intoxication: a case report

Various symptoms manifest after organophosphate intoxication due to muscarinic, nicotinic, and central nervous system effects. Complications are common, and morbidity occurs due to respiratory center depression, cardiovascular complications, aspiration pneumonia, general weakness, and neurological symptoms. Some studies have reported a statistically significant association between organophosphate intoxication and deep vein thrombosis. However, cases of pulmonary thromboembolism (PTE) resulting from organophosphate poisoning are very rare. A 45-year-old male patient was transferred to our hospital after ingesting an unknown amount of an insecticide and receiving 6 L of gastric lavage at a local hospital. Other than nausea, no symptoms (e.g., dyspnea) were present, but a hemodynamic test showed an elevated lactic acid level, and metabolic acidosis worsened over time. Accordingly, we conducted initial treatment including continuous renal replacement therapy. After 7 hours, the poisoning analysis result was confirmed, and lambda-cyhalothrin and chlorpyrifos (0.441 µg/mL and 0.401 µg/mL, respectively) were detected. We introduced pralidoxime. Although no increase in pseudocholinesterase was found during hospitalization, continuous renal replacement therapy and pralidoxime were discontinued because the patient did not show symptoms of intermediate syndrome, including dyspnea and altered consciousness. The patient complained of abdominal pain on hospital day 8. Abdominal computed tomography was performed to evaluate the possibility of a corrosive injury to the stomach or esophagus, and we confirmed PTE. The D-dimer level was 1.96 mg/L (normal range, 0–0.55 mg/dL). A radiologic examination showed a PTE in the main pulmonary artery leading to the segmental pulmonary artery. After heparinization, the patient was discharged after being prescribed a vitamin K-independent oral anticoagulant. Through this case, we would like to emphasize the need for a thorough evaluation of clinical symptoms because atypical symptoms can occur after poisoning with organophosphate pesticides.

Tumor lactic acid: a potential target for cancer therapy

Tumor development is influenced by circulating metabolites and most tumors are exposed to substantially elevated levels of lactic acid and low levels of nutrients, such as glucose and glutamine. Tumor-derived lactic acid, the major circulating carbon metabolite, regulates energy metabolism and cancer cell signaling pathways, while also acting as an energy source and signaling molecule. Recent studies have yielded new insights into the pro-tumorigenic action of lactic acid and its metabolism. These insights suggest an anti-tumor therapeutic strategy targeting the oncometabolite lactic acid, with the aim of improving the efficacy and clinical safety of tumor metabolism inhibitors. This review describes the current understanding of the multifunctional roles of tumor lactic acid, as well as therapeutic approaches targeting lactic acid metabolism, including lactate dehydrogenase and monocarboxylate transporters, for anti-cancer therapy.

CARDIOGENIC SHOCK AND CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY: DID STEROIDS MAKE MY HEART GO ON?

CARDIOGENIC SHOCK AND CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY: DID STEROIDS MAKE MY HEART GO ON?

Metabolic and structural changes in the myocardium of rats with hypercholesterolemia after prolonged administration of simvastatin

BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin.
 AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin.
 MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) intact animals; comparison group (35 animals) intact animals treated with simvastatin for two months; experimental group divided into: subgroup 1 (35 individuals) animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied.
 RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins.
 CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.

Prognostic value of serum ammonia in critical patients with non-hepatic disease: A prospective, observational, multicenter study.

Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU). This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia. A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia (P < 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07-2.80, P = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, P < 0.001) remained the most predictive factor for patient prognosis by ROC analysis. Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.

