LABORATORIO DE URGENCIAS

 

1. Virol J. 2020 Jun 19;17(1):80. doi: 10.1186/s12985-020-01354-6.

Non-optimal effectiveness of convalescent plasma transfusion and  hydroxychloroquine in treating COVID-19: a case report.

Xu TM(1), Lin B(2), Chen C(3), Liu LG(4), Xue Y(5).

Author information:

(1)Department of Infectious Diseases, the Third People's Hospital of Changzhou,  Changzhou, Jiangsu, China.

(2)Department of Infectious Diseases, the First People's Hospital of Jintan, Changzhou, Jiangsu, China.

(3)Changzhou Center for Disease Control and Prevention, Changzhou, Jiangsu, China.

(4)Institute of Hepatology, the Third People's Hospital of Changzhou, No. 300 Lanling North Road, Changzhou, 213000, Jiangsu, China.

(5)Institute of Hepatology, the Third People's Hospital of Changzhou, No. 300  Lanling North Road, Changzhou, 213000, Jiangsu, China. xueyuan80908@163.com.

 

BACKGROUND: Convalescent plasma (CP) transfusion was reported to be effective in  treating critically ill patients with COVID-19, and hydroxychloroquine could  potently inhibit SARS-CoV-2 in vitro. Herein, we reported a case receiving  combination therapy with CP transfusion and hydroxychloroquine for the first time.
CASE PRESENTATION: Laboratory findings showed high lactic acid level (2.1 mmol/L) and C-reactive protein (CRP, 48.8 mg/L), and low white blood cell count (1.96 × 109/L) in a 65-year-old Chinese man, who was diagnosed with severe COVID-19. CP was intravenously given twice, and hydroxychloroquine was orally administrated for a week (0.2 g, three times a day). The lactic acid and C-reactive protein levels remained high (2.1 mmol/L and 73.23 mg/L, respectively), while the arterial oxyhemoglobin saturation decreased to 86% with a low oxygenation index (OI, 76 mmHg) on day 4 after CP transfusion. His  temperature returned to normal and the OI ascended above 300 on day 11.
Moreover, the RNA test remained positive in throat swab, and computed tomography revealed severe pulmonary lesions on day 11 after admission.
CONCLUSION: These findings suggested that the effectiveness of combination therapy with CP and hydroxychloroquine may be non-optimal, and specific therapy needs to be explored.

DOI: 10.1186/s12985-020-01354-6

PMCID: PMC7303939

PMID: 32560646 [Indexed for MEDLINE]

 

1. PLoS Pathog. 2020 Jun 9;16(6):e1008568. doi: 10.1371/journal.ppat.1008568. eCollection 2020 Jun.

Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling.

Wu Z(1), Jia J(1), Xu X(1), Xu M(1), Peng G(2), Ma J(1), Jiang X(1), Yao J(1), Yao K(1), Li L(3), Tang H(1)(4).

Author information:

(1)Department of Immunology, Nanjing Medical University, Nanjing, P. R. China.

(2)Division of Infectious Diseases, Allergy & Immunology and Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.

(3)Department of Medical Genetics, Nanjing Medical University, Nanjing, P. R. China.

(4)Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, P. R. China.

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and  immunomodulatory virus worldwide. However, whether and how HHV-6 infection  influences the metabolic machinery of the host cell to provide the energy and  biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy.

DOI: 10.1371/journal.ppat.1008568

PMCID: PMC7282626

PMID: 32516328 [Indexed for MEDLINE]

1. Medicine (Baltimore). 2020 May 29;99(22):e20274. doi: 10.1097/MD.0000000000020274.

 
STAPLAg: a convenient early warning score for use in infected patients in the intensive care unit.

Zhang K(1), Lv D(1), Deng Y(2), Zhu C(1), Gao Y(2), Huang Y(3), Xu X(1).

Author information:

(1)Department of Emergency.

(2)Department of Surgery Intensive Care Unit, Ren Ji Hospital.

(3)Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.

 Sepsis is a life-threatening disease in the intensive care unit (ICU). The current diagnostic criteria for sequential organ failure assessment (SOFA) scores do not reflect the current understanding of sepsis. We developed a novel and convenient score to aid early prognosis. Retrospective multivariable regression analysis of 185 infected emergency ICU (EICU) patients was conducted to identify independent variables associated with death, to develop the new "STAPLAg" score; STAPLAg was then validated in an internal cohort (n = 106) and an external cohort (n = 78) and its predictive efficacy was compared with that of the initial SOFA score.Age, and initial serum albumin, sodium, PLR, troponin and lactate tests in the emergency department were independent predictors of death in infected EICU patients, and were used to establish the STAPLAg score (area under the curve [AUC] 0.865). The initial SOFA score on admission was predictive of death (AUC 0.782).Applying the above categories to the derivation cohort yielded mortality risks of 7.7% for grade I, 56.3% for grade II, and 75.0% for grade III. Internal (AUC 0.884) and external (AUC 0.918) cohort validation indicated that the score had good predictive power.The STAPLAg score can be determined early in infected EICU patients, and exhibited better prognostic capacity than the initial SOFA score on admission in both internal and external cohorts. STAPLAg constitutes a new resource for use in the clinical  diagnosis of sepsis and can also predict mortality in infected EICU patients.

DOI: 10.1097/MD.0000000000020274

PMID: 32481394 [Indexed for MEDLINE]

 

1. Int J Sports Physiol Perform. 2020 May 1;15(5):632-638. doi: 10.1123/ijspp.2019-0361.

The Acute Effect of Mental Fatigue on Badminton Performance in Elite Players

Kosack MH, Staiano W, Folino R, Hansen MB, Lønbro S.

PURPOSE: Several studies have examined the effect of MF on sport performance, but no studies have been conducted on badminton performance. The purpose of the present study was to examine the acute effect of mental fatigue (MF) on badminton performance in elite players.
METHODS: In total, 19 elite Danish badminton players completed 2 test days in randomized order, separated by 48 h. On day 1, to elicit MF, a 60-min incongruent Stroop task was performed. On day 2, 60 min of an emotionally neutral documentary was used for the control condition. After either condition, subjects performed a badminton-specific test (BST) where performance time was measured, as well as countermovement-jump height, heart rate, rating of perceived exertion, and lactate. Psychological questionnaires were answered under both conditions.
RESULTS: Subjects were significantly more mentally fatigued (P = .002) after the Stroop intervention than in the control. No differences between conditions were detected in the BST (control 32.43 [1.96] vs MF 32.43 [2.36] s; P = .99, Student t test). In addition, no effect of condition (P = .64), time (P = .14), or condition × time (P = .87) was found (2-way analysis of variance).
Furthermore, no differences in heart rate, countermovement jump, or rating of perceived exertion were observed between conditions. Lactate showed no effect of condition (P = .46).
CONCLUSION: Despite being more mentally fatigued after the Stroop test than in the control condition, performance was not negatively affected during a BST. In addition, no differences in physiological measures were observed.

DOI: 10.1123/ijspp.2019-0361

PMID: 31968307 [Indexed for MEDLINE]

 

1. Int J Sports Physiol Perform. 2020 May 1;15(5):741-747. doi: 10.1123/ijspp.2019-0177.

The Effect of Sodium Bicarbonate Supplementation on the Decline in Gross Efficiency During a 2000-m Cycling Time Trial.

Voskamp AE, van den Bos S, Foster C, de Koning JJ, Noordhof DA.

BACKGROUND: Gross efficiency (GE) declines during high-intensity exercise. Increasing extracellular buffer capacity might diminish the decline in GE and thereby improve performance.
PURPOSE: To examine if sodium bicarbonate (NaHCO3) supplementation diminishes the decline in GE during a 2000-m cycling time trial.
METHODS: Sixteen male cyclists and 16 female cyclists completed 4 testing sessions including a maximal incremental test, a familiarization trial and two 2000-m GE tests. The 2000-m GE tests were performed after ingestion of either NaHCO3 supplements (0.3 g/kg body mass) orplacebo supplements (amylum solani, magnesium stearate, and sunflower oil capsules). The GE tests were conducted using a double-blind, randomized, crossover design. Power output, gas exchange, and time to complete the 2000-m time trials were recorded. Capillary blood samples were analyzed for blood bicarbonate, pH and lactate concentration. Data were analyzed using magnitude-based inference. Smaller in male and female groups after NaHCO3 than  placebo ingestion, the effect in both groups combined being unclear. The effect on performance was likely trivial for males (placebo 164.2 [5.0] s, NaHCO3 164.3 [5.0] s; Δ0.1; ±0.6%), unclear for females (placebo 178.6 [4.8] s, NaHCO3 178.0 [4.3] s; Δ-0.3; ±0.5%), and very likely trivial when effects were combined. Blood bicarbonate, pH, and lactate concentration were substantially elevated from rest to pretest after NaHCO3 ingestion.
CONCLUSIONS: NaHCO3 supplementation results in an unclear effect on the decrease in GE during high-intensity exercise and in a very likely trivial effect on performance.

DOI: 10.1123/ijspp.2019-0177

PMID: 31952047 [Indexed for MEDLINE]

 

1. Int J Sports Physiol Perform. 2020 May 1;15(5):654-662. doi: 10.1123/ijspp.2019-0190.

Comparison of Training Monitoring and Prescription Methods in Sprint Kayaking.

Hogan C, Binnie MJ, Doyle M, Lester L, Peeling P.

PURPOSE: To compare methods of monitoring and prescribing on-water exercise intensity (heart rate [HR], stroke rate [SR], and power output [PO]) during sprint kayak training.
METHODS: Twelve well-trained flat-water sprint kayak athletes completed a preliminary on-water 7 × 4-min graded exercise test and a 1000-m time trial to delineate individual training zones for PO, HR, and SR into a 5-zone model (T1-T5). Subsequently, athletes completed 2 repeated trials of an on-water training session, where intensity was prescribed based on individual PO zones.
Times quantified for T1-T5 during the training session were then compared between PO, HR, and SR.
RESULTS: Total time spent in T1 was higher for HR (P < .01) compared with PO. Time spent in T2 was lower for HR (P < .001) and SR (P < .001) compared with PO. Time spent in T3 was not different between PO, SR, and HR (P > .05). Time spent in T4 was higher for HR (P < .001) and SR (P < .001) compared with PO. Time spent in T5 was higher for SR (P = .03) compared with PO. Differences were found between the prescribed and actual time spent in T1-T5 when using PO (P < .001).
CONCLUSIONS: The measures of HR and SR misrepresented time quantified for T1-T5 as prescribed by PO. The stochastic nature of PO during on-water training may  explain the discrepancies between prescribed and actual time quantified for power across these zones. For optimized prescription and monitoring of athlete training loads, coaches should consider the discrepancies between different measures of intensity and how they may influence intensity distribution.

DOI: 10.1123/ijspp.2019-0190

PMID: 31743095 [Indexed for MEDLINE]

 

1. Int J Sports Med. 2020 Jul;41(8):539-544. doi: 10.1055/a-1103-2001. Epub 2020 Apr 14.

Physiological Correlates to In-race Paratriathlon Cycling Performance.

Stephenson BT(1)(2), Shill A(1)(2), Lenton J(1)(3), Goosey-Tolfrey V(1).

Author information:

(1)Peter Harrison Centre for Disability Sport, School of Sport Exercise and Health Sciences, Loughborough University, Loughborough, UK.

(2)English Institute of Sport, Performance Centre, Loughborough University, Loughborough, UK.

(3)British Cycling, National Cycling Centre, Manchester, UK.

The purpose was to determine the physiological correlates to cycling performance within a competitive paratriathlon. Five wheelchair user and ten ambulant paratriathletes undertook laboratory-based testing to determine their: peak rate of oxygen uptake; blood lactate- and ventilatory-derived physiological thresholds; and, their maximal aerobic power.These variables were subsequently expressed in absolute (l∙min -1 or W), relative (ml∙kg-1∙min -1 or W∙kg -1) and scaled relative (or ml∙kg - 0.82 ∙min -1, ml∙kg - 0.32 ∙min 1 or W∙kg -0.32) terms. All athletes undertook a paratriathlon race with 20 km cycle. Pearson's correlation test and linear regression analyses were produced between laboratory-derived variables and cycle performance to generate correlation coefficients (r), standard error of estimates and 95% confidence intervals. For wheelchair users, performance was most strongly correlated to relative aerobic lactate threshold (W∙kg -1) (r=-0.99; confidence intervals: -0.99 to -0.99; standard error of estimate=22 s). For ambulant paratriathletes, the greatest correlation was with maximal aerobic power (W∙kg -0.32) (r=-0.91; -0.99 to -0.69; standard error of estimate=88 s). Race-category-specificity exits regarding physiological correlates to cycling performance in a paratriathlon race with further differences between optimal scaling factors between paratriathletes. This suggests aerobic lactate threshold and maximal aerobic power are the pertinent variables to infer cycling performance for wheelchair users and ambulant paratriathletes, respectively. 

DOI: 10.1055/a-1103-2001

PMID: 32289842 [Indexed for MEDLINE]

 

1. Braz J Med Biol Res. 2020 Apr 6;53(4):e9200. doi: 10.1590/1414-431X20209200. eCollection 2020.

Ingestion of a moderate dose of alcohol enhances physical exercise-induced changes in blood lactate concentration.

Teixeira-Coelho F(1)(2), Santos DFC(1), Santos GA(1)(3), Sousa TF(1), Moreira SR(3), Souza MVC(2), Wanner SP(4).

Author information:

(1)Centro de Formação de Professores, Universidade Federal do Recôncavo da Bahia, Amargosa, BA, Brasil.

(2)Departamento de Ciências do Esporte, Instituto de Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brasil.

(3)Programa de Pós-Graduação em Educação Física, Universidade Federal do Vale do São Francisco, Petrolina, PE, Brasil.

(4)Laboratório de Fisiologia do Exercício, Escola de Educação Física, Fisioterapia e Terapia Ocupacional, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.

The consumption of alcoholic beverages influences carbohydrate and lipid metabolism, although it is not yet clear whether metabolism during physical exercise at different intensities is also affected. This was the objective of the present study. Eight young and healthy volunteers performed a treadmill test to identify the running speed corresponding to a lactate concentration of 4 mM (S4mM). At least 48 h later, they were subjected to two experimental trials (non-alcohol or alcohol) in which they performed two 1-km running sessions at the following intensities: 1) S4mM; 2) 15% above S4mM. In both trials, blood lactate, triglycerides, and glucose concentrations were measured before and after exercise. The acute alcohol intake increased triglycerides, but not lactate concentration under resting conditions. Interestingly, alcohol intake enhanced the exercise-induced increase in lactate concentration at the two intensities: S4mM (non-alcohol: 4.2±0.3 mM vs alcohol: 4.8±0.9 mM; P=0.003) and 15% above S4mM trial (P=0.004). When volunteers ingested alcohol, triglycerides concentration remained increased after treadmill running (e.g., at S4mM - at rest; non-alcohol: 0.2±0.5 mM vs alcohol: 1.3±1.3 mM; P=0.048). In contrast, glucose concentration was not modified by either alcohol intake, exercise, or their combination. We concluded that an acute alcohol intake changed lactate and lipid metabolism without affecting blood glucose concentration. In addition, the increase in lactate concentration caused by alcohol was specifically observed when individuals exercised, whereas augmented triglycerides concentration was already observedbeforeexercise and was sustained thereafter.

DOI: 10.1590/1414-431X20209200

PMCID: PMC7162590

PMID: 32267309 [Indexed for MEDLINE]

 

1. PLoS One. 2020 Mar 26;15(3):e0230691. doi: 10.1371/journal.pone.0230691. eCollection 2020.

Changes in mitochondrial function in patients with neuromyelitis optica; correlations with motor and cognitive disabilities.

Foolad F(1), Khodagholi F(2), Nabavi SM(3)(4), Javan M(1)(4).

Author information:

(1)Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

(2)Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

(3)Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

(4)Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

 BACKGROUND: Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease that mainly affects optic nerves and spinal cord. Besides, loss of motor and cognitive function has been reported as important symptoms of disease.
OBJECTIVE: Here we investigated the mitochondrial dysfunction and metabolic alterations in NMO patients and evaluate their correlation with disease progress, disability and cognitive impairment.
METHODS: The individuals (12 controls and 12 NMO) were assessed for disease severity by expanded disease status scale (EDSS), cognitive function via symbol digit modalities test(SDMT) and fine motor disability by 9-hole peg test (9-HPT). We have measured Sirtuin 1 (SIRT1), SIRT3, mitochondrial complex I, complex IV, aconitase and α-ketoglutarate dehydrogenase (α-KGD) activity in peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate and cytochrome c (Cyt c) were determined in plasma.
RESULTS: Our results exhibited increased 9-HPT time in NMO patients. 9-HPT results correlated with EDSS; and SDMT negatively correlated with disease duration and number of attacks in patients. Investigation of PBMCs of NMO patients exhibited a decrease of mitochondrial complex I and IV activity that was significant for complex IV. Besides, complex I activity was negatively correlated with 9-HPT time in NMO group. In the plasma samples, a correlationbetween pyruvate to lactate ratio and EDSS in NMO patients was found and a negative correlation between Cyt c concentration and SDMT was detected.
CONCLUSION: Our data support the hypothesis that mitochondrial dysfunction occurred in the CNS and the peripheral blood may contribute to disease progress, disability level and the cognitive impairment in NMO patients.

DOI: 10.1371/journal.pone.0230691

PMCID: PMC7098571

PMID: 32214385 [Indexed for MEDLINE]

 

1. PLoS One. 2020 Mar 9;15(3):e0229135. doi: 10.1371/journal.pone.0229135. eCollection 2020.

Lactate indices as predictors of in-hospital mortality or 90-day survival after admission to an intensive care unit in unselected critically ill patients.

Hayashi Y(1), Endoh H(1)(2), Kamimura N(1)(2), Tamakawa T(1)(2), Nitta M(1).

Author information:

(1)Advanced Emergency and Critical Care Center, Niigata University Medical & Dental Hospital, Niigata City, Niigata, Japan.

(2)Department of Emergency & Critical Care Medicine, Niigata University Faculty of Medicine, Niigata City, Niigata, Japan.

BACKGROUND: We performed an exclusive study to investigate the associations between a total of 23 lactate-related indices during the first 24h in an intensive care unit (ICU) and in-hospital mortality.
METHODS: Nine static and 14 dynamic lactate indices, including changes in lactate concentrations (Δ Lac) and slope (linear regression coefficient), were calculated from individual critically ill patient data extracted from the Multiparameter Intelligent Monitoring for Intensive Care (MIMIC) III database.
RESULTS: Data from a total of 781 ICU patients were extracted, consisted of 523 survivors and 258 non-survivors. The in-hospital mortality rate for this cohort was 33.0%. A multivariate logistic regression model identified maximal lactate concentration at 24h after ICU admission (max lactate at T24) as a significant predictor of in-hospital mortality (odds ratio = 1.431, 95% confidence interval [CI] = 1.278-1.604, p<0.001) after adjusting for predefined confounders (age, gender, sepsis, Elixhauser comorbidity score, mechanical ventilation, renal replacement therapy, vasopressors, ICU severity scores). Area under curve (AUC) for max lactate at T24 was larger (AUC = 0.776, 95% CI = 0.740-0.812) than other indices (p<0.001), comparable to an APACHE III score of 0.771. When combining max lactate at T24 with APACHE III, the AUC was increased to 0.815 (95% CI:0.783-0.847). The sensitivity, specificity, and positive and negative predictive values for the cut-off value of 3.05 mmol/L were 64.3%, 77.4%, 58.5%, and 81.5%, respectively. Kaplan-Myer survival curves of the max lactate at T24 for 90-day survival after admission to ICU demonstrated significant difference according to the cut-off value (p<0.001).
CONCLUSIONS: These data indicate that the maximal arterial lactate concentration at T24 is a robust predictor of in-hospital mortality as well as 90-day survival in unselected ICU patients with predictive ability as comparable with APACHE III score.

DOI: 10.1371/journal.pone.0229135

PMCID: PMC7062275

PMID: 32150560 [Indexed for MEDLINE]

 

1. Ann Rheum Dis. 2020 Apr;79(4):499-506. doi: 10.1136/annrheumdis-2019-216374. Epub 2020 Feb 20.

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis.

Souto-Carneiro M(1), Tóth L(#)(2)(3), Behnisch R(#)(4), Urbach K(2), Klika KD(5), Carvalho RA(2)(6), Lorenz HM(2).

Author information:

(1)Medizin 5, Hämatologie, Onkologie und Rheumatologie, UniversitätsKlinikum Heidelberg, Heidelberg, Germany margarida.souto-carneiro@med.uni-heidelberg.de.

(2)Medizin 5, Hämatologie, Onkologie und Rheumatologie, UniversitätsKlinikum Heidelberg, Heidelberg, Germany.

(3)Internal Medicine, Semmelweis University of Medicine, Budapest, Hungary.

(4)Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany.

(5)Department of Molecular and Structural Biology, German Cancer Research Centre, Heidelberg, Germany.

(6)Department of Life Sciences, University of Coimbra Faculty of Sciences and Technology, Coimbra, Portugal.

OBJECTIVES: The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases.
METHODS: Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort.
Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model.
RESULTS: Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%.
Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified.
CONCLUSIONS: PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.

DOI: 10.1136/annrheumdis-2019-216374

PMCID: PMC7147174

PMID: 32079570 [Indexed for MEDLINE]

 

1. Am J Respir Crit Care Med. 2020 Feb 15;201(4):423-429. doi: 10.1164/rccm.201905-0968OC.

Effects of a Resuscitation Strategy Targeting Peripheral Perfusion Status versus Serum Lactate Levels among Patients with Septic Shock. A Bayesian Reanalysis of the ANDROMEDA-SHOCK Trial.

Zampieri FG(1)(2), Damiani LP(1), Bakker J(3)(4)(5)(6), Ospina-Tascón GA(7), Castro R(3), Cavalcanti AB(1), Hernandez G(3).

Author information:

(1)Research Institute, HCor-Hospital do Coração, São Paulo, Brazil.

(2)D'Or Research Institute, São Paulo, Brazil.

(3)Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

(4)Department of Pulmonary and Critical Care Medicine, Columbia University Medical Center, New York, New York.

(5)Department of Pulmonary and Critical Care Medicine, NYU Langone Health, New York.

(6)Department of Intensive Care Adults, Erasmus MC University Medical Center Rotterdam, the Netherlands; and.

(7)Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia.

Comment in

    Am J Respir Crit Care Med. 2020 Feb 15;201(4):396-398
    Ann Transl Med. 2020 Jun;8(12):800.
    Ann Transl Med. 2020 Jun;8(12):802
    Ann Transl Med. 2020 Jun;8(12):804.

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significance threshold (P = 0.06). We tested different analytic methods to aid in the interpretation of these results.
Objectives: To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks.Methods: All patients recruited in ANDROMEDA-SHOCK were included. Both a post hoc Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks
Measurements and Main Results: In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability of benefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% confidence interval [CI], 0.38-0.92) and 0.70 (95% CI, 0.45-1.08), respectively.
The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessment scores in the lower quartile at 72 hours was 1.55 (95% CI, 1.02-2.37).Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy.

DOI: 10.1164/rccm.201905-0968OC

PMID: 31574228 [Indexed for MEDLINE]

 

1. Scand J Med Sci Sports. 2020 May;30(5):858-864. doi:10.1111/sms13628. Epub 2020 Feb 5.

Effect of exercise on key pharmacokinetic parameters related to metformin absorption in healthy humans: A pilot study.

Nikolaidis S(1)(2), Virgiliou C(3)(4)(5), Vekiou M(6), Skari A(1), Kechagidou A(7), Gika H(3)(4)(8), Theodoridis G(3)(4)(5), Pappas P(2), Leondaritis G(2), Mougios V(1)(3)(4).

Author information:

(1)Laboratory of Evaluation of Human Biological Performance, School of Physical Education and Sport Science, Aristotle University of Thessaloniki, Thessaloniki, Greece.

(2)Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.

(3)BIOMIC_AUTh, Center for Interdisciplinary Research and Innovation, Thermi, Greece.

(4)FoodOmicsGR RI, Center for Interdisciplinary Research and Innovation, Thermi, Greece.

(5)School of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.

(6)Department of Critical Care and Emergency, General Hospital of Grevena,  Greece.

(7)Evexia Rehabilitation Center, Thessaloniki, Greece.

(8)School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Exercise is widely accepted as having therapeutic effects; thus, it is important to know whether it interacts with medications. The aim of the present pilot study was to examine the effect of high-intensity interval exercise (known to have antidiabetic action) on key pharmacokinetic parameters related to absorption of metformin (the first-line medication against type 2 diabetes). Ten healthy men participated in two sessions, spaced one to two weeks apart in random, counterbalanced order. In both sessions, participants received 1000 mg of metformin orally, 1-1.5 hours after breakfast. Then, they either ran for 60 minutes at alternating intensity, starting at 40 minutes after metformin administration, and rested without food consumption over the next 3 hours or they rested without food consumption during the entire testing period. Venous blood samples were collected before and at 0.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after metformin administration for metformin determination by liquid chromatography-mass spectrometry. Capillary blood samples were collected for lactate and glucose measurements  
Data from the two sessions were compared through Wilcoxon or Student's t test, as appropriate. Maximum plasma concentration of metformin (Cmax ) was higher at exercise compared to rest (P = .059). Time to reach Cmax (Tmax ) decreased with exercise (P = .009), and the area under the metformin concentration vs time curve was higher at exercise(P =.047). The addition of exercise to metformin administration did not cause hypoglycemia or lactic acidosis. In conclusion, our results provide the first evidence that pharmacokinetic values related to metformin absorption are affected by exercise.

DOI: 10.1111/sms.13628

PMID: 31975547 [Indexed for MEDLINE]

 

1. Medicine (Baltimore). 2020 Feb;99(7):e18894. doi: 10.1097/MD.0000000000018894.

Thiamine status and lactate concentration in sepsis: A prospective observational study.

Heming N(1), Salah A(2), Meng P(2), Sivanandamoorthy S(2), Bounab R(2), Chevret S(3), Annane D(1).

Author information:

(1)General Intensive Care Unit, Raymond Poincaré Hospital, Garches, France and U1173 Lab Inflammation & Infection, University of Versailles SQY-Paris Saclay - INSERM, Montigny-Le-Bretonneux.

(2)General Intensive Care Unit, Raymond Poincaré Hospital, Garches.

(3)Biostatistical Unit, Saint Louis Hospital, Paris, France.

Thiamine is an essential co-factor for aerobic metabolism. Both thiamine  eficiency and sepsis may be associated with hyperlactatemia and hypotension. We assessed the relationship between thiamine compounds, lactate concentrations and clinical outcomes in septic patients.We undertook a prospective observational single-center study. Erythrocyte levels of total thiamine, free thiamine, thiamine mono, di and triphosphate (TMP, TDP, and TTP respectively), the erythrocyte transketolase activity (ETKA) and the effect of thiamine diphosphate on ETKA were measured in septic patients by high performance liquid chromatography and correlated with arterial lactate. Vital status at the end of intensive care unit stay was recorded.Overall, 28 patients suffering from sepsis were included. Median (interquartile range [IQR]) age was 60 [44-77.3] years, 15 (53.6%) patients were male, median [IQR] simplified acute physiology score II was 40 [27-50]. There was no correlation between total thiamine and lactate levels (P = .33). There was no correlation between free thiamine (P = .81), TMP (P = .71), TDP (P = .31), TTP (P = .86), and lactate levels in our population.
There was no correlation between ETKA (P = .58) or the effect of TDP on ETKA (P = .40) and lactate concentration. Total thiamine and TDP concentration were  significantly higher in intensive care unit (ICU) survivors than in nonsurvivors (P = .03 and P = .03). The effect of TDP on ETKA was significantly higher in nonsurvivors compared to survivors (P = .04).We found no correlation between thiamine compounds and lactate concentration in sepsis. Thiamine deficiency in sepsis may be associated with ICU-mortality.

DOI: 10.1097/MD.0000000000018894

PMCID: PMC7035069

PMID: 32049788 [Indexed for MEDLINE]

 

1. PLoS One. 2020 Jan 29;15(1):e0227862. doi: 10.1371/journal.pone.0227862. eCollection 2020.

Effect of phase-change material blood containers on the quality of red blood cells during transportation in environmentally-challenging conditions.

Yi X(1), Liu M(1), Wang J(1), Luo Q(2), Zhuo H(2), Yan S(1), Wang D(1), Han Y(1).

Author information:

(1)Beijing Key Laboratory of Blood Safety Supply Technologies, Key Laboratory of Blood Safety Supply Technologies of PLA, Institute of Transfusion Medicine, Academy of Military Medical Science, Beijing, China.

(2)Transfusion Department, Beijing, China.

 BACKGROUND: The effect of phase-change material blood containers on the quality of stored red blood cells (RBCs) transported in the Qinghai-Tibet Plateau remains to be studied.
STUDY DESIGN AND METHODS: RBCs stored in a phase-change material blood container were transported from Chengdu to Tibet and then back to Chengdu. The detection time points were the 1st day of fresh-collected RBCs (group 1), the 14th day of resting refrigerated storage (group 2), and the 14th day of plateau transportation under refrigerated storage in the container (group 3). RBC counts, hemoglobin (HGB) content, free hemoglobin (FHb) content, blood biochemical indexes, hemorheologic indexes and 2,3-DPG content were detected.
RESULTS: Compared with group 2, RBC counts and HGB were decreased, and the mean corpuscular volume (MCV), FHb and K+ content were increased in group 3. The glucose consumption and lactic acid production were significantly increased in groups 2 and 3. Compared with group 2, the 2,3-DPG content and whole blood viscosity were decreased in group 3. After resting refrigerated storage and plateau transportation, the RBC quality still met the national standard (GB18469-2012 whole blood and component blood quality requirements).
CONCLUSION: The phase-change material blood container can be maintained at a constant temperature under plateau environmental conditions, ensuring that the quality of the stored RBCs is compliant with GB18469-2012 whole blood and component blood quality requirements.

DOI: 10.1371/journal.pone.0227862

PMCID: PMC6988926

PMID: 31995595 [Indexed for MEDLINE]

 

1. Int J Sports Med. 2020 May;41(5):318-327. doi: 10.1055/a-0975-9532. Epub 2020 Jan 23.

Anaerobic Threshold Biophysical Characterisation of the Four Swimming Techniques.

Carvalho DD(1)(2), Soares S(1), Zacca R(1)(2)(3), Sousa J(1), Marinho DA(4)(5), Silva AJ(5)(6), Vilas-Boas JP(1)(2), Fernandes RJ(1)(2).

Author information:

(1)Faculty of Sport, Centre of Research, Education, Innovation and Intervention in Sport, University of Porto, Porto, Portugal.

(2)Porto Biomechanics Laboratory, University of Porto, Porto, Portugal.

(3)CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.

(4)Department of Sport Sciences, University of Beira Interior, Covilhã, Portugal.

(5)Research Center in Sports Sciences, Health Sciences and Human Development, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.

(6)Department Sport Sciences, University Trás-os-Montes and Alto Douro, Vila Real, Portugal.

The anaerobic threshold (AnT) seems to be not only a physiologic boundary but also a transition after which swimmers technique changes, modifying their biomechanical behaviour. We expanded the AnT concept to a biophysical construct in the four conventional swimming techniques. Seventy-two elite swimmers performed a 5×200 m incremental protocol in their preferred swimming technique (with a 0.05 m·s-1 increase and a 30 s interval between steps). A capillary blood samples were collected from the fingertip and stroke rate (SR) and length (SL) determined for the assessment of [La], SR and SL vs. velocity inflexion points (using the interception of a pair of linear and exponential regression curves). The [La] values at the AnT were 3.3±1.0, 3.9±1.1, 2.9±1 .34 and 4.5±1.4 mmol·l-1 (mean±SD) for front crawl, backstroke, breaststroke and butterfly, and its corresponding velocity correlated highly with those at SR and SL inflection points (r=0.91-0.99, p<0.001). The agreement analyses confirmed that AnT represents a biophysical boundary in the four competitive swimming techniques and can be determined individually using [La] and/or SR/SL. Blood lactate increase speed can help characterise swimmers' anaerobic behaviour after AnT and between competitive swimming techniques.

DOI: 10.1055/a-0975-9532

PMID: 31975360 [Indexed for MEDLINE]

1. J Sports Med Phys Fitness. 2020 Mar;60(3):361-366. doi: 10.23736/S0022-4707.19.10166-1. Epub 2020 Jan 20.

Mild dehydration following voluntary water intake reduction does not affect anaerobic power performance.

Hosick PA(1), Sheris A(2), Alencewicz JS(2), Matthews EL(2).

Author information:

(1)Department of Exercise Science and Physical Education, Montclair State University, Montclair, NJ, USA - hosickp@montclair.edu.

(2)Department of Exercise Science and Physical Education, Montclair State University, Montclair, NJ, USA.

BACKGROUND: Dehydration is common among athletes. The negative impact of dehydration on aerobic performance is well characterized. However, little is known about the effect of dehydration on anaerobic performance particularly when dehydration results from insufficient water intake, not water loss due to body temperature regulation. The purpose of this study was to examine the effect of dehydration on anaerobic performance following voluntary water intake reduction.
METHODS: Fifteen healthy adults completed two exercise sessions, euhydrated (EUD) and dehydrated (DEH). Sessions consisted of baseline anthropometric and blood lactate measurement followed by a 30-second Wingate test and three vertical jump trials to measure anaerobic performance. Additional blood lactate measurements were taken immediately and at 5, 10, and 15 minutes after taking the Wingate test.
RESULTS: The dehydration protocol resulted in a reduction in body mass (EUD 69.1±17.2 kg, DEH 68.1±16.6 kg, P=0.039). The 30-s Wingate peak power (EUD 971±302 W, DEH 960±316 W, P=0.578) was not different between conditions, nor was the vertical jump height (EUH 26.4±4.5 cm, DEH 26.6±3.6 cm, P=0.778). Blood lactate (P<0.001) was elevated immediately following the 30-s Wingate test which remained throughout the trial. There were no differences in blood lactate between conditions.
CONCLUSIONS: Acute anaerobic power and exercise performance is not negatively affected by voluntary dehydration.

DOI: 10.23736/S0022-4707.19.10166-1

PMID: 31958003 [Indexed for MEDLINE]

 

1. PLoS One. 2020 Jan 15;15(1):e0227640. doi: 10.1371/journal.pone.0227640. eCollection 2020.

Comparison of blood lactate and perceived exertion responses in two matched time-under-tension protocols.

Vargas-Molina S(1)(2), Martín-Rivera F(3), Bonilla DA(4), Petro JL(5), Carbone L(6), Romance R(2), deDiego M(1), Schoenfeld BJ(7), Benítez-Porres J(2).

Author information:

(1)EADE-University of Wales Trinity Saint David, Málaga, Spain.

(2)Human Kinetics and Body Composition Laboratory, University of Málaga, Spain.

(3)Research Unit in Sports and Health, University of Valencia, Valencia, Spain.

(4)Research Division, DBSS International, Bogotá, Colombia.

(5)Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba, Montería, Colombia.

(6)University of Salvador, Buenos Aires, Argentina.

(7)Health Sciences Department, CUNY Lehman College, Bronx, NY, United States of America.

PURPOSE: The aim of this study was to compare the concentration of blood lactate [bLa-] and the subjective perception of exertion of trained men in a moderate repetition protocol (MRP) versus a high repetition protocol (HRP) equated for time under tension.
METHODS: A sample of 40 healthy young men (aged, 23.2 ± 4.0 years; height, 177.3 ± 7.0 cm; BMI, 24.3 ± 2.2) performed two sessions of 8 sets of bicep curls with a one-week recovery interval between the trials. In the HRP protocol, 20 repetitions were performed with a cadence of 2 seconds of eccentric and 1 second of concentric, while in the MRP protocol 10 repetitions were performed with 4 seconds of eccentric and 2 seconds of concentric. Cadences were controlled by a metronome. At the beginning and end of each of the sessions, blood lactate was taken at 2, 15, and 30 minutes, and rating of perceived exertion (OMNI-RES) was assessed immediately after completion of each session.
RESULTS: There were [bLa-] differences between protocols in the MRP 2 min, (5.2 ±1.4); 15 min, (3.2 ±1.2); 30 min, (1.9 ±0.6); p< 0.05, and the HRP 2 min, (6.1 ±1.6); 15 min, (3.7 ±1.1); 30 min, (2.2 ±0.6); p<0.01. OMNI-RES was higher in HRP, (8.8 ±0.7) than in MRP, (7.7 ±0.9). Additionally, a correlation was found between the RPE and [bLa-] values in the HRP protocol (rs = 0.35, p < 0.01).
CONCLUSIONS: Training protocols with high times under tension promote substantial increases in metabolic stress, however, our findings indicate that HRP generates more [bLa-] than MRP. In addition, there were higher RPE values in the HRP protocol compared to MRP in single-joint exercises.

DOI: 10.1371/journal.pone.0227640

PMCID: PMC6961884

PMID: 31940407 [Indexed for MEDLINE
 

1. Nat Biotechnol. 2020 Mar;38(3):309-313. doi: 10.1038/s41587-019-0377-7. Epub 2020 Jan 13.

An engineered enzyme that targets circulating lactate to alleviate intracellular NADH:NAD(+) imbalance.

Patgiri A(1)(2)(3), Skinner OS(1)(2)(3), Miyazaki Y(4), Schleifer G(4), Marutani E(4), Shah H(1)(2)(3), Sharma R(1)(2)(3), Goodman RP(1)(2)(3)(5), To TL(1)(2)(3), Robert Bao X(1)(2)(3)(6), Ichinose F(4), Zapol WM(4), Mootha VK(7)(8)(9).

Author information:

(1)Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.

(2)Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

(3)Broad Institute, Cambridge, MA, USA.

(4)Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital, Boston, MA, USA.

(5)Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.

(6)iLISATECH, Inc., Houston, TX, USA.

(7)Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA. vamsi@hms.harvard.edu.

(8)Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

 (9)Broad Institute, Cambridge, MA, USA. vamsi@hms.harvard.edu.

 An elevated intracellular NADH:NAD+ ratio, or 'reductive stress', has been associated with multiple diseases, including disorders of the mitochondrial electron transport chain. As the intracellular NADH:NAD+ ratio can be in near equilibrium with the circulating lactate:pyruvate ratio, we hypothesized that reductive stress could be alleviated by oxidizing extracellular lactate to pyruvate. We engineered LOXCAT, a fusion of bacterial lactate oxidase (LOX) and catalase (CAT), which irreversibly converts lactate and oxygen to pyruvate and water. Addition of purified LOXCAT to the medium of cultured human cells with a defective electron transport chain decreased the extracellular lactate:pyruvate ratio, normalized the intracellular NADH:NAD+ ratio, upregulated glycolytic ATP production and restored cellular proliferation. In mice, tail-vein-injected LOXCAT lowered the circulating lactate:pyruvate ratio, blunted a metformin-induced rise in blood lactate:pyruvate ratio and improved NADH:NAD+ balance in the heart and brain. Our study lays the groundwork for a class of injectable therapeutic enzymes that alleviates intracellular redox imbalances by directly targeting circulating redox-coupled metabolites.

DOI: 10.1038/s41587-019-0377-7

PMCID: PMC7135927

PMID: 31932725 [Indexed for MEDLINE]

 

1. Neurology. 2020 Feb 18;94(7):e687-e698. doi: 10.1212/WNL.0000000000008861. Epub 2020 Jan 2.

Safety and efficacy of omaveloxolone in patients with mitochondrial myopathy: MOTOR trial.

Madsen KL(1), Buch AE(2), Cohen BH(2), Falk MJ(2), Goldsberry A(2), Goldstein A(2), Karaa A(2), Koenig MK(2), Muraresku CC(2), Meyer C(2), O'Grady M(2), Scaglia F(2), Shieh PB(2), Vockley J(2), Zolkipli-Cunningham Z(2), Haller RG(2), Vissing J(2).

Author information:

(1)From Copenhagen Neuromuscular Center (K.L.M., A.E.B., J.V.), Rigshospitalet, University of Copenhagen, Denmark; Akron Children's Hospital (B.H.C.), OH; Mitochondrial Medicine Frontier Program, Department of Pediatrics (M.J.F., C.C.M., Z.Z.C.), The Children's Hospital of Philadelphia; University of Pennsylvania Perelman School of Medicine (M.J.F., Z.Z.C.), Philadelphia; Reata Pharmaceuticals (A. Goldsberry, C.M., M.O.), Irving, TX; University of Pittsburgh School of Medicine (A. Goldstein, J.V.), Children's Hospital of Pittsburgh of UPMC, PA; Genetics Unit (A.K.), Massachusetts General, Boston; University of Texas Medical School (M.K.K.); Baylor College of Medicine (F.S.); Texas Children's Hospital (F.S.), Houston; BCM-CUHK Center of Medical Genetics (F.S.), Prince of Wales Hospital, ShaTin, New Territories, Hong Kong; University of California Los Angeles (P.B.S.); and University of Texas Southwestern Medical Center and Neuromuscular Center (R.G.H.), Institute for Exercise & Environmental Medicine, Dallas. karen.lindhardt.madsen@regionh.dk.

(2)From Copenhagen Neuromuscular Center (K.L.M., A.E.B., J.V.), Rigshospitalet, University of Copenhagen, Denmark; Akron Children's Hospital (B.H.C.), OH; Mitochondrial Medicine Frontier Program, Department of Pediatrics (M.J.F., C.C.M., Z.Z.C.), The Children's Hospital of Philadelphia; University of Pennsylvania Perelman School of Medicine (M.J.F., Z.Z.C.),Philadelphia; Reata Pharmaceuticals (A. Goldsberry, C.M., M.O.), Irving, TX; University of Pittsburgh School of Medicine (A. Goldstein, J.V.), Children's Hospital of Pittsburgh of UPMC, PA; Genetics Unit (A.K.), Massachusetts General, Boston; University of Texas Medical School (M.K.K.); Baylor College of Medicine (F.S.); Texas Children's Hospital (F.S.), Houston; BCM-CUHK Center of Medical Genetics (F.S.), Prince of Wales Hospital, ShaTin, New Territories, Hong Kong; University of California Los Angeles (P.B.S.); and University of Texas Southwestern Medical Center and Neuromuscular Center (R.G.H.), Institute for Exercise & Environmental Medicine, Dallas.

OBJECTIVE: To investigate the safety and efficacy of escalating doses of the semi-synthetic triterpenoid omaveloxolone in patients with mitochondrial myopathy.
METHODS: In cohorts of 8-13, 53 participants were randomized double-blind to 12 weeks of treatment with omaveloxolone 5, 10, 20, 40, 80, or 160 mg, or placebo.
Outcome measures were change in peak cycling exercise workload (primary), in 6-minute walk test (6MWT) distance (secondary), and in submaximal exercise heart rate and plasma lactate (exploratory).
RESULTS: No differences in peak workload or 6MWT were observed at week 12 with omaveloxolone treatment vs placebo for all omaveloxolone dose groups. In contrast, omaveloxolone 160 mg reduced heart rate at week 12 by 12.0 ± 4.6 bpm (SE) during submaximal exercise vs placebo, p = 0.01, and by 8.7 ± 3.5 bpm (SE) vs baseline, p = 0.02. Similarly, blood lactate was 1.4 ± 0.7 mM (SE) lower vs placebo, p = 0.04, and 1.6 ± 0.5 mM (SE) lower vs baseline at week 12, p = 0.003, with omaveloxolone 160 mg treatment. Adverse events were generally mild and infrequent.
CONCLUSIONS: Omaveloxolone 160 mg was well-tolerated, and did not lead to change in the primary outcome measure, but improved exploratory endpoints lowering heart rate and lactate production during submaximal exercise, consistent with improved mitochondrial function and submaximal exercise tolerance. Therefore, omaveloxolone potentially benefits patients with mitochondrial myopathy, which encourages further investigations of omaveloxolone in this patient group.
CLINICALTRIALSGOV IDENTIFIER: NCT02255422.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, for patients with mitochondrial myopathy, omaveloxolone compared to placebo did not significantly change peak exercise workload.

DOI: 10.1212/WNL.0000000000008861

PMCID: PMC7176297

PMID: 31896620 [Indexed for MEDLINE]

 

1. Nat Rev Rheumatol. 2020 Jan;16(1):4. doi: 10.1038/s41584-019-0344-1.

Lactate rewires synovial T cells in RA.

Clarke J(1).

Author information:

(1)Nature Reviews Rheumatology, . nrrheum@nature.com.

Comment on Cell Metab. 2019 Dec 3;30(6):1055-1074.e8.

DOI: 10.1038/s41584-019-0344-1

PMID: 31772291 [Indexed for MEDLINE]

 

1. World J Surg. 2020 Jan;44(1):21-29. doi: 10.1007/s00268-019-05181-x.

The Combined SIRS + qSOFA (qSIRS) Score is More Accurate Than qSOFA Alone in Predicting Mortality in Patients with Surgical Sepsis in an LMIC Emergency Department.

Green SL(1), Smith MTD(2), Cairns C(3), Clarke DL(2), Bruce J(2), Bekker W(2), Kong V(2), Laing GL(2).

Author information:

(1)Department of Anaesthesia, Critical Care and Pain Management, University of KwaZulu Natal, 201 Townbush Road, Pietermaritzburg, 3201, South Africa.

 (2)Department of Surgery, University of KwaZulu Natal, 201 Townbush Road,Pietermaritzburg, 3201, South Africa.

(3)Department of Anaesthesia, Critical Care and Pain Management, University of KwaZulu Natal, 201 Townbush Road, Pietermaritzburg, 3201, South Africa.

BACKGROUND: qSOFA has been proposed as a prognostic tool in patients with sepsis. This study set out to assess the sensitivity of several scores, namely: the pre-ICU qSOFA, the qSOFA with lactate (qSOFA L), SIRS score, qSOFA + SIRS score (qSIRS) and qSIRS with lactate (qSIRS L) in predicting in-hospital mortality in patients with surgical sepsis as well as the sensitivity of these scores in predicting high-grade sepsis. The secondary aim was to determine which of these scores is best suited to predict high-grade surgical sepsis.
METHODS: This was a retrospective cohort study that was conducted between December 2012 and August 2017 in a public metropolitan surgical service. Data from patients aged > 13 years, who were admitted to the hospital and who had an emergency surgical procedure for source control were retrieved from a prospectively maintained hybrid electronic database. The qSOFA, qSOFA plus lactate (qSOFA L), SIRS and qSOFA + SIRS (qSIRS), as well as the qSIRS plus lactate (qSIRS L), were calculated for each patient. A lactate level that was greater than 2mmol/L was deemed to be a positive finding. Any score ≥2 was deemed to be a positive score. The outcome measure was in-hospital mortality.
The prognostic value of qSOFA, qSOFA L, SIRS, qSIRS and qSIRS L was studied.
Receiver operating characteristic analyses were performed to determine the area under the curve (AUC), sensitivity, specificity and positive and negative likelihood ratios for positive qSOFA, qSOFA L, SIRS, qSIRS, and qSIRS L.
Contingency tables were used to calculate the sensitivity, specificity, PPV and NPV for predicting severe or high-grade surgical sepsis.
RESULTS: There were a total number of 1884 patients in the sample group of whom 855 were female (45.4%). The median patient age was 36 years (IQR 23-56). A total of 1489 patients (79%) were deemed to have high-grade sepsis based on an advanced EGS AAST grading, whilst 395 patients (21%) had low-grade sepsis. A total of 71 patients died (3.8%). Of these patients who died, 67 (94.4%) had high-grade sepsis and 4 (5.6%) had low-grade sepsis. The mortality rate in the high-grade sepsis group was 4.5%, whilst the mortality rate in the low-grade sepsis group was 1%. The scores with the greatest accuracy in predicting mortality were qSIRS (AUROC 0.731, 95% CI 0.68-0.78), followed by SIRS (AUROC 0.70, 95% CI 0.65-0.75). The qSOFA and qSOFA L were the least accurate in predicting mortality (AUROC 0.684, 95% CI 0.63-0.74 for both). The addition of lactate had no significant effect on the accuracy of the five scores in predicting mortality. Patients with a qSOFA ≥ 2 have an increased risk of dying (OR 5.8), as do patients with a SIRS score ≥2 (OR 2.7). qSIRS L had the highest sensitivity (69%) in predicting the presence of high-grade surgical sepsis, followed by qSIRS (65.5% sensitivity). qSOFA showed a very low sensitivity of only 4.5% and a high specificity of 99.2%. The addition of lactate to the score marginally improved the sensitivity. Lactate of 2mmol/L or more was also an independent predictor of high-grade sepsis.
CONCLUSION: The qSIRS score is most accurate in predicting mortality in surgical sepsis. The qSOFA score is inferior to both the SIRS and the qSIRS scores in predicting mortality. The qSIRS score with the addition of lactate to the qSIRS score made it the most sensitive score in predicting high-grade surgical sepsis.

DOI: 10.1007/s00268-019-05181-x

PMID: 31641836 [Indexed for MEDLINE]

 

1. Med Sci Sports Exerc. 2020 Jan;52(1):187-195. doi: 10.1249/MSS.0000000000002098.

Muscle Glycogen Content during Endurance Training under Low Energy Availability.

Kojima C(1)(2), Ishibashi A(2), Tanabe Y(2)(3), Iwayama K(4), Kamei A(2), Takahashi H(2), Goto K(1).

Author information:

(1)Graduate School of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, JAPAN.

(2)Japan Institute of Sports Sciences, Nishigaoka, Kitaku, Tokyo, JAPAN.

(3)Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, JAPAN.

(4)Department of Budo and Sport Studies, Tenri University, Tenri, Nara, JAPAN.

PURPOSE: The present study investigated the effects of three consecutive days of endurance training under conditions of low energy availability (LEA) on the muscle glycogen content, muscle damage markers, endocrine regulation, and endurance capacity in male runners.
METHODS: Seven male long-distance runners (19.9 ± 1.1 yr, 175.6 ± 4.7 cm, 61.4 ± 5.3 kg, maximal oxygen uptake [V˙O2max]: 67.5 ± 4.3 mL·kg·min) completed two trials consisting of three consecutive days of endurance training under LEA (18.9 ± 1.9 kcal·kg FFM·d) or normal energy availability (NEA) (52.9 ± 5.0 kcal·kg FFM·d).The order of the two trials was randomized, with a 2-wk interval between trials. The endurance training consisted of 75 min of treadmill running at 70% of V˙O2max. Muscle glycogen content, respiratory gas variables, and blood and urine variables were measured in the morning for three consecutive days of training (days 1-3) and on the following morning after training (day 4). As an indication of endurance capacity, time to exhaustion at 19.0 ± 0.8 km·h to elicit 90% of V˙O2max was evaluated on day 4.
RESULTS: During the training period, body weight, fat-free mass, and skeletal muscle volume were significantly reduced in LEA (P = 0.02 for body weight and skeletal muscle volume, P = 0.01 for fat-free mass). Additionally, muscle glycogen content was significantly reduced in LEA (~30%, P < 0.001), with significantly lower values than those in NEA (P < 0.001). Time to exhaustion was not significantly different between the two trials (~20 min, P = 0.39).
CONCLUSIONS: Three consecutive days of endurance training under LEA decreased muscle glycogen content with lowered body weight. However, endurance capacity was not significantly impaired.

DOI: 10.1249/MSS.0000000000002098

PMID: 31343520 [Indexed for MEDLINE]

 

1. J Strength Cond Res. 2020 Jan;34(1):152-161. doi: 10.1519/JSC.0000000000003065.

Effect of a Carbohydrate-Electrolyte Solution on Fluid Balance and Performance at a Thermoneutral Environment in International-Level Fencers.

Chryssanthopoulos C(1)(2), Tsolakis C(1), Bottoms L(3), Toubekis A(1), Zacharogiannis E(1), Pafili Z(4), Maridaki M(1).

Author information:

(1)School of Physical Education and Sports Science, National and Kapodistrian University of Athens, Athens, Greece.

(2)Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

(3)Department of Psychology and Sports Science, School of Life and Medical Science, University of Hertfordshire, Hatfield, United Kingdom.

(4)Department of Dietetics, Achillopoulion General Hospital, Volos, Greece.

The purpose of the study was to examine a possible effect of a carbohydrate-electrolyte (CHO-E) solution on fluid balance and performance in fencing at a thermoneutral environment. Sixteen fencers performed two 120-minute training sessions separated by 7-14 days under similar environmental conditions (temperature: 20.3° C and humidity: 45-47%). Each session consisted of 60-minute conditioning exercises followed by 10 bouts of 3 minutes against the same opponent with 3-minute interval between each bout. Participants ingested at regular intervals either a 6% CHO-E solution or an artificially sweetened water (PL) in a counterbalanced order. No difference was observed between conditions in the heart rate responses, perceived exertion, changes in plasma volume, urine specific gravity, number of bouts won or lost, or points for and against.
Considerable variability was observed in body mass changes that revealed significant differences at the time level (i.e., pre- vs. post-exercise) (F1,15 = 9.31, p = 0.008, η = 0.38), whereas no difference was found between conditions (i.e., CHO-E vs. PL) (F1,15 = 0.43, p = 0.52, η = 0.03) and conditions × time interaction (F1,15 = 3.57, p = 0.078, η = 0.19). Fluid loss was not significantly different between conditions (p = 0.08, d = 0.47). The blood glucose level was higher (p < 0.01) after exercise in CHO-E, whereas the blood lactate level was similar between conditions. In conclusion, the CHO-E solution was as effective as the artificially sweetened water in terms of fluid balance and fencing performance at a thermoneutral environment. Because of large individual variability, fencers should monitor their fluid intake and body fluid loss in training and competition.

DOI: 10.1519/JSC.0000000000003065

PMID: 30741860 [Indexed for MEDLINE]

 

1. J Neurosurg Anesthesiol. 2020 Jan;32(1):77-81. doi: 10.1097/ANA.0000000000000563.

Prognostic Value of Tissue Oxygen Monitoring and Regional Cerebral Oxygen Saturation Monitoring and Their Correlation in Neurological Patients with Sepsis: A Preliminary, Prospective, Observational Study.

Das BP(1), Sharma M, Bansal S, Philip M, Umamaheswara Rao GS.

Author information:

(1)Department of Neuroanaesthesia and Neurocritical Care, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

 BACKGROUND: There is paucity of literature on the prognostic value of tissue oxygen saturation (StO2) and regional cerebral oxygen saturation (rSO2) in neurological patients with sepsis. In this preliminary study, we investigated the prognostic value of StO2 and rSO2 in a group of neurological patients and correlated StO2 and rSO2 with hemodynamic and metabolic parameters.
MATERIALS AND METHODS: This preliminary, prospective observational study was conducted in 45 adult neurological patients admitted to intensive care unit.
Once a diagnosis of sepsis or septic shock was established, parameters of oxygenation (StO2, rSO2, central venous oxygen saturation [ScvO2]), serum lactate, illness severity scores (Acute Physiology and Chronic Health Evaluation score, Sequential Organ Failure Assessment score, Glasgow Coma Scale) were recorded at 0, 6, 12, 24, 36, and 48 hours, and once dailythereafter. Outcomes were in-hospital mortality attributable to sepsis and the Glasgow outcome score at hospital discharge.
RESULTS: There was a moderately positive correlation between StO2 and rSO2 at baseline (r=0.599; P=0.001). StO2, illness severity scores and serum lactate, but not rSO2, were significantly different between survivors (n=29) and nonsurvivors (n=16) at baseline and during the first 48 hours. An rSO2 of 62.5% had a sensitivity of 83% and specificity of 67% to differentiate survivors and nonsurvivors of septic shock at 48 hours. StO2 had a higher correlation with ScvO2 and serum lactate than rSO2.
CONCLUSIONS: StO2 prognosticates su