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Background This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis. Methods This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity. Results 1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0–45.9) and 43.1 (10.1–184.0)). Conclusions MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.

Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan–Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future.

Hyperlactatemia occurs during or after extracorporeal circulation in the form of lactic acidosis, increasing the risk of postoperative complications and the mortality rate. The aim of this study was to evaluate whether continuous high-volume hemofiltration with volume replacement through a polyethersulfone filter during the extracorporeal circulation procedure decreases postoperative lactatemia and its consequences. This was a randomized controlled trial. Patients were randomly divided into two groups of 32: with or without continuous high-volume hemofiltration through a polyethersulfone membrane. Five patients were excluded from each group during the study period. The sociodemographic characteristics, filter effects, and blood lactate levels at different times during the procedure were evaluated. Secondary endpoints were studied, such as the reduction in the intubation time and time spent in ICU. Lactatemia measurements performed during the preoperative and intraoperative phases were not significantly different between the two groups. However, the blood lactate levels in the postoperative period and at 24 hours in the intensive care unit showed a significant reduction and a possible clinical benefit in the hemofiltered group. Following extracorporeal circulation, the mean lactate level was higher (difference: 0.77 mmol/L; CI 0.95: 0.01-1.53) in the nonhemofiltered group than in the hemofiltered group (p<0.05). This effect was greater at 24 hours (p = 0.019) in the nonhemofiltered group (difference: 1.06 mmol/L; CI 0.95: 0.18-1.93) than in the hemofiltered group. The reduction of lactatemia is associated with a reduction of inflammatory mediators and intubation time, with an improvement in liver function. The use and control of continuous high-volume hemofiltration through a polyethersulfone membrane during heart-lung surgery could potencially prevent postoperative complications. The reduction of lactatemia implied a reduction in intubation time, a decrease in morbidity and mortality in the intensive care unit and a shorter hospital stay.

This study investigated whether two exopolysaccharides could serve as exogenous carbon sources to enhance fermentation quality in oat silage, providing a theoretical foundation for their future application in silage. The oats were harvested at the heading stage and, following a period of wilting, were chopped into 2–3 cm lengths for the ensiling experiment. The treatments applied were as follows: (1) a control group (CK), which received only sterile water; (2) a group with added dextran (D); and (3) a group with added levan (L). The fermentation process was monitored at various intervals: 3, 7, 14, 30 and 60 days (d), respectively. Following 60 days of ensiling, the silage was subjected to a 5‐day period of aerobic exposure (AE). EPS changed the fermentation quality of silage, altered the composition of the bacterial community, and had an impact on the feature dissimilarity between sample groups. Meanwhile, EPS showed different regulatory effects on carbohydrate metabolism at different fermentation times. EPS treatment increased the lactic acid content and decreased the pH of silage. After 60 days of fermentation, the treatment also increased the relative abundance of Lactobacillus. Dextran and levan increased the relative abundance of Hafnia–Obesumbacterium and Sediminibacterium, respectively. Under the treatment of dextran, silage retained more WSC content and achieved higher aerobic stability. Upon comparing the bacterial correlation networks, it became evident that the fermentation time altered the composition of inter‐bacterial correlations. In conclusion, EPS can effectively enhance the fermentation quality of oat silage, with dextran yielding the most pronounced positive effects. Bacterial extracellular polysaccharides can serve as an external carbon source to provide additional substrates for microbial fermentation in oat silage.

Background In high resource settings, lactate and pH levels measured from fetal scalp and umbilical cord blood are widely used as predictors of perinatal mortality. However, the same is not true in low resource settings, where much of perinatal mortality occurs. The scalability of this practice has been hindered by difficulty in collecting fetal scalp and umbilical blood sample. Little is known about the use of alternatives such as maternal blood, which is easier and safer to obtain. Therefore, we aimed to compare maternal and umbilical cord blood lactate levels for predicting perinatal deaths. Methods This was secondary analysis of data from a randomized controlled trial assessing the effect of sodium bicarbonate on maternal and perinatal outcomes among women with obstructed labour at Mbale regional referral hospital in Eastern Uganda. Lactate concentration in maternal capillary, myometrial, umbilical venous and arterial blood was measured at the bedside using a lactate Pro 2 device (Akray, Japan Shiga) upon diagnosis of obstructed labour. We constructed Receiver Operating Characteristic curves to compare the predictive ability of maternal and umbilical cord lactate and the optimal cutoffs calculated basing on the maximal Youden and Liu indices. Results Perinatal mortality risk was: 102.2 deaths per 1,000 live births: 95% CI (78.1–130.6). The areas under the ROC curves were 0.86 for umbilical arterial lactate, 0.71 for umbilical venous lactate, and 0.65 for myometrial lactate, 0.59 for maternal lactate baseline, and 0.65 at1hr after administration of bicarbonate. The optimal cutoffs for predicting perinatal death were 15 0.85 mmol/L for umbilical arterial lactate, 10.15mmol/L for umbilical venous lactate, 8.75mmol/L for myometrial lactate, and 3.95mmol/L for maternal lactate at recruitment and 7.35mmol/L after 1 h. Conclusion Maternal lactate was a poor predictor of perinatal death, but umbilical artery lactate has a high predictive value. There is need for future studies on the utility of amniotic fluid in predicting intrapartum perinatal deaths.

With increasing age, a number of physiological changes take place which are reflected in immune and bowel function. These changes may relate to the commonly assumed age-related changes in intestinal microbiota; most noticeably a reduction in bifidobacteria. The current study aimed at modifying the intestinal microbiota with a potential synbiotic on selected immune and microbiota markers. Healthy elderly subjects were randomised to consume during 2 weeks either a placebo (sucrose) or a combination of lactitol and Lactobacillus acidophilus NCFM twice daily in a double-blind parallel trial. After the intervention, stool frequency was higher in the synbiotic group than in the placebo group and a significant increase in faecal L. acidophilus NCFM levels was observed in the synbiotic group, after baseline correction. In contrast to the generally held opinion, the study subjects had faecal Bifidobacterium levels that were similar to those reported in healthy young adults. These levels were, nevertheless, significantly increased by the intervention. Levels of SCFA were not changed significantly. Of the measured immune markers, PGE2 levels were different between treatments and IgA levels changed over time. These changes were modest which may relate to the fact that the volunteers were healthy. Spermidine levels changed over time which may suggest an improved mucosal integrity and intestinal motility. The results suggest that consumption of lactitol combined with L. acidophilus NCFM twice daily may improve some markers of the intestinal microbiota composition and mucosal functions.

This study examined intra-individual variations in salivary lactate (sLac), alpha-amylase (sAA) and chromogranin A (sCgA) with reference to the accumulation of blood lactate (bLac) during incremental maximal exercise in swimmers. Samples of blood and saliva were collected simultaneously from 12 male professional athletes during an incremental test that consisted of eight series of 100 m in front crawl with increasing velocity (0.03 m  s −1 each) and 70-s intervals. The concentration of blood and salivary lactate was determined by an electro-enzymatic assay, whereas sAA and CgA were analysed by Western blotting. Inflection points in the concentration of bLAc, sLac, sAA and CgA were found in all subjects. The accumulation of lactate in saliva followed the same pattern observed in blood with a high correlation between the two ( r  = 0.91). Similar results were observed between the dynamics of sAA ( r  = 0.81) and sCgA ( r  = 0.82) in relation to bLac. These findings support the usefulness of saliva for the determination of the lactate threshold and provide the first demonstration of sCgA as a novel marker of exercise intensity in well-trained men.

Cupping worldwide has been part of traditional medicine systems and is in the western world used as CAM therapy mainly for treating pain syndromes. The mode of action is up to now unclear. In order to investigate its mechanism we measured in parallel metabolic changes in the tissue under the cupping glass and pressure pain thresholds. In 12 volunteers (6 healthy subjects and 6 patients with chronic neck pain) a microdialysis system was implanted subcutaneously on both sides (left and right) above the trapezius muscle. After baseline measures cupping was performed at one randomly selected side (left or right), the other side served as control. Every 20min during baseline measures and for 280min after cupping, microdialysis probes for detection of lactate, pyruvate, glucose and glycerin were taken. In addition, pain thresholds were measured before and after cupping with algometry. Cupping resulted in a strong increase of lactate (beginning 160min after cupping until the end of the measurements) and the lactate/pyruvate ratio, indicating an anaerobe metabolism in the surrounding tissue. Baseline pain thresholds were non-significantly lower in neck pain patients compared to healthy controls and slightly increased immediately after cupping (p<0.05 compared to baseline close to the area of cupping in healthy subjects and on the foot in neck pain patients). After 280min no more significant changes of pain thresholds were detected. Cupping induces >280min lasting anaerobe metabolism in the subcutaneous tissue and increases immediate pressure pain thresholds in some areas.

Propofol, an anesthetic agent acting as an analogue of vitamin E, has been advocated to be an ideal neuroprotective agent both in animal models and in clinical practice, due to its positive effects on oxidative stress. Nevertheless, no studies have compared this agent to another sedative agent used for sedation after traumatic brain injury (TBI). The objective was to compare the effects of propofol to midazolam on cerebral biomarkers at the acute phase of severe TBI patients. Thirty patients aged 35±18 years were prospectively randomized to receive propofol or midazolam and 29 were analyzed (n=15 for propofol, and n=14 for midazolam). A cerebral microdialysis catheter was used to measure the lactate:pyruvate (L:P) ratio, glutamate, glycerol, and glucose for 72 h. No difference between groups was observed for the L:P ratio (time effect p=0.201, treatment effect p=0.401, time×treatment interaction p=0.101). Similarly, no difference was observed for glutamate (time effect p=0.930, treatment effect p=0.651, time×treatment interaction p=0.353), glycerol (time effect p=0.223, treatment effect p=0.922, time×treatment interaction p=0.308), or glucose (time effect p=0.116, treatment effect p=0.088, time×treatment interaction p=0.235). These results do not support a difference between propofol and midazolam for sedation for the cerebral metabolic profile in severe TBI.

Acidogenicity and the levels of mutans streptococci (MS) in dental plaque after the use of Lactobacillus rhamnosus GG (LGG) and Lactobacillus reuteri were determined. The study had a randomised, double-blind, crossover design. Thirteen volunteers used tablets containing LGG or a combination of L. reuteri SD2112 and PTA 5289 for 2 weeks. At baseline and at the end of each tablet period, all available supragingival plaque was collected. Lactic acid production was determined from a fixed volume (8 μl) of fresh plaque and the rest of the plaque was used for culturing MS and lactobacilli. The retention of probiotics to the plaque was assessed using PCR techniques. No probiotic-induced changes were found in the acidogenicity of plaque. Also, MS counts remained at the original level. The number of subjects with lactobacilli in plaque increased in the L. reuteri group ( p  = 0.011) but not in the LGG group. PCR analysis of plaque revealed the presence of LGG in four and L. reuteri in six subjects after the use of the probiotic. The use of the lactobacilli did not affect the acidogenicity or MS levels of plaque. Short-term consumption of LGG and L. reuteri appeared not to influence the acidogenicity of plaque.