Elevated serum lactic acid level is an independent risk factor for the incidence and mortality of sepsis-associated acute kidney injury

To explore the effect of serum lactic acid (Lac) level on acute kidney injury (AKI) in patients with sepsis and whether Lac level affects the in-hospital mortality of patients with sepsis-associated AKI. A retrospective cohort study was conducted. Clinical data of patients with sepsis admitted to the internal intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020 were collected. According to the first quartile of Lac within 24 hours of admission to ICU, the patients were divided into Lac ≤ 1.4 mmol/L group (group Q1), Lac 1.5-2.4 mmol/L group (group Q2), Lac 2.5-4.0 mmol/L group (group Q3), and Lac ≥ 4.1 mmol/L group (group Q4). The incidence of sepsis-associated AKI after admission to ICU and hospital mortality were compared among four groups. The effect of elevated Lac on the incidence and mortality of sepsis-associated AKI was investigated by binary Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of Lac on the incidence and mortality of sepsis-associated AKI, and the cut-off value was obtained to analyze the incidence and death risk of sepsis-associated AKI at different Lac levels. A total of 655 sepsis patients were enrolled, of which 330 patients (50.4%) developed AKI and 325 patients (49.6%) did not. Among 330 patients with sepsis-associated AKI, 134 (40.6%) died and 196 (59.4%) survived. With the increase of Lac level, the incidence of sepsis-associated AKI increased gradually (34.5%, 41.0%, 58.4%, 66.3%, respectively, in group Q1-Q4), meanwhile, the in-hospital mortality also increased gradually (23.4%, 29.2%, 33.1%, 43.4%, respectively, in group Q1-Q4), the differences were statistically significant (both P < 0.01). Compared with the non-AKI group, the Lac level in the AKI group was significantly increased [mmol/L: 3.08 (1.84, 5.70) vs. 1.91 (1.20, 3.10), P < 0.01]. After adjustment for factors such as gender (male), site of infection (abdominal cavity), vasoactive drugs, basal mechanical ventilation, mean arterial pressure (MAP), basal renal insufficiency, uric acid, procalcitonin (PCT), platelet count (PLT), basal serum creatinine (SCr) and basal estimated glomerular filtration rate (eGFR), and other influencing factors, multivariate Logistic regression analysis showed that elevated Lac was an independent risk factor for sepsis-associated AKI [odds ratio (OR) = 1.096, 95% confidence interval (95%CI) was 1.022-1.175, P = 0.010]. Compared with the survival group, the Lac level in the death group was significantly increased [mmol/L: 3.55 (2.00, 6.76) vs. 3.00 (1.70, 4.50), P < 0.01]. After adjusting for age, diabetes, vasoactive drugs, basal eGFR, and other factors, multivariate Logistic regression analysis suggested that increased Lac was an independent risk factor for in-hospital mortality in sepsis-associated AKI patients (OR = 1.074, 95%CI was 1.004-1.149, P = 0.037). ROC curve analysis showed that the area under the ROC curve (AUC) of Lac for predicting the incidence and mortality of sepsis-associated AKI was 0.653 (95%CI was 0.611-0.694) and 0.593 (95%CI was 0.530-0.656, both P < 0.01), respectively, and the cut-off values were 2.75 mmol/L (sensitivity was 57.8%, specificity was 69.2%) and 5.95 mmol/L (sensitivity was 56.7%, specificity was 83.7%). When the Lac ≥ 2.75 mmol/L, the risk of sepsis-associated AKI was 2.772 times higher than that of < 2.75 mmol/L (OR = 2.772, 95%CI was 1.754-4.380, P < 0.001). When the Lac ≥ 5.95 mmol/L, the patients with sepsis-associated AKI had a 2.511 times higher risk of in-hospital death than those with Lac < 5.95 mmol/L (OR = 2.511, 95%CI was 1.378-4.574, P = 0.003). Elevated Lac level is an independent risk factor for the incidence and mortality of sepsis-associated AKI. When Lac ≥ 2.75 mmol/L, the risk of AKI in patients with sepsis increased by 1.772 times; when Lac ≥ 5.95 mmol/L, the risk of in-hospital death in patients with sepsis related AKI increased by 1.511 times.

Association between fecal levels of Short-Chain Fatty Acids and serum Pro- and Anti-Inflammatory Cytokines in patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders characterized by dysbiosis and altered short-chain fatty acid (SCFA) level. The association between individual SCFA levels and cytokine levels is unknown. We aimed to determine the fecal SCFA levels in patients with IBD in relation to disease severity and the serum levels of pro- and anti-inflammatory cytokines. The study included 61 patients with IBD (inactive, 22; active, 39) and 16 controls. Fecal levels of organic acids (acetic, lactic, propionic, butyric, isovaleric, isobutyric, and valeric), serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), IL-17, and IL-22, complete blood count and C-reactive protein (CRP) were measured. Patients with active IBD had reduced butyric, acetic, valeric, and isovaleric acid levels and elevated lactic acid levels in stool. Hemoglobin levels were positively correlated with the levels of acetic and butyric acids (R = 0.266 and R = 0.346, respectively; P <0.05). In addition, CRP levels were inversely correlated with butyric acid levels (R = -0.573; P <0.05). Higher serum TNF-α levels were observed in patients with active IBD compared with controls (6.64 pg/ml vs 2.05 pg/ml, P <0.05). No relationship was noted between the SCFA profile and cytokine levels. The study showed that determination of SCFA levels can be used to evaluate the activity of IBD. The relationship between individual SCFA and cytokine levels seems to be complex and requires further studies.

Significance of Elevated Synovial Fluid Lactic Acid and Lactate Dehydrogenase Levels in Differentiating Between Septic Arthritis, Inflammatory Arthritis and Non-Inflammatory Arthritis

Objective: To determine the lactic acid and lactate dehydrogenase levels in synovial fluid and differentiate between inflammatory and non-inflammatory arthritis.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Department of Rheumatology, Liaquat National Hospital, Karachi, from Feb to May 2019.&#x0D; Methodology: All patients of age &gt;18 years, of either gender, who presented with knee joint effusion were enrolled in the study. Synovial fluid aspiration for the analysis of lactate and lactate dehydrogenase (LDH) was done for all patients.&#x0D; Results: Seventy-seven patients were enrolled, of which 75 were included in the analysis. Two patients were excluded as one had lymphoma and the other had recent joint trauma. 31 (41.3 %) patients had non-inflammatory, or osteoarthritis, and 44 (58.7 %) had inflammatory arthritis. The mean value of synovial LDH in inflammatory and non-inflammatory arthritis was 737.38 ± 102.76 mmol/L and 265.5 ± 17.43 mmol/L, respectively, (p&lt;0.001). The mean value of synovial lactate in inflammatory arthritis (32.16 ± 2.84 mmol/L) was higher than the mean value of synovial lactate in non-inflammatory arthritis (19.81 ± 1.08 mmol/L) (p&lt;0.001). There mean plasma LDH in inflammatory arthritis and non-inflammatory arthritis was 495.77 ± 41.67 mg/dl and 437.90 ± 30.99 mg/dl, respectively (p&gt;0.05). The plasma lactate in inflammatory arthritis and noninflammatory arthritis was 12.84 ± 0.59 mg/dl and 12.97 ± 0.78 mg/dl, respectively (p&gt;0.05).&#x0D; Conclusion: Synovial fluid lactic acid and synovial LDH can serve as rapid diagnostic and cost-effective tests to differentiate between non-inflammatory and inflammatory arthritis.

Characteristics and outcomes of cancer patients who develop pulmonary embolism: A cross-sectional study.

Pulmonary embolism (PE), along with deep vein thrombosis, are collectively known as venous thromboembolism (VTE). Predisposing factors for PE include post-operative conditions, pregnancy, cancer and an advanced age; of note, a number of genetic mutations have been found to be associated with an increased risk of PE. The association between cancer and VTE is well-established, and cancer patients present a higher risk of a thrombotic event compared to the general population. In addition, PE is a significant cause of morbidity and mortality among cancer patients. The aim of the present study was to illustrate the clinical characteristics, laboratory findings, radiology features and outcomes of cancer patients who developed PE, collected from an anticancer hospital. For this purpose, adult cancer patients diagnosed with PE by imaging with computed tomography pulmonary angiography were enrolled. The following data were recorded: Demographics, comorbidities, type of cancer, time interval between cancer diagnosis and PE occurrence, the type of therapy received and the presence of metastases, clinical signs and symptoms, predisposing factors for PE development, laboratory data, radiological findings, electrocardiography findings, and the type of therapy received for PE and outcomes in a follow-up period of 6 months. In total, 60 cancer patients were enrolled. The majority of the cancer patients were males. The most common type of cancer observed was lung cancer. The majority of cases of PE occurred within the first year from the time of cancer diagnosis, while the majority of patients had already developed metastases. In addition, the majority of cancer patients had received chemotherapy over the past month, while they were not receiving anticoagulants and had central obstruction. A large proportion of patients had asymptomatic PE. The in-hospital mortality rate was 13.3% and no relapse or mortality were observed during the follow-up period. The present study demonstrates that elevated levels of lactic acid and an increased platelet count, as well as low serum levels of carcinoembryonic antigen, albumin and D-dimer, may be potential biomarkers for asymptomatic PE among cancer patients.

Influence of brief immersion in an aqueous solution of sodium chloride and/or copper sulphate on pikeperch (Sander lucioperca (L.)) blood parameters

Abstract Research focusing on the effects of chemotherapeutics on the physiological state of fish determines their application in aquaculture. The aim of the study was to determine the impact of sodium chloride (NaCl) and/or copper sulphate (CuSO4) on the hematological and biochemical parameters of the blood plasma of pikeperch, Sander lucioperca (body weight – 346.42 ± 44.82 g; body length – 29.8 ± 1.3 cm) during rearing in recirculating aquaculture systems (RAS). Three groups of fish were subjected to treatment with NaCl (5 g/L), CuSO4 (1.5 mg/L), and NaCl+CuSO4 (5 g/L + 1.5 mg/L). Blood was drawn 0, 24 and 48 h following immersion. Significant differences were noted immediately following the conclusion of immersion: mean corpuscular volume (MCV; elevated values in the NaCl+CuSO4 group) and mean corpuscular hemoglobin concentration (MCHC; elevated values in the NaCl group). Immediately following fish exposure in all three experimental groups (0 h), significantly elevated glucose and lactic acid levels were recorded as were lowered levels of chloride ions (Cl-). After 24 and 48 h, significant differences were observed in Cl-. In the NaCl group lowered levels of this parameter were sustained after 48 h, while in the other two groups this was sustained for 24 h. It was confirmed that the physiological impact on the pikeperch of the prophylactic bath in sodium chloride and/or copper sulphate was short and that the treatments did not have a significant impact on the health condition of pikeperch.

Chronic progressive external ophthalmoplegia that could not be diagnosed by biceps muscle biopsy, but was genetically diagnosed by extraocular muscle biopsy

A 48-year-old Japanese male experienced slowly progressive diplopia. He had no family history and was negative for the edrophonium chloride test. Blood analysis showed elevated lactic acid and pyruvic acid levels, suggesting mitochondrial disease. A muscle biopsy from the biceps brachii was performed, but no pathological or genetical mitochondrial abnormalities were detected. Subsequently, he underwent muscle plication for diplopia in which the right inferior rectus muscle was biopsied. Genetic examination of genomic DNA extracted from the extraocular muscle tissue revealed multiple mitochondrial gene deletions, with a heteroplasmy rate of approximately 35%, resulting in the diagnosis of chronic progressive external ophthalmoplegia. In mitochondrial diseases, the tissue distribution of mitochondria with disease-associated variants in mtDNA should be noted, and it is important to select the affected muscle when performing a biopsy for an accurate diagnosis.