Elimination Rate of Serum Lactate is Correlated with Amyotrophic Lateral Sclerosis Progression

Background： Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis （ALS）. We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to examine the relationship between mitochondrial dysfunction with motor deterioration. Methods： We enrolled 116 patients and observed clinical variables, including the survival state. Results： Patients with a rapid slope of revised ALS functional rating scales （ALSFRS-r） （〉20 U/year） exhibited the slowest elimination rate （median -4.67 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation, 590.15%）, the shortest duration （0.63 ± 0.28 years） and the worst ALSFRS-r （32.59±4.93）. Patients with a moderate slope ofALSFRS-r （1~20 U/year） showed a moderate elimination rate （median -11.33 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation, 309.89%）, duration （1.16± 0.45 years）, and ALSFRS-r （34.83 ± 6.11）. The slower progressing （〈10 U/year group） patients exhibited a rapid elimination rate （median： - 12.00 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation： 143.08%）, longer duration （median： 3 years, coefficient of variation： 193.33%）, and adequate ALSFRS-r values （39.58 ± 9.44）. Advanced-phase ALS patients also showed slower elimination rate （ER, quartiles - 17.33, -5.67, 4.00） and worse ALSFRS-r （34.88 ± 9.27）, while early-phase patients showed a more rapid ER （quartiles -25.17, -11.33, -3.50） and better ALSFRS-r （39.28 ± 7.59）. These differences were statistically significant. Multiple linear regression analysis revealed strong direct associations among ER, ALSFRS-r slope （standard beta = 0.33, P = 0.007）, and forced vital capacity （predict %） （standard beta = -0.458, P = 0.006, adjusted for ALSFRS-r, course and onset region）. However, the data obtained from 3 years of follow-up showed no statistically significant difference in the survival rates between the most rapid and slowest ER groups. Conclusion： There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.

Modified model for end-stage liver disease improves shortterm prognosis of hepatitis B virus-related acute-on-chronic liver failure

AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.

Factors associated with refractory pain in emergency patients admitted to emergency general surgery

BACKGROUND: Oligoanalgesia in emergency departments (EDs) is multifactorial. A previousstudy reported that emergency providers did not adequately manage patients with severe paindespite objective findings for surgical pathologies. Our study aims to investigate clinical andlaboratory factors, in addition to providers’ interventions, that might have been associated witholigoanalgesia in a group of ED patients with moderate and severe pains due to surgical pathologies.METHODS: We conducted a retrospective study of adult patients who were transferred directlyfrom referring EDs to the emergency general surgery (EGS) service at a quaternary academic centerbetween January 2014 and December 2016. Patients who were intubated, did not have adequaterecords, or had mild pain were excluded. The primary outcome was refractory pain, which wasdefi ned as pain reduction <2 units on the 0–10 pain scale between triage and ED departure.RESULTS: We analyzed 200 patients, and 58 (29%) had refractory pain. Patients with refractory painhad signifi cantly higher disease severity, serum lactate (3.4±2.0 mg/dL vs. 1.4±0.9 mg/dL, P=0.001), and lessfrequent pain medication administration (median [interquartile range], 3 [3–5] vs. 4 [3–7], P=0.001), whencompared to patients with no refractory pain. Multivariable logistic regression showed that the number of painmedication administration (odds ratio [OR] 0.80, 95% confi dence interval [95% CI] 0.68–0.98) and ED serumlactate levels (OR 3.80, 95% CI 2.10–6.80) were signifi cantly associated with the likelihood of refractory pain.CONCLUSIONS: In ED patients transferring to EGS service, elevated serum lactate levelswere associated with a higher likelihood of refractory pain.