Advanced biomarker clustering analysis reveals mortality predictors in burn patients with sepsis.

This study addresses the challenge of predicting mortality in sepsis among burn patients. Given the heterogeneity of sepsis, especially in the context of burn injuries, this study aims to identify reliable biomarkers for mortality prediction. The study is a retrospective review, focusing on the evaluation of various biomarkers and their changes over time in a burn patient cohort. Conducted in the Burn Intensive Care Unit of Hangang Sacred Heart Hospital, the study involved a retrospective review of 1,659 adult burn patients from January 2010 to December 2022. Key biomarkers analyzed include lactate levels, pH, platelets, procalcitonin, and others. Advanced clustering methodologies, such as dynamic time warping and hierarchical clustering, were utilized to classify patients into distinct groups based on their biomarker profiles and clinical outcomes. The study identified four patient clusters with unique lactate level trajectories. Significant findings include the identification of procalcitonin, pH, and platelets as key predictors of mortality, with varying degrees of efficacy across different clusters. For instance, in the "Persistent Rise" cluster, pH and platelet count showed Area Under the Curve (AUC) values of 0.756 and 0.753, respectively, indicating their strong predictive power. The study concludes that a combination of biomarkers, especially lactate dynamics, can effectively predict mortality in burn-induced sepsis. The results advocate for a more personalized approach in managing sepsis in burn patients, considering the specific biomarker trajectories. These findings are crucial for enhancing treatment strategies and improving patient outcomes in burn care.

Relation Between Multiplication of Venous Carbon Dioxide Partial Pressure (PvCO2) and the Ratio of Gas Flow to Pump Flow (Ve/Q) with Hyperlactatemia During Cardiopulmonary Bypass.

BACKGROUND: The incidence of hyperlactatemia due to hypoperfusion during cardiopulmonary bypass (CPB) increases morbidity. Carbon dioxide production during CPB is one of the lactate production markers, in addition to other markers such as delivery oxygen (DO2), oxygen consumption (VO2), mixed vein oxygen saturation (SvO2), and oxygen extraction ratio (O2ER). METHOD: This observational analytic study was conducted on 40 adult cardiac surgery patients using a CPB machine. Initial lactate is taken when entering CPB and final lactate is examined 15 min after coming off bypass. The values of DO2, VO2, SvO2, VCO2, respiratory quotient (RQ), DO2/VCO2, PvCO2 × Ve/Q were calculated from the results of blood and venous gas analysis 1 h after entering CPB in the nadir of core temperature and lowest pump flow. RESULT: The multivariate test showed that the value of PvCO2 × Ve/Q was more effective than other oxygenation and carbon dioxide parameters in predicting an increase in the percentage of lactate. Each increase of 1 mmHg PvCO2 ×× Ve/Q can predict a final lactate increase of 29% from the initial lactate. The high PvCO2 × Ve/Q value is also the strongest correlation factor for the incidence of hyperlactatemia after CPB (final lactate >3 mmol/L). The cutoff value of this marker is >19.3 mmHg, which has a sensitivity of 100% and a specificity of 55.6% with a strong correlation value. CONCLUSION: The PvCO2 × Ve/Q value proved to be one of the significant markers in predicting hyperlactatemia during cardiac surgery using CPB.

Association of Weight-indexed Conventional Ultrafiltration Volume with Post-operative Lactate in Patients Undergoing Cardiopulmonary Bypass.

Background: Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) is utilized to minimize hemodilution. However, removing high volumes leads to tissue hypoperfusion by activating the anaerobic glycolysis pathways. This study aimed to determine the association between weight-indexed CUF volumes and lactate in patients who underwent coronary artery bypass grafting (CABG). Methods: In this single-center retrospective study, 641 CABG patients, who were referred to Al-Zahra Hospital (Shiraz, Iran) and underwent CPB, during 2019-2021, were recruited. Peri-operative parameters were extracted from the patient's records. The patients with non-elective status, pre-existing liver and renal diseases, ejection fraction<35%, and repeated sternotomy were excluded from the study. An increase in post-operative lactate level≥4 mmol/L after 6 hours was defined as hyperlactatemia (HL). To predict HL, univariable and multiple logistic regression modeling, while controlling confounding factors, were employed. Results: The patients' mean age was 58.8±11.1 years, and 39.2% were women. The incidence of HL was 14.5% (93 patients). There was a significant association between weight-indexed CUF volume and HL. The volume removed in the HL patients was almost doubled (43.37±11.32 vs. 21.41±8.15 mL/Kg, P<0.001), and the higher the weight-indexed CUF volume, the more likely to develop an HL at a rate of 1.38 (Odds ratio=1.38 [1.27-1.49], 95% CI, P<0.001). Furthermore, the multiple logistic regression model showed that HL was associated with the lowest mean arterial pressure (MAP) during CPB. Conclusion: A higher volume of ultrafiltration was associated with increased post-operative serum lactate levels.

Prognostic indicators in patients with isolated thoracic trauma: A retrospective cross-sectional study.

BACKGROUND: Thoracic trauma is a significant cause of mortality, especially among those arriving at hospitals. This study explores the associations between mortality, the shock index (SI), and specific metabolic and biochemical markers in patients with isolated thoracic trauma. METHODS: This retrospective cross-sectional study included all consecutive adult patients presenting with isolated thoracic trauma to a high-volume emergency department from January 2019 to December 2023. The predictive capability of SI levels and selected biomarkers upon admission for estimating mortality was assessed by determining the areas under the receiver operating characteristic curves (AUCs). Optimal cutoff values were determined using the Youden index method. RESULTS: The study involved 352 patients, with 285 (81%) being males and an average age of 50.0±17.7 years. The mortality rate was 9.6%. Mortality was significantly associated with higher shock index (odds ratio [OR]: 14.02, [95% confidence interval [CI] 0.847-0.916], AUC=0.885, p=0.001), glucose/potassium ratio (OR: 1.24 [95% CI 1.14-1.35], AUC=0.869, p<0.001), and lactate levels (OR: 4.30 [95% CI 2.29-8.07], AUC=0.832, p<0.001). The optimal cutoff values determined for the shock index, glucose/potassium ratio, ionized calcium, and lactate were 1.02 (sensitivity, 94.1%; specificity 69.5%; positive predictive value [PPV], 24.8; negative predictive value [NPV], 99.1), 36.85 (sensitivity, 76.5%; specificity, 87.7%; PPV, 40.0; NPV, 97.2), 1.23 (sensitivity, 94.1%; specificity, 56.0%; PPV, 18.6; NPV, 98.9), and 1.98 (sensitivity, 70.6%; specificity, 80.5%; PPV, 27.9; NPV, 96.2), respectively. CONCLUSION: This study demonstrates that higher shock index, glucose/potassium ratio, and lactate levels are significantly associated with increased mortality in patients with isolated thoracic trauma. These findings suggest that these markers can be effective prognostic indicators, potentially guiding clinical decision-making and improving patient outcomes.

Relationships between Spatial Biology and Physiological Ecology in the Gopher Tortoise, Gopherus polyphemus.

AbstractThe overlap between spatial and physiological ecology is generally understudied, yet both fields are fundamentally related in assessing how individuals balance limited resources. Herein, we quantified the relationships between spatial ecology using two parameters of home range (annual home range area and number of burrows used in 1 yr) and four measures of physiology that integrate stress and immunity (baseline plasma corticosterone [CORT] concentration, plasma lactate concentration, heterophil-to-lymphocyte [H∶L] ratio, and bactericidal ability [BA]) in a wild free-ranging population of the gopher tortoise (Gopherus polyphemus) to test the hypothesis that space usage is correlated with physiological state. We also used structural equation models (SEMs) to test for causative relationships between the spatial and physiological parameters. We predicted that larger home ranges would be negatively correlated with traditional biomarkers of stress and positively correlated with immunity, consistent with our hypothesis that home ranges are determined based on individual condition. Males had larger home ranges, used more burrows, and had higher baseline CORT than females. We found significant negative correlations between lactate and home range (r=-0.456, df=21, P=0.029). CORT was negatively correlated with the number of burrows used in both sexes (F=7.322, df=2,20, P=0.003, adjusted R2=0.383). No correlations were observed between space use and BA or, notably, H∶L ratio. SEMs suggested that variation in the number of burrows used was a result of variation in baseline CORT. The lack of a relationship between H∶L ratio and home range suggests that home range differences are not associated with differences in chronic stress, despite the pattern between baseline CORT and number of burrows used. Instead, this study indicates that animals balance trade-offs in energetics, likely by way of baseline corticosteroid, in such a way as to maintain function across continuously variable home range strategies.

Backyard running: Pushing the boundaries of human performance.

Ultrarunning is gaining in popularity but no information is available on the physiological and psychological responses during backyard ultrarunning events. The aim of this study was to determine changes in cognitive function, markers of physiological resilience, and running performance during a backyard-running event. Twelve male ultrarunners (38 ± 8 years old, BMI: 23.5 ± 1.6 kg/m2, and VO2max: 60.8 ± 4.7 mL/min/kg) were monitored before, during, and after the event. Cognitive performance was determined using a cognitive test battery before, during, and after the event. During the event, the rating of perceived exertion (RPE), blood lactate concentration, and heart rate (HR) were assessed. Physical performance was investigated using the total number of completed laps and running speed per lap. Athletes completed 34 ± 17 laps equaling 227.8 ± 113.9 km with average speeds starting at 9.0 km/h and slowing down to 7.5 km/h at the end of the event. Physiological resilience (estimated using HR/speed) varied between athletes, with significantly lower values in the more proficient backyard runners at the end of the event (p < 0.05). HR and lactate levels remained constant, whereas a progressive increase in RPE was noticed (p ≤ 0.001). A significantly worsened reaction time was observed for several cognitive tasks after the event compared to baseline measures (p ≤ 0.05). These observations show that physiological resilience differs depending on the level of endurance performance of the athletes. Furthermore, the backyard ultrarunning event negatively impacted psychomotor speed. Therefore, the results suggest that implementing strategies that enhance physiological resilience and/or psychomotor speed could potentially have a positive effect on performance in ultraendurance activities.

Combining the vasoactive-inotropic score with lactate levels to predict mortality in post-cardiotomy patients supported with venoarterial extracorporeal membrane oxygenation.

OBJECTIVES: Our goal was to determine the predictive role of the combined assessment of the vasoactive-inotropic score (VIS) and lactate levels for the prognosis of patients with postcardiotomy cardiogenic shock (PCS) requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: The data of adult patients with PCS requiring VA-ECMO between January 2015 and December 2018 at a tertiary hospital were analysed retrospectively. The incidence of in-hospital mortality and other clinical outcomes was analysed. The associations of the VIS and the lactate concentration and in-hospital mortality were assessed using logistic regression analysis. RESULTS: A total of 222 patients were included and divided into 4 groups according to the cut-off points of the VIS (24.3) and the lactate level (6.85 mmol/L). The in-hospital mortality rates were 37.7%, 50.7%, 54.8% and 76.5% for the 4 groups (P < 0.001), and the rates of successful weaning off VA-ECMO were 73.9%, 69%, 61.3% and 39.2%, respectively (P = 0.001). Groups 1 and 2 exhibited significant differences compared to group 4 in both in-hospital mortality and weaning rates (P < 0.05). There was a statistically significant difference in the incidence of multiple organ dysfunction between group 1 and group 4 (P < 0.05). Groups 1, 2 and 3 demonstrated significantly improved cumulative 30-day survival compared with group 4 (log-rank test, P < 0.05). Logistic regression analysis revealed that age, a VIS > 24.3 and lactate levels > 6.85 mmol/L were independently predictive of in-hospital mortality. CONCLUSIONS: Among patients with PCS requiring VA-ECMO, the initiation before reaching a VIS > 24.3 and lactate levels > 6.85 mmol/L was associated with improved in-hospital and 30-day outcomes, suggesting that the combined assessment of the VIS and lactate levels may be instructive for determining the initiation of VA-ECMO.

Hypoxia-acclimation adjusts skeletal muscle anaerobic metabolism and burst swim performance in a marine fish.

Red drum, Sciaenops ocellatus, are a marine teleost native to the Gulf of Mexico that routinely experiences periods of low oxygen (hypoxia). Recent work has demonstrated this species has the capacity to improve aerobic performance in hypoxia through respiratory acclimation. However, it remains unknown how hypoxia acclimation impacts anaerobic metabolism in red drum, and the consequences of exhaustive exercise and recovery. Juvenile fish were acclimated to normoxia (n = 15, DO 90.4 ± 6.42 %) or hypoxia (n = 15, DO 33.6 ± 7.2 %) for 8 days then sampled at three time points: at rest, after exercise, and after a 3 h recovery period. The resting time point was used to characterize the acclimated phenotype, while the remaining time points demonstrate how this phenotype responds to exhaustive exercise. Whole blood, red muscle, white muscle, and heart tissues were sampled for metabolites and enzyme activity. The resting phenotype was characterized by lower pHe and changes to skeletal muscle ATP. Exhaustive exercise increased muscle lactate, and decreased phosphocreatine and ATP with no effect of acclimation. Interestingly, hypoxia-acclimated fish had higher pHe and pHi than control in all exercise time points. Red muscle ATP was lower in hypoxia-acclimated fish versus control at each sample period. Moreover, acclimated fish increased lactate dehydrogenase activity in the red muscle. Hypoxia acclimation increased white muscle ATP and hexokinase activity, a glycolytic enzyme. In a gait-transition swim test, hypoxia-acclimated fish recruited anaerobic-powered burst swimming at lower speeds in normoxia compared to control fish. These data suggest that acclimation increases reliance on anaerobic metabolism, and does not benefit recovery from exhaustive exercise.

A New Genetic Signature of Lactate Metabolism-Associated Genes Predicting Clinically Distinctive Features and Tumor Microenvironment in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is characterized by its high malignancy and challenging prognosis. A significant aspect of cancer is metabolic reprogramming, where lactate serves as a crucial metabolite that contributes to the development of cancer and the tumor microenvironment (TME). Current studies have indicated that lactate plays a significant role in the progression of CRC. However, the relationship between lactate and the tumor microenvironment remains understudied, underscoring the potential of lactate as a novel biomarker. METHODS: We sourced transcriptomic data for colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO) portals, along with the corresponding clinical information. Utilizing univariate Cox regression in conjunction with LASSO regression analysis, we identified genes involved in lactate metabolism that are associated with CRC prognosis. Subsequently, we developed models based on multi-factor Cox regression. To evaluate the correlation between tumor mutational burden (TMB), tumor microenvironment (TME), and lactate scores with patient survival, we conducted gene set enrichment analysis (GSEA) and immunogenic signature analyses. RESULTS: 3 lactate metabolism-related genes (LMRGs) (SLC16A8, GATA1, and PYGL) were used to construct models that categorized patients into 2 subgroups based on their lactate scores. The function of the differential genes between the 2 subgroups was mainly enriched in cell cycle and mRNA division, and the prognosis of patients in the high score subgroup was poor. Furthermore, a significant positive correlation was observed between TMB and LMRGs scores in the high-scoring group (P = 0.003, r2 = 0.12). Lastly, LMRGs also reflected the characteristics of TME, with differences in immune cells and immune checkpoints between the 2 subgroups. CONCLUSIONS: LMRGs may serve as a promising biomarker for predicting prognostic survival in CRC patients and to assess the TME.

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Outcomes and prognosis of postpartum hemorrhage according to management protocol: an 11-year retrospective study from two referral centers.

BACKGROUND: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. METHODS: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). RESULTS: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively). CONCLUSIONS: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications.

A Flavonoid Concentrate from Moringa Oleifera Lam. Leaves Extends Exhaustive Swimming Time by Improving Energy Metabolism and Antioxidant Capacity in Mice.

Moringa oleifera Lam. leaves contain various nutrients and bioactive compounds. The present study aimed to assess the anti-fatigue capacity of a flavonoids concentrate purified from M. oleifera Lam. leaves. The total flavonoids in the purified extract were analyzed by ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-MS/MS). The mice were supplemented with purified M. oleifera Lam. leaf flavonoid-rich extract (MLFE) for 14 days. The weight-loaded forced swimming test was used for evaluating exercise endurance. The 90-min non-weight-bearing swimming test was carried out to assess biochemical biomarkers correlated to fatigue and energy metabolism. UPLC-MS/MS analysis identified 83 flavonoids from MLFE. MLFE significantly increased the swimming time by 60%. Serum lactate (9.9 ± 0.9 vs. 8.9 ± 0.7), blood urea nitrogen (BUN) (8.8 ± 0.8 vs. 7.2 ± 0.5), and nonesterified fatty acid (NEFA) (2.4 ± 0.2 vs. 1.7 ± 0.3) were significantly elevated; phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GCK), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression were significantly downregulated; and heme oxygenase 1 mRNA expression was significantly upregulated in muscle after swimming. MLFE supplement significantly decreased serum lactate (8.0 ± 1.0 vs. 9.9 ± 0.9), BUN (8.6 ± 0.4 vs. 8.9 ± 0.8), and NEFA (2.3 ± 0.4 vs. 2.4 ± 0.2) and increased the protein and mRNA expression of GCK, PEPCK, and Nrf2. The enhancement of glucose metabolism and antioxidant function by MLFE contributes partly to its anti-fatigue action.

Influence of menstrual cycle and oral contraceptive phases on strength performance, neuromuscular fatigue, and perceived exertion.

The primary aim of the study was to assess differences in strength performance, neuromuscular fatigue, and perceived exertion across phases of the menstrual cycle [MC; early follicular (eFP), late follicular (lFP), and mid-luteal phase (mLP)] and oral contraceptives [OCs; active pill phase (aPP) and nonactive pill phase (nPP)]. The secondary aim was to analyze the influence of fluctuating serum 17ß-estradiol and progesterone concentrations on these parameters in naturally menstruating women. Thirty-four women (21 with a natural MC and 13 using OCs) completed three or two experimental sessions, respectively. Mean propulsive velocity (MPVmean) and total number of repetitions (REPtotal) were assessed during a power [3 × 8 at 60% 1RM (one-repetition maximum)] and hypertrophy squat loading (3 sets to failure at 70% 1RM), respectively. Changes in bench press and squat MPV at 60% 1RM in response to the loadings were used as surrogates for nonlocal and local fatigue, respectively. Total blood lactate accumulation (BLAA) and markers of perceived exertion were assessed in each session. No significant differences between any of the MC or OC phases were observed for MPVmean, REPtotal, nonlocal and local fatigue, and markers of perceived exertion (all P > 0.050). A higher intraindividual 17ß-estradiol concentration was significantly associated with a lower MPVmean (P = 0.019). BLAA was significantly higher in the lFP than in the mLP (P = 0.019) and negatively associated with the intraindividual progesterone concentration (P = 0.005). Although 17ß-estradiol may negatively influence the MPV, it appears that fluctuations of both sex hormones across the MC and OC phases are not prominent enough to induce significant or practically relevant changes in the assessed parameters.NEW & NOTEWORTHY Although a high intraindividual 17ß-estradiol concentration was associated with a lower movement velocity, markers of strength performance and surrogates for nonlocal and local fatigue remained unaffected by MC and OC phases. Blood lactate accumulation was significantly reduced in the mLP. Furthermore, our findings suggest that the impact of the MC phases varies greatly among individuals. Individuals with high fluctuations in sex hormone concentrations may experience relevant changes in the assessed parameters.

The Method but Not the Protocol Affects Lactate-Threshold Determination in Competitive Swimmers.

PURPOSE: The study validated variables corresponding to lactate threshold (LT) in swimming. Speed (sLT), blood lactate concentration (BLLT), oxygen uptake (VO2LT), and heart rate (HRLT) corresponding to LT were calculated by 2 different incremental protocols and validated in comparison with maximal lactate steady state (MLSS). METHODS: Ten competitive swimmers performed a 7 × 200-m front-crawl incremental "step test" with 2 protocols: (1) with 30-second rests between repetitions (short-rest incremental protocols) and (2) on a 5-minute cycle (swim + rest time, long-rest incremental protocols). Five methods were used for the assessment of sLT and corresponding BLLT, VO2LT, and HRLT: intersection of 2 lines, Dmax, modified Dmax, visual inspection, and intersection of combined linear and exponential regression lines. Subsequently, swimmers performed two to three 30-minute continuous efforts to identify speed (sMLSS) and physiological parameters corresponding to MLSS. RESULTS: Both protocols resulted in similar sLT and corresponding physiological variables (P > .05). Bland-Altman plots showed agreement between protocols (sLT, bias: -0.017 [0.002] m·s-1; BLLT, bias: 0.0 [0.5] mmol·L-1; VO2LT, bias: -0.1 [2.2] mL·kg-1·min-1; HRLT. bias: -2 [8] beats·min-1). However, sLT calculated by modified Dmax using short rest was higher compared with speed at MLSS (1.346 [0.076] vs 1.300 [0.101] m·s-1; P < .05). CONCLUSIONS: Calculated sLT, BLLT, VO2LT, and HRLT using all other methods in short-rest and long-rest incremental protocols were no different compared with MLSS (P > .05). Both 7 × 200-m protocols are valid for determination of sLT and corresponding physiological parameters, but the modified Dmax method may overestimate sLT.

Association of Serum Lactate Levels Measured in the Emergency Department with 30-Day Mortality in Older Patients with Unilateral Hip Fractures.

BACKGROUND: Hip fractures are frequent injuries in older patients and are associated with high mortality rates. This study assessed the association between serum lactate level and 30-day mortality in older patients with unilateral hip fractures and examined the prognostic value of this association on the clinical outcomes of these patients. METHODS: This retrospective, single-center study included patients aged ≥65 years admitted to the emergency department due to low-energy trauma and diagnosed with unilateral hip fracture upon admission. The additional inclusion criteria were patients with independent ambulation or walker or cane assistance before the injury, with available data on serum lactate levels on venous blood gas analysis, and who underwent surgery. RESULTS: Among the 330 included patients, 30.9% experienced postoperative complications and 10.3% died within 30 days. Using a lactate cut-off value of 2 mmol/L to distinguish between living and deceased patients, the sensitivity and specificity were 41% and 88%, respectively. Multivariate logistic regression analysis revealed that high lactate and low albumin levels and male sex were associated with mortality. CONCLUSION: Identifying risk factors for mortality in geriatric patients with hip fractures is important. Male sex, low albumin levels, and particularly increased lactate levels were independent predictors of short-term mortality in these patients.

Association between Peripheral Arterial Lactate Levels and Malignant Brain Edema Following Endovascular Treatment for Ischemic Stroke.

AIMS: To investigate the factors of postoperative malignant brain edema (MBE) in patients with acute ischemic stroke (AIS) treated with endovascular treatment (EVT). BACKGROUND: MBE is a severe complication following EVT for AIS, and it is essential to identify risk factors early. Peripheral arterial lactate (PAL) levels may serve as a potential predictive marker for MBE. OBJECTIVE: To determine whether immediate postoperative PAL levels and the highest PAL level within 24 hours of EVT are independently associated with MBE development in AIS patients. METHODS: We retrospectively analyzed patients with AIS who underwent EVT from October 2019 to October 2022. Arterial blood was collected every 8 h after EVT to measure PAL, and record the immediate postoperative PAL and the highest PAL level within 24 h. Brain edema was evaluated using brain computed tomography scans within 7 days of EVT. RESULTS: The study included 227 patients with a median age of 71 years, of whom 59.5% were male and MBE developed in 25.6% of patients (58/227). Multivariate logistic regression analysis showed that the immediate postoperative PAL (odds ratio, 1.809 [95% confidence interval (CI), 1.215-2.693]; p = 0.004) and the highest PAL level within 24 h of EVT (odds ratio, 2.259 [95% CI, 1.407-3.629]; p = 0.001) were independently associated with MBE. The area under the curve for predicting MBE based on the highest PAL level within 24 hours of EVT was 0.780 (95% CI, 0.711-0.849). CONCLUSION: Early increase in PAL levels is an independent predictor of MBE after EVT in AIS patients.

Amyloid A and lactic acid as a predictor in patients with sepsis in patients with liver cirrhosis.

BACKGROUND: Sepsis is triggered by pathogenic microorganisms, resulting in a systemic inflammatory response. Liver cirrhosis and sepsis create a vicious cycle: cirrhosis weakens immune function, raising infection risk and hindering pathogen clearance. Optimal treatment outcomes depend on understanding liver cirrhosis patients' sepsis risk factors. Thus, preventing sepsis involves addressing these risk factors. Therefore, early identification and understanding of clinical characteristics in liver cirrhosis patients with sepsis are crucial for selecting appropriate antibiotics. A case-control study using logistic regression was conducted to examine the prognostic value of amyloid A/lactate level monitoring in identifying sepsis risk factors in liver cirrhosis patients. METHODS: From March 2020 to March 2022, 136 liver cirrhosis patients treated at our hospital were divided into a sepsis group (n = 35) and a non-sepsis group (n = 101) based on sepsis complications. General clinical data were collected. Univariate analysis screened for liver cirrhosis patients' sepsis risk factors. Multivariate logistic analysis was subsequently employed to evaluate the risk factors. Sepsis patients were followed up for a month. Based on prognosis, patients were categorized into a poor prognosis group (n = 16) and a good prognosis group (n = 19). Serum amyloid A (SAA) and blood lactic acid (BLA) levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of both individual and combined SAA/BLA monitoring. RESULTS: Patient data, including age, diabetes history, liver cancer, hepatic artery embolization, recent antibiotic use, invasive procedures within two weeks, APACHE II Scoring, ALB and SAA and BLA levels, were compared between the sepsis and non-sepsis groups, showing significant differences (P < 0.05). Logistic regression identified factors such as age ≥ 70, recent antibiotic use, recent invasive procedures, history of liver cancer, hepatic artery embolization history, high APACHE II scores, decreased albumin, and elevated SAA and BLA levels as independent sepsis risk factors in liver cirrhosis patients (P < 0.05). Among the 35 sepsis patients, 16 had a poor prognosis, representing an incidence rate of 45.71%. Serum SAA and BLA levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). The AUC for serum SAA and BLA was 0.831 (95%CI: 0.738-0.924), 0.720 (95%CI: 0.600-0.840), and 0.909 (95%CI: 0.847-0.972), respectively. The combined diagnostic AUC was significantly higher than that of single factor predictions (P < 0.05). The predictive value ranked as follows: joint detection > SAA > BLA. CONCLUSION: In treating liver cirrhosis, prioritize patients with advanced age, a history of hepatic artery embolization, recent invasive operations, history of liver cancer, recent antibiotic exposure, high APACHE II scores and low albumin. Closely monitoring serum SAA and BLA levels in these patients can offer valuable insights for early clinical prevention and treatment.

Endurance Training Improves Leg Proton Release and Decreases Potassium Release During High-Intensity Exercise in Normoxia and Hypobaric Hypoxia.

AIM: To assess the impact of endurance training on skeletal muscle release of H+ and K+. METHODS: Nine participants performed one-legged knee extension endurance training at moderate and high intensities (70%-85% of Wpeak), three to four sessions·week-1 for 6 weeks. Post-training, the trained and untrained (control) leg performed two-legged knee extension at low, moderate, and high intensities (40%, 62%, and 83% of Wpeak) in normoxia and hypoxia (~4000 m). The legs were exercised simultaneously to ensure identical arterial inflow concentrations of ions and metabolites, and identical power output was controlled by visual feedback. Leg blood flow was measured (ultrasound Doppler), and acid-base variables, lactate- and K+ concentrations were assessed in arterial and femoral venous blood to study K+ and H+ release. Ion transporter abundances were assessed in muscle biopsies. RESULTS: Lactate-dependent H+ release was similar in hypoxia to normoxia (p = 0.168) and was lower in the trained than the control leg at low-moderate intensities (p = 0.060-0.006) but similar during high-intensity exercise. Lactate-independent and total H+ releases were higher in hypoxia (p < 0.05) and increased more with power output in the trained leg (leg-by-power output interactions: p = 0.02). K+ release was similar at low intensity but lower in the trained leg during high-intensity exercise in normoxia (p = 0.024) and hypoxia (p = 0.007). The trained leg had higher abundances of Na+/H+ exchanger 1 (p = 0.047) and Na+/K+ pump subunit α (p = 0.036). CONCLUSION: Moderate- to high-intensity endurance training increases lactate-independent H+ release and reduces K+ release during high-intensity exercise, coinciding with increased Na+/H+ exchanger 1 and Na+/K+ pump subunit α muscle abundances.

A predictive study of genes related to lactic acid metabolism in cervical carcinoma.

OBJECTIVES: Lactic acid metabolism, a hallmark of carcinogenesis, may play potential roles in cervical carcinoma, assisting the prognosis prediction. MATERIALS AND METHODS: A regression analysis was conducted to identify the ones with the most frequent variation in mutations and CNV changes in lactate metabolism-related (L-related) genes, after which a prognostic nomogram was built based on selected genes and clinical features by machine learning methods. RESULTS: EGLN1, IL1, IL12RB1, ENO1, and 10 other genes had the most frequent changes and prognostic differences in overall survival (OS). The lactated associated risk (LAR) score model can distinguish the patients in OS (p = 0.046, HR = 101.9, 95%CI 1.1-9447.6), and together with clinical features has a higher AUC (AUC = 0.839). Furthermore, CD8+ T, activated CD4+ memory T and resting mast cells were significantly negatively associated with the LAR score. CONCLUSIONS: Lactic acid metabolism is closely related to the prognosis of cervical carcinoma, where the immune microenvironment may play an important role.

Hypocapnia in women with fibromyalgia.

OBJECTIVES: The purpose of this study was to investigate whether people with fibromyalgia (FM) have dysfunctional breathing by examining acid-base balance and comparing it with healthy controls. METHODS: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate acid-base balance, arterial blood was sampled from the radial artery. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for between-group differences. Blood gas analyses were performed stepwise on each individual to detect acid-base disturbance, which was categorized as primary respiratory and possible compensation indicating chronicity. A three-step approach was employed to evaluate pH, carbon dioxide and bicarbonate in this order. RESULTS: Women with FM had significantly lower carbon dioxide pressure (p = 0.013) and higher lactate (p = 0.038) compared to healthy controls at the group level. There were no significant differences in oxygen pressure, bicarbonate, pH and base excess. Employing a three-step acid-base analysis, 11 individuals in the FM group had a possible renally compensated mild chronic hyperventilation, compared to only 4 among the healthy controls (p = 0.042). CONCLUSIONS: In this study, we could identify a subgroup of individuals with FM who may be characterized as mild chronic hyperventilators. The results might point to a plausible dysfunctional breathing in some women with FM.

Heparin-binding protein as a biomarker for the diagnosis of sepsis in the intensive care unit: a retrospective cross-sectional study in China.

OBJECTIVES: This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU). DESIGN: Clinical retrospective cross-sectional study. SETTING: A comprehensive teaching tertiary hospital in China. PARTICIPANTS: Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU. MAIN OUTCOME MEASURES: HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded. RESULTS: Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p<0.001). The area under the curve (AUC) value of HBP for diagnosing sepsis was 0.733, which was lower than those corresponding to PCT, CRP and SOFA but higher than those of IL-6, LAC and APACHE II. Multivariate logistic regression analysis identified HBP, PCT, CRP, IL-6 and SOFA as valuable indicators for diagnosing sepsis. A sepsis diagnostic model was constructed based on these indicators, with an AUC of 0.901, a sensitivity of 79.7% and a specificity of 86.9%. CONCLUSIONS: HBP could serve as a biomarker for the diagnosis of sepsis in the ICU. Compared with single indicators, the sepsis diagnostic model constructed using HBP, PCT, CRP, IL-6 and SOFA further enhanced the diagnostic performance of sepsis